Podcast appearances and mentions of Kevin Davies

GEN editors discuss both the news and history of DNA and genetic engineering. We present a recap of the 50th anniversary Asilomar conference, delving into some of the history from the 1975 Asilomar conference and relating to the current discussions around genetic engineering. Science has been under fire recently and many people attended the Stand Up for Science Rally at one of a few dozen locations across the United States. One of the speakers at the rally in Washington, DC, was former NIH director Francis Collins, MD, PhD, a key member of the Human Genome Project. We discuss some of his career in this episode. Join GEN's managing editor Corinna Singleman, PhD, editor in chief John Sterling, and editorial director Kevin Davies for a discussion of DNA news and history. Listed below are links to the GEN stories referenced in this episode of Touching Base: Scientists in NYC Rally to Defend and Stand Up for Science By Corinna Singleman, PhD, GEN, March 10, 2025 Former NIH Director Francis Collins Praises the Institution as He Abruptly Departs After Three Decades By Kevin Davies, PhD, GEN, March 3, 2025 Hosted on Acast. See acast.com/privacy for more information.

Send us a textIn the latest episode of Too Hot For TV Dylan is joined by Joe Ford & Michael Mills to discuss 'Shakedown: Return of the Sontarans' written by Terrance Dicks, directed by Kevin Davies and starring Jan Chappell. Brian Croucher, Carole Ann Ford, Sophie Aldred, Rory O'Donnell and Michael Wisher. Then they listen to 'Sontarans: Silent Warrior' written by Peter Grehan and directed by Tim Saward. Together they answer the burning questions: Who is too straight for large parts of Doctor Who? What is the eternal bed time battle? Why did you never seeThe Stranger on the Big Breakfast? 

Where should humans draw the line with gene editing? Is CRISPR the "holy grail" of science, or is editing human DNA ethical at all? Zachary and Emma speak with Kevin Davies, executive editor of The CRISPR Journal and author of "Editing Humanity." They discuss gene editing, specifically CRISPR, and its implications for mankind's future, the successes of gene editing for agriculture and treating sickle cell disease, and Chinese biophysicist He Jiankui's unlawful meddling in the DNA of three embryos, now kids living in China with unknown health effects. What Could Go Right? is produced by The Progress Network and The Podglomerate. For transcripts, to join the newsletter, and for more information, visit: theprogressnetwork.org Watch the podcast on YouTube: https://www.youtube.com/theprogressnetwork And follow us on X, Instagram, Facebook, TikTok: @progressntwrk Learn more about your ad choices. Visit megaphone.fm/adchoices

Who is the Premier League's greatest striker? This week the boys debate and rank the top Premier League Strikers. Will Bobby convince Jim to put Kevin Davies in the top 10? Plus news on: Tonali The Ballon D'Or Jude Bellingham and Fury vs Ngannou

On Faster, Please! — The Podcast, I've interviewed guests on exciting new technologies like artificial intelligence, fusion energy, and reusable rockets. But today's episode explores another Next Big Thing: biotechnology. To discuss recent advances in CRISPR gene editing and their applications for medicine, I'm sitting down with Kevin Davies.Kevin is executive editor of The CRISPR Journal and author of the excellent 2020 book, Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing.In This Episode* CRISPR advances over the past decade (1:13)* What CRISPR therapies will come next? (8:46)* Non-medical applications of gene editing (13:11)* Bioweapons and the ethics of CRISPR (18:43)* Longevity and genetic enhancements (25:48)Faster, Please! is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Below is an edited transcript of our conversationCRISPR advances over the past decadeWhen people talk about AI, for instance, they might be talking about different versions or applications of AI—machine learning being one. So when we talk about CRISPR, are we just talking about one technique, the one they figured out back in 2012? Are there different ones? Are there improvements? So it's really a different technique. So how has that progressed?You're right. CRISPR has become shorthand for genome editing. But the version of CRISPR that was recognized with the Nobel Prize three years ago in 2020 to Jennifer Doudna and Emmanuelle Charpentier was for one, we can call it the traditional form of CRISPR. And if I refer to it again, I'll call it CRISPR-Cas9. Cas9 is the shorthand name for the enzyme that actually does the cutting of the DNA. But we are seeing extraordinary progress in developing new and even more precise and more nuanced forms of genome editing. They still kind of have a CRISPR backbone. They still utilize some of the same molecular components as the Nobel Prize–winning form of CRISPR. But in particular, I'm thinking of techniques called base editing and prime editing, both of which have commercial, publicly funded biotech companies pushing these technologies into the clinic. And I think over the next five to 10 years, increasingly what we refer to as “CRISPR genome editing” will be in the form of these sort of CRISPR 2.0 technologies, because they give us a much broader portfolio of DNA substitutions and changes and edits, and give the investigators and the clinicians much more precision and much more subtlety and hopefully even more safety and more guarantees of clinical efficiency.Right. That's what I was going to ask. One advantage is the precision, because you don't want to do it wrong. You don't want mutations. Do no harm first. A big advantage is maybe limiting some of the potential downsides.In the ideal gene-editing scenario, you would have a patient with, say, a genetic disease that you can pinpoint to a single letter of the genetic code. And we want to fix that. We want to zero in on that one letter—A, C, T, or G is the four-letter alphabet of DNA, as I hope most of your listeners know—and we want to revert that back to whatever most normal, healthy people have in their genetic code at that specific position. CRISPR-Cas9, which won the Nobel Prize, is not the technology to do that sort of single base edit. It can do many other things, and the success in the clinic is unquestionable already in just a few years. But base editing and, in particular, prime editing are the two furthest developed technologies that allow investigators to pinpoint exactly where in the genome we want to make the edit. And then without completely cutting or slicing the double helix of DNA, we can lay up the section of DNA that we want to replace and go in and just perform chemistry on that one specific letter of DNA. Now, this hasn't been proven in the clinic just yet. But the early signs are very, very promising that this is going to be the breakthrough genome-editing technology over the next 10 to 20 years.Is CRISPR in the wild yet, or are we still in the lab?No, we're in the clinic. We are in human patients. There are at least 200 patients who have already been in or are currently enrolled in clinical trials. And so far, the early results—there are a few caveats and exceptions—but so far the overwhelming mood of the field is one of bullish enthusiasm. I don't want to complete this interview without singling out this one particular story, which is the clinical trial that has been sponsored by CRISPR Therapeutics and Vertex Pharmaceuticals for sickle cell disease. These are primarily African-American patients in this country because the sickle cell mutation arose in Africa some 7,000 years ago.We're talking about a pretty big share of the African-American population.This is about 100,000 patients just in America, in the US alone. And it's been a neglected disease for all kinds of reasons, probably beyond the scope of our discussion. But the early results in the first few dozen patients who have been enrolled in this clinical trial called the exa-cel clinical trial, they've all been cured. Pretty much all cured, meaning no more blood transfusions, no more pain crises, no more emergency hospitalizations. It is a pretty miraculous story. This therapy is now in the hands of the FDA and is speeding towards—barring some unforeseen complication or the FDA setting the bar so high that they need the investigators to go back and do some further checks—this should be approved before the end of this year.There's a catch, though. This will be a therapy that, in principle, will become—once approved by the FDA and the EMA in Europe, of course—will become available to any sickle cell patient. The catch will, of course, be the cost or the price that the companies set, because they're going to look for a return on their investment. It's a fascinating discussion and there's no easy answer. The companies need to reward their shareholders, their investors, their employees, their staff, and of course build a war chest to invest in the next wave, the next generation of CRISPR therapies. But the result of that means that probably we're going to be looking at a price tag of, I mean, I'm seeing figures like $1.9 million per patient. So how do you balance that? Is a lifetime cure for sickle cell disease worth $2, maybe $3 million? Will this patient population be able to afford that? In many cases, the answer to that will be simply, no. Do you have to remortgage your house and go bankrupt because you had a genetic quirk at birth? I don't know quite how we get around this.Different countries will have different answers with different health systems. Do you have a sense of what that debate is going to be like in Washington, DC?It's already happening in other contexts. Other gene therapies have been approved over the last few years, and they come with eye-watering price tags. The highest therapy price that I've seen now is $3.5 million. Yes, there are discounts and waiver programs and all this sort of stuff. But it's still a little obscene. Now, when those companies come to negotiate, say, with the UK National Health Service, they'll probably come to an agreement that is much lower, because the Brits are not going to say that they're going to be able to afford that for their significant sickle cell population.Is it your best guess that this will be a treatment the government pays for?What's interesting and what may potentially shift the calculus here is that this particular therapy is the disease affects primarily African-Americans in the United States. That may change the political calculus, and it may indeed change the corporate calculus in the boardrooms of Vertex and CRISPR Therapeutics, who may not want the backlash that they're going to get when they say, “Oh, by the way, guys, it's $2 million or you're out of luck.”There are companies that are studying using CRISPR to potentially correct the mutations that cause genetic forms of blindness, genetic forms of liver disease.What CRISPR therapies will come next?And after this CRISPR treatment for sickle cell disease is available, what therapies will come next?Probably a bunch of diseases that most people, unless they are unfortunate enough to have it in their family, won't have heard of. There are companies that are studying using CRISPR to potentially correct the mutations that cause genetic forms of blindness, genetic forms of liver disease. It turns out the liver is an organ that is very amenable to taking up medicines that we can inject in the blood. The other big clinical success story has come from another company in the Boston area called Intellia Therapeutics. Also publicly traded. They've developed CRISPR therapies that you can inject literally into the body, rather than taking cells out and doing it in the lab and then putting those cells back in, as in the case of sickle cell.I'm not sure that was actually even clear: that you can do it more than one way.Yes.And obviously it sounds like it would be better if they could just inject you.Exactly. That's why people are really excited about this, because this now opens up the doors for treating a host of diseases. And I think over the next few years we will see a growing number of diseases, and it won't just be these rare sort of genetic diseases with often unpronounceable names. It may be things like heart disease. There's another company—they're all in Boston, it seems—Verve Therapeutics, which is taking one of these more recent gene-editing technologies that we talked about a minute ago, base editing, and saying that there's a gene that they're going to target that has been clearly linked with cholesterol levels. And if we can squash production of this gene, we can tap down cholesterol levels. That will be useful, in the first instance, for patients with genetic forms of high cholesterol. Fair enough. But if it works in them, then the plan is to roll this out for potentially thousands if not millions of adults in this country who maybe don't feel that they have a clearly defined genetic form of high cholesterol, but this method may still be an alternative that they will consider versus taking Atorvastatin for the rest of your life, for example.Where are the CRISPR cancer treatments?They're also making progress, too. Those are in clinical trials. A little more complicated. Of course, cancer is a whole slew of different diseases, so it's a little hard to say, “Yeah, we're making progress here, less so there.” But I think one of the most heartwarming stories—this is an n of one, so it's an anecdotal story—but there was a teenager in the UK treated at one of the premier London medical schools who had a base editing form of CAR T therapy. A lot of people have heard of CAR T therapy for various cancers. And she is now in remission. So again, early days, but we're seeing very positive signs in these early clinical tests.It sounds like we went from a period where it was all in the lab and that we might be in a period over the next five years where it sounds like a wave of potential treatments.I think so, yeah.And for as much as we've seen articles about “The Age of AI,” it really sounds like this could be the age of biotechnology and the age of CRISPR…I think CRISPR, as with most new technologies, you get these sort of hype cycles, right? Two and a half years ago, CRISPR, all the stocks were at peak valuations. And I went on a podcast to say, why are the CRISPR stocks so high? I wasn't really sure, but I was enjoying it at the time. And then, of course, we entered the pandemic. And the biotech sector, perversely, ironically, has really been hit hard by the economy and certainly by the market valuations. So all of the CRISPR gene-editing companies—and there are probably at least eight or 10 now that are publicly traded and many more poised to join them—their valuations are a fraction of what they were a couple of years ago. But I suspect as these first FDA approvals and more scientific peer review papers, of course, but more news of the clinical success to back up and extend what has already been clearly proven as a breakthrough technology in the lab with the Nobel Prize—doesn't get much better than that, does it?—then I think we're going to start to see that biotech sector soar once again.Certainly, there are a lot of computational aspects to CRISPR in terms of designing the particular stretches of nucleic acid that you're going to use to target a specific gene. And AI can help you in that quest to make those ever more precise.Non-medical applications of gene editingThere are also non-medical applications. Can you just give me a little state of play on how that's looking?I think one of the—when CRISPR…And agriculture.Feeding the planet, you could say.That's certainly a big application.It's a human health application—arguably the biggest application.I think one of the fun ones is the work of George Church at Harvard Medical School, who's been on 60 Minutes and Stephen Colbert and many other primetime shows, talking about his work using CRISPR to potentially resurrect the woolly mammoth, which sort of sounds like, “That's Jurassic Park on steroids. That's crazy.” But his view is that, no, if we had herds—if that's the technical term—of woolly mammoths—roaming Siberia and the frozen tundra, they'll keep the ground, the surface packed down and stop the gigatons of methane from leaching out into the atmosphere. We have just seen a week, I've been reading on social media, of the hottest temperatures in the world since records began. And that's nothing compared to what we're potentially going to see if all these greenhouse gases that are just under the surface in places like Siberia further leach into the atmosphere. So that's the sort of environmental cause that Church is on. I think many people think this is a rather foolish notion, but he's launched a company to get this off the ground called Colossal Biosciences, and they're raising a lot of money, it appears. I'm curious to see how it goes. I wish him well.Also, speaking of climate change, making crops more resilient to the heat. That's another I've heard…One of the journals I'm involved in, called GEN Biotechnology, just published a paper in which investigators in Korea have used CRISPR to modify a particular gene in the tomato genome to make it a higher source of vitamin D. And that may not seem to be the most urgent need, but the point is, we can now engineer the DNA of all kinds of plants and crops, many of which are under threat, whether it's from drought or other types of climate change or pests, bacteria, parasites, viruses, fungi, you name it. And in my book Editing Humanity, which came out a couple of years ago, there was a whole chapter listing a whole variety of threats to our favorite glass of orange juice in the morning. That's not going to exist. If we want that all-natural Florida orange juice, we're not going to have that option. We've either got to embrace what technology will allow us to do to make these orange crops more resistant to the existential threat that they're facing, or we're going to have to go drink something else.I started out talking about AI and machine learning. Does that play a role in CRISPR, either helping the precision of the technology or in some way refining the technology?Yeah, hopefully you'll invite me back in a year and I'll be able to give you a more concrete answer. I think the short answer is, yes. Certainly, there are a lot of computational aspects to CRISPR in terms of designing the particular stretches of nucleic acid that you're going to use to target a specific gene. And AI can help you in that quest to make those ever more precise. When you do the targeting in a CRISPR experiment, the one thing you don't want to have happen is for the little stretch of DNA that you've synthesized to go after the gene in question, you don't want that to accidentally latch onto or identify another stretch of DNA that just by statistical chance has the same stretch of 20 As, Cs, Ts, and Gs. AI can help give us more confidence that we're only honing in on the specific gene that we want to edit, and we're not potentially going to see some unforeseen, off-target editing event.Do you think when we look back at this technology in 10 years, not only will we see a wider portfolio of potential treatments, but we'll look at the actual technique and think, “Boy, back in 2012, it was a butchery compared to what we're doing; we were using meat cleavers, and now we're using lasers”?I think, yeah. That's a slightly harsh analogy. With this original form of CRISPR, published in 2012, Nobel Prize in 2020, one of the potential caveats or downsides of the technology is that it involves a complete snip of the double helix, the two strands of DNA, in order to make the edit. Base editing and prime editing don't involve that double-stranded severance. It's just a nick of one strand or the other. So it's a much more genetically friendly form of gene editing, as well as other aspects of the chemistry. We look forward to seeing how base and prime editing perform in the clinic. Maybe they'll run into some unforeseen hurdles and people will say, “You know what? There was nothing wrong with CRISPR. Let's keep using the originally developed system.” But I'm pretty bullish on what base and prime editing can do based on all of the early results have been published in the last few years on mice and monkeys. And now we're on the brink of going into the clinic.One medical scenario that they laid out would be, what if two people with a deadly recessive disease like sickle cell disease, or perhaps a form of cystic fibrosis, wanted to have a healthy biological child?Bioweapons and the ethics of CRISPRThis podcast is usually very optimistic. So we're going to leave all the negative stuff for this part of the podcast. We're going to rush through all the downsides very quickly.First question: Especially after the pandemic, a lot more conversation about bioweapons. Is this an issue that's discussed in this community, about using this technology to create a particularly lethal or virulent or targeted biological weapon?Not much. If a rogue actor or nation wanted to develop some sort of incredibly virulent bioweapon, there's a whole wealth of genetic techniques, and they could probably do it without involving CRISPR. CRISPR is, in a way, sort of the corollary of another field called synthetic biology or synthetic genomics that you may have talked about on your show. We've got now the facility, not just to edit DNA, but to synthesize custom bits of DNA with so much ease and affordability compared to five or 10 years ago. And we've just seen a global pandemic. When I get that question, I've had it before, I say, “Yeah, did we just not live through a global pandemic? Do we really need to be engineering organisms?” Whether you buy the lab leak hypothesis or the bioengineering hypothesis, or it was just a natural transfer from some other organism, nature can do a pretty good job of hurting human beings. I don't know that we need to really worry too much about bioweapons at this point.In 2018, there was a big controversy over a Chinese researcher who created some genome-edited babies. Yeah. Is there more to know about that story? Has that become a hotter topic of discussion as CRISPR has advanced?The Chinese scientist, He Jiankui, who performed those pretty abominable experiments was jailed for the better part of three years. He got early release in China and slowly but surely he's being rehabilitated. He's literally now moved his operation from Shenzhen to Beijing. He's got his own lab again, and he's doing genome editing experiments again. I saw again on social media recently, he's got a petition of muscular dystrophy families petitioning Jack Ma, the well-known Chinese billionaire, to fund his operation to devise a new gene editing therapy for patients with Duchenne muscular dystrophy and other forms of muscular dystrophy. I wouldn't want He Jiankui let within a thousand miles of my kids, because I just wouldn't trust him. And he's now more recently put out a manifesto stating he thinks we should start editing embryos again. So I don't know quite what is going on.It seems the Chinese threw the book at him. Three years is not a trivial prison sentence. He was fined about half a million dollars. But somebody in the government there seems to be okay with him back at the bench, back in the lab, and dabbling in CRISPR. And I don't know that he's been asked, does he have any regrets over the editing of Lulu and Nana. There was a third child born a few months later as well. All he will say is, “We moved too fast.” That is the only caveat that he has allowed himself to express publicly.We know nothing more about the children. They're close to five years old now. There's one particular gene that was being edited was pretty messed up. But we know it's not an essential gene in our bodies, because there are many people walking around who don't have a functional copy of this CCR5 receptor gene, and they're HIV resistant. That was the premise for He Jiankui's experiment. But he has said, “No, they are off limits. The authorities are not going to reveal their identities. We are monitoring them, and we will take care of them if anything goes wrong.” But I think a lot of people in the West would really like to help, to study them, to offer any medical assistance. Obviously, we have to respect their privacy. The twin girls and the third child who was born a bit later, maybe they're being protected for their own good. How would you like it if you grew up through childhood and into your teenage years, to walk around knowing that you were this human experiment? That may be a very difficult thing to live with. So more to come on that.There's no legitimate discussion about changing that in the West or anywhere else?Obviously, in the wake of what He Jiankui did, there were numerous blue ribbon panels, including one just organized by the National Academy of Sciences, just a stone's throw from where we're talking today. And I thought that report was very good. It did two things. This was published a couple of years ago. Two important things came out of it. One is this all-star group of geneticists and other scientists said, “We don't think that human embryo editing should be banned completely. There may be scenarios down the road where we actually would want to reserve this technology because nothing else would help bring about a particular medical outcome that we would like.” And the one medical scenario that they laid out would be, what if two people with a deadly recessive disease like sickle cell disease, or perhaps a form of cystic fibrosis, wanted to have a healthy biological child?There are clinics around the country and around the world now doing something called pre-implantation genetic diagnosis. If you have a family history of a genetic disease, you can encourage the couple to do IVF. We form an embryo or bunch of embryos in the test tube or on the Petri dish. And then we can do a little biopsy of each embryo, take a quick sneak peek at the DNA, look to see if it's got the bad gene or perhaps the healthy gene, and then sort of tag the embryos and only implant the embryos that we think are healthy. This is happening around the country as we speak for hundreds, if not thousands, of different genetic diseases. But it won't work if mom and dad have a recessive, meaning two copies of a bad gene, because there's no healthy gene that you can select in any of those embryos. It would be very rare, but in those scenarios, maybe embryo editing is a way we would want to go. But I don't see a big clamor for this right now. And the early results have been published using CRISPR on embryos in the wake of He Jiankui did have said, “It's a messy technique. It is not safe to use. We don't fully understand how DNA editing and DNA repair works in the human embryo, so we really need to do a whole lot more basic science, as we did in the original incarnation of CRISPR, before we even dare to revisit editing human embryos.” Longevity is interesting because, of course, in the last 18 months there's a company in Silicon Valley called Altos, funded by Yuri Milner, employing now two dozen of the top aging researchers who've been lured away from academia into this transnational company to find hopefully cures or insights into how to postpone aging. Longevity and genetic enhancementsAnother area is using these treatments not to fix things, but to enhance people, whether it's for intelligence or some other trait. A lot of money pouring into longevity treatments from Silicon Valley. Do we know more about the potential of CRISPR for either extending lifespans or selecting for certain desirable traits in people?This sort of scenario is never going to go away. When it comes up, if I hear someone say, “Could we use CRISPR or any gene editing technology to boost intelligence or mathematical ability or music musical ability, or anything that we might want…”Or speed in the hundred meters.“…or speed in the hundred meters, to enhance our perfect newborn?” I would say, what gene are you going to enhance? Intelligence—are you kidding me? Half of the 10,000 genes are expressed in the human brain. You want to start meddling with those? You wouldn't have a prayer of having a positive outcome. I think we can pretty much rule that out. Longevity is interesting because, of course, in the last 18 months there's a company in Silicon Valley called Altos, funded by Yuri Milner, employing now two dozen of the top aging researchers who've been lured away from academia into this transnational company to find hopefully cures or insights into how to postpone aging. That's going to be a long, multi-decade quest to go from that to potentially, “Oh, let's edit a little embryo, our newborn son or daughter so they have the gift of 120 years on this decaying, overheating planet…” Yes, there's a lot to wade through on that.And you have another book coming out. Can you give us a preview of that?I'm writing a book called Curved Air, which is about the story of sickle cell disease. It was first described in a paper from physicians in Chicago in 1910 who were studying the curious anemia of a dental student who walked into their hospital one day. That gentleman, Walter Noel, is now buried back in his homeland, the island of Grenada. But in the 1940s, it was described and characterized as the first molecular disease. We know more about sickle cell disease than almost any other genetic disease. And yet, as we touched on earlier, patients with this who have not had the wealth, the money, the influence, they've been discriminated against in many walks of life, including the medical arena.We're still seeing terribly, tragically, videos and stories and reports of sickle cell patients who are being turned away from hospital rooms, emergency rooms, because the medical establishment just looks at a person of color in absolute agony with one of these pain crises and just assumed, “Oh, they want another opioid hit. Sickle cell? What is that?” There's a lot of fascinating science. There's all this hope in the gene editing and now in the clinic. And there's all this socioeconomic and other history. So I'm going to try to weave all this together in a format that hopefully everyone will enjoy reading.Hopefully a book with a happy ending. Not every book about a disease has a wonderful…I think a positive note to end on is the first American patient treated in this CRISPR clinical trial for sickle cell disease four years ago,Victoria Gray, has become something of a poster child now. She's been featured on National Public Radio on awhole series of interviews and just took her first overseas flight earlier this year to London to speak at a CRISPR gene editing conference. She gave a lovely 15-minute personal talk, shaking with nerves, about her personal voyage, her faith in God, and what's brought her here now, pain-free, traveling the world, and got a standing ovation. You don't see many standing ovations at medical conferences or genetics conferences. And if ever anybody deserved it, somebody like Victoria Gray did. Early days, but a very positive journey that we're on. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit fasterplease.substack.com/subscribe

Former Bolton, Southampton and Blackburn striker Kevin Davies is this week's guest on the pod and you can listen to it first on BBC Sounds. He answers some key questions from his career: how did a hotel room chat with Big Sam help revitalise his career? Why did he love playing against John Terry and did Bolton deserve their long ball tag? He also recalls Chesterfield's FA Cup semi-final defeat to Middlesbrough, reveals why he fell foul of Gordon Strachan at Southampton and explains why his big money move to Blackburn didn't work out. BBC Sounds is the best place to listen to Kammy and Ben's Proper Football Podcast with new episodes available first, a month before anywhere else.

The football season is over, so we fill the hole with some of the best of our Summer Sessions. This week, Guðni Bergsson recalls his dramatic debut, Kevin Davies remembers the trip to Bayern Munich and Adam Le Fondre on the iconic final day win against Nottingham Forest.

Kevin Davies, author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, teases his keynote at the ACCC 49th Annual Meeting and Cancer Center Business Summit, where he will talk about the history of genome technology and its potential to change precision medicine.  The first FDA approval for a CRISPR therapy is imminent. But can this game-changing technology deliver safe and affordable precision medicine for patients?  Guest: Kevin Davies, PhD, Executive Editor of The CRISPR Journal and GEN Biotechnology and author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, Breakthrough: The Race for the Breast Cancer Gene, and Cracking the Genome; co-author of DNA: The Story of the Genetic Revolution. “Rather than just adding a healthy gene to a bunch of cells in a patient and hoping that the gene can correct the disease in question, we now have tools, including CRISPR, to go in and actually surgically fix or repair the broken sequence in the DNA we have inherited…we are literally performing precision chemistry on the double helix.” Hear Kevin speak live at the ACCC 49th Annual Meeting and Cancer Center Business Summit. Resources: CRISPR-Directed Gene Editing in a Community Cancer Center AI's Role in Advancing Cancer Prevention Detection Diagnosis Treatment and Precision Medicine Precision Medicine Stewards: A Case Study from Sanford Health Manipulating Data to Make Precision Medicine Magic Eliminating Precision Medicine Disparities Development of a Model Precision Cancer Therapies Program in a Community Setting ACCESS: The First Step Toward Analyzing Precision Medicine Data

0:00:00 Introduction Richard Saunders 0:03:08 You Can Count on Adrienne. With Adrienne Hill WikiProject Skeptical With the help Richard Saunders, Adrienne takes a look at the top ten list of topics at "WikiProject Skeptical", which is "dedicated to creating, improving, and monitoring articles related to Scientific skepticism (British English spelling: scepticism), also known as rational skepticism or skeptical inquiry. The focus includes articles about claims which are contrary to the current body of scientific evidence, or which involve the paranormal. The project ensures that these articles are written from a neutral point of view, and do not put forward invalid claims as truth." https://en.wikipedia.org/wiki/Wikipedia:WikiProject_Skepticism https://en.wikipedia.org/wiki/Wikipedia:WikiProject_Skepticism/Popular_pages WikiProject Report, Special:FAQs https://Wikipedia.org/wiki/Wikipedia:Wikipedia_Signpost/2013-04-01/WikiProject_report 0:28:12 ChatGPT on Skeptical Topics Another trip down the rabbit hole of Artificial Intelligence as we seek answers from ChatGTP on skeptical topics including Psychics, Bigfoot, Spoon Bending, Homeopathy, Ghosts, Astrology and Palmistry. 0:40:19 A Dive into a Trove A wander through the decades of digitised Australian newspapers on a search for references to "Creationism". The Mercury - 18 Feb 1933 The Canberra Times - 29 March 1984 The Canberra Times - 6 Jan 1986 Woroni - 9 Sept 1985 http://www.trove.nla.gov.au Also   10 Years Ago The Skeptic Zone #222 - 21.Jan.2013 Maynard's Spooky Action.. An interview with Dr Krissy Wilson about talking to the dead - Danger 5. Just for fun, Richard Saunders checks in with Maynard as he hosts a public Q & A with the cast of this Australian TV show - Skeptical BBQ. Richard Saunders travels to Canberra for a screening of "Here be Dragons" by Brian Dunning and enjoys a chat with Kevin Davies, the president of Canberra Skeptics - The Think Tank. Join a host of Canberra Skeptics as they chat about Conspiracy Theories. https://skepticzone.libsyn.com/the-skeptic-zone-222-21-jan-2013

0:00:00 Introduction Richard Saunders 0:04:22 You Can Count on Adrienne. With Adrienne Hill Vale 'SkepDoc' Dr Harriet Hall MD Adrienne pays tribute to Harriet, who was a retired family physician, former U.S. Air Force flight surgeon, author, science communicator and skeptic of international acclaim, who wrote about alternative medicine and quackery for magazines and articles discussing evidence-based medicine for the Science-Based Medicine blog. She usually wrote under her own name or used the pseudonym "The SkepDoc". She was also a frequent speaker at science and skepticism related conventions in the US and around the world. https://tinyurl.com/skepdocseries https://skepticzone.libsyn.com/size/5/?search=Harriet 0:17:42 Sydney Skeptics in the Pub At long last Sydney Skeptics in the pub is back and looking forward to 2023. We hear from new pubber Stephen Bavaro, who was a recent speaker at the Australian Skeptics convention. Also from Tim Mendham and Richard Saunders as they address the crowd to talk about the Bent Spoon Award and more. 0:32:00 Australian Skeptics Newsletter What skeptical news has caught the eye of Tim Mendham this week? Read by Adrienne Hill. http://www.skeptics.com.au 0:40:28 A Dive into a Trove A wander through the decades of digitised Australian newspapers on a search for references to "Medical Quackery". http://www.trove.nla.gov.au Also https://pintofscience.com.au/eoi 10 Years Ago The Skeptic Zone #222 - 21.Jan.2013 Maynard's Spooky Action.. An interview with Dr Krissy Wilson about talking to the dead - Danger 5. Just for fun, Richard Saunders checks in with Maynard as he hosts a public Q & A with the cast of this Australian TV show - Skeptical BBQ. Richard Saunders travels to Canberra for a screening of "Here be Dragons" by Brian Dunning and enjoys a chat with Kevin Davies, the president of Canberra Skeptics - The Think Tank. Join a host of Canberra Skeptics as they chat about Conspiracy Theories. https://skepticzone.libsyn.com/the-skeptic-zone-222-21-jan-2013

Join Af as he learns about the incredible advances in DNA manipulation with Kevin Davies, the author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. Kevin has 30+ years in science publishing as an editor of leading academic journals (with Nature Genetics, Nature and Cell Press); in trade publishing (Bio-IT World), and as a publisher (C&EN). In 2018, he spearheaded the launch of The CRISPR Journal, published by Mary Ann Liebert Inc. His books include "The $1,000 Genome"​ (Free Press, 2010), "Cracking the Genome" (Free Press, 2001), and "Breakthrough: The Race for the Breast Cancer Gene." Kevin is the founding editor of Nature Genetics, the first offshoot from Nature. He holds an undergraduate degree in Biochemistry from Oxford University and a PhD in molecular genetics from the University of London.

It is now clear that genetically editing human beings is not only possible, but increasingly simple. The ethical considerations of this development on the other hand remain complex. To discuss the mapping and editing of the human genome, Adam Boulton is joined by Dr George Church, the 'father of genomics', and Kevin Davies, science author, journalist and the executive editor of the CRISPR journal. Image description: Genetic editing and gene research in vitro. Credit: Brain light / Alamy Stock Photo.

It is now clear that genetically editing human beings is not only possible, but increasingly simple. The ethical considerations of this development on the other hand remain complex. To discuss the mapping and editing of the human genome, Adam Boulton is joined by Dr George Church, the 'father of genomics', and Kevin Davies, science author, journalist and the executive editor of the CRISPR journal. Image description: Genetic editing and gene research in vitro. Credit: Brain light / Alamy Stock Photo.

Support us: buymeacoffee.com/colemansdream BagsyBags.com sponsors Coleman Had A Dream - use CHAD10 for 10% off! After the frustrating draw against the Americans, and the dispiriting defeat against Iran, Dai and Ruth discuss the tournament so far, and what might come next for Cymru. We answer a whole host of your questions about the tournament and the future. Finally, we pass our condolences to the family and friends of Kevin Davies - a member of the Red Wall who passed away watching Wales in Qatar.

#crispr #geneticediting #editinghumanity #biotech CRISPR- EDITING HUMANITY'S FUTURE & RE-IMAGINING HEALTHCARE Kevin Davies is a renowned British science journalist and the executive editor of The CRISPR Journal Plus Nature Genetics. He has authored various books such as Breakthrough: The Race to Find the Breast Cancer Gene in the early 1990s Cracking the Genome, which details the dramatic story of one of the greatest scientific feats ever accomplished: the mapping of the human genome The $1,000 Genome, DNA: The Story of the Genetic Revolution And his most recent release, Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, for which he won a Guggenheim Fellowship for science writing in 2017. Kevin studied at Oxford University and moved to the US in 1987 after earning his Ph.D. in genetics. He is the founding editor of the Nature Genetics journal and Bio-IT World magazine, former editor-in-chief of Cell Press, and the first publisher of C&EN, the weekly magazine of the American Chemical Society. https://www.linkedin.com/in/kevin-davies-52b912 https://twitter.com/kevinadavies Watch our highest viewed videos: 1-India;s 1st Quantum Computer- https://youtu.be/ldKFbHb8nvQDR R VIJAYARAGHAVAN - PROF & PRINCIPAL INVESTIGATOR AT TIFR 2-Breakthrough in Age Reversal- -https://youtu.be/214jry8z3d4DR HAROLD KATCHER - CTO NUGENICS RESEARCH 3-Head of Artificial Intelligence-JIO - https://youtu.be/q2yR14rkmZQShailesh Kumar 4-STARTUP FROM INDIA AIMING FOR LEVEL 5 AUTONOMY - SANJEEV SHARMA CEO SWAAYATT ROBOTS -https://youtu.be/Wg7SqmIsSew 5-TRANSHUMANISM & THE FUTURE OF MANKIND - NATASHA VITA-MORE: HUMANITY PLUS -https://youtu.be/OUIJawwR4PY 6-MAN BEHIND GOOGLE QUANTUM SUPREMACY - JOHN MARTINIS -https://youtu.be/Y6ZaeNlVRsE 7-1000 KM RANGE ELECTRIC VEHICLES WITH ALUMINUM AIR FUEL BATTERIES - AKSHAY SINGHAL -https://youtu.be/cUp68Zt6yTI 8-Garima Bharadwaj Chief Strategist IoT & AI at Enlite Research -https://youtu.be/efu3zIhRxEY 9-BANKING 4.0 - BRETT KING FUTURIST, BESTSELLING AUTHOR & FOUNDER MOVEN -https://youtu.be/2bxHAai0UG0 10-E-VTOL & HYPERLOOP- FUTURE OF INDIA"S MOBILITY- SATYANARAYANA CHAKRAVARTHY -https://youtu.be/ZiK0EAelFYY 11-NON-INVASIVE BRAIN COMPUTER INTERFACE - KRISHNAN THYAGARAJAN -https://youtu.be/fFsGkyW3xc4 12-SATELLITES THE NEW MULTI-BILLION DOLLAR SPACE RACE - MAHESH MURTHY -https://youtu.be/UarOYOLUMGk Connect & Follow us at: https://in.linkedin.com/in/eddieavil https://in.linkedin.com/company/change-transform-india https://www.facebook.com/changetransformindia/ https://twitter.com/intothechange https://www.instagram.com/changetransformindia/ Listen to the Audio Podcast at: https://anchor.fm/transform-impossible https://podcasts.apple.com/us/podcast/change-i-m-possibleid1497201007?uo=4 https://open.spotify.com/show/56IZXdzH7M0OZUIZDb5mUZ https://www.breaker.audio/change-i-m-possible https://www.google.com/podcasts?feed=aHR0cHM6Ly9hbmNob3IuZm0vcy8xMjg4YzRmMC9wb2RjYXN0L3Jzcw Kindly Subscribe to CHANGE- I M POSSIBLE - youtube channel www.youtube.com/ctipodcast

In a day and age when it feels like there are drugs for everything—from restless legs to toenail fungus to stage fright—it's strange the drug industry has almost completely ignored one of our most important organs: our ears. Given that 15 percent of people in the U.S. report at least some level of hearing loss, you'd think drug makers would be doing more to figure out how they can help. Well, now there's at least one company that is. Cambridge, Massachusetts-based Decibel Therapeutics went public in 2021 to help raise money to fund its research on ways to treat a specific form of deafness caused by a rare genetic mutation. Decibel is testing a gene therapy that would be administered only to cells in the inner ear and would provide patients with a correct, working copy of the otoferlin gene, which is inactive in about 10 percent of kids born with auditory neuropathy. Harry's guest this week is Decibel's CEO Laurence Reid, who explains how the company's research is going, and how Decibel hopes to make up for all those decades when the pharmaceutical business had basically zero help to offer for people with hearing loss.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.These days, it feels like there's a medicine for almost everything.There are drugs to calm your restless legs. There are drugs to treat fungal infections under your toenails or fingernails. There are even drugs to calm down performers who suffer from stage fright.So it feels odd that the drug industry has almost completely ignored one of our most important organs: our ears.15 percent of people in the U.S. report at least some level of hearing loss, so you'd think drug makers would be doing more to figure out how they can help.Well, now there's at least one company that is. It's a six-year-old company based in Cambridge, Massachusetts called Decibel Therapeutics.Decibel went public in 2021 to help raise money to fund its research on ways to treat a specific form of deafness caused by a rare genetic mutation. It turns out that in about 10 percent of children who are born with auditory neuropathy, the problem is a mutation in the gene for a protein called otoferlin.It's involved in the formation of tiny bubbles or vesicles that carry neurotransmitters across the synapses between the inner hair cells that pick up sound and auditory neurons in the brain.Decibel is testing a gene therapy that would be administered only to cells in the inner ear and would provide patients with a correct, working copy of the otoferlin gene.Otoferlin wasn't even discovered until 1999. So the fact that there's a drug company working to correct mutations in the gene for the protein is a great example of how genomics is enabling big advances in medicine.My guest today is Decibel's CEO Laurence Reid.And in our conversation he explained how the company's work is coming along, and how Decibel hopes to make up for all those decades when the pharmaceutical business had basically zero help to offer for people with hearing loss.Harry Glorikian: Laurence, welcome to the show. It's great to have you here.Laurence Reid: Yeah. Hey, good morning, Harry. Great to see you again. Thank you. Thanks very much for the opportunity to join you. I'm looking forward to it.Harry Glorikian: Yeah, I mean, we've known each other for, my God. I remember. Like, I want to go back in time to Warp or one of those companies way back when you were there.Laurence Reid: Like ten or 15 years ago, I think I think we're both compressing our compressing our memories. I think it was a while before that. But, you know, you've been a student of personalized medicine, of course, a leader. Those ideas and I know a lot of those ideas for me started at least personally when I was at Millennium. And I think we were pretty you know, there was a lot of fantastic thinking that some of what was ahead of where we really were technologically. But I think that's when you and I first met. So, no, it's great to reconnect.Harry Glorikian: Yeah. And now you're CEO of a company called Decibel, which is ironic because I remember when the company literally was coming out, they called me to help them think through diagnostics.Laurence Reid: Oh, interesting. I wasn't aware of that. Yeah, the company got incubated at Third Rock and got launched in 2016. So we're about six years old now. And, you know, we believe that the time is is now for sort of molecular innovation coming to hearing loss. And I'd love to talk more about that. But the diagnosis remains, there's an interesting, there's almost a dichotomy because at least in the in the Western world, we put our babies religiously through a hearing test within 24, 48, 96 hours of being born. And then and then beyond that, like we sort of like almost, we don't quite ignore it, that would be unfair, but the caliber of follow up care, never mind when you're our kind of ages, is really poor. So we're like we're really good out of the gate. And then after that and part of that is diagnosis. I mean, we think a lot about it, which, you know, you would love, is trying to think about improved molecular diagnostics, particularly with respect to the genetic components of hearing loss. So love to talk more about that.Harry Glorikian: Yeah. I mean, you know, you were talking to Kevin Davies on on another show. I mean, I think you mentioned you said something like "Hearing is a backwater of the pharmaceutical industry." And most of the focus is is what I would call a device, not necessarily a drug. So, you know, if we let's I mean, starting there, where do you see or how do you see that changing? And, you know, how have genomic tools and and these things made a difference in the direction that we're going. And I think that's what Decibel was sort of formed around, if I remember correctly.Laurence Reid: Yeah, no, you're exactly right. But those are, those are the central questions. So where we are today is there are, so, so, both. And we think about both hearing loss and balance disorders, because they're both mediated by evolutionarily related organs that sit inside inside the inner ear. And, you know, the hearing loss afflicts literally hundreds of millions of people around the globe at all ages. It can come on, you can whether it's congenital or it's sort of later in life or noise induced. So it's a massive unmet need. And, you know, and there are no approved therapies. So it's it's a field of medicine today that is that is completely served, to the degree it is served, by assistive devices, namely hearing aids and then cochlear implants. And there are no approved therapies. And I think the pharmaceutical industry has been really, is just not invested in the field at all. Astellas works with our friends at Frequency and has been committed and a couple of other big companies have sort of dabbled and then and then exited. Translation has been has been a challenge. We should talk about that preclinical work not really replicating once you get to you know, human beings. And so it's been a quite a difficult field for for many years. And and so the pharmaceutical industry has really not dived in and, you know, in Third Rock was really incubating decibel which is how they how they start companies. It was one of their ones that was was a slow burn.Laurence Reid: And they had they looked at assets out of one or two pharmaceutical companies and were really trying to get their heads around, is the time really now. And they they pulled the trigger in 2016 and went into it with a belief that that molecular innovation was coming and is coming and that that would that would give rise to therapies. So here we are six years later. And the playing field, as I like to say, is really, you know, dominated by small companies. We like to think about Decibel as a leader there, but there are other companies doing fine science, but they're small companies. And but that's going to change. It has to change. And it's going to be exciting from many aspects. When it changes, it affects how you build a company, when pharmaceutical companies are sort of watching, but they're not committed and they're not they're certainly not investing yet. But I think that's going to change. And I think we're going to see it change, I don't know, in the next couple of years. And I think 5 to 10 years from now, all the major pharmaceutical companies would have to be playing in this because, you know, there's the aging component, there's the cognitive health later in life. You could talk more about the specifics of why hearing is so important to our existence as human beings. And that's really not just a quality of life issue. And that's going to change. To have that happen.Harry Glorikian: That's why I was going to I was going to say I mean, I think if I remember correctly and it was fascinating to me when I went into Decibel, like, you know, when it was first getting started and how it was having conversations, it was like the number of people that are losing, you know, certain parts of their hearing earlier in life because of all the headphones and how loud they listen to things and so forth, was staggering. And then the economic impact of that was even more staggering. And so you would think that it's not just the pharma industry that would be interested, but anybody that—-like I've got my AirPods in now. So I mean, Apple should be interested.Laurence Reid: Those guys, those guys are working around the field. Bose, of course, a fine Massachusetts company with some of the best sound equipment. They've been investing in the hearing aid technology field for in recent years and have just launched a new generation of technology under that umbrella and come out with some pretty sophisticated marketing, trying to really get people to think about the quality of their hearing and why it's important. And so, as you say, so new people coming at it despite perhaps their contributions to it. And so, you know, so I think I think that's really very, very interesting. And but it is now devices, as you say. It's devices. So today, you know, a lot of it is treated nominally with hearing aids and then for very severe forms, particularly in in in young kids, but in adults as well. There's a technology which has been around for about 20 years now, known as a cochlear implant, where you have a surgical implantation of a very sophisticated device into your cochlea. And essentially it essentially hard wires, really a microphone directly to the onto the auditory nerve.Laurence Reid: And so there's a device inside your head and then there's a detection device that is visible outside. But both of these we view as assistive devices. And I mean, with some of the things that we're thinking about for molecular therapies, you know, we really think we can be disease modifying. And the devices are, they're an attempt to sort of palliate, effectively, the manifestations of hearing loss. They don't work 24/7 because they can't and kids in particular hate wearing them. But, you know, our parents hate wearing them as well, particularly the hearing aids. And so the compliance is very poor. But I think more importantly, they can only be so effective, and particularly if you're very severely deaf, the difference between that status and, you know, what the kid next to you in the classroom is hearing and picking up and how that's affecting their development is really massive and to me is one of the big drivers certainly why I got excited about the field personally.Harry Glorikian: Oh yeah. I mean, you know, if you're in a crowded restaurant and you can't hear the person across from you, there's all of a sudden it changes the entire dynamics of what's going on. I mean, that you know, that said, I think if my wife could implant a microphone that was directly wired into my brain, she would probably take advantage of that to make sure I hear everything.Laurence Reid: And hard wired up straight into her larynx. And then then everything would be would be beautifully aligned. Yeah, I know. It's really interesting. So my beloved mother is 84 and you have a one on one conversation with her and it's fine. You know, it's absolutely it's completely normal, like you and I chatting or talking to a 20 year old. But you put her in a crowded restaurant and it's very hard for her to participate at all. And so it's a really interesting. So on one level that's trivial, right? It's a night out in a restaurant. But it's indicative of the challenge. So I always think most easily comes to me with thinking about congenital deafness and then deafness or loss of hearing in in older people. But that restaurant is sort of an analog for in the case of the older people losing, you know, we talk a lot about connection, losing connection with their loved ones or their coworkers or their family. And, you know, hearing loss is the number one risk factor in cognitive decline later in life. And nobody is suggesting it's necessarily causative. But that loss of connectivity clearly in some way is contributing to, you know, to a cognitive decline. And I think that's really the way to think about it. For me, I think about hearing loss as why, why does it matter? And it's not because I think it's, if you haven't dealt with it, you probably think about it in terms of a social discourse. But actually why it really matters is the impact on, I use the phrase cognitive health, which is probably not a phrase of professional would use. It's really how is your overall ability to interact with people, to process information and and to share it? And if you're disconnected, it's clearly contributing to that lack of of of interaction and ability to, you know, to have discourse with our with our with our families. And so you see that. Pivoting to loss of interactions later in life. And then for a kid.Harry Glorikian: And how it affects the economy. I mean, if you're not going out to dinner or you're not or you don't hear everything at work or things like that, I think the impact is is dramatic. But you know how many I know you guys are working on different therapeutic approaches to solve this problem. So, you know. How many different forms of deafness right now, or maybe balance disorders, are monogenic or or caused by mutations of a single gene that, say, we can get in there and do something about it, because I think that's where you guys are starting.Laurence Reid: That's where we're starting. And that's exactly the right way to think about it. So let me let me step back and then I'll answer your specific question. So the strategy that we've taken and other people have different views of this is really that the most robust understanding in 2022 of the molecular etiology of any form of hearing loss is, is that it's driven by overtly by monogenic conditions. So two mutated genes inherited from mom and dad that good old recessive genetics and that therefore we're able to understand precisely what's causing it and we're able to understand the impact of that of a child born with bi-allelic mutations in the otoferlin gene for example. And and the promise of gene therapy is the ultimate to put back a a functioning copy of the gene very early in life and put a child back to a physiological state of of hearing that mimics the kid down the street. And that's and that's the ambition. And what we think will that will enable is both these modifying treatments, maybe even cures for for those sections of the population. But it'll teach us about how to do gene therapy safely in the ear. We think the ear is a wonderful organ in which to do gene therapy. We should probably talk about that in a moment.Harry Glorikian: Yeah, absolutely.Laurence Reid: But that over time, the Holy Grail. So as you get into the bigger populations, it's a classic, you know, genetics and environment, viruses, noise, lots of chemicals or lots of things  that damage areas over the course of life. And we just naturally lose the sensory hair cells in areas over the course of life. Everybody approximately linearly is losing that, that sensitive and that sensitivity. So eventually you hit a threshold and we all suffer from some form of hearing loss or balance, you know, lack of equilibrium as we get to be a little bit older and. For for many different causes. So the Holy Grail is can we really have regenerative medicines that regenerate the sensory the sensory hair cells, as they're called, in the inner ear, potentially as a treatment for hearing loss or balance disorders. And so the way we think about this is our strategy is really to to start with the monogenic forms of hearing loss have a chance for very clear diagnosis, driving, very precise clinical trials, driving potentially therapies that are directly addressing mechanism and with very high potential molecular upside. And to build from there into a pipeline of gene therapies that will start to go into broader populations, populations of much older people, and that will be gene therapies that are regenerative medicine. So that's our sort of long term vision of how this will how this will evolve. But it's starting with the monogenic conditions which which are which are rare diseases, orphan diseases by all definitions. And I think for the reasons that rare diseases have been such an intellectual driver of our industry in the past 20 to 30 years, is because you can link mechanism and etiology and a potential molecular cure in a very linear fashion. But it teaches you so much about how to manipulate an organ and how to develop therapies that eventually will treat broader populations.Harry Glorikian: Yeah. Laurence, you need to move faster, because I think I went to one too many rock concerts when I was younger. And, you know, I could tell you that.Laurence Reid: I had friends, when I was in high school who were who were into certain, you know, I hated heavy metal when I was a kid, but I had friends and they would come back and they'd been to a concert and they'd they'd stuck their head inside the speaker and they they couldn't hear for like a day or two. And I, I think back to those I worry about where those guys are now because they're hearing I'm sure they're otherwise.Harry Glorikian: Yeah. I mean, when you're when you're when your ear is ringing like a day afterwards, you probably recognized that was probably, it was a lot of fun at the time. But you pay for it later. But but stepping back, though, even if we were able to match every form of deafness to a specific genetic cause. Right. Very few infants or children get the kind of tests that would be needed. Like how widely available are these genetic tests for the hearing neuropathies today or.Laurence Reid: Oh, it's. I'm sorry. Go ahead.Harry Glorikian: No, no, no, go ahead. Because that would be my first question.Laurence Reid: It's the minority. And so by definition and I appreciate you've worked and thought a lot about this over the last years. You know, good diagnosis is is gating to everything that can follow. And so part of our broader I mean, at some level actually even step back from molecular diagnosis, which I know is where you'd want to go, that just overall how we manage hearing how is is almost rudimentary compared to how we think about about our eyes for example. And just I had my annual physical a couple of days ago and and a new physician and and the doctor was like, oh, you know, you go and get your eyes tested on, on an annual basis and which I do. And we talked about all the the good things that are cutting edge, you know, ophthalmologists does these days to look at your optic health. And then I was like, you know, the real question you should be asking me is, when did I get my hearing tested? And but when did you last get. We just we just it just doesn't it's just not part of adult health care in a routine way unless you get really I mean, my wife and I joke about it occasionally. I'm like, oh, well, let's go together and get our hearing tested.Laurence Reid: Not that, not that it's at all funny, it's not. It's a serious issue, but it's just not part of routine health care for helping adults think about about how how they manage their health. So. So we sort of we start with a, a broader set of educational issues. And then and then we dive down pretty quickly into how do we educate people about about the need and potential power of molecular diagnostics for children who, when we begin to figure out that they're hearing is developing, you know, in the early either days or early years of their life and as as in in the developed world, most children have a basic hearing test, you know, within hours of being born, literally, often while they're still in the hospital. And it's like, you know, in many, many places they catch them while mom is still, you know, literally in the hospital and and they do a basic hearing test so we can catch a lot of it like that. If it if you start if the hearing degenerates after that, it is still very challenging for that to get properly understood and picked up and diagnosed and managed even in, you know, developed cities and, you know, in the United States.Laurence Reid: And the the ability to to reflex to molecular testing is is very variable. If you talk to our our audiology team, it starts to be very dependent on which city do you live in and what's the ability? I mean, we're sort of privileged in Boston, Mass Eye and Ear is obviously one of the world's leading hospitals. But but how do you get from a an early "Yeah there's an issue here" to any form of molecular. What that path looks like of your pediatrician driving you to real audiological analysis, driving you to a molecular diagnosis. It's a pretty fraught path. You think about it in in in cities like Boston. Fair enough. And aren't we privileged to live here? We're lucky to live here from that perspective, but it's very heterogeneous. And so part of our work is really we have a collaboration with our friends at Invitae, part of which is trying to just it's almost educational. It's offering a free genetic testing service for important genes related to your hearing health. But part of the purpose is, is educational, really.Harry Glorikian: Yeah. Yeah, I was going to I was going to ask about that. I mean, in making it available, I mean, this is somewhat of a crusade, right, to educate people and get them on board, right. Because if you just don't know what's available, you may not think about it for your child. And if a parent knows they can help their child, I think most parents would go out of their way to do something positive. But just for everybody who's on the phone, you know, can you walk us through an example of, let's say, a single gene mutation can cause deafness? I mean, maybe you can concentrate on the example of, I think it's otoferlin, if I'm saying correctly, which you know, basically, if I've understood it correctly, it's the formation of the synaptic vesicles that carry neurotransmitters across the synapse, which is very, very tiny. And if the hair pulls away just enough, you start losing that ability to hear at that level because the chemical can't jump across to make that connection, which is, I think what's happening to me as I get older.Laurence Reid: Yeah. Very good. Yeah. And I'd love to talk about otoferlin. So otoferlin is our first program where we and other people are thinking about this as well. Our friends are also are working hard on this problem as well. But it's the vanguard program for Decibel and the field in terms of gene therapy for modern forms of hearing loss. And so obviously, we we know the gene that causes this particular subset of severe hearing loss. The children are born profoundly deaf. They really have almost no no signaling capability whatsoever. Despite that, when you study their ears and when you look at animal animal genetic models of the condition, the ear, functionally, structurally appears to be normally constituted. So what you see start with a belief that we may be able to instate normal hearing in these people by in these children, by, by by providing a a wild type, a normal copy of the gene. And there are other forms of of genetic hearing loss where by the time the kids are born, the children are born, their ear has not developed properly, structurally and functionally. And I think that's a much harder problem and may be impossible to to solve postnatally. So so as we think about areas where we think we can have an impact with the first generations, we're looking for clear genetics. We're looking for an ear that appears to develop normally and in which we therefore have the chance to instate normal hearing. Otoferlin is a calcium sensor and it functions at the interface between the hair cells in the cochlea, the inner hair cells, as they're called, which are the cells that transduce... Sound is effectively a mechanical signal. It comes to us as a sound wave, and it disturbs structures and eventually molecular structures inside your inner ear and creates a molecular signal that is transmitted by the hair cell through the synapse. As you say, to the auditory nodes, there's a direct interface between these cells that are that are detecting the sound wave into the into the auditory nerve. And if you lack otoferlin your calcium sensing functionality and that synapse is not present and and there's essentially no signal. So we measure this with something called an auditory brainstem response, which is a test you could run in a human or an animal. And there essentially it's a flat line, which from a from a restoration of a normal signal, it's a really excellent clinical endpoint because we're going to, we hope, instate, a signal, a quantitative signal with quantitative richness as well, that we're going to be able to measure relatively early after we administer our therapy. But the children have this is what we call an auditory neuropathy. They have no ability to signal from the cell into the brain. And as I say, the structures appeared to be intact. And what we know is that in an animal, if you create an animal model of this genetic animal model, that we can go into that now with DB-OTO, as we call it, which is which is a adeno associated virus vector to to basically deliver a normal form of the gene. And we can do that within weeks of this mouse being born. But interestingly, we could also go to those animals as long as a year after they're born, which which for a small furry animal is is about half of their life.Laurence Reid: So it's a big piece of their life. And and we can go in we can intervene at that at that one year point and still rescue the phenotype. So the is structurally intact. And when we provide the signaling molecule, we fairly quickly instate a normal signal. So that's that's exciting. Right. And A), it's a fantastic signal to measure in an animal. B) it gives us a lot of optimism that if we can get the gene to the right cells and get it turned on, then decent chance to to to solve to solve the signalling problem. So that's sort of our reason to believe. And actually maybe the last component, and then I'll breathe, is we think the ear is, is a fantastic place for gene therapy broadly because your inner ear is this tiny enclosed compartment. So we need a surgical route to get there, but we can then go directly to the site where one is trying to elicit a molecular effect and deposit a tiny amount of drug compared to what's required -- three or four orders of magnitude less drug than is required for systemic gene therapy -- directly at the site where we're looking to elicit the biological effect. And then almost none of it leaks out into the into the systemic circulation. So the ear, we think, is a fantastic order or organ for gene therapy, and we think we know some great genes to go after us, our first generation.Harry Glorikian: Yeah. I mean, you know, whenever if if people have followed any type of gene therapy, like the eye has been in optimal place to sort of start with. And so, you know, I think you guys are learning from what has been done in ophthalmology to sort of transition this to the ear, which, you know, I always say to people like we always start on the outside because it's a lot easier and then we then we figure out how to go deeper in because it's a lot harder. But, you know, what kind of results are you seeing so far when you transfer genes into, maybe nonhuman primates.Laurence Reid: Yeah. Yeah. No. So we've just in the last year or two, transitioned from rodent studies to non-human primates. You are correct that the characteristics of the ear that make us so excited about the possibility here, a lot of them are very much learning from why the eye has been really such a primary site of our efforts in gene therapy in the last ten years or so. And so as we move from small animals to larger animals to human beings, we start with, as I mentioned, genetic rodent models that we can knock genes out in the mouse that replicate the human genetics. The ear, it turns out, is it is evolutionarily highly conserved. So the the ear of a rodent is a lot smaller than than your ear in my ear. But structurally and molecularly and cellularly it's very analogous. And we can come back to your point about genomics and how it's opened up our understanding of these cells. But nonetheless, the basic structure and physiology is highly conserved from from lower mammals to to higher mammals. So so we start with genetic models that we can manipulate the genome and create what we believe is a pretty interesting analog rodent analog of the human condition. We don't have genetic models in non-human primates, so we end up doing studies in non-human primates where we we we mimic exactly the surgical procedure by which we will access the inner ear, and then we end up either using a surrogate marker, GFP, or we end up detecting the human otoferln, in the non-human primate, which is quite hard.Laurence Reid: But we've sort of figured out how to do that now. And really what you're looking at is, is, is really is efficiency of the delivery and expression process. And then when you can't measure a fixing of the genetic burden and so at Decibel, we spend a lot of time using our genomics platform to really be able to define molecular control of our gene therapy. So we're really trying to express the transgene selectively in the cell types where nature intended it to function. So, you know, calcium sensor in the wrong in the wrong cell type one might fear, and we have data that suggests, that that may be a problem. So Decibel is really invested very significantly in sophisticated molecular control of our gene therapies. And so when we do the experimentation in the non-human primate we're looking at, are we getting good delivery throughout the cochlea? Are we getting good infectivity throughout the cochlea and then expression of basically a surrogate marker? Because we we can't change the physiology of a of a normal non-human primate. So it's really all about about surgery, delivery expression. And then obviously you then got a stable transgene expression, it turns out, rises over the over the weeks and months after after after the transduction. And so we're measuring that. And that's going to play ultimately into clinical trial design, both in terms of safety and an end points that will measure in human being. [musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude] Harry Glorikian: I would assume that some level of spatial genomics, the new technologies that are out there, must be hugely helpful to see the different cell types, where they are and what type they are. And you know is actually lighting up and changing versus what you don't want to light up and change. So yeah. So I had a great interview with Resolve on their system, which I think is going to be the next frontier, because what you're saying is, what cell type, where it is, and did I make the change in the exact one that I wanted?Laurence Reid: That's exactly right. So my my colleagues, long before I was here, invested in building a platform that we think is still, we have a database of over 3 million molecular profiles of the cells of the inner ear, which we think is a unique asset. And basically applying the tools of single cell genomics, which is the ability at the level of individual cells in the organ of an individual animal to analyze comprehensive gene expression. And so what we've been able to do, and I think this is part of just changing our attitude to how do we understand the cells of the inner ear and therefore how can we think about manipulating them pharmacologically to open up the field? And so we have a complete molecular characterization of, there are about 30 or so important cells in the inner ear and there's two or three subsets of those cells, starting with the cells that I talked about that are probably the critical therapeutic targets. And so we have a detailed molecular understanding of the composition of the level of gene expression of each of these different cell types. And we look at them a lot as they as they as they differentiate and form in a natural process, because we think that holds the answer ultimately to regenerating them as part of this next part of our strategy. But it's also taught us about how individual cells control gene expression. And I mean, otoferlin is expressed essentially in an adult animal only in the so-called inner hair cells. And that's what we then aim to replicate with our gene therapy. And so we've been able to take our genomics platform to define genetic regulatory elements that drive our trans genes in our gene therapies to express selectively in the most important cell type where you need it and not elsewhere. We know from our animal studies that that has a beneficial impact on on on the therapy and that the durability of the therapy. So that's our overall molecular goal, but it leverages this platform of single cell genomics.Harry Glorikian: So I've seen company presentations. Like you guys are, you know, you intend to initiate a phase one, clinical trial of of DB-OTO. I mean, how is that going? I mean, what are the big technical or medical barriers, where you're thinking about testing gene therapy? Like, I mean, you know, where are you guys in all that?Laurence Reid: Yeah. So so we what we've and I'm going to be precise as a public company, I need to be careful with my disclosures. So apologies in advance. But what we said is that we'll initiate will file an IND or a CTA in Europe this year and and move into our first in human study this year. And so we're in the you know, we're deep in all the almost classical, you know, pre-IND work of making material and, you know, and testing it in, in the final, you know, GMP tox studies and making material of a caliber that'll that'll go into human beings, which is very exciting. And that's, you know, that's that's what we're working on. Those are the two sort of basic barriers. I mean, we have published and talk publicly about a lot of our animal data, what I sort of recited a few minutes ago, small animals to large animals. I think we understand the basic pharmacology and now it's okay, scale up, make the material for human being, you know, GMP material for human beings, test the material, you know, in more prolonged formal toxicology studies, you know, and move it into human beings so that that work is ongoing. The other part that's really fascinating that you would appreciate is, you know, in a rare disease like this, a lot of very interesting discussions about about what's the exact patient cadre in which one starts a clinical trial.Laurence Reid: And we spend a lot of time building relationships with with clinicians, particularly in Europe, but also in the US, who really invested in understanding the genetic basis of of children in their region with genetic forms of auditory neuropathy. And we have a fantastic collaboration with our colleagues in Madrid at the Roman y Cajal, who have a database that is essentially all of the all of the known diagnoses of otoferlin deficiency in Spain. And so they've done so we have been able to help them do a lot of natural history work. What is what is the progression of the condition and how do we find these kids? And so we ultimately not necessarily immediately, but the ultimate goal is to treat children very early in life. These kids are now once they're diagnosed, they would get a cochlear implant really probably around the end of their first year of life. It used to be more like two, but that age has come down from a medical perspective. Being born profoundly deaf is the phrase is is a neurodevelopmental emergency. And I talked a lot about about old people. But for a kid, the the or a baby, the issue is that hearing lack of hearing impacts that their initial social interactions that their generation of language skills and their ability there and that and that feeds into their cognitive development.Laurence Reid: So there's a there's a whole set of emotional interactions that are happening very early in life. And of course, with so much cognitive development going on and the hearing is, is the absolute gate to a lot of that happening. And so it's widely, widely agreed that this phrase, a neurodevelopmental emergency, is what physicians use. So so ultimately, we need to be treating these kids in the first year or two of their life. And you know, how soon we'll get there remains to be seen. And it is an ongoing discussion. But that's that's where that's where ideally we would end up. While at the same time, as I said, we know we can intervene in animals later in their lives. So we're optimistic that we're going to be able to take adolescents and and children beyond the first year or two of life and still be able to have a positive impact on them. Well, that's the vision for sort of the broader applicability, not just in a newborn baby.Harry Glorikian: Yeah. I mean, you know, I mean, a child's, you know, the neuroplasticity or how easily that their brain or their system adapts and changes. I could see, you know, the drug having a much more profound effect in that population. I mean, in older people, I like to believe that we still have neuroplasticity, because I'm constantly evolving and changing. But, you know, I also sometimes think we're sort of stuck and maybe maybe don't have. But, you know, the human body is an amazing machine. But, you know, it brings me like one of the biggest themes on this show is like data, data, data and how that intersects biology. And, you know, what you're talking about is identifying the right sets of data, the right patients to have this work done on so that you can achieve a level of success. We all know that if you pick the wrong patients. Like you're utterly almost doomed for failure, or you're going to have an effect that you really didn't want to have. So how much of of Decibel's work or approach is is rooted in "Here's the data, here's the patient." How much are you guys using that to drive every decision that you're making?Laurence Reid: It's a it's a really great question, actually. And the answer is a lot. In fact, as I think about Decibel and where I think the team that my predecessor built, Steve Holtzman, who of course, you know, is really, really exceptional, is is effectively translation in its broadest sense. Right. I think what differentiates Decibel is an outstanding understanding of the biology of the inner ear and that we've invested in in turning that into a genomic molecular understanding of every cell type. But it's then, okay, who's my patient? What, their molecular profile. And how do I link that back, feed that back into my discovery process? What are my animal models look like and how am I looking forward, you know, into ultimately into a clinical trial? And with people suffering from from congenital hearing loss age, which we try and intervene, becomes a big variable, as you're suggesting. And so, you know, if you're in the pharmaceutical R&D, it's like, okay, that's translational medicine he's talking about. And and it is I just think we do it really well. And it's really the essence of the scientific core of Decibel is linking our molecular work in the cells of the inner ear to a fantastic understanding of the patients, their individual phenotypes and how we look to bridge that gap between preclinical research and the clinic. And the the the truth is, I mean, there are no approved therapies and there hasn't been a lot of work, as I said, up front.Laurence Reid: But but it's not like we're we're complete, we're not we're not going to be the first people either to do a gene therapy in the ear, nor to try and develop a therapy. But the translation has been really poor. And I think that our ability to understand the mechanistic pharmacology, preclinical and clinically and then be confident that that was going to work in a human being has been really poor. And obviously genetics from a simplistic perspective is a fantastic way to bridge that gap. Right. We know which gene we're trying to fix. And therefore, is the ear able to be fixed in a child of one two years old? And can we get the gene there safely and effectively and turn it on in the right place? Right. But those are problems that you can break down and solve and you can analyze them in smaller animals and larger animals. Whereas I think historically, the preclinical data, how do you validate it in a human being or do we really know those mechanisms are going to work in a human being? Well, the outcomes have shown us that we didn't have all the understandings of that. And I think you look back on it and the ability to translate has been has been weak. And that's why the genetics is is so appealing as a formative place to to start and try and build a pipeline of therapeutics, at least in our opinion.Harry Glorikian: Yeah. It's funny because we're always coming back to this genetic part of it. And I remember like somebody saying to me way back, No, it wasn't that long ago, relatively speaking, but why would you want to sequence anything? Right? And now it's like it's the cornerstone of everything we're doing. Yeah, but. But you guys have another drug, right?Laurence Reid: We do.Harry Glorikian: That prevents ototoxicity, right. Damage to the inner ear.Laurence Reid: Yep.Harry Glorikian: And it's that's one of the most common side effects of chemotherapeutic drugs like cisplatin. I mean, for those people that are listening, right, these little hairs, it's the same thing as like maybe the hair on your head.Laurence Reid: Please don't go there. It confuses people.Harry Glorikian: But essentially, you've got a drug that you're working on this in this space.Laurence Reid: Yes, we do. So firstly, how are you just upset because of our relative quantity of hair here. The hair cells in your hair are very different than the hair cells on top of your head or other parts of your body. Their role is to transducer signals on the inside of your cochlea into the brain. So but the cisplatin based chemotherapy is still very, very commonly used around around the world and is quite efficacious in certain types of tumors. It's widely used, for example, in testicular cancer, just one example. And it comes but it comes with a couple of of fairly severe toxicities, one of which is it kills the hair cells in your ear. And it also damages their interactions with the nervous system. And earlier in Decibel's life when we were sort of using our biological thinking before we. That's what I would say when we started as a biology company and we explored different molecular molecular modalities as the right way to treat it. And now we are significantly focused on gene therapy. As we've been talking about, this program was home grown and we're pretty excited about it despite our core investment in gene therapy now. And what we have is a proprietary formulation of a molecule of sodium sulfate, which is a natural metabolite, and it chemically inactivates cisplatin. And so we actually administer this by an injection into the middle ear and then the active ingredient leaches into the inner ear. And we administer that about 3 hours or so in advance of the Cisplatin IV, so that by the time the cisplatin gets to the ear, the inner ear is already bathed in sodium sulfate. And so and then you have a chemical reaction in situ inactivates the cisplatin.Laurence Reid: And you know, it's interesting because some people don't find that very sort of biotech sexy, but it's actually an incredibly elegant way to to to stop the side effects of a molecule that has multiple, multiple molecular forms of damage that are probably being imposed on different cell types. So solving that biologically or biochemically is a very hard, diverse problem, whereas solving it chemically in situ we think is is very powerful. The principle to give some credit was validated by a company called Fennec, but they have an IV administration and they are constantly fighting between achieving good things in. As you might imagine, preventing against that toxicity without inhibiting the efficacy of the drug. And it's correct. And that's that is a very and they hopefully eventually will get approval for a fairly narrow pediatric population because it's been very hard to sort of thread the needle of can I protect without inhibiting the efficacy? Now if you go directly to the organ where the damage is being done, local administration of a proprietary formulation, so it sits in the ear, it's there in advance. Essentially, none of it leaches out into the circulation. So we have, we believe, negligible risk of inhibiting in any way the cancer benefit of the circulating cisplatin. So we're achieving a local protection and we're looking where we will be reporting some human proof of concept data. We've said in the first half of this year. So pretty excited about that, actually.Harry Glorikian: Yeah. I mean, you know, I don't need sexy. I just need something to, like, work, right? I mean, sexy is nice, but, you know, if it's working, it's working sometimes, you know.Laurence Reid: Right. So, so not not to compare protection of hearing against protection from people who are going to die of cancer. But it's an interesting example of where hearing health or ear health gets neglected. So in the context, you know, cisplatin is used in many cases with what people refer to as an intent to cure and so people can get cured. Young men, I think the cure rate is something like 95%. So you're talking about a young man, maybe 20 years old. He's going to live for 100 years, right? Maybe more. Maybe more. And nowadays and so the the importance of protecting his hearing at that age. And there are female cancers as well. But his hearing at that age for his long term health is incredibly important. But it gets it gets, unsurprisingly, neglected because the focus is on is on the cancer, which is which is understandable. But but we think that there's a really important opportunity to, you know, to provide a better overall solution for for those people that's going to have an incredible impact later in their life as their hearing would be naturally degenerating anyway. And and I think because of the the understandable stress when you're going through chemotherapy, you know, worrying about the hearing decrement, is it's just not top of mind. And so we've got some awareness. We've got some work to do to increase awareness there and hoping that some of our animal data might replicate in human beings because we think this could be fairly effective and really hopefully get it into the minds of oncology physicians. Is the goal that you should be thinking about this. You're trying to cure this patient. You're trying to whether it's a woman with ovarian cancer in her fifties or a young man with testicular cancer, they're going to live for decades to come. And we think it's important that they're hearing health is protected and we can help you do that potentially in a very powerful, rather simple way, actually.Harry Glorikian: So. I'm going to assume and you can correct me if I'm wrong, that if this gets through sooner than the gene therapy and can generate some revenue in the short term, you can then utilize that revenue to continue to fund the gene therapy programs.Laurence Reid: We're all always looking for money to do this, right, Harry?Harry Glorikian: So, unfortunately, that's the business we're in.Laurence Reid: That's the nature of the beast. Certainly, after we have our data in hand on the proof of concept, we'll be looking for an FDA interaction to define the path to registration, which we think could be relatively efficient. We have, you know, the medicine that effectively becomes an oncology supportive care medicine. It needs to be administered probably in the chemotherapy suite right in advance of a patient receiving their chemotherapy. So it needs to be marketed to an oncologist with a lot of education in the audiology community so that they're leaning on their oncology colleagues to you need to do this and you need to think about this as you're putting your patient through through chemotherapy. Ultimately, I think that that marketing to the oncologists, I don't think that's what's going to do that in itself. We're going to eventually bring a partner partner in to do that who is a specialist in marketing to the oncology community. And we want to be involved in rethinking about making sure that the ideological education and understanding is transferred into the cancer into the cancer world. And so that's that's a commercial strategy and structure that will will put together, you know, potentially starting when the data is in hand, but certainly some time between now and approval of the drug.Harry Glorikian: Well, Laurence, you know, I can only wish you the greatest success because and working in older people would be great, because I'm sure that I'm going to need this at some point, and some of my friends may also need it. But it was great to catch up with you. Great to talk. You know, I hope, you know, it's not as many years past again before we we get a chance to connect. So great to have you on the show.Laurence Reid: Thanks, Harry. I really appreciate it. And hopefully I've been able to provide some of the color and why we're so excited and think we're opening up a new area of therapy here for people with hearing loss and balance disorders beyond that. So really appreciate the opportunity. Thanks very much and great to see you.Harry Glorikian: Thank you.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe. Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

Kevin Davies is a renowned British science journalist and the executive editor of The CRISPR Journal, based in New York. His literary career began with Breakthrough: The Race to Find the Breast Cancer Gene in the early 1990s, followed by Cracking the Genome, which details the dramatic story of one of the greatest scientific feats ever accomplished: the mapping of the human genome. His other titles include the $1,000 Genome, DNA: The Story of the Genetic Revolution, and his most recent release, Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, for which he won a Guggenheim Fellowship for science writing in 2017. Kevin studied at Oxford University and moved to the US in 1987 after earning his Ph.D. in genetics. He is the founding editor of the Nature Genetics journal and Bio-IT World magazine, former editor-in-chief of Cell Press, and the first publisher of C&EN, the weekly magazine of the American Chemical Society. In today's episode, Kevin elaborates on his career trajectory and explains why he believes that hanging up his lab coat was the best decision he ever made. We also touch on the common themes that run through his books, some of the challenges scientific publishers and editors face, and the importance of promoting the work of women scientists. We also cover vectors, CRISPR babies, the cost of gene therapy, and so much more! Make sure not to miss this fascinating discussion with the remarkable Kevin Davies. “How we turn this stunning 21st-century medicine into therapies that are affordable is going to be a Nobel Prize-winning discovery if anybody can crack that one.” — @KevinADavies Key Points From This Episode: Kevin's career trajectory and his so-called “desperate” shift to science journalism. How Kevin believes the field of genetics has evolved since he was a geneticist in the 1980s. Learn about the impetus behind the Nature Genetics journal and The CRISPR Journal. What motivated Kevin to write Breakthrough, including a meeting with Mary-Claire King. Three elements in all of his books: genetics, medical or societal impact, and personal drama. Hanging up his lab coat to join Nature and the access to authors that it afforded him. Kevin reflects on the demographic representation and “race to the finish line” issues in scientific publishing and the burden editors face. The lens through which Nobel Prizes are considered and how it can shift perspectives. The importance of promoting women in science, who have traditionally been overlooked. How Kevin's book, Editing Humanity, coincided with Doudna and Charpentier making history as the first two women to share a Nobel Prize. Stanley Qi's role in the CRISPR story, which Kevin calls an “unsung contribution.” Speculation and trepidation surrounding vectors: Kevin shares some new thinking. Germline genome editing, CRISPR babies, He Jiankui, and controversy in Hong Kong. Learn more about the exponential cost of gene therapies and gene editing drugs.

Welcome to season 2 of Info Under the Radar. New topics and new guests with your familiar hosts. In the first episode of this new season, we are talking about one of the most revolutionary gene-editing technologies, CRISPR. We are talking about various facets of CRISPR with none other than Kevin Davies, who is the author of EDITING HUMANITY: The Crispr Revolution and the New Era of Genome Editing and many other books, links of all of which can be found below. Timestamps (06:15) - Why should a layperson care about CRISPR and how CRISPR came about? (25:00) - Recap of how CRISPR works and what has been achieved on humans using CRISPR (27:45) - Sickle cell anemia and technical details of how CRISPR can potentially cure it (33:20) - Intermission (34:00) - Ethical dilemmas related to CRISPR and the infamous story of CRISPR babies in China (46:30) - Was doing gene editing of CRISPR babies for a valid reason? (50:10) - Is it possible to tell if someone's gene was edited by looking at their DNA  signature? (53:20) - Side effects of CRISPR based editing (59:00) - Future of CRISPR based therapeutics and pricing policy for such therapeutics (66:00) - Commercial aspects of CRISPR (69:50) - Resources to learn more about the field of CRISPR and gene editing Reach out to Kevin on his Twitter: @KevinADavies (https://twitter.com/KevinADavies) Kevin's new Book -  Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing Kevin's other Books: https://www.amazon.com/Kevin-Davies/e/B001H6V3M0 Resources mentioned by Kevin: The Code Breaker by Walter Isaacson: https://www.goodreads.com/en/book/show/54968118-the-code-breaker The Human Gene Editing Debate by John H. Evans: https://www.goodreads.com/book/show/51456306-the-human-gene-editing-debate The Mutant Project: Inside the Global Race to Genetically Modify Humans by Eben Kirksey: https://www.goodreads.com/en/book/show/49127465-the-mutant-project Reach out to us with your comments, suggestions, or critique here: Twitter: @infounderradar Instagram: @infoundertheradar Your hosts on Twitter: Devendra: @InDevOut Vishwajeet: @vishwajeets3 Music Credits: Origami by Johny Grimes https://soundcloud.com/johny-grimesCreative Commons — Attribution 3.0 Unported — CC BY 3.0 Free Download / Stream: http://bit.ly/_-origamiMusic promoted by Audio Library https://youtu.be/m-pdlZ7VaDE --- Send in a voice message: https://podcasters.spotify.com/pod/show/info-under-radar/message

Incontro con Kevin Davies. Presenta Simona Regina Che cosa accadrebbe se l'umanità potesse alterare la sostanza stessa del codice genetico? Questa domanda è rimasta a lungo confinata al campo della fantascienza, ma tutto questo sta per cambiare, come ci rivela Kevin Davies, portandoci per mano all'interno dell'affascinante mondo di una nuova tecnica di editing genetico chiamata CRISPR, una potente cassetta degli attrezzi che permette di correggere il DNA di qualsiasi organismo. Edizione 2021 www.pordenonelegge.it

Darryl, Jacko and Maggie take a look a the draw to Stockport in the FA Cup and hear from striker Eoin Doyle on his thirst for more goals. Plus, the team are joined by Super Kevin Davies and Gethin Jones as they prepare for the star studded charity match.

Harry's guest this week is Matthew Might, director of the Hugh Kaul Precision Medicine Institute at the University of Alabama at Birmingham. Might trained as a computer scientist, but a personal odyssey inspired him to make the switch into precision medicine. Now he uses computational tools such as knowledge graphs and natural language processing to find existing drug compounds that might help cure people with rare genetic disorders.Might's odyssey began with the birth of his first child, Bertrand, in 2007. Bertrand seemed healthy at first, but soon developed a cluster of symptoms including developmental delay, lack of motor control, inability to produce tears, and epilepsy-like seizures.  For more than four years, doctors were unable to diagnose Bertrand's condition. But eventually a technique called whole exome sequencing revealed that he had no functioning gene for NGLY1, an enzyme that normally removes sugars from misfolded proteins. Bertrand, it turned out, was the first person in the world to be diagnosed with NGLY1 deficiency—and as with so many other "N of 1" diseases, there was no known treatment.After the diagnosis, Matthew and and his wife Cristina decided to used social media and the Internet to locate other patients with NGLY1 disorders around the world. Eventually the couple discovered 70 patients with the condition. Reasoning from first principles about the role of NGLY1, Might discovered that giving Bertrand a sugar called N-acetylglucosamine, a metabolite of NGLY1, helped restore his ability to form tears. (Around the same time Might, co-founded a startup that screened existing drugs to see whether they could treat ion-channel-driven epilepsy similar to what Bertrand experienced; the company was quickly sold to Q State Biosciences.)Working with collaborators at the University of Utah, Might studied planarian worms that had been engineered to lack NGLY1, and found that those that also lacked a second gene had a higher survival rate. That meant one way to treat Bertrand might be to inhibit the analogous gene in humans, in this case a gene for an enzyme called ENGase. Might used computational screening to look for existing drugs that would be inverse in shape and charge to the catalytic domain on ENGase, and might therefore inhibit it. He found more than a dozen drugs that were already FDA-approved. One was Prevacid, a proton-pump inhibitor sold as common over-the-counter medication for acid reflux. It turned out that as a previously unsuspected side effect, Prevacid is an ENGase inhibitor. Bertrand started taking the drug, and Might says it was one of the treatments that helped to extend and enrich his life.Sadly, Bertrand died in 2020 at the age of 12. But by that point, his father's work to apply computation to basic biology, and thereby speed up the treatment of rare disorders, had sparked a movement that will long outlive him. Years before, Bertrand's story had caught the attention of the Obama administration, which invited Matthew to the White House to work on a range of precision-medicine projects. One was an NIH program called the All of Us initiative, which is collecting the genomes and medical records of a million Americans to search for correlations between mutations and health impacts. Might also launched a smaller pilot program called the Patient Empowered Precision Medicine Alliance (PEPMA) with the goal of repeating what he and Cristina had done for NGLY1 deficiency—that is, quickly diagnose the problem and identify possible treatments. Might resigned from his White House role about one year into the Trump administration, then got an offer from University of Alabama to come to Birmingham to set up an institute to scale up the PEPMA idea. One project there called mediKanren involves using logic programming to highlight what Might calls the "unknown knowns" in the medical literature and identify existing, approved drugs that might treat rare disorders.Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to the page of the MoneyBall Medicine podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3.Scroll down to find the subhead titled "Ratings & Reviews."4.Under one of the highlighted reviews, select "Write a Review."5.Next, select a star rating at the top — you have the option of choosing between one and five stars. 6.Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7.Once you've finished, select "Send" or "Save" in the top-right corner. 8.If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9.After selecting a nickname, tap OK. Your review may not be immediately visible.Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: My guest today is Matthew Might. He's a computer scientist who transitioned into precision medicine and now builds computational tools to find new treatments for rare diseases. Since 2017 he's been the director of the Hugh Kaul Precision Medicine Institute at the University of Alabama at Birmingham. Might's journey from pure computer science into medicine is a deeply personal story that began with the birth of his first child Bertrand in 2007. Bertrand seemed healthy at first. But soon he showed a mysterious cluster of symptoms including seizures, lack of motor control, and inability to produce tears. For more than four years, doctors were unable to diagnose Bertrand's condition. But eventually, using a then-new technology called whole exome sequencing, they determined that he had no functioning gene for NGLY1, an enzyme that normally helps to clear junk proteins out of cells. It turned out that Bertrand was the first person ever to be diagnosed with NGLY1 deficiency. There was no obvious treatment available. Matthew says that's when he began his transformation into an amateur biologist. He shared Bertrand's story on social media and in the press, and was able to locate and organize the families of dozens of other patients around the world who had the same mutation. He worked with colleagues at the University of Utah to make genetically engineered planarian worms that had a similar mutation. Experiments on the worms led showed that knocking out a second gene, for another enzyme called ENGase, seemed to help the worms live longer.So on a hunch, Might set off on a computational search for compounds that might bind to ENGase in humans and inhibit its activity. He discovered that there was a drug on the market called Prevacid that was approved to treat acid reflux but also, as an unexpected side effect, inhibits ENGase. So Bertrand started taking Prevacid, and it helped. Matthew says it was one of the treatments that helped to extend and enrich his life.Sadly, Bertrand passed away last year at the age of 12. But by that point, his father's work to apply computation to basic biology, and thereby speed up the treatment of rare disorders, had sparked a movement that will long outlive him.The story caught the attention of the Obama White House, which asked Matthew to lead several new initiatives in genomics and precision medicine. One of those was a pilot called the Patient-Empowered Precision Medicine Alliance, which had the goal of quickly diagnosing rare conditions and identifying treatments for more patients. Now Might is continuing that work at the University of Alabama, Birmingham, where the Precision Medicine Institute uses computer science techniques like knowledge graphs and natural language processing to find more drugs that can be repurposed to fight rare diseases.We covered all of that ground and more when we talked in late August. And once you hear our interview, I think you'll agree with Might that computation is accelerating the genomics revolution in a way that's going to change healthcare not just for people with rare diseases, but for everyone.Harry Glorikian: Matthew, welcome to the show. Matthew Might: Oh, thanks. Good to be here. Harry Glorikian: [I] spent a lot of time reading about what you're doing your past and sort of the history here, but I want to start off with, which sort of which fits right into the show, is you've said that data is the greatest drug of the 21st century and that precision medicine delivers data as a drug. Can you expand on what you mean by thatMatthew Might: Yeah. And I've said this a few times in a few ways, but the principle here is that I think we need to look at data itself as a kind of intervention,that exposure to one's own data could have ramifications for your health. And you can imagine this in a very general sense.Like if you get detailed data about your health and you might do something about it,  but if you give extremely detailed data to your physician, they might be able to do something with.  and, and oftentimes I'm thinking in terms of the very molecular in that case. And that's really where I spend a lot of my time, but giving clinicians molecular resolution on the nature of your specific health problems is really what I think is so revolutionary about medicine, right now. And the ways in which we can gather that data and the computational tools that will be available someday to physicians, and even to a certain extent right now will enable them to do things that no drug can do on its own. Harry Glorikian: Well, it's, it's interesting that you say data and, in that sense is I was just playing with something that pulled in all my medical data and put out all the longitudinal charts for me and highlighted all the ones where I was out of whack. And I texted my doctor. I'm like, we need to get on a Zoom call. I need to show you a couple of things that are out of whack, and I want to figure out why they're out of whack. So I agree with you that molecular will be that, that really high resolution level to get to. But even I think the simple data to give patients I think is powerful. It can move the needle,  if we can communicate it to them effectively. Matthew Might: Yeah. I mean, I think even the simplest incarnation of this could do some good, like imagine if your scale not only told you your current weight, but just drew a line between your last three readings and said, this is where you're going to be in 10 weeks. Something that simple might help.Harry Glorikian: My scale does do that and it tells me that you are getting fat, so you gotta, need to do something. So I try to intervene when I can. But, so, you have an interesting history and past, I mean, you went from pure computer scientist from the university of Utah into precision medicine at the University of Alabama. I mean, that's, I almost want to say based on what I was reading like that revolves around your personal experience from finding a diagnosis and treatment for your son. Can you give the listeners may be a condensed version of that story and how did it turn out that your experience studying things like functional programming turned out to be so useful for studying rare diseases?Matthew Might: Yeah, well, that's a wonderfully broad question. And yeah, I've had an unusual path to this point. So I'm currently the director of the Precision Medicine Institute at UAB. And so it's, it's a, very focused medical research institute. We want to help patients find tailored therapies for them.My background in computation and computer science certainly influences that. We have a host of computational tools to help do that. Some are based on  artificial intelligence. Some are very systems biology focused, that start to invoke aspects of functional programming. And you're right. And the reason I started all this is my oldest son, who unfortunately passed away in October,  had an undiagnosed [disease]. And for four years I had no idea what he had. Eventually through a novel application of exome sequencing was able to determine that he had the first case ever known of this ultra rare disease called NGLY1 deficiency.And I think that's safely the point where I really flipped in my head from a computer scientist to an amateur biologist. I knew enough to try to get him diagnosed, but that's one where I said, I've got to find some way to help him. And even though he passed away, it's hard to look back on his life and see it as anything but a major success in many ways, because he was born with a very short life expectancy and yet he made it to almost 13 years old and that would not have happened without sort of a sequence of emerging technologies that came just barely in time to extend and enrich his life and bring him a lot of joy.I miss him every day, but I'm lucky that I have the opportunity to work every day, literally every day towards his legacy of helping patients with science. A lot of which is computational, but much of which is sometimes just good old fashioned wet biology where we go to the bench and try something out. Harry Glorikian: Yeah. I mean, you've sort of described the Precision Medicine Institute as a form of research consultative service, where the goal is to find the next step for any patient that reaches out on their diagnostic or therapeutic odyssey. I mean, that sounds amazing. I mean, maybe you could describe more of what happens on a day-to-day basis. Matthew Might: Yeah. So, it all comes down to Monday. So Monday is case review day. So if someone has reached out to the institute or if we are sort of currently working on something for them, Monday is where we all synchronize and put our heads together and try to figure out that next step.So for patients that have reached out for the first time, it's, “Okay. What's the direction of a therapy.” And for those that are in flight, if there's been a change, if some experiment has completed, if some lab has come back, if new information has been introduced, we check to see, is there a new next step? Is there some, is there some new insight? And sometimes on those Mondays information will come back that enables a query to be run on one of our computational tools where, the best example would be, targets emerged. Like, if we modulate the behavior of this gene, we think it will be therapeutic for this patient now. And so we can run queries to see, can we modulate the behavior of that gene using some kind of small molecule or some other approach. Harry Glorikian: So, but when you're doing all this, I mean, are you, do you have a mission to sort of either scale up or automate? And if you do, how's that going? Matthew Might: Yeah, so it's, it's both. And in fact, it's, it's scaling through automating. We realized pretty early on that humans are an essential part of this process, right now, in the sense that humans really do need to—in this case, when I say humans, I mean, undergraduate students, because they're the ones within the institute that act effectively as the case managers and reach out and sort of pull in the information, digest it to some kind of structured format that the tools can process.They might engage with the physician. They might reach out to some basic scientists that have insight on the relevant biological processes and figure out how do we drive it to a query or a recommendation for an experiment. And so, in some sense, when I think about scale, what I'm really thinking about is the efficiency of these undergraduates. How many cases per week can we get them to process and how much tooling and automation can we build to make them better and better at what they do? So that's how I think about scale. And then I think about replicating this as a process and every academic medicine, medical center across the country. There's no reason you couldn't have a team of extremely bright students in every center of the country that run this kind of process for their patients locally.Harry Glorikian: Yeah. I mean, I would think that that would be one hell of an experience for the students to sort of see something actually being practically applied,as opposed to reading it in a book and it being a little bit more theoretical. Matthew Might: It is actually, in fact, I've noticed that literally 100% of the students that have participated in this program, I mean, all of them have gone on to graduate school, either for an MD, a PhD or both. So it's a 100% success rate to getting students in the grad school or med school.And now we have a course version of it. And so in fact, several course versions of this, where you can take this class and you'll get to practice on some existing solved cases, but we even throw some unsolved ones in the mix to see how they do. And when they take these courses, and then for the honors students now at UAB, they can take a special course sequence as freshmen, where they'll get into the lab and build model organisms that represent some of the patients, which could ultimately enable the discovery of therapies for them. So I have to say it's, I can't think of a lot of other places where you get that kind of experience as an undergraduate. Harry Glorikian: Well, no, that's what I was thinking. I was thinking, “Hmm. How do we get this more broadly out there so that more people are doing this and, and get their head in that, in that zone and understand these issues.”But I think one of the projects that I was looking at was mediKanren, if I'm pronouncing it correctly. What is it meant to do?Matthew Might: So mediKanren is really our flagship artificial intelligence tool that we use primarily for drug repurposing. We kind of built it with the end application in mind. So I'll tell you what it's really good at doing. If you tell it a gene and you tell it a direction to go, like, I want to make this gene more active or make this gene less active, it does very well on those kinds of questions and it can scour a number of data sets to do this. So we're part of a, actually a larger effort through the NIH called the Translator Consortium. This is a huge research effort. We have lots of teams working together to both mine out all biomedical knowledge and make it structured. And another set of teams are trying to do automated reasoning on top of all of that knowledge. So we're on the automated reasoning side. We can do some of the mining too, but,  the other teams do such a fantastic job that we mostly just consume what they produce in terms the mining. And then we try to stitch it together,  so that we can find interesting ways to go after targets of interest. Harry Glorikian: So it's reasoning over medical knowledge graphs, I think, that you're trying to do. And so it sounds like a promising way to find unexpected connections between diseases and existing drugs. But if you had to explain that to a layman, how would you explain sort of a knowledge graph and what you guys are doing with it? Or do you have a favorite example? Matthew Might: I have pictures, but I can also do it with words. Knowledge graph. So let's talk about what it represents. Ultimately, there's a structure, but that's not actually all that important. A knowledge graph is a collection of facts,  and in facts are sentences. And they're sentences of the form “A somehow relates to B in some sense.” and knowledge graph is just a huge collection of these sentences, “A is related to B,” where there's a specific relationship.So a biomedical knowledge graph is going to have some constraints on it. So the A's and the B's that you're connecting are going to be nouns from medicine and biology. So there'll be drugs and diseases and genes and metabolites and all the other stuff that you typically read about in and medical papers. And the relationships are going to be biomedical in nature too. So it's going to be things like A inhibits B, A activates B, A causes B, A treats B. And so if you collect all of these sentences together, you have what we call a knowledge graph. And the cool thing about a knowledge graph is that you can do logic on top of it and try to look for relationships that are there, but not explicitly stated.The simplest example of this is let's suppose there's two sentences in this knowledge graph, there's Aa increases B and B increases C. We can infer logically that if you increase A, you should also increase C, because B went up and so C should go up. So that's an example of logical inference on top of one of these knowledge graphs.Harry Glorikian: And so that's typically—there's a human intervention at some point to sort of look at this and then say, yes, this makes sense? Matthew Might: Yes, absolutely. So one of the major roles of these undergraduate analysts is to actually double check what comes back from a tool like this, because it's going to admit a logic argument. It's going to say, “I believe that this is going to influence the right target because,” and then the analyst can look at the because, and it's going to have references into biomedical data sets. It's going to have references to papers in PubMed, and they can go read those. They can look at the data sets and they can double-check the reasoner and say, you know what, I think you got this right. Or no, you made a mistake. And it does make mistakes sometimes. So a lot of the knowledge from the literature has been done by natural language processing and that makes mistakes. It's critical to have a human in the loop to double-check that.And towards your earlier question about how we do scale, one of the things that we've added to the tool is ways to make that check go faster. So, for example, on the latest interface, when it tells you that it believes, for example, A increases B and you click on that, it's going to jump straight to the sentence that it pulled that from in the paper. And so you can just look directly at that sentence and say, do I believe this? Do I believe it got A right? Do I think it got B right? Do I think it got the relationship right? It's sitting right in front of the analyst. Whereas previously that was a few clicks away. They had to click on that. They had to click on the paper it found they had to go to the paper on their web browser. They had to look at the abstract, they had to find the sentence that it got it from,  and then figure it out. That's a long process actually now, and going from, a few minutes to verify and inference to a few seconds, that's a huge increase in efficiency for these analysts. Harry Glorikian: one of the things I would say is I always try to find out, is it shortens the overall process of even finding this relationship. I mean, if you had to put sort of time scales on this, how much faster you think that we're speeding up this whole process of being able to even identify something that might have this effect?Matthew Might: Yeah. Yeah. I mean, we we've had some natural experiments in this regard where in some cases there were answers sort of buried in the literature that seemed to have been therapeutically relevant and yet, very motivated disease communities hadn't stumbled across them, and motivated physician-scientists researching these diseases had not run across them, or didn't sort of connect the dots to realize that this could actually be relevant to a patient. Probably the most recent example of this is ADNP-driven autism, where there were results in the literature that could imply the key finding, which is that low-dose ketamine will increase ADNP. That's the key thing that the researchers trying to treat this disease were after. And in some sense that was out publicly known, if you will, in the literature. And yet it took running this query to find it,to sort of make the realization that this was true.It's kind of interesting actually to think about the fact that there's stuff out there that as a species we know, but we don't know that we know. So we call that sometimes the “unknown known.” It actually happens a lot in different contexts. And I even remember this happening in computer science, where there were communities out there so disparate that one had solved a problem the other had been trying to solve for three decades, and they just didn't know that I had effectively been solved. I mean, it can happen, actually.Harry Glorikian: Yes. And I talked to different groups that are working on systems that will make those unknowns more easily findable,  or at least highlight them so that people know they're there. But you guys search scientific literature, drug databases, for existing and approved [drugs]. And basically you're looking to find something that's going to perturb an ultra-rare disease. Why is it better to look for an existing drug rather than a new one? I'm just, curious of the practical arguments around that. Matthew Might: I'm not against developing a novel drug for a single patient. It's just that most patients don't have $2.6 billion. So it's a little out of their price range. That said, of course there's technologies that are changing this equation substantially. So I would say oligonucleotide therapies in general, it's not down to a thousand dollars a patient, but it's dramatically less than $2.6 billion. We're probably closer to the range of a couple million dollars, and that's falling fast, to do these sort of custom-programmed therapeutics for individual patients. So,  yeah, I'm not against finding novel matter. It's just that it's still outside the budget of what most ultra-rare patients can handle.Harry Glorikian: Right. Right. Well, I was talking to, it hasn't even come out yet, but I was talking to Kevin Davies in one of my last podcasts about CRISPR and just exactly that same discussion. So I don't know if you guys have sort of done a ballpark or sort of a thumbnail of what do you think, what fraction of rare conditions do you think, are treatable the way that you're you guys are approaching it? Is it fair to say that eventually you'll exhaust that approach in that we'll have to develop a new drug for the next disease?Matthew Might: Yeah and I guess we've got to sort of clarify what we mean by approach. So there's the AI-based approach or sort of strictly computational approach. And then there is what we can do if we're allowed to go to the wet lab for a little bit of stuff.If you play the game where you can only use a computer, there's the answer for today and the answer in the limit. Once we've sort of saturated biomedical knowledge graphs, if you will, with everything wherever we're going to know—and already, right off the bat, I think we jumped to a reasonable suggestion somewhere between 5 and 10% of the time, for the case of ultra-rare genetic diseases, and there are factors that can influence that. So for example, if it's a dominant disorder where the genetic insult has really just sort of tweaked the thermostat on a gene, so it's a little overactive or a little underactive, we tend to have a better success rate jumping straight to an answer with a computational tool than if the gene has been wiped out and now we have to find a way to replace that activity. Now the good news is if you look at sort of the census of rare disease, 70 or 75% of all patients fall into that bucket of the genes have become a little overactive or a little underactive. And so it's very amenable to an approach like this. And for the patients that where the gene is missing, there are still things we can do computationally. The call I had right before this one was exactly that case for you. What can we do computationally? And by playing with the tool, we found some alternate targets to go after. But it takes some play to do it at that point. It's not quite as automated, but you're still using the tool as targets emerge to ask the right questions. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian: Before you moved to UAB, you were working on precision medicine initiatives for the Obama White House, I believe, and then briefly for the Trump White House. Can you update the status of the, was it, the All for Us initiative and then the Patient Empowered Precision Medicine Alliance? Matthew Might: Sure. So, yeah, I did spend, I think, in total, about three years either working with or working for the White House,  under both Obama and Trumpm on the precision medicine initiative and related initiatives, like the Million Veterans program, as well as micro-initiatives, like the Patient Empowerment Precision Medicine Alliance, where we were just kind of trying to test it out, to see if these ultra-tailored approaches would work. So as far as where things stand today, All of Us is a very successful, large scale clinical genomics research program, which is, I think on the way to hitting its target of enrolling a million Americans. And the way I described that program even at the time was like you're trying to build the Rosetta stone of the human genome. It turns out we reached a point where it's really easy to sequence a genome. Not so easy to interpret a genome. So if I sequence you or me and we find mutations, we go, “huh. Well, that's interesting. What does that mean?” And we go, I don't know. But let's suppose you got a million people that donate their health records and their genomes. Well, now you can start to draw statistical connections between what this mutation or this collection of mutations means in terms of actual human health. So it's finally a way to start decoding it. And so that's really what All of Us is about in my view. It's about building that Rosetta stone for the human genome.For the Million Veterans program, it's actually sort of inside of it, yet also outside of it and really trying to do the same thing, but leveraging the extensive clinical records and histories that the VA happens to have access to,  and taking a slightly different method to get there in terms of genomic data, starting with SNP chips and genotyping, as opposed to full-on sequencing.And then for PEPMA, that was really a pilot project where we just said, okay, can we take a small number of patients and can we actually sort of run this process all the way forward, where we get a genotype and try to find a medication that might help them. And it turns out for a handful of cases, we were actually able to do it. It was all thanks to getting a group of private entities, like, companies and universities to come together so that we actually had enough infrastructure in one place to run the process. And so we were actually able to do that. Harry Glorikian: Yeah, it's funny because I always think to myself, like all these silos, if we could just have them integrate in some way, you'd have a lot more data to work with. I always find that in the beginning, you always find those low hanging fruit that sort of fall out and then it gets harder. If you have enough to start with, something interesting falls out of it. You've said that in precision medicine, for a lot of cases that we deal with, we don't have sort of the right drug right away, but we can always prescribe an experiment. What do you mean by that?Matthew Might: Yeah, by that, I mean, and so this gets into sort of like the philosophy of medicine itself. So you'll hear clinicians use terms like “This is not actionable.” And then you hear that an awful lot in rare disease. You hear it a lot at the end of cancer, where they'll say, oh, there's nothing we can do, or there's no clinical utility in this. And, and I think precision medicine subverts that whole approach and says that, well, if you've run out of clinical options, you can still do some science.And increasingly I think we can systematize that science, so that it's not okay. We need to do something. It's, here's a set of things that you could reasonably do at this point, a set of experiments that if run, might point to what to do or might point to another next step. And a great example of that is,  for, for, particularly for a rare genetic disorder, in many cases you can build a model organism, you can build a fly and you can build a worm pretty inexpensively,  to model that genetic disease, using things like CRISPR. People don't appreciate, I think, the full importance of gene editing. People think about editing human genomes, but the fact that it made it so much easier to edit animal genomes was actually in many ways an even bigger impact and a more immediate one as well.So yeah, you could for virtually any genetic disease, if there's an animal equivalent to that gene, you can build the animal. And if it's a small animal, you can test a lot of drugs on it, pretty inexpensively. So, I've got a friend and collaborator, Ethan Perlstein, who built a company around this approach and was very successful actually in treating, some patients this way. I have a collaborator, Clement Chow, who is an academic doing this on the academic side, focused on Drosophila, doing this very successfully.So, that's not a drug, it's not a procedure, not a medical procedure anyway, but it's a very well-defined process. And it's a process whose outcomes could be measured statistically. So you might even know what your odds of success are before you try it, whether or not you're going to find something. So I think it takes an evolution in our thinking to realize that this is a perfectly reasonable thing to do for a lot of patients: build that fly, build that worm and test a bunch of drugs. Harry Glorikian: And, there's a lot of times where things seem perfectly normal for me to suggest, and I've had people look at me, like I just grew like two more heads off, off my shoulders.So, but this sounds like if this is your fundamental belief that there is nothing that is not actionable, medicine or otherwise. Matthew Might: Right, right. And I think it also requires a degree of stoicism because just because there's something to do, it doesn't mean it's going to work in time. And this was something I was always mindful of during my son's life, was that while there was always something to do, I was mindful that it was probably not going to always happen in time. It was always a race against the clock. But there was always something to do. And even today there's still, as I say, I'm still working on his condition. I'm still very actively engaged in drug development for his disorder. So even now there's something to do. As a parent it's still brings me benefit to know that it, it will benefit others. So it does require a shift in perspective about the meaning of actionable. Harry Glorikian: It feels like finding [computational] ways to use existing drugs, to help people with rare problems, was waiting to be solved with someone with your exact skillset in computer science and your exact set of motivations as a father of a child with a genetic disorder. And so many other key players that I've talked to in this sort of that have this N of 1 stories have very similar biographies. I mean, there's been a few movies made about it, right? It makes somebody wonder that if you know your son hadn't been born to you with your expertise, who could apply knowledge and bring that experience to it, that you wouldn't be moving the ball forward. How does that make you feel about the state of science or medicine? Matthew Might: Yeah. And, you're not the first to make an observation that I sort of ended up in the right place at the right time with the right set of motivations. And there's a lot of truth to that. I think about if he'd been born even a few years earlier, or a few years later, how things would have played out differently.I realized early on that there's a desperate need for computer science within medicine, that there is so much opportunity just left on the table for lack of expertise. But I made a deeper observation, which is that as much as medicine needs computer science, what it needs even more is computer scientists.The problem is that the average computer scientist doesn't have sufficient motivation to go learn. Medicine's big, it's messy. And I got to say, biology is so messy that to the mind of a computer scientist at times, you're just like, God, what a disaster biology is. It's like every time you have a rule or a law, most of the time at the end of it, there's nothing ever that's always true. And when you come from a field like computer science, where you can put clean little theorems around everything and layers of abstraction that never break, it's like, oh gosh, who designed all this? Who was the engineer that thought that was a good idea?That that's how I feel half the time when I dive into biology. And yet there are abstractions that you can borrow from computer science and you can use these things to start to describe the way biology does what it does. And so I do think of the cell as a computer or a machine—maybe a Rube Goldberg machine, but a machine nonetheless. And one that you can sort of intellectually approach, from the direction of computer science. Within computer science, I happen to have a background in functional programming. And there are times when, describing the mechanics of how biological processes operate, where this kind of feels like, I'm playing with a little functional programming language. Like I'm doing graphic writing instead of term rewriting. There's been these moments where I'm like, yeah, this is just a programming language. It's weird, but it is one. And then I think, gosh, I mean, it is strange that I arrived with that particular skill set at this point in biology's history,  to make these observations and use that profitably towards helping patients.So in terms of how they makes me feel? Lucky, I guess, that I've, I've just sort of been there on the right place at the right time. And the same thing is true for almost everything else that's occurred since,  since Bertrand was born, from the timing of the precision medicine initiative itself, to getting his story in front of President Obama at just that moment, to getting the invitation to go, to getting the invitation to participate, and then join the team. I mean, the timing on all of it was just so ridiculous to me that I look back and think, I can't believe that happened. Harry Glorikian: Wow. I mean, timing. Being in the right place at the right time, a little luck, I'll take that every day, right, where everything starts ti come together.I think back to, because I was involved at Applied Biosystems when we did the genome and wow, that was such a big deal. And then every once in a while I still see an article saying. Yeah, the genome hasn't really done much. And I'm like, these people, how do they write these things with a straight face? And it gets published in a reasonable journal. And I'm like, these people are out of their minds, considering everything in biotech, everything in, functional genomics, all this stuff is, is grounded in that information.Matthew Might: I see the same stuff and I think, what do you mean nothing has come out of it. What are you talking about? Everything has come from that. And then, when I point to success stories with individual patients, which are growing and growing, they're like, yeah, but that's the exception. It's turning into the rule more and more, and I think what you're seeing now is that as with any new technology, the barrier to entry starts very high. But that barrier has been falling fast to the point where, people who start off, the parent side, like me, are increasingly finding that they can get into the game and that they can do something.And I think it's at a level now where almost any, patient or parent that has a technical background can jump over and do something. But even patients without that background are making the jump now, too. So barrier to entry is falling so fast that it really has changed everything when it comes to patients moving the needle for themselves using the fruits of the genomic era. Harry Glorikian: Yeah. And I think computational, power and costs and ease of use are starting to come down dramatically, which then brings the two together, which is of course the idea of behind the whole show and everybody that I talk to, and I see the, some of the companies I talked to they're like, yep, we sort of eliminated three years of work. We could get it done in, a week to two weeks because of what we're looking at, how we've applied our computer science. How many new pathways we can sort of identify of course, for new drugs. Matthew Might: And I, I can give you examples of where the barriers fell overnight as I needed them to, just by luck. Or when it came to creating model organisms, right? Before CRISPR, gosh, that was an expensive, daunting. process, it took a lot of time. And then CRISPR shows up and they're like, oh yeah, no, it'll be a few months and $10,000. And it was just, I mean, just like that it happened. And there's equivalent revolutions happening on the computational side too. If you look at your protein folding technology, it was a joke, that like, yeah, it'll never happen in silico. And then all of a sudden, like now some say maybe the only way we'll ever get some structures is in silico.  And then that was kind of an overnight thing too. Obviously it wasn't overnight for the engineers on the project at Google. But once it appears like, oh my gosh, what a game changer. Harry Glorikian: Well, and then as soon as somebody does it, it motivates more people to sort of grow and it sort of moves the space forward that much faster. That's the part I find interesting is most people have trouble understanding the speed of change, and it's moving faster now than—and I'm used to, trying to keep track of how fast everything's going, and I'm finding myself having trouble keep up with how quickly things are shifting. Matthew Might: It really is changing faster than I think any one person can predict. And the disruptions are coming almost out of nowhere. Like no one saw CRISPR coming. You might reasonably foresee that at some point, some efficient gene editing technology would have emerged. But I think it emerged much faster than was expected.I remember when I would work with patients, five or six years ago, I'd say, yeah, there's this thing, these antisense oligonucleotides, and maybe someday, but we're probably, I would say at the time, like maybe 20 years away. Then you see oligonucleotide therapies really take off and, then I think it was two years later there's an FDA approval. Then a couple of years after that, there's the first big N of 1 introduction. And then like a year and a half later, we were all injecting mRNA into ourselves. Well, that happened pretty fast. It wasn't a couple years. Harry Glorikian: Yeah. And, and for people like you and me that are in this, like, my, my mind is like, wow, this is awesome. And then I try to explain to someone and they don't understand the impact that some of this is happening in the implications of what we're talking about. Matthew Might: Yeah. And, I think that, going forward, it's going to be a much steeper acceleration than anybody can really predict because we've suddenly just burst into the era of programmable therapeutics. I mean, COVID really suddenly just threw it on the table. There it is. And an example as well, people said, okay, well, if you can just give mRNA directly, instead of trying to deliver these complicated proteins to do the gene editing, why don't you deliver the mRNA for the CRISPR protein or, for, for CAS9 and deliver this along with the guide RNAs, well that's much easier. And my, my gosh, it looks like it might actually work. So these things, they couple in unexpected ways, and very quickly too. And so I I'm excited cause I have no way to know what's coming now. Harry Glorikian: I've always felt, I don't know what's coming. That's why I try to read such a broad array of, sources, everything that's going on in, you know, chip development to what's going on in our world. But I think the next big wave of shifts is going to be how a lot of this gets implemented, the business models behind it. And that's the next big shift because you don't have to do it exactly the same way you had been doing it up til now.Matthew Might: Oh, I agree. And, and oddly enough, yeah, I spent a fair amount of time thinking about stuff as mundane as how do we get payers to actually pay for some of these things? How do we show them that there is value to be captured already? And, because there is, I think we're not far away from a future where payers realize that it's going to be cheaper to take this very expensive patient with a complex disease and look for sort of a root cause treatment than to continue paying for symptomatic treatment. I think we're at the threshold of that era. Harry Glorikian: Well, I think, the CEO of Illumina said we want to get whole genome down to $60. Right. I mean, at some point you're like, okay, when are you going to stop being worried about the cost of this? Because it's going to be a rounding error at some point. Matthew Might: Yeah. Over the course of someone's life, it's already a rounding error you know it's already there.Harry Glorikian: But $60, yeah. I mean, I was, I was,  talking to a company where they could do, if you could do the initial analytics for $60 and then do the computational on top of it for another $60, at some point you're like, look, we should just be doing this for everybody. The problem is the implementation. And can physicians keep up with, what does it all mean and what am I supposed to do? Matthew Might: Yeah. And that's why I think, when I talk about precision medicine and data as a drug, I always have to highlight the importance of computational aid for the physician. Because if you were to give a physician [raw DNA data[, they would go, “What, I don't know what to do with that.”  Even if you distill it down to the individual mutations, the average physician goes, “I still don't know what to do with that.” It's gotta be broken down into something far more actionable for them.And I think we're going to look back at now as sort of like the dark ages of IT in medicine, because we're in a situation where I don't know any physician that loves the EHR they use. In fact, they all hate it. It is a disastrous user experience across the board. And this is a classic problem in software where the people who pay for the things are not the people who use the things, and say, so what are EHRs optimized for? Billing. There's only one EHR as far as I can tell it's optimized for patient care, and that's at the VA, where they're not really concerned about billing. And so people like that one,  which is, not, not a big surprise. Harry Glorikian: Well, and they were talking about, they wanted to put in Epic. I was like, who got paid like behind some closed door to make that decision? That was the dumbest decision I've ever heard anybody make. Matthew Might: I thought the same thing as you, having worked in the Million Veterans program. Like, no, that's the crown jewel. That thing actually works and it works well, and it gets great data,  do not replace that. Keep it as is. Harry Glorikian: Yeah. Well you need to, unfortunately whoever's making that decision has no skin in that game as far as I can tell, but I agree with you. I mean, I've said over and over, if anything's gonna break medicine, it's going to be the existing EMR systems because you can't innovate if you can't get the data out. And Google and Microsoft and Apple and everybody's innovating because they get to change their system at will, right. Everybody gets to jump on AWS and innovate. The system is sort of stuck in stasis and can't move out of it, which is what I find worrisome. Matthew Might: I agree. You've either got to get the data out or the computation in. Preferably both. I've dealt with physicians where I can say, “Hey, we could give you this really cool genomic test for your patients. And then if they try to take a drug, you'll know if it's not going to work for them.” And they go, “Well, will there be automated decision support in the EHR to tell me if that happens? Or do I have to sort of look at the note and see that they have this variant?” I go, “Well, you can have to look at the note.” And they say, “No, I do not want that, because if that note is in there and I don't figure that out, and I prescribe a drug that causes an adverse event. I'll get sued. But if the information's not there at all, I can't be sued.” That's the world we live in.Harry Glorikian: Well, listen, it was great to speak to you. The stuff you're doing is awesome. I wish more people knew about it. I wish more students were involved in it so they could get firsthand experience. Like you said, I think that's when we can start to teach people the crossover between medicine and computational work in general, because I'm always trying to find people that know both, and there's not a lot of fruit on that tree at the moment. More is growing, but not as much as you'd like.Matthew Might: I agree. We need to get people going more often in both directions. And that's one of my missions at the Institute as well as to cross-train folks in into both sides, biology and computer science.Harry Glorikian: Excellent. Well, it was great to talk to you. I appreciate the time. Matthew Might: Likewise. It has been a pleasure.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian. Thanks for listening, and we'll be back soon with our next interview.

This week Harry is joined by Kevin Davies, author of the 2020 book Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. CRISPR—an acronym for Clustered Regularly Interspaced Short Palindromic Repeats—consists of DNA sequences that evolved to help bacteria recognize and defend against viral invaders, as a kind of primitive immune system. Thanks to its ability to precisely detect and cut other DNA sequences, CRISPR has spread to labs across the world in the nine years since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking 2012 Science paper describing how the process works. The Nobel Prize committee recognized the two scientists for the achievement in 2020, one day after Davies' book came out. The book explains how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused. Today's interview covers all of that ground and more.Davies is a PhD geneticist who has spent most of his career in life sciences publishing. After his postdoc with Harvey Lodish at the Whitehead Institute, Davies worked as an assistant editor at Nature, the founding editor of Nature Genetics (Nature's first spinoff journal), editor-in-chief at Cell Press, founding editor-in-chief of the Boston-based publication Bio-IT World, and publisher of Chemical & Engineering News. In 2018 he helped to launch The CRISPR Journal, where he is the executive editor. Davies' previous books include Breakthrough (1995) about the race to understand the BRCA1 breast cancer gene, Cracking the Genome (2001) about the Human Genome Project, The $1,000 Genome (2010) about next-generation sequencing companies, and DNA (2017), an updated version of James Watson's 2004 book, co-authored with Watson and Andrew Berry.Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to the page of the MoneyBall Medicine podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3.Scroll down to find the subhead titled "Ratings & Reviews."4.Under one of the highlighted reviews, select "Write a Review."5.Next, select a star rating at the top — you have the option of choosing between one and five stars. 6.Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7.Once you've finished, select "Send" or "Save" in the top-right corner. 8.If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9.After selecting a nickname, tap OK. Your review may not be immediately visible.Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: We talk a lot on the show about how computation and data are changing the way we develop new medicines and the way we deliver healthcare. Some executives in the drug discovery business speak of the computing and software side of the business as the “dry lab” —to set it apart from the “wet labs” where scientists get their hands dirty working with actual cells, tissues, and reagents.But the thing is, recent progress on the wet lab side of biotech has been just as amazing as progress in areas like machine learning. And this week, my friend Kevin Davies is here to talk about the most powerful tool to come along in the last decade, namely, precise gene editing using CRISPR.Of course, CRISPR-based gene editing has been all over the news since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking Science paper in 2012 describing how the process works in the lab. That work earned them a Nobel Prize in medicine just eight years later, in 2020.But what's not as well-known is the story of how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused.Kevin put that whole fascinating story together in his 2020 book Editing Humanity. And as the executive editor of The CRISPR Journal, the former editor-in-chief of Bio-IT World, the founding editor at Nature Genetics, and the author of several other important books about genomics, Kevin is one of the best-placed people in the world to tell that story. Here's our conversation.Harry Glorikian: Kevin, welcome to the show. Kevin Davies: Great to see you again, Harry. Thanks for having me on.Harry Glorikian: Yeah, no, I mean, I seem to be saying this a lot lately, it's been such a long time since, because of this whole pandemic, nobody's really seeing anybody on a regular basis. I want to give everybody a chance to hear about, you had written this book called Editing Humanity, which is, you know, beautifully placed behind you for, for product placement here. But I want to hear, can you give everybody sort of an overview of the book and why you feel that this fairly technical laboratory tool called CRISPR is so important that you needed to write a book about it?Kevin Davies: Thank you. Yes. As you may know, from some of my previous “bestsellers” or not, I've written about big stories in genetics because that's the only thing I'm remotely qualified to write about. I trained as a human geneticist in London and came over to do actually a pair of post-docs in the Boston area before realizing my talents, whatever they might be, certainly weren't as a bench researcher. So I had to find another way to stay in science but get away from the bench and hang up the lab coats.So moving into science publishing and getting a job with Nature and then launching Nature Genetics was the route for me. And over the last 30 years, I've written four or five books that have all been about, a) something big happening in genomics, b) something really big that will have both medical and societal significance, like the mapping and discovery of the BRCA1 breast cancer gene in the mid-90s, the Human Genome Project at the turn of the century, and then the birth and the dawn of consumer genetics and personalized medicine with The $1,000 Genome. And the third ingredient I really look for if I'm trying to reach a moderately, significantly large audience is for the human elements. Who are they, the heroes and the anti heroes to propel the story? Where is the human drama? Because, you know, we all love a good juicy, gossipy piece of story and rating the good guys and the bad guys. And CRISPR, when it first really took off in 2012, 2013 as a gene editing tool a lot of scientists knew about this. I mean, these papers are being published in Science in particular, not exactly a specialized journal, but I was off doing other things and really missed the initial excitement, I'm embarrassed to say. It was only a couple of years later, working on a sequel to Jim Watson's DNA, where I was tasked with trying to find and summarize the big advances in genomic technology over the previous decade or whatever, that I thought, well, this CRISPR thing seems to be taking off and the Doudnas and the Charpentiers are, you know, winning Breakthrough Prizes and being feted by celebrities. And it's going on 60 Minutes. They're going to make a film with the Rock, Dwayne Johnson. What the heck is going on. And it took very little time after that, for me to think, you know, this is such an exciting, game-changing disruptive technology that I've got to do two things. I've gotta, a) write a book and b) launch a journal, and that's what I did. And started planning at any rate in sort of 2016 and 17. We launched the CRISPR Journal at the beginning of 2018. And the book Editing Humanity came out towards the end of 2020. So 2020, literally one day before the Nobel Prize—how about that for timing?—for Doudna and Charpentier for chemistry last year. Harry Glorikian: When I think about it, I remember working with different companies that had different types of gene editing technology you know, working with some particularly in the sort of agriculture space, cause it a little bit easier to run faster than in the human space. And you could see what was happening, but CRISPR now is still very new. But from the news and different advances that are happening, especially here in the Boston area, you know, it's having some real world impacts. If you had to point to the best or the most exciting example of CRISPR technology helping an actual patient, would you say, and I've heard you say it, Victoria Gray, I think, would be the person that comes to mind. I've even, I think in one of your last interviews, you said something about her being, you know, her name will go down in history. Can you explain the technology that is helping her and what some of the similar uses of CRISPR might be?Kevin Davies: So the first half of Editing Humanity is about the heroes of CRISPR, how we, how scientists turned it from this bizarre under-appreciated bacterial antiviral defense system and leveraged it and got to grips with it, and then figured out ways to turn it into a programmable gene editing technology. And within a year or two of that happening that the classic Doudna-Charpentier paper came out in the summer of 2012. Of course the first wave of biotech companies were launched by some of the big names, indeed most of the big names in CRISPR gene editing hierarchies. So Emmanuel Charpentier, Nobel Laureate, launched CRISPR Therapeutics, Jennifer Doudna co-founded Editas Medicine with several other luminaries. That didn't go well for, for reasons of intellectual property. So she withdrew from Editas and became a co-founder of Intellia Therapeutics as well as her own company, Caribou, which just went public, and Feng Zhang and others launched Editas Medicine. So we had this sort of three-way race, if you will, by three CRISPR empowered gene editing companies who all went public within the next two or three years and all set their sights on various different genetic Mendelian disorders with a view to trying to produce clinical success for this very powerful gene editing tool. And so, yes, Victoria Gray is the first patient, the first American patient with sickle cell anemia in a trial that is being run by CRISPR Therapeutics in close association with Vertex Pharmaceuticals. And that breakthrough paper, as I think many of your listeners will know, came out right at the end of 2020 published in the New England Journal of Medicine. Doesn't get much more prestigious than that. And in the first handful of patients that CRISPR Therapeutics have edited with a view to raising the levels of fetal hemoglobin, fetal globin, to compensate for the defective beta globin that these patients have inherited, the results were truly spectacular.And if we fast forward now to about two years after the initial administration, the initial procedures for Victoria Gray and some of her other volunteer patients, the results still look as spectacular. Earlier this year CRISPR Therapeutics put out of sort of an update where they are saying that the first 20 or 24 patients that they have dosed with sickle cell and beta thallasemia are all doing well. There've been little or no adverse events. And the idea of this being a once and done therapy appears very well founded. Now it's not a trivial therapy. This is ex-vivo gene editing as obviously rounds of chemotherapy to provide the room for the gene edited stem cells to be reimplanted into the patient. So this is not an easily scalable or affordable or ideal system, but when did we, when will we ever able to say we've pretty much got a cure for sickle cell disease? This is an absolutely spectacular moment, not just for CRISPR, but for medicine, I think, overall. And Victoria Gray, who's been brilliantly profiled in a long running series on National Public Radio, led by the science broadcaster Rob Stein, she is, you know, we, we can call her Queen Victoria, we can call it many things, but I really hope that ,it's not just my idea, that she will be one of those names like Louise Brown and other heroes of modern medicine, that we look and celebrate for decades to come.So the sickle cell results have been great, and then much more recently, also in the New England Journal, we have work led by Intellia Therapeutics, one of the other three companies that I named, where they've been also using CRISPR gene editing, but they've been looking at a rare liver disease, a form of amyloidosis where a toxic protein builds up and looking to find ways to knock out the production of that abnormal gene.And so they've been doing in vivo gene editing, really using CRISPR for the first time. It's been attempted using other gene editing platforms like zinc fingers, but this is the first time that I think we can really say and the New England Journal results prove it. In the first six patients that have been reported remarkable reductions in the level of this toxic protein far, not far better, but certainly better than any approved drugs that are currently on the market. So again, this is a very, very exciting proof of principle for in vivo gene editing, which is important, not just for patients with this rare liver disorder, but it really gives I think the whole field and the whole industry enormous confidence that CRISPR is safe and can be used for a growing list of Mendelian disorders, it's 6,000 or 7,000 diseases about which we know the root genetic cause, and we're not going to tackle all of them anytime soon, but there's a list of ones that now are within reach. And more and more companies are being launched all the time to try and get at some of these diseases.So as we stand here in the summer of 2021, it's a really exciting time. The future looks very bright, but there's so much more to be done. Harry Glorikian: No, we're just at the beginning. I mean, I remember when I first saw this, my first question was off target effects, right? How are we going to manage that? How are they going to get it to that place that they need to get it to, to have it to that cell at that time, in the right way to get it to do what it needs to do. And you know, all these sorts of technical questions, but at the same time, I remember I'm going to, trying to explain this to my friends. I'm like, “You don't understand, this can change everything.” And now a high school student, I say this to people and they look at me strangely, a high school student can order it and it shows up at your house.Kevin Davies: Yeah, well, this is why I think, and this is why one reason why CRISPR has become such an exciting story and receives the Nobel Prize eight years after the sort of launch publication or the first demonstration of it as a gene editing tool. It is so relatively easy to get to work. It's truly become a democratized or democratizing technology. You don't need a million-dollar Illumina sequencer or anything. And so labs literally all around the world can do basic CRISPR experiments. Not everyone is going to be able to launch a clinical trial. But the technology is so universally used, and that means that advances in our understanding of the mechanisms, new tools for the CRISPR toolbox new pathways, new targets, new oftware, new programs, they're all coming from all corners of the globe to help not just medicine, but many other applications of CRISPR as well.Harry Glorikian: Yeah. I always joke about like, there, there are things going on in high school biology classes now that weren't, available, when I was in college and even when we were in industry and now what used to take an entire room, you can do on a corner of a lab bench.Kevin Davies: Yeah. Yeah. As far as the industry goes we mentioned three companies. But you know, today there's probably a dozen or more CRISPR based or gene editing based biotech companies. More undoubtedly are going to be launched before the end of this year. I'm sure we'll spend a bit of time talking about CRISPR 2.0, it seems too soon to be even thinking about a new and improved version of CRISPR, but I think there's a lot of excitement around also two other Boston-based companies, Beam Therapeutics in Cambridge and Verve Therapeutics both of which are launching or commercializing base editing. So base editing is a tool developed from the lab of David Lu of the Broad Institute [of MIT and Harvard]. And the early signs, again, this technology is only five or six years old, but the early signs of this are incredibly promising. David's team, academic team, had a paper in Nature earlier this year, really reporting successful base editing treatment of sickle cell disease in an animal model, not by raising the fetal globin levels, which was sort of a more indirect method that is working very well in the clinic, but by going right at the point mutation that results in sickle cell disease and using given the chemical repertoire of base editing.Base editing is able to make specific single base changes. It can't do the full repertoire of single base changes. So there are some limitations on researchers' flexibility. So they were unable to flip the sickle cell variant back to the quote unquote wild type variants, but the change they were able to make is one that they can live with, we can live with because it's a known benign variant, a very rare variant that has been observed in other, in rare people around the world. So that's completely fine. It's the next best thing. And so that looks very promising. Beam Therapeutics, which is the company that David founded or co-founded is trying a related approach, also going right at the sickle cell mutation. And there are other companies, including one that Matthew Porteus has recently founded and has gone public called Graphite Bio.So this is an exciting time for a disease sickle cell disease that has been woefully neglected, I think you would agree, both in terms of basic research, funding, medical prioritization, and medical education. Now we have many, many shots on goal and it doesn't really, it's not a matter of one's going to win and the others are going to fall by the wayside. Just like we have many COVID vaccines. We'll hopefully have many strategies for tackling sickle cell disease, but they are going to be expensive. And I think you know the economics better than I do. But I think that is the worry, that by analogy with gene therapies that have been recently approved, it's all, it's really exciting that we can now see the first quote, unquote cures in the clinic. That's amazingly exciting. But if the price tag is going to be $1 million or $2 million when these things are finally approved, if and when, that's going to be a rather deflating moment. But given the extraordinary research resources that the CRISPRs and Intellias and Beams and Graphites are pouring into this research, obviously they've got to get some return back on their investment so that they can plow it back into the company to develop the next wave of of gene editing therapies. So you know, it's a predicament Harry Glorikian: One of these days maybe I have to have a show based on the financial parts of it. Because there's a number of different ways to look at it. But just for the benefit of the listeners, right, who may not be experts, how would you explain CRISPR is different from say traditional gene therapies. And is CRISPR going to replace older methods of, of gene therapy or, or will they both have their place? Kevin Davies: No, I think they'll both have their place. CRISPR and, and these newer gene editing tools, base editing and another one called prime editing, which has a company behind it now called Prime Medicine, are able to affect specific DNA changes in the human genome.So if you can target CRISPR, which is an enzyme that cuts DNA together with a little program, the GPS signal is provided in the form of a short RNA molecule that tells the enzyme where to go, where to go in the genome. And then you have a couple of strategies. You can either cut the DNA at the appropriate target site, because you want to inactivate that gene, or you just want to scramble the sequence because you want to completely squash the expression of that gene. Or particularly using the newer forms of gene editing, like base editing, you can make a specific, a more nuanced, specific precision edit without, with one big potential advantage in the safety profile, which is, you're not completely cutting the DNA, you're just making a nick and then coaxing the cell's natural repair systems to make the change that you sort of you're able to prime.So there are many diseases where this is the way you want to go, but that does not in any way invalidate the great progress that we're making in traditional gene therapy. So for example today earlier today I was recording an interview or for one of my own programs with Laurence Reid, the CEO of Decibel Therapeutics, which is looking at therapies for hearing loss both genetic and other, other types of hearing disorders.And I pushed him on this. Aren't you actually joinomg with the gene editing wave? And he was very circumspect and said, no, we're very pleased, very happy with the results that we're getting using old fashioned gene replacement therapy. These are recessive loss of function disorders. And all we need to do is get the expression of some of the gene back. So you don't necessarily need the fancy gene editing tools. If you can just use a an AAV vector and put the healthy gene back into the key cells in the inner ear. So they're complimentary approaches which is great.Harry Glorikian: So, you know, in, in this podcast, I try to have a central theme when I'm talking to people. The relationships of big data, computation, advances in new drugs, and other ways to keep people healthy. So, you know, like question-wise, there's no question in my mind that the whole genomics revolution that started in the ‘90s, and I was happy to be at Applied Biosystems when we were doing that, would have been impossible in the absence of the advances in computing speed and storage in the last three decades. I think computing was the thing that held up the whole human genome, which gave us the book of life that CRISPR is now allowing us to really edit. But I wonder if you could bring us sort of up-to-date and talk about the way CRISPR and computation are intertwined. What happens when you combine precision of an editing tool like CRISPR with the power of machine learning and AI tools to find meaning and patterns in that huge genetic ball? Kevin Davies: Yeah. Well, yeah. I'm got to tread carefully here, but I think we are seeing papers from some really brilliant labs that are using some of the tools that you mentioned. AI and machine learning with a view to better understanding and characterizing some of the properties and selection criteria of some of these gene editing tools. So you mentioned earlier Harry, the need to look out for safety and minimize the concern of off-target effects. So I think by using some of these some algorithms and AI tools, researchers have made enormous strides in being able to design the programmable parts of the gene editing constructs in such a way that you increase the chances that they're going to go to the site that you want them to go to, and nnot get hung up latching onto a very similar sequence that's just randomly cropped up on the dark side of the genome, across the nucleus over there. You don't want that to happen. And I don't know that anybody would claim that they have a failsafe way to guarantee that that could never happen. But the you know, the clinical results that we've seen and all the preclinical results are showing in more and more diseases that we've got the tools and learned enough now to almost completely minimize these safety concerns. But I think everyone, I think while they're excited and they're moving as fast as they can, they're also doing this responsibly. I mean, they, they have to because no field, gene therapy or gene editing really wants to revisit the Jesse Gelsinger tragedy in 1999, when a teenage volunteer died in volunteering for a gene therapy trial at Penn of, with somebody with a rare liver disease. And of course that, that setback set back the, entire field of gene therapy for a decade. And it's really remarkable that you know, many of the sort of pioneers in the field refuse to throw in the towel, they realized that they had to kind of go back to the drawing board, look at the vectors again, and throw it out. Not completely but most, a lot of the work with adenoviruses has now gone by the wayside. AAV is the new virus that we hear about. It's got a much better safety profile. It's got a smaller cargo hold, so that's one drawback, but there are ways around that. And the, the explosion of gene therapy trials that we're seeing now largely on the back of AAV and now increasingly with, with non-viral delivery systems as well is, is very, very gratifying. And it's really delivery. I think that is now the pain point. Digressing from your question a little bit, but delivery, I think is now the big challenge. It's one thing to contemplate a gene therapy for the eye for rare hereditary form of blindness or the ear. Indeed those are very attractive sites and targets for some of these early trials because of the quantities that you need to produce. And the localization, the, the physical localization, those are good things. Those help you hit the target that you want to. But if you're contemplating trying something for Duchenne muscular dystrophy or spinal muscular atrophy, or some of the diseases of the brain, then you're going to need much higher quantities particularly for muscular disorders where, you run into now other challenges, including, production and manufacturing, challenges, and potentially safeguarding and making sure that there isn't an immune response as well. That's another, another issue that is always percolating in the background.But given where we were a few years ago and the clinical progress that we've talked about earlier on in the show it, I think you can safely assume that we've collectively made enormous progress in, in negating most, if not all of these potential safety issues.Harry Glorikian: No, you know, it's funny, I know that people will say like, you know, there was a problem in this and that. And I look at like, we're going into uncharted territories and it has to be expected that you just…you've got people that knew what they were doing. All of these people are new at what they are doing. And so you have to expect that along the way everything's not going to go perfectly. But I don't look at it as a negative. I look at it as, they're the new graduating class that's going to go on and understand what they did right. Or wrong, and then be able to modify it and make an improvement. And, you know, that's what we do in science. Kevin Davies: Well, and forget gene editing—in any area of drug development and, and pharmaceutical delivery, things don't always go according to plan. I'm sure many guests on Moneyball Medicine who have had to deal with clinical trial failures and withdrawing drugs that they had all kinds of high hopes for because we didn't understand the biology or there was some other reaction within, we didn't understand the dosing. You can't just extrapolate from an animal model to humans and on and on and on. And so gene editing, I don't think, necessarily, should be held to any higher standard. I think the CRISPR field has already in terms of the sort of market performance, some of the companies that we've mentioned, oh my God, it's been a real roller coaster surprisingly, because every time there's been a paper published in a prominent journal that says, oh my God, there's, there's a deletion pattern that we're seeing that we didn't anticipate, or we're seeing some immune responses or we're seeing unusual off target effects, or we're seeing P53 activation and you know, those are at least four off the top of my head. I'm sure there've been others. And all had big transient impact on the financial health of these companies. But I think that was to be expected. And the companies knew that this was just an overreaction. They've worked and demonstrated through peer review publications and preclinical and other reports that these challenges have been identified, when known about, pretty much completely have been overcome or are in the process of being overcome.So, you know, and we're still seeing in just traditional gene therapy technologies that have been around for 15, 20 years. We're still seeing reports of adverse events on some of those trials. So for gene editing to have come as far as it's common, to be able to look at these two big New England Journal success stories in sickle cell and ATTR amyloidosis, I don't think any very few, except the most ardent evangelists would have predicted we'd be where we are just a few years ago. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian:One of your previous books was called The $1,000 Genome. And when you published that back in 2010, it was still pretty much science fiction that it might be possible to sequence someone's entire genome for $1,000. But companies like Illumina blew past that barrier pretty quickly, and now people are talking about sequencing individual genome for just a few hundred dollars or less. My question is, how did computing contribute to the exponential trends here. And do you wish you'd called your book The $100 Genome?Kevin Davies: I've thought about putting out a sequel to the book, scratching out the 0's and hoping nobody would notice. Computing was yes, of course, a massive [deal] for the very first human genome. Remember the struggle to put that first assembly together. It's not just about the wet lab and pulling the DNA sequences off the machines, but then you know, the rapid growth of the data exposure and the ability to store and share and send across to collaborators and put the assemblies together has been critical, absolutely critical to the development of genomics.I remember people were expressing shock at the $1,000 genome. I called the book that because I heard Craig Venter use that phrase in public for the first time in 2002. And I had just recently published Cracking the Genome. And we were all still recoiling at the billions of dollars it took to put that first reference genome sequence together. And then here's Craig Venter, chairing a scientific conference in Boston saying what we need is the $1,000 genome. And I almost fell off my chair. “what are you? What are you must you're in, you're on Fantasy Island. This is, there's no way we're going to get, we're still doing automated Sanger sequencing. God bless Fred Sanger. But how on earth are you going to take that technology and go from billions of dollars to a couple of thousand dollars. This is insanity.” And that session we had in 2002 in Boston. He had a local, a little episode of America's Got Talent and he invited half a dozen scientists to come up and show what they had. And George Church was one of them. I think Applied Biosystems may have given some sort of talk during that session. And then a guy, a young British guy from a company we'd never heard of called Celexa showed up and showed a couple of pretty PowerPoint slides with colored beads, representing the budding DNA sequence on some sort of chip. I don't know that he showed any data. It was all very pretty and all very fanciful. Well guess what? They had the last laugh. Illumina bought that company in 2006. And as you said, Harry you know, I think when, when they first professed to have cracked the $1,000 dollar genome barrier, a few people felt they needed a pinch of salt to go along with that. But I think now, yeah, we're, we're, we're well past that. And there are definitely outfits like BGI, the Beijing Genomics Institute being one of them, that are touting new technologies that can get us down to a couple of hundred. And those were such fun times because for a while there Illumina had enormous competition from companies like 454 and Helicose and PacBio. And those were fun heady times with lots and lots of competition. And in a way, Illumina's had it a little easy, I think over the last few years, but with PacBio and Oxford Nanopore gaining maturity both, both in terms of the technology platforms and their business strategy and growth, I think Illumina' gonna start to feel a little bit more competition in the long read sequence space. And one is always hearing whispers of new companies that may potentially disrupt next-gen sequencing. And that would be exciting because then we'd have an excuse to write another book. Harry Glorikian: Well, Kevin, start writing because I actually think we're there. I think there are a number of things there and you're right, I think Illumina has not had to bring the price down as quickly because there hasn't been competition. And you know, when I think about the space is, if you could do a $60 genome, right, it starts to become a rounding error. Like what other business models and opportunities now come alive? And those are the things that excite me. All right. But so, but you have a unique position as editor of the journal of CRISPR and the former editor of a lot of prominent, you know, publications, Nature Genetics, Bio-IT World, Chemical & Engineering News. Do you think that there's adequate coverage of the biological versus the computing side of it? Because I, I have this feeling that the computing side still gets a little overlooked and underappreciated. Kevin Davies: I think you're right. I mean I think at my own company Genetic Engineering News, we still have such deep roots in the wet lab vision and version of biotechnology that it takes a conscious effort to look and say, you know, that's not where all the innovation is happening. Bio-IT World, which you mentioned is interesting because we launched that in 2002. It was launched by the publisher IDG, best-known from MacWorld and ComputerWorld and this, this whole family of high-tech publications.And we launched in 2002 was a very thick glossy print magazine. And ironically, you know, we just couldn't find the advertising to sustain that effort, at least in the way that we'd envisioned it. And in 2006 and 2007, your friend and mine Phillips Kuhl, the proprietor of Cambridge Healthtech Institute, kind of put us out of our misery and said, you know what I'll, take the franchise because IDG just didn't know what to do with it anymore. But what he really wanted was the trade show, the production. And even though at the magazine eventually we fell on our sword and eventually put it out of its misery, the trade show went from strength to strength and it'll be back in Boston very soon because he had the vision to realize there is a big need here as sort of supercomputing for life sciences.And it's not just about the raw high-performance computing, but it's about the software, the software tools and data sharing and management. And it's great to go back to that show and see the, you know, the Googles and Amazons and yeah, all the big household names. They're all looking at this because genome technology, as we've discussed earlier has been one of the big growth boom areas for, for their services and their products.Harry Glorikian: Right. I mean, well, if you look at companies like Tempus, right. When I talked to Joel Dudley over there on the show it's, they want to be the Amazon AWS piping for all things genomic analysis. Right. So instead of creating it on your own and building a, just use their platform, basically, so it's definitely a growth area. And at some point, if you have certain disease states, I don't see how you don't get you know, genomic sequencing done, how a physician even today in oncology, how anybody can truly prescribe with all the drugs that are being approved that have, you know, genomic biomarkers associated with them and not use that data.Kevin Davies: On a much lower, lo-fi scale, as I've been doing a lot of reading about sickle cell disease lately, it's clear that a lot of patients who are, of course, as you, as you know, as your listeners know, are mostly African-American because the disease arose in Africa and the carrier status gives carriers a huge health advantage in warding off malaria. So the gene continues to stay, stay high in in frequency. Many African-American patients would benefit from some generic drugs that are available in this country that provide some relief, but aren't aware of it and maybe their physicians aren't completely aware of it either. Which is very sad. And we've neglected the funding of this disease over many decades, whereas a disease like cystic fibrosis, which affects primarily white people of Northern European descent that receives far more funding per capita, per head, than than a disease like sickle cell does. But hopefully that will begin to change as we see the, the potential of some of these more advanced therapies.I think as far as your previous comment. I think one of the big challenges now is how we tackle common diseases. I think we're making so much progress in treating rare Mendelian diseases and we know thousands of them. But it's mental illness and asthma and diabetes you know, diseases that affect millions of people, which have a much more complicated genetic and in part environmental basis.And what can we learn, to your point about having a full genome sequence, what can we glean from that that will help the medical establishment diagnose and treat much more common diseases, not quite as simple as just treating a rare Mendelian version of those diseases? So that's, I think going to be an important frontier over the next decade.Harry Glorikian: Yeah. It's complicated. I think you're going to see as we get more real-world data that's organized and managed well, along with genomic data, I think you'll be able to make more sense of it. But some of these diseases are quite complicated. It's not going to be find one gene, and it's going to give you that answer.But I want to go back to, you can't really talk about CRISPR without talking about this specter of germline editing. And a big part of your book is about this firestorm of criticism and condemnation around, you know, the 2018 when the Chinese researcher He Jankui, I think I said it correctly.Yep.Kevin Davies: He Jankui is how I say it. Close. Harry Glorikian: He announced that he had created twin baby girls with edits to their genomes that were intended to make them immune to HIV, which sort of like—that already made me go, what? But the experiment was, it seems, unauthorized. It seems that, from what I remember, the edits were sloppy and the case spurred a huge global discussion about the ethics of using CRISPR to make edits that would be inherited by future generations. Now, where are we in that debate now? I mean, I know the National Academy of Sciences published a list of criteria, which said, don't do that. Kevin Davies: It was a little more nuanced than that. It wasn't don't do that. It was, there is a very small window through which we could move through if a whole raft of criteria are met. So they, they refuse to say hereditary genome editing should be banned or there should be a moratorium. But they said it should not proceed until we do many things. One was to make sure it is safe. We can't run before we can walk. And by that, I mean, we've got to first demonstrate—because shockingly, this hasn't been done yet—that genome editing can be done safely in human embryos. And in the last 18 months there've been at least three groups, arguably the three leading groups in terms of looking at genetic changes in early human embryos, Kathy Niakan in London, Shoukhrat Mitalipov in Oregon, and Dieter Egli in New York, who all at roughly the same time published and reports that said, or posted preprints at least that said, when we attempt to do CRISPR editing experiments in very early human embryos, we're seeing a mess. We're seeing a slew of off-target and even on-target undesirable edits.And I think that says to me, we don't completely understand the molecular biology of DNA repair in the early human embryo. It may be that there are other factors that are used in embryogenesis that are not used after we're born. That's speculation on my part. I may be wrong. But the point is we still have a lot to do to understand, even if we wanted to.And even if everybody said, “Here's a good case where we should pursue germline editing,” we've gotta be convinced that we can do it safely. And at the moment, I don't think anybody can say that. So that's a huge red flag.But let's assume, because I believe in the power of research, let's assume that we're going to figure out ways to do this safely, or maybe we say CRISPR isn't the right tool for human embryos, but other tools such as those that we've touched on earlier in the show base editing or prime editing, or maybe CRISPR 3.0 or whatever that is right now to be published somewhere. [Let's say ] those are more safe, more precise tools. Then we've got to figure out well, under what circumstances would we even want to go down this road? And the pushback was quite rightly that, well, we already have technologies that can safeguard against families having children with genetic diseases. It's called IVF and pre-implantation genetic diagnosis. So we can select from a pool of IVF embryos. The embryos that we can see by biopsy are safe and can therefore be transplanted back into the mother, taken to term and you know, a healthy baby will emerge.So why talk about gene editing when we have that proven technology? And I think that's a very strong case, but there are a small number of circumstances in which pre-implantation genetic diagnosis will simply not work. And those are those rare instances where a couple who want to have a biological child, but have both of them have a serious recessive genetic disease. Sickle cell would be an obvious case in point. So two sickle cell patients who by definition carry two copies of the sickle cell gene, once I have a healthy biological child preimplantation genetic diagnosis, it's not going to help them because there are no healthy embryos from whatever pool that they produce that they can select. So gene editing would be their only hope in that circumstance. Now the National Academy's report that you cited, Harry, did say for serious diseases, such as sickle cell and maybe a few others they could down the road potentially see and condone the use of germline gene editing in those rare cases.But they're going to be very rare, I think. It's not impossible that in an authorized approved setting that we will see the return of genome editing, but that's okay. Of course you can can issue no end of blue ribbon reports from all the world's experts, and that's not going to necessarily prevent some entrepreneur whose ethical values don't align with yours or mine to say, “You know what, there's big money to be made here. I'm going offshore and I'm going to launch a CRISPR clinic and you know, who's going to stop me because I'll be out of the clutches of the authorities.” And I think a lot of people are potentially worried that that scenario might happen. Although if anyone did try to do that, the scientific establishment would come down on them like a ton of bricks. And there'll be a lot of pressure brought to bear, I think, to make sure that they didn't cause any harm.Harry Glorikian: Yeah. It's funny. I would like to not call them entrepreneurs. I like entrepreneurs. I'd like to call them a rogue scientist. Kevin Davies: So as you say, there's the third section of four in Editing Humanity was all about the He Jankui debacle or saga. I had flown to Hong Kong. It's a funny story. I had a little bit of money left in my travel budget and there were two conferences, one in Hong Kong and one in China coming up in the last quarter of 2018. So I thought, well, okay, I'll go to one of them. And I just narrowed, almost a flip of a coin, I think. Okay, let's go to the Hong Kong meeting.It's a bioethics conference since I don't expect it to be wildly exciting, but there are some big speakers and this is an important field for the CRISPR Journal to monitor. So I flew there literally, you know, trying to get some sleep on the long flights from New York and then on landing, turn on the phone, wait for the new wireless signal provider to kick in. And then Twitter just explode on my feed as this very, very astute journalists at MIT Technology Review, Antonio Regalado, had really got the scoop of the century by identifying a registration on a Chinese clinical trial website that he and only he had the foresight and intelligence to sort of see. He had met He Jankui in an off the record meeting, as I described in the book, about a month earlier. A spider sense was tingling. He knew something was up and this was the final clue. He didn't know at that time that the Lulu and Nana, the CRISPR babies that you mentioned, had actually been born, but he knew that there was a pregnancy, at least one pregnancy, from some of the records that he'd seen attached to this registration document. So it was a brilliant piece of sleuthing. And what he didn't know is that the Asociated Press chief medical writer Marilynm Marchion had confidentially been alerted to the potential upcoming birth of these twins by an American PR professional who was working with He Jankui in Shenzhen. So she had been working on an embargoed big feature story that He Jankui and his associates hoped would be the definitive story that would tell the world, we did this quote unquote, “responsibly and accurately, and this is the story that you can believe.” So that story was posted within hours.And of course the famous YouTube videos that He Jankui had recorded announcing with some paternal pride that he had ushered into the world these two gene edited, children, screaming and crying into the world as beautiful babies I think was [the phrase]. And he thought that he was going to become famous and celebrated and lauded by not just the Chinese scientific community, but by the world community for having the ability and the bravery to go ahead and do this work after Chinese researchers spent the previous few years editing human embryos. And he was persuaded that he had to present his work in Hong Kong, because he'd set off such a such an extraordinary firestorm. And I think you've all seen now you're the clips of the videos of him nervously walking onto stage the muffled, the silence, or the only sound in the front row, the only sound in the big auditorium at Hong Kong university—[which] was absolutely packed to the rim, one side of the auditorium was packed with press photographers, hundreds of journalists and cameras clicking—and the shutters clattering was the only, that was the applause that he got as he walked on stage.And to his credit, he tried to answer the questions directly in the face of great skepticism from the audience. The first question, which was posed by David Liu, who had traveled all the way there, who just asked him simply, “What was the unmet medical need that you are trying to solve with this reckless experiment? There are medical steps that you can do, even if the couple that you're trying to help has HIV and you're trying to prevent this from being passed on. There are techniques that you can use sperm washing being one of them. That is a key element of the IVF process to ensure that the no HIV is transmitted.”But he was unable to answer the question in terms of I'm trying to help a family. He'd already moved out and was thinking far, far bigger. Right? And his naiveté was shown in the manuscript that he'd written up and by that point submitted to Nature, excerpts of which were leaked out sometime later.So he went back to Shenzhen and he was put under house arrest after he gave that talk in Hong Kong. And about a year later was sentenced to three years in jail. And so he's, to the best of my knowledge that's where he is. But I often get asked what about the children? As far as we know, there was a third child born about six months later, also gene-edited. We don't even know a name for that child, let alone anything about their health. So one hopes that somebody in the Chinese medical establishment is looking after these kids and monitoring them and doing appropriate tests. The editing, as you said, was very shoddily performed. He knocked out the gene in question, but he did not mimic the natural 32-base deletion in this gene CCR5 that exists in many members of the population that confers, essentially, HIV resistance. So Lulu and Nana on the third child are walking human experiments, sad to say. This should never have been done. Never should have been attempted. And so we hope that he hasn't condemned them to a life of, you know, cancer checkups and that there were no off-target effects. They'll be able to live, hopefully, with this inactivated CCR5 gene, but it's been inactivated in a way that I don't think any, no other humans have ever been recorded with such modifications. So we, we really hope and pray that no other damage has been done. Harry Glorikian: So before we end, I'd love to give you the chance to speculate on the future of medicine in light of CRISPR. Easy, fast, inexpensive genome sequencing, give us access to everybody's genetic code, if they so choose. Machine learning and other forms of AI are helping understand the code and trace interactions between our 20,000 genes. And now CRISPR gives us a way to modify it. So, you know, it feels like [we have] almost everything we need to create, you know, precise, targeted, custom cures for people with genetic conditions. What might be possible soon, in your view? What remaining problems need to be solved to get to this new area of medicine? Kevin Davies: If you know the sequence that has been mutated to give rise to a particular disease then in principle, we can devise a, some sort of gene edit to repair that sequence. It may be flipping the actual base or bases directly, or maybe as we saw with the first sickle cell trial, it's because we understand the bigger genetic pathway. We don't have to necessarily go after the gene mutation directly, but there may be other ways that we can compensate boost the level of a compensating gene.But I think we, we should be careful not to get too carried away. As excited as I am—and hopefully my excitement comes through in Editing Humanity—but for every company that we've just mentioned, you know, you can go on their website and look at their pipeline. And so Editas might have maybe 10 diseases in its cross hairs. And CRISPR [Therapeutics] might have 12 diseases. And Intellia might have 14 diseases and Graphite has got maybe a couple. And Beam Therapeutics has got maybe 10 or 12. And Prime Medicine will hasn't listed any yet, but we'll hopefully have a few announced soon. And so I just reeled off 50, 60, less than a hundred. And some of these are gonna work really, really well. And some are going to be either proven, ineffective or unviable economically because the patient pool is too small. And we've got, how many did we say, 6,000 known genetic diseases. So one of the companies that is particularly interesting, although they would admit they're in very early days yet, is Verve Therapeutics. I touched on them earlier because they're looking at to modify a gene called PCSK9 that is relevant to heart disease and could be a gene modification that many people might undergo because the PCSK9 gene may be perfectly fine and the sequence could be perfectly normal, but we know that if we re remove this gene, levels of the bad cholesterol plummet, and that's usually a good thing as far as heart management goes. So that's an interesting, very interesting study case study, I think, to monitor over the coming years, because there's a company looking at a much larger patient pool potentially than just some of these rare syndromes with unpronounceable names. So the future of CRISPR and gene editing is very bright. I think one of the lessons I took away from CRISPR in Editing Humanity is, looking at the full story, is how this technology, this game-changing gene-editing technology, developed because 25 years ago, a handful of European microbiologists got really interested in why certain microbes were thriving in a salt lake in Southeastern Spain. This is not exactly high-profile, NIH-must-fund-this research. There was a biological question that they wanted to answer. And the CRISPR repeats and the function of those repeats fell out of that pure curiosity, just science for science's sake. And so it's the value of basic investigator-driven, hypothesis-driven research that led to CRISPR being described and then the function of the repeats.And then the story shifted to a yogurt company in Europe that was able to experimentally show how having the right sequence within the CRISPR array could safeguard their cultures against viral infection. And then five years of work people in various groups started to see, were drawn to this like moths to a flame. Jennifer Doudna was intrigued by this from a tip-off from a coffee morning discussion with a Berkeley faculty colleagues, Jill Banfield, a brilliant microbiologist in her own. And then she met meets Emmanuelle Charpentier in Puerto Rico at a conference, and they struck up a friendship and collaboration over the course of an afternoon. And that, why should that have worked? Well, it did, because a year later they're publishing in Science. So it's serendipity and basic research. And if that can work for CRISPR, then I know that there's another technology beginning to emerge from somewhere that may, yet trump CRISPR.And I think the beauty of CRISPR is its universal appeal. And the fact is, it's drawn in so many people, it could be in Japan or China or South Korea or parts of Europe or Canada or the U.S. or South America. Somebody is taking the elements of CRISPR and thinking well, how can we improve it? How can we tweak it?And so this CRISPR toolbox is being expanded and modified and updated all the time. So there's a hugely exciting future for genome medicine. And you know, whether it's a new form of sequencing or a new form of synthetic biology, you know, hopefully your show is going to be filled for many years to come with cool, talented, young energetic entrepreneurs who've developed more cool gadgets to work with our genome and other genomes as well. We haven't even had time to talk about what this could do for rescuing the wooly mammoth from extinction. So fun things, but maybe, maybe another time. Harry Glorikian: Excellent. Well, great to have you on the show. Really appreciate the time. I hope everybody got a flavor for the enormous impact this technology can have. Like you said, we talked about human genome, but there's so many other genomic applications of CRISPR that we didn't even touch. Kevin Davies: Yup. Yup. So you have to read the book. Harry Glorikian: Yeah. I will look forward to the next book. So, great. Thank you so much. Kevin Davies: Thanks for having me on the show, Harry. All the best.Harry Glorikian: Take care.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian.  Thanks for listening, and we'll be back soon with our next interview.

In episode 18 Dylan and Jack return to do a commentary on 90's straight to video spin off 'Shakedown: Return of the Sontarans', written by Terrance Dicks and directed by Kevin Davies. With an all star cast including Jan Chappell,  Brian Croucher,  Carole Ann Ford, Sophie Aldred and Michael Wisher.

In the summer of 2002, Bolton manager Sam Allardyce was once again scouring the market for new players.Without a big budget, being resourceful had become second nature to Big Sam, often using his powers of persuasion to lure players to the Reebok Stadium. Nigeria superstar Jay-Jay Okocha was available on a free transfer after dazzling in leagues across Europe, but surely out of Bolton's reach?You tell that to Big Sam! Here, Football's Cult Heroes tells the story of how the man that mentored Ronaldinho at PSG came to lead Bolton's ‘galacticos' to the brink of the Champions League, embarrassing defenders and upsetting the elite.Team-mates speak of the “humble” captain that led by example whether on the pitch or on nights out in Manchester, journalists reveal the “business-like” character behind the entertainer image, and fans tell of the man that made Bolton cool. This is the story of Jay-Jay Okocha, the greatest showman.Contributions from Colin Udoh, Ed Aarons, Nicky Hunt, Maggie Tetlow, Gordon Sharrock and Kevin Davies. Interviews conducted in 2020 and 2021 in accordance with UK coronavirus restrictions.You can vote for Football's Cult Heroes in the Sports Podcast Awards by following this link: https://bit.ly/3qrEdEV

What if our genetic code could be re-written as easily as spell checking a Word document? That science-fiction daydream became reality with the 2012 discovery of CRISPR-Cas9, a gene-editing technique that holds the promise of eradicating disease, growing healthier foods, and bringing extinct species back to life. In this week's episode of CrossBorder Solutions' Genius Beats Fear podcast, we speak to Kevin Davies, author of 'Editing Humanity: The CRISPR Revolution and the New Era in Genome Editing', to find out how gene-editing technology may change the course of human development. And whether woolly mammoths are making a comeback.

Jimbo brings you Part 2 of our Euro 2020 preview with Duncan Alexander, Julien Laurens and a motley crew of continental experts.Group F is the group of death. Is victory a foregone conclusion for France? Will Benzema rock the boat or rock the tournament? Raphael Honigstein tells us why Germany are feeling fearful.In Group C, we've got some frank opinions on De Boer and Holland and some high hopes for Malinovskyi and Ukraine.Luis Enrique might be great but Covid-19 is playing havoc with Spain's preparations – could Sweden take advantage in Group E?Plus how Kevin Davies could be the English Goran Pandev. And why Robert Lewandowski is the Polish Martin Peters.RUNNING ORDER:  • PART 1a: Group F – France, Portugal & Hungary (05m 00s)• PART 1b: Group F – Germany feeling fearful, with Rafa Honigstein (19m 30s)• PART 2a: Group C – Netherlands preview, with Michiel Jongsma (28m 00s)• PART 2b: Group C – Ukraine preview with Sasha Goryunov (36m 30s)• PART 2b: Group C – North Macedonia & Austria (42m 30s)• PART 3a: Group E – Sweden – dark horses? (46m 30s)• PART 3b: Group E – Spain's chaotic build-up, with Alvaro Romeo (49m 30s)• PART 3c: Group E – Poland & Slovakia (57m 00s)• PART 4: The odds with Paddy Power (59m 30s)• PART 5: Tournament fever rising (61m 00s)SIGN UP TO THE ATHLETIC FOR £1 A MONTH FOR YOUR FIRST 6 MONTHS:• theathletic.com/totally GET IN TOUCH:• follow us on Instagram• find us on Facebook• send us a tweet: @TheTotallyShow PARISH NOTICES:• we're sponsored by Paddy Power - home of the Money Back Special READ STUFF ON OUR WEBSITE:• check out thetotallyfootballshow.com. Hosted on Acast. See acast.com/privacy for more information.

Jimbo brings you Part 2 of our Euro 2020 preview with Duncan Alexander, Julien Laurens and a motley crew of continental experts. Group F is the group of death. Is victory a foregone conclusion for France? Will Benzema rock the boat or rock the tournament? Raphael Honigstein tells us why Germany are feeling fearful. In Group C, we've got some frank opinions on De Boer and Holland and some high hopes for Malinovskyi and Ukraine. Luis Enrique might be great but Covid-19 is playing havoc with Spain's preparations – could Sweden take advantage in Group E? Plus how Kevin Davies could be the English Goran Pandev. And why Robert Lewandowski is the Polish Martin Peters. RUNNING ORDER:    • PART 1a: Group F – France, Portugal & Hungary (05m 00s) • PART 1b: Group F – Germany feeling fearful, with Rafa Honigstein (19m 30s) • PART 2a: Group C – Netherlands preview, with Michiel Jongsma (28m 00s) • PART 2b: Group C – Ukraine preview with Sasha Goryunov (36m 30s) • PART 2b: Group C – North Macedonia & Austria (42m 30s) • PART 3a: Group E – Sweden – dark horses? (46m 30s) • PART 3b: Group E – Spain's chaotic build-up, with Alvaro Romeo (49m 30s) • PART 3c: Group E – Poland & Slovakia (57m 00s) • PART 4: The odds with Paddy Power (59m 30s) • PART 5: Tournament fever rising (61m 00s) SIGN UP TO THE ATHLETIC FOR £1 A MONTH FOR YOUR FIRST 6 MONTHS: • theathletic.com/totally   GET IN TOUCH: • follow us on Instagram • find us on Facebook • send us a tweet: @TheTotallyShow   PARISH NOTICES: • we're sponsored by Paddy Power - home of the Money Back Special   READ STUFF ON OUR WEBSITE: • check out thetotallyfootballshow.com. Learn more about your ad choices. Visit megaphone.fm/adchoices

Bolton Wanderers icon Kevin Davies sits down with Rob McCaffrey to talk about his goal scoring career, his future plans and also reveals the most talented players he has shared the field with. 

QuoteUnquote with KK and Dr Kevin Davies, Executive Editor, The CRISPR Journal. Author of “Editing Humanity”, “The $1,000 Genome" ,"Cracking the Genome” https://kapilkhandelwal.com/season2/

In this podcast, Mendelspod host Theral Timpson interviews Kevin Davies about his latest book, "Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing". {Episode Sponsored by Mendelspod}

https://www.alainguillot.com/kevin-davies/ Kevin Davies is a science journalist and editor. His latest book is Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. Get the book right here: https://amzn.to/3syR3Qs

Kevin Davies, the executive editor of The CRISPR Journal, has closely watched the genetics space evolve over the last decades. His expertise and experience were the perfect foundation for his latest book "Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing." In this episode, Kevin discusses his motivation for the book, along with some behind-the-scenes stories when writing this timely literature piece.

Tom and Joe are joined by Bolton Wanderers legend Kevin Davies; veteran of more than 800 games over 21 seasons, who also played for the likes of Southampton, Blackburn and Chesterfield.Kevin tells us what it was like playing in a Bolton team full of international stars and how Big Sam’s man-management skills were the key to their success.Also how his deteriorating relationship with referee Mark Clattenburg resulted in Kevin putting him in a headlock at Linekers Bar in 2010, and why he still isn’t on Sir Alex Ferguson’s Christmas card list.

We are joined by former Leicester City striker Helen Busby to discuss the women's game and how it is evolving and growing. We ask her about her playing career, how she thinks the women's game is changing and current events surrounding high profile women in football.Si embarrasses himself by mentioning Kevin Davies and mispronouncing an out of trend liquor. Enjoy.http://theoutsiderspodcast.co.uk/https://www.instagram.com/theoutsidercast/https://www.youtube.com/channel/UCunNZ_Rst0LKdGB9YaWnteghttps://www.facebook.com/The-Outsiders-a-football-and-philosophy-podcast-100666458697650/ Hosted on Acast. See acast.com/privacy for more information.

We are still excited to be joined by Joost van der Leij, an academic philosopher with an incredible knowledge and understanding of how philosophy and statistical analysis of football helps to mould and shape a club and the effectiveness of players. Joost has worked with some of the top Dutch teams and we are delighted to have him on our two part special.Head over to his website at http://footballphilosophy.org/ for more information about his ideas.In other news, we discuss our favourite chocolate by merely listing the names of them (apologies for any offence), some special Valentines plans and Si's weekly update on his feelings about all things Kevin Davies.Enjoy.http://theoutsiderspodcast.co.uk/https://www.instagram.com/theoutsidercast/https://www.youtube.com/channel/UCunNZ_Rst0LKdGB9YaWnteghttps://www.facebook.com/The-Outsiders-a-football-and-philosophy-podcast-100666458697650/ Hosted on Acast. See acast.com/privacy for more information.

First, we discuss the implications of Johnson & Johnson's any-day-now data on a one-shot vaccine for Covid-19. Then, Kevin Davies, executive editor of the CRISPR Journal, joins us to talk about the strange boom in genome editing stocks and the future of the revolutionary technology. Finally, we talk to Megan Ranney, an emergency room physician and Brown University professor, about the challenges of Covid-19 science communication in a post-Trump world.

A twosome becomes a threesome as we kick off our podcast series on the intermingling of philosophy and football.Jim is now part of the team and we are back to discuss all things metaphysical whilst Si keeps bringing up Kevin Davies in every single debate.In this episode we discuss Ocamm's razor and the quickest way to goal.Enjoy. Hosted on Acast. See acast.com/privacy for more information.

Hitchhikers archivist Kevin Davies welcomes an all-star panel of Hitchhikers legends to commemorate Douglas Adams' iconic series, featuring John Lloyd, James Thrift, Sandra Dickinson, Philip Pope and Toby Longworth. Part of bluedot's A Weekend In Outer Space, July 2020. See acast.com/privacy for privacy and opt-out information.

A discovery here. A paper there. An important paper gets passed over. A fortuitous encounter in a coffee shop among two ambitious scientists. A yogurt company just being a yogurt company. Science moves forward in fits and starts. By the time we read the headline in the paper, “breakthrough of the year,” it can have an inevitable quality about it. Then, in a few years, the historian comes and shows us just how random, messy, and, yes, how beautiful is the business of science.

A discovery here. A paper there. An important paper gets passed over. A fortuitous encounter in a coffee shop among two ambitious scientists. A yogurt company just being a yogurt company. Science moves forward in fits and starts. By the time we read the headline in the paper, “breakthrough of the year,” it can have an inevitable quality about it. Then, in a few years, the historian comes and shows us just how random, messy, and, yes, how beautiful is the business of science.

On this edition of Parallax Views, last month two female scientists, Jennifer Doudna and Emmanuele Charpentier, won the 2020 Nobel Prize in Chemistry for their revolutionary work on CRISPR-Cas9, a technology that opens the door gene editing in ways previously unimagined. The win has been, rightfully, seen as a pivotal moment for women in science, but what, beyond that, what is the broader story of CRISPR and gene editing? What are the broader implications of gene editing and what does it entail for bioethics (ie: could CRISPR be used for darker purposes such as eugenics or bioterrorism)? What are the potential uses of this incredible technology? And what are the stories of the people involved in this game-changing scientific discovery? Kevin Davis, Founding Editor of Nature Genetics, Executive Editor of The CRISPR Journal, and author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, joins us to answer those questions and much more.Among the topics we cover:- What is CRISPR-Cas9? - The troublesome story of Chinese scientist He Jiankui, who used CRISPR-Cas9 on two babies and caused a massive backlash in the scientific community as a result. - Where does the idea of gene editing arise?; The history of gene therapy; James Watson and the Double Helix - The potential agricultural uses of CRISPR - Harvard University geneticist George M. Church, who played a pivotal role in the story of CRISPR, and his notion that, theoretically, CRISPR could be used to resurrect the wholly mammoth and address the climate change crisis - Concerns about CRISPR technology related to misuses for eugenics and bioterrorism; CRISPR, bioterrorism, and COVID - "Biohacking" and the ready availability of CRISPR kits - And much, much more!

From The Tube to The pit lane!A tale of twists and turns and platformed shoes. 

This week on the Finish More Music Podcast we're doing something a little different:    I've asked the members of Finish More Music to share the ONE thing that's been transformational for them as a music producer.   And what's come out of it is astonishing…   A whole bunch of open, honest, and heartfelt stories told straight from the heart of the FMM community, sharing incredible breakthroughs and invaluable lessons that all aspiring music producers can benefit from.If you're in need of a dose of inspiration for your music, or advice on how to overcome your challenges in the studio, you NEED to hear this! Check out all the producers featured in today's podcast:    Adam Loving - https://soundcloud.com/adamloving Barry Johnstone - https://soundcloud.com/darkkandy Cesar Morera - https://soundcloud.com/dynamostar  Dante Scaffidi - https://soundcloud.com/djteddyrockspin David Briggs - https://soundcloud.com/be-kind-1989  Dylan Jonker - https://soundcloud.com/om-japa Henry Garnett - https://soundcloud.com/henry_charles_garnett Ian Randall - https://soundcloud.com/ian_randall?ref=clipboard&p=i&c=1 John Ruddy - https://soundcloud.com/bigred  Kevin Davies - https://soundcloud.com/futureremnants Mark Allin - https://soundcloud.com/mark-allin  Mark Tamsett - https://soundcloud.com/mark-tammo Nando Ferrándiz - https://soundcloud.com/nando-ferrandiz Ray Gill - https://soundcloud.com/arkatekt_productions William Trilogy - https://soundcloud.com/tbm2001

This week Rob and Chris look back at the National League as Maidenhead pull off a shock victory at Notts County , we hear from the scorer of the winning goal Danilo Orsi-Dadomo.  Rob also catches up with Eastleigh manager Ben Strevens and former Bolton, Southampton striker turned pundit, Kevin Davies.  We also look at how Covid could affect the season's conclusion.Dickie takes the lead on the North division as Gloucester head to the top  with a sixy victory over Blyth, his beloved Telford are in second and we hear how they beat Gateshead.  In the South Ian Herring reviews the South as Dorking look Unstoppable as Braintree struggle to get out of neutral.  Hungerford are on the chase, but is this a surprise?All this plus lots lots more!Don't forget to subscribe via Itunes or Spotify Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

This week Rob and Chris look back at the National League as Maidenhead pull off a shock victory at Notts County , we hear from the scorer of the winning goal Danilo Orsi-Dadomo.  Rob also catches up with Eastleigh manager Ben Strevens and former Bolton, Southampton striker turned pundit, Kevin Davies.  We also look at how Covid could affect the season's conclusion. Dickie takes the lead on the North division as Gloucester head to the top  with a sixy victory over Blyth, his beloved Telford are in second and we hear how they beat Gateshead.   In the South Ian Herring reviews the South as Dorking look Unstoppable as Braintree struggle to get out of neutral.  Hungerford are on the chase, but is this a surprise? All this plus lots lots more! Don't forget to subscribe via Itunes or Spotify

Kevin Davies explains how the development of CRISPR will revolutionize the field of genome editing, with massive innovative and ethical implications for humanity to contend with. The post https://www.aei.org/multimedia/kevin-davies-genome-editing-and-the-crispr-revolution/ (Kevin Davies: Genome editing and the CRISPR revolution) appeared first on https://www.aei.org (American Enterprise Institute - AEI).

In the last eight years, geneticists have figured out how to edit humanity’s genetic code by harnessing a natural phenomenon known as CRISPR. This innovation has the potential to let us cure horrible genetic diseases, and perhaps augment humanity even further. But this also raises the ethical question: How far should genome editing go, if […]Join the conversation and comment on this podcast episode: https://ricochet.com/podcast/political-economy-james-pethokoukis/kevin-davies-genome-editing-and-the-crispr-revolution/.Now become a Ricochet member for only $5.00 a month! Join and see what you’ve been missing: https://ricochet.com/membership/.Subscribe to Political Economy with James Pethokoukis in Apple Podcasts (and leave a 5-star review, please!), or by RSS feed. For all our podcasts in one place, subscribe to the Ricochet Audio Network Superfeed in Apple Podcasts or by RSS feed.

Kevin Davies chats with Trey Elling about EDITING HUMANITY: THE CRISPR REVOLUTION AND THE NEW ERA OF GENOME EDITING, including: the difference between CRISPR and CRISPR genome editing, the evolution of CRISPR editing, the wild story behind (and fallout from) #CRISPRbabies in 2018, whether CRISPR-edited babies are truly on the horizon, George Church's attempt to resurrect the wooly mammoth, and more.

Manchester City sweep aside Real Madrid in possibly their biggest European statement yet. Alvaro Romeo assesses whether Real need a revamp to become a Champions League force again Duncan Alexander, Julien Laurens and James Horncastle watch Juventus crash out to Lyon on away goals. Do the Old Lady rely on Ronaldo too much? And is Maurizio Sarri on borrowed time? Rafa Honigstein is in Munich where Bayern are looking to avoid another miraculous Chelsea performance in their backyard. Plus why Barca need to turn to the new blood and why Pixar need to pull their finger out. RUNNING ORDER • PART 1: Man City 2-1 Real Madrid (02m 30s) • PART 2: Lyon knock Juventus out with Julien Laurens & James Horncastle (11m 00s)  • PART 3: Bayern Munich v Chelsea preview with Raphael Honigstein (21m 00s) • PART 4: The odds with Lee Price from Paddy Power (28m 00s) • PART 5: Barcelona v Napoli preview (29m 30s) GET IN TOUCH: • follow us on Instagram (https://www.instagram.com/totallyfootballshow/) • find us on Facebook (https://www.facebook.com/thetotallyfootballshow/) • send us a tweet: @TheTotallyShow (http://www.twitter.com/thetotallyshow)   PARISH NOTICES: • we’re sponsored by Paddy Power - home of the Money Back Special (http://www.paddypower.com/)   READ STUFF ON OUR WEBSITE: • check out thetotallyfootballshow.com (http://thetotallyfootballshow.com/) .

Super Kevin Davies is our guest, to travel back to the FA Cup run of 2011.

It seems like it's football overload as leagues across Europe race to their finish. The race for the top four takes top billing in the Premier League. Whereas, Sergio Ramos is dragging Real Madrid to the La Liga crown and Lazio look to be succumbing to the might of Juventus who look destined to claim a 9th straight Scudetto.On this supersized 5 part episode of the MatchDay Review Podcast we discuss and analyse the latest action from the Premier League, Southampton's impressive turn around and victory over Man City, Leicester seem to be fading in the race for Champions League football, Arteta slowly improving the Arsenal team, Chelsea's knack of grinding out key results, and do Chelsea resemble their manager Frank Lampard.We take an in-depth look at Tottenham Hotspur and Jose Mourinho, cutting through the media hysteria. We talk about the media witch-hunt of Jose Mourinho, who seem to be hellbent on getting him sacked as Spurs manager, and give our insights on how Jose will improve Spurs in the long term. Plus, is it time for Harry Kane to leave Tottenham in pursuit of major trophies?Also, we discuss the Serie A title race, AC Milan resoundingly beating the title contenders in Italy, Real Madrid's impending La Liga title win and as always we talk about the Barcelona crisis and latest developments at the Camp Nou.Plus we discuss the England Euro 2020 squad, players we think will break into the squad for next summers tournament and as always we indulge in a bit of transfer talk.All this and more, such as the comparison between Nikki Minaj and Kevin Davies, on the latest edition of the MatchDay Review Podcast. Time StampsPart 1 00:00 to 31:10 Premier League discussion focused on Southampton, Arsenal, the relegation battle, Chelsea and Frank Lampard's impact.Part 2 31:11 - 59:07Tottenham analysis, Jose Mourinho discussion, the media witch-hunt against him, how he makes Tottenham a force in the Premier League, will the Mourinho revelution be too late for Harry Kane a Heung Min Son, Tottenham is a different challenge for Jose compared to previous clubs. North London Derby Preview, will missing out on the Europa League be a blessing in disguise for the North London clubs.Part 3 59:08 - 1:20:15Serie A and La Liga title race analysis, Cristiano Ronaldo’s Juventus goal scoring record, Lazio faltering, AC Milan winning big games again, A tribute to the San Siro, Sergio Ramos leading the charge towards the title for Real Madrid, more Barcelona talk.Part 4 1:20:15 - 1:34:57Who will break into the England squad for the Euros next summer? What do we think the team looks like for next years tournament, and are there any players that are in danger of missing the squad. Will Mason Greenwood go to the Euro’s?Part 5 Transfer Talk 1:35:00

Confidence crises, spotfixing drama, beautiful Kevin Davies, encountering Van Dyke, no Cup medal. Graham Cummins has had a well-traveled and colourful career that gradually eroded his love for football. But Waterford boss Alan Reynolds has rekindled the fire.

Join Will, Eddie, Tom & James as they chat to BWFC club legend Kevin Davies Learn more about your ad choices. Visit megaphone.fm/adchoices

Join Will, Eddie, Tom & James as they chat to BWFC club legend Kevin Davies Learn more about your ad choices. Visit podcastchoices.com/adchoices

En este capítulo explico porqué no me subí al flamante Ferrari rojo de Kevin Davis cuando llegué al Southampton.

Show Notes 0:00:00 Introduction Richard Saunders 0:03:15 "Chemtrails" on TV Ken Mcleod is a retired air traffic controller and national manager of aviation search and rescue, Australian aviation representative on two UN committees, and once upon a time a private pilot. Recently he appeard on national TV in Australia to cross swords with a Chemtrail Conspiracy Theorist. Video: Studio 10 segment https://youtu.be/UkLfPtYiidQ 0:18:36 UFOs - the first 50 years From the pages of 'The Skeptic', the journal of Australian Skeptics. Dr Steve Roberts takes a look at how UFOs and movie cultures have interacted from the 1940s up to the 1990s. http://www.skeptics.com.au 0:38:06 Pint of Science in Canberra Belinda Wilson is a conservation ecologist who specialises in reintroduction biology, behavioural ecology, and spatial dynamics. She has worked in the university, government and private sectors, and is currently undertaking a PhD in the Fenner School of Environment and Society at The Australian National University, researching the reintroduction biology of the eastern quoll. Interview by Kevin Davies. https://www.facebook.com/ecologibel https://belindawilsonresearch.weebly.com 0:43:43 Maynard's Spooky Action.... Join Maynard and Lance Leopard in Glebe, Sydney on the 4th of June for Maynard's Movie Night. http://maynard.com.au/maynard-lance-leopard-barbarella/  Also Skepticon 2019 https://skepticon.org.au Skepticamp Brisbane https://www.eventbrite.com.au/e/skepticamp-2019-tickets-60661983626

In a French bistro in New York City, Emmanuelle Charpentier (Founding Director, Max Planck Unit for the Science of Pathogens, Berlin) discusses with Kevin Davies her nomadic career, the high points in her CRISPR journey, and previews her future plans.

On this week's episode, Kevin Davies (Hulen Mall) joins the podcast to discuss his work in transforming the food scene at the Hulen Mall. Part of that process involved bringing in David Webber (The Hot Potato) and his food truck. Together they are working to change the food culture at the Hulen Mall. Photo courtesy of Kevin Davies. "Punch on the TV" performed by Bruno Freitas on www.hooksounds.com. Check out our website: www.fwfoodstories.com/ For more information about The Culinary School of Fort Worth's programs, visit: www.csftw.edu/

Football Podcast brought to you by 3 midfield generals and all round top geezers

We started the week with the bad footing. Ratings agency Moody's warning that the South African economy's slide into recession in the second quarter will exacerbate the fiscal and monetary challenges the country is facing. The ratings agency is the last of the "big three" international agencies to put South Africa's long-term foreign-currency debt in investment grade. Kevin Davies, Business editor at the Mail and Guardian had this to say about this and other stories of the week & SABC Acting Assignment Editor Tshepo Phagane

0:00:00 Introduction Richard Saunders 0:05:45 Interview with Celestia Ward Squaring the Strange brings evidence-based analysis and commentary to a wide variety of topics, ranging from the paranormal to the political. Investigating ghosts. Debunking conspiracies. Dodging chupacabras. If a claim seems strange, Ben and Pascual will try to square it with the facts. https://squaringthestrange.libsyn.com/ 0:15:00 A Random RANT! With Dr Paulie Interview with Hana Svobodová from Save Turtle. Save Turtle Organization is Czech NGO founded in 2017. It concentrates on the protection of sea turtles and their natural habitat. They wish for a world where people care for nature and take an interest in sea turtles. http://saveturtle.net/ 0:28:20 Open letter to the RSL : Let the Dead Rest in Peace Through its clubs, the Returned Services League commemorates our servicemen and women, including some who made the ultimate sacrifice. We are concerned that those clubs are occasionally used for a form of entertainment that is disrespectful to the departed, and to their relatives and friends. https://www.skeptics.com.au/2018/09/04/open-letter-to-the-rsl-let-the-dead-rest-in-peace/ 0:32:36 Kevin Davies and Star Wars Can the Star Wars movies be used as a real guide to help in military strategy? Kevin chats to Mick Cook and Major General Mick Ryan in Canberra. Strategy Strikes Back: How Star Wars Explains Modern Military Conflict The Dead Prussian Podcast http://www.thedeadprussian.com/ Mick Cook https://twitter.com/mick_cook Mick Ryan https://twitter.com/warinthefuture 0:39:10 Talk like an Australian! Skepticon Speaker Interview We chat to Lee Murray, a teaching associate and PhD candidate, Linguistics Program School of Languages, Literatures, Cultures & Linguistics at Monash University. http://artsonline.monash.edu.au/llcl/ 0:48:08 Ian Bryce and the Higgs Ian qualified at Monash University in science (BSc, physics) and engineering (BE Hons). His career has involved applying science to spaceflight for companies including Hawker de Havilland, Optus and Asia Pacific Space Centre. He created several space courses and lectured for eight years at four universities. Recently he has turned these skills toward communicating science and philosophy. He is also the challenge coordinator for Australian Skeptics Inc. https://www.youtube.com/watch?v=TPOc7TzXhvA Also... RSVP for Australian Skeptics FREE Friday night trivia and meetup 12 Oct. https://www.skeptics.com.au/event/national-convention  

0:00:00 Introduction Richard Saunders   0:04:30 Kate Browne Kate is an investigative journalist and leader of the news team at CHOICE. She is also known as 'The Gulty Mum' from the ABC TV show 'The Checkout' and will be the M.C. for the upcoming Skepticon in October. https://www.choice.com.au/authors/kate-browne https://www.youtube.com/playlist?list=PLcnP8uT1FzoUVv3WOpQDFNlU_YmVszNoP   0:14:33 Maynard's Spooky Action.... The launch of Science Week #2 Maynard heads to Australian Museum to attend the launch of Science Week 2018. Interviews with Dr Karl Kruszelnicki - All round Science Communicator http://drkarl.com/ Catherine Polcz - Program Producer (Science) Museum of Applied Arts and Sciences - producer of the Sydney Science Festival. https://catherinepolcz.com/   0:27:10 Interview with Alethea Dean from Australian Skeptics Over a coffee or two, Alethea tells us of some of the people lined up for Skepticon 2018. Also news about a possible crèche and sign language interpreter at the convention. https://convention.skeptics.com.au   0:34:00 Speed Meet the Scientists at the Powerhouse Museum #1 This week, interviews with... Dr Camilla Hoyos - Sleep researcher https://woolcock.org.au/sleep-research Amelie Vanderstock - Ecologist https://www.crosspollinating.org/ Dr Alexandra Thomson - Marine Ecologist and Biogeochemist https://www.uts.edu.au/ Frankie Lee - Event Coordinator Cara Van Der Wal - Marine biologist https://sydney.edu.au/science/people/cara.vanderwal.168.php   0:49:22 Mrs Mac and Morse Code Our Canberra reporter Kevin Davies chats to author David Dufty about Florence Violet McKenzie OBE. Affectionately known as "Mrs Mac", she was Australia's first female electrical engineer, founder of the Women's Emergency Signalling Corps and lifelong promoter for technical education for women. The Secret Code-Breakers of Central Bureau: how Australia’s signals-intelligence network helped win the Pacific War https://tinyurl.com/ycemoee7  

Founder of Hop Compost 

Tim Fuell and Dave Anderson cover the world of non league football in a bumper show. Stockport County's commentator and Communications Director Jon Keighren looks ahead to his side's big FA Trophy match against Kevin Davies' Southport and the juggle of being a fan on a board and managing expectations. Steve King speaks openly about the challenge he has taken on at Whitehawk, on searching for that first win, the need for a good striker and why he still believes he will turn it around this season. Director of Football Martin Ling is equally as honest in his reasons for staying solely upstairs at Leyton Orient, how tough he has found it in the National League, why they aren't rushing to make the next appointment of Head Coach and why he has so much respect for the fans of the club. Assistant Manager at Southern League Merthyr Town Dean Clark explains the position at the club and why him and the coaching staff have chosen to stay to try to save their club and muddle through with very limited resources. Join in the debate throughout the week on Twitter @nonleagueshow

We're back following the international break, ahead of the visit of Bolton Wanderers on Friday evening. This week host Guy Clarke talks with two former PNE and Bolton strikers as well as catching up with defender Kevin O'Connor. The Irishman gives his take on breaking into the first team, teammates Ben Pearson and Jordan Hugill winning awards at the North West Football Awards and much more. Ex-Lilywhites frontman Jermaine Beckford reflects on his time at Deepdale, ahead of the visit of Bolton, plus discusses his role as club captain at Bury. Kevin Davies sits down with iFollow PNE following his first move into management with Southport. Plus the latest instalment of the 'Clubman' series sees Head of Ground Safety Mark Farnworth offer his advice ahead of the derby. All feedback is much welcomed, email media@pne.com, while you can also discuss and debate on social media using the hashtag PNEPodcast. Any ratings, reviews, shares and downloads are all very much appreciated.

0:00:00 Introduction Richard Saunders 0:05:00 Reports from NECSS Sharon Roney from Guerrilla Skepticism on Wikipedia and Richard Saunders wander around the auditorium before the start of the Northeast Conference on Science and Skepticism in New York. https://www.facebook.com/GSoWproject Later Richard catches up with Dr Harriet Hall, MD to chat about her video series. https://sciencebasedmedicine.org/author/harriet-hall 0:12:20 Brew Ha Ha: Science in less time than it takes to order a coffee With Shuj Esufali A smart device with AI called emergency services during a domestic violence incident and possibly saved lives as a result. When it comes to domestic violence, AI could save a lot more. https://www.australiascience.tv 0:15:00 Dr Rachie Reports... wih Dr Rachael Dunlop This week Dr Rachie interviews Craig Egan about the Vaxxed bus is tour across the USA, spreading fear and disinformation about vaccines. Craig is following their route, refuting them with facts and evidence and sometimes lulz at every stop. https://www.gofundme.com/craigs-provax-world-tour http://www.jhrl.com/toxic-puzzle-hunt-hidden-killer 0:36:15 TGA’s list of medical indications full of pseudoscience The Therapeutic Goods Administration (TGA) has published a draft list of “permitted indications” for listed complementary medicines that includes many terms and concepts that are straight out of the pseudoscience catalogue. http://www.skeptics.com.au/2017/07/10/tgas-list-of-medical-indications-full-of-pseudoscience/ 0:42:00 Kevin Davies interviews Professor John Carver Professor John Carver has been Director of the Research School of Chemistry at the Australian National University in Canberra. He undertook his undergraduate (First-class Honours) degree in Chemistry at the University of Adelaide. In 1983, he was awarded his Ph.D. in Biological Chemistry from the Australian National University and subsequently undertook post-doctoral studies in Biochemistry at the Universities of Oxford and Adelaide. http://www.publish.csiro.au/book/7366 Also... CSI Con - Las Vagas http://csiconference.org European Skeptics Congress - Wroclaw http://euroscepticscon.org QED - Manchester qedcon.org Skepticon Sydney http://www.skeptics.com.au

Let’s Get Technical with Stacey Marien and Alayne Mundt On today’s episode we cover a number of topics. First off is Katina Strauch with her weekly Rumors segment. Then we hear from Katina’s husband Bruce Strauch as he tells us a fascinating “Case of Note” story involving reality TV, violent street gangs and the anti-SLAPP statute. We then hear three articles from ATG Column Editors Stacey Marien (Acquisitions Librarian, American University Library) and Alayne Mundt (Resource Description Librarian, American University Library) focusing on practical problems and solutions in Technical Services departments. This is the first of a series of articles that Stacey and Alayne will be presenting on the podcast. This week’s Katina’s Rumors: There are many people who help us to keep the Charleston Conference and ATG running! One of our main technical advisers is Matt Branton. Matt has worked at the College of Charleston for most of his young lifetime! He has two darling girls – Lockie and Tallulah and a wonderful wife Leighton. The family has recently welcomed a brother. Benjamin Luke Branton was born April 22 and is hard at work getting bigger! Matt helps us with every eventuality quickly and efficiently whenever we need him! Thank you, Matt and congratulations to the Branton family! We met many years ago in Fiesole, Italy, when she as working for Casalini Libri and later at Ithaka. And the vivacious Çolleen Campbell has a new position as Partner Development in the Open Access 2020 Initiative at the Max Planck Society’s Max Planck Digital Library. The Max Planck Digital Library (MPDL) in Munich is a central unit of the Max Planck Society that supports scientists from all Max Planck Institutes with a broad portfolio of services in the fields of information provision, publication support and research data management. In the era of digital information, big data, the World Wide Web and web-based collaboration, MPDL makes a substantial contribution to the Max Planck Society's competitiveness in the international science community. The MPDL and its predecessors have featured as one of Europe's largest purchasers of scientific information for more than 10 years now. The MPDL arranges for access to a wide range of scientific journals, eBooks, specialist databases and extensive open access publication services. Together with the libraries at the Max Planck Institutes, it takes care of an excellent supply of scientific information and opportunities for publication. Teams from the MPDL have been playing an active role in preparing and supplying research data and research results from the 80 Max Planck Institutes since 2007. The MPDL has been working for many years with both Max Planck Society born data collections and commercial resources, developing cyber-infrastructures and specialist applications for research data. It regularly combines data flows from more than a hundred different sources and performs ongoing analyses of usage statistics and constantly growing, complex data pools with entry volumes in the order of 1011 or more. https://www.mpg.de/mpdl-en https://www.mpdl.mpg.de/en/about-us/mission.html Kevin Davies has joined Mary Ann Liebert, Inc., publishers as Executive Vice President, Strategic Development. In this new role, Davies will oversee strategy development for the company’s life science franchise, including GEN (Genetic Engineering & Biotechnology News) and Clinical OMICS, as well as spearhead innovative new content initiatives for Mary Ann Liebert, Inc. Davies’s career as an editor, author, and publisher has spanned more than 25 years. He has held a number of prominent editorial and publishing positions, including founding editor of Nature Genetics, Editor-in-Chief of Cell Press, launch editor for Bio-IT World, and vice president of the American Chemical Society, where he served as publisher of Chemical & Engineering News. Davies is the author of three successful science books exploring the medical and societal impact of advances in DNA sequencing and analysis — Breakthrough: The Race to Find the Breast Cancer Gene; Cracking the Genome: The Race to Unlock Human DNA; and The $1,000 Genome: The Revolution in DNA Sequencing and the New Era of Personalized Medicine — as well as co-author with Nobel laureate Jim Watson of an updated edition of DNA: The Story of the Genetic Revolution. In April of this year, Davies won a prestigious Guggenheim Fellowship for science writing. “I am delighted to be joining the Mary Ann Liebert team,” said Davies. “I have long admired the company’s penchant for identifying emerging areas of science and medicine, and sought to emulate the longstanding success of Genetic Engineering and Biotechnology News. I hope my ideas and experience in launching new journals and managing various science and technology publications will help the Liebert organization grow and flourish in the years ahead.” http://www.alphagalileo.org/ViewItem.aspx?ItemId=175170&CultureCode=en Listen Online: “Libraries in The 21st Century” was Discussed on Florida Matters Public Radio Program. This was posted by Gary Price on InfoDocket. The program guests include Todd Chavez, Dean of Libraries, Univ of South Florida, Ava Edhe, Services Manager, Manatee County Public Library and regular ATG columnist Mark Y. Herring Dean of Library Services, Winthrop University http://www.infodocket.com/2017/05/02/listen-online-libraries-in-the-21st-century-discussed-on-florida-matters-public-radio-program/ And to finish out Rumors this time, learn about a debate in British Parliament at Westminster. They are concerned over what to print legislation on. Since Medieval times, Parliament has recorded its acts on sheep and goat skins made into parchment, and since 1849 only on vellum which costs Parliament $45 on an A4-size sheet versus 16 pence for archival paper. There’s much discussion and passion about the merits of paper versus vellum. Traditionalists say that the Magna Carta was printed on vellum. Britain’s House of Lords switched to paper in 1999. Laws and resolutions of the US government were printed on parchment until 1920. It appears that paper has won the battle so far but anything could happen still as we all know. https://www.wsj.com/articles/britains-next-pressing-question-paper-or-parchment-1494179108  

0:00:00 Introduction Richard Saunders 0:04:45 Grain of Salt.... with Eran Segev More in the series of interviews from QED. This week Eran talks with Britt Hermes, a former naturopathic 'doctor' who shares the hard truths about naturopathic medicine to protect patients. Her message is "Please don't be fooled by natural and alternative medicine." https://www.naturopathicdiaries.com 0:14:09 New Zealand Skeptics 2016 Conference This week we chat to Susan Gerbic and find out the latest on Guerrilla Skepticism on Wikipedia. What can you do to help? Susan Gerbic at Puzzling World (Video) https://www.youtube.com/watch?v=OObcuaiLwI8&t=7s 0:26:16 Brew Ha Ha: Science in less time than it takes to order a coffee https://www.australiascience.tv/tags/brew-ha-ha With Casey Harrigan 2016 has been a momentous year. Here we give our top 3 biggest science news of 2016! Here's to 2017! Watch more: Zika virus: http://bit.ly/2hm2o1i Paris agreement: http://bit.ly/2gcXP8f Gravitational waves: http://bit.ly/LKgravwaves It's been a big year for sci-fi films, but who pulled it off the best? We review the best and worst movie scientists from 2016. Ever think "I wish my robot could sweat"? Well your dreams have been answered thanks to ingenious research from Japan. Say hello to Kengoro, a 1.7m tall, 56kg musculoskeletal humanoid. Further reading via IEEE Spectrum: http://bit.ly/2eHscrk 0:31:34 Cancer Reseach in Australia Guest reporter Kevin Davies interviews Prof. Ross Hannan, head of the department of cancer biology and therapeutics at The John Curtin School of Medical Research, ANU College of Medicine. What is the latest news on cancer research and what is the link to Jackie Chan? http://jcsmr.anu.edu.au/people/ross-hannan Also... Richard Saunders talks in California, Dec. 2016 BAS Skeptalk : Thursday, December 29, 2016 - 7:30pm La Pena Cultural Center 3105 Shattuck Ave, Berkeley, CA OC Science Club : Friday, December 30, 2016 - 7:00pm Del Frisco's Grille 772 Spectrum Center Dr, Irvine, California 92618

This week, on episode 63 of the Lion of Vienna Suite podcast, Dan is joined by Chris, Jonny and Tom Wilson as they laugh at CM Punk, Disect yet another Bolton Wanderers draw and look ahead to next weeks match. Once the plesantries, the jokes about CM Punk's embaressig UFC debut and awful analysis of Brook v Golovkin were out of the way, the quartet got stuck into the Wanderers chatter. The Whites drew 1-1 for the third week on the bounce on Saturday, this time at home to MK Dons, and the lads discusses if the three game streak without a win is a cause for concern, despite still being top of the league. Then each Bolton player was analysed in-depth, with Mark Howard, Jay Spearing and Mark Beevers receiving tones of praise, where as the likes of Lewis Buxton, Jamie Proctor, Josh Vela and Liam Trotter weren't so luck. Kevin Davies' less than savoury comments on Dougie Freedman were then discusses, which went to some rather strange places. All that before the group look ahead to Saturday's tie with Walsall, and debate as to who should take the suspended Spearing's place.   Learn more about your ad choices. Visit podcastchoices.com/adchoices

This week, we are joined by Kevin Davies of the Transformers : Cybertronological podcast (  ).  We talk how pervasive Pearl Jam was in 1992, how Mike Patton is possibly the greatest vocalist of our generation and what Dream Theatre meant to one 15 year old kid. Follow us on twitter at @tstsylpod and visit eartrumpetaudio.com for all our networked podcasts.

Kevin Davies, BComm' 14, founder and CEO of HOP Compost, has created a fertilizer alternative that is certified organic and non-GMO.

The FL72 Podcast was at the Football League awards as Kevin Davies picked up the prestigious Sir Tom Finney award - he gives his thoughts on Bolton's season. Emile Heskey puts the Wanderers relegation down to bad luck. The League One and League Two players of the season, Bradley Dack and Kemar Roofe, reveal what an honor the award is. David Prutton gives his thoughts on the Championship promotion race. Plus, George Friend takes on "10 to Tackle".

On Episode 36 of the LOVpod Chris returns and steps in as host, with Rob reuced back to mere tech wiz Rob. They are both joined by Liam and new boy to the site and the show, Jonny Eckersley.  First port of call for the boys, well after Chris' very strange intro, was an in-depth look into Lion of Vienna Suite's world exclusive story on the possible Dean Holdsworth-led takeover of Bolton Wanderers. The lads cover all the details of the potentia deal and offer their own opinions. They then look ahead to next weekend's visit to Reading, before reviewing the latest Wanderers news - including a possible new loan signing and rumours around Kevin Davies' testimonial. Proceedings are brought to a close by a very shady game of Guess Who?, before the boys look back at your responses to this week's Twitter question. Listen on iTunes or Blog Talk Radio.   Learn more about your ad choices. Visit podcastchoices.com/adchoices

Garry Monk, Dion Dublin and Kevin Davies (with his Star Wars collection) join Wrighty & Stoney after Chelsea end their Blues on Absolute Radio

In this week's episode of the Lion of Vienna Suite Podcast Chris returns from his jolly holidays and is joined by Dan, Tom and momentarily Rob, as they analyse Neil Lennon's comments at the BWSA meeting and look back on Kevin Davies' time at Bolton Wanderers.   Running Order 1) Motherwell 1-2 Bolton Should we be playing a friendly at this point? Players getting much needed minutes  Andy Kellett leaving for Wigan Athletic Youngsters getting game time 2) Wolves Preview The returns of Adam Le Fondre and Benik Afobe The threat of Wolves How the game will go Our team Score prediction 3) Analysing Neil Lennon's comments at the BWSA meeting Paul Rachubka Interest in Vela and Clough Neil Danns covers more ground and is more dynamic than Jay Spearing No takers for Medo Tim Ream wasn't physical enough to play centre back Knew Gary Madine would miss his penalty Wants us to shoot from range Not heard from Stu Holden We're a striker away from the play offs 4) Kevin Davies Kevin Davies has retired from football What he means to us Favourite memoires End. Download on iTunes or listen on Blog Talk Radio. Learn more about your ad choices. Visit podcastchoices.com/adchoices

0:00:00 Introduction Richard Saunders and Jo Alabaster with a review of Neil deGrasse Tyson in Sydney.   0:05:43 Bad Science Watch in Canada  We chat to Michael Kruse about the Canadian Government's crack down on the far-fetched claims of homeopathy.   0:27:48 The Raw Skeptic Report with Heidi Robertson This week Heidi looks at the facts and myths behind influenza and interviews Kelly who lost her mother to the disease.   0:46:45 A Week in Science The Royal Institution of Australia (RiAus) is a national scientific not-for-profit organisation with a mission to bring science to people and people to science.   0:50:20 Deep Space with Kevin Davies  Guest reporter Kevin Davies chats to Glen Nagle, the Education and Public Outreach Manager at the Canberra Deep Space Communication Complex. Pluto and beyond!       

0:00:00 Introduction Richard Saunders   0:04:00 Evidence, Please with Jo Alabaster. What's in your food? Before you run downsatirs and open the fridge, have a listen to Jo's report on food additives.   0:19:44 A Week in Science The Royal Institution of Australia (RiAus) is a national scientific not-for-profit organisation with a mission to bring science to people and people to science.   0:27:26 Promoting Women of Science Guest reporter Kevin Davies chats to Kylie Walker from the Australian Academy of Science. Learn how you can help promote Australian Women of Science.   0:27:26 Saunders on the Radio Last week, the weeeeee small hours, Richard Saunders in San Francisco, called in to Sydney radio to chat with Luke Boner about people who claim to talk with the dead and much more. Now... what is this about Saunders and rats?

Episode 30, Si Steers, Sakho, Kolo, Stevie, Fat Sam, Big Andy, Kevin Davies, Office Talk, Bodily Functions, Oiled up. What more can you want. Seriously. Buy the single for the @JFT96Collective - and buy it more than onceAnd get your body in gear and involved with the Walk for the 96 on Saturday in Dublin if you can make it. 2.30pm start.

0:00:00 Introduction Richard Saunders 0:02:50 Dr Pamela Gay  Pamela tells us about CosmoQuest and what you can do to help this wonderful endeavour. 0:14:25 A Week in Science The Royal Institution of Australia (RiAus) is a national scientific not-for-profit organisation with a mission to bring science to people and people to science. 0:17:25 An chat with Evan Bernstien One of the rouges tells us about the early days of SGU 0:35:00 Kevin Davies from Canberra Skeptics More news on the upcoming Australian Skeptics National Convention 0:38:50 Maynard's Spooky Action... Maynard heads to the Power House Museum in Sydney and reports of the Big Night of Science with the Mystery Investigators Richard Saunders and Dr Rachie Dunlop. Also a chat to and Isabelle Kingsley from the Museum.

Emergency temporal shift! Appolgies if you were expecting Dick Mills this week, he's been kidnapped by Daleks of the 60s variety, but I hear he'll have escaped in time for next week's show. Change of schedule because last weekend I attended a special screening of the Peter Cushing Dalek movies in Hammersmith, West London there was cake, merchandise and two special guests actor Ray Brookes "The Man With The Knack" from Daleks Invasion Earth 2150AD and producer/director Kevin Davies maker of the documentary Dalekmania, tribute was also paid to Peter Cushing who would have been 100 this week(hence the cake) If you want to send me comments or feedback you can email them to tdrury2003@yahoo.co.uk or contact me on twitter where I'm @tdrury or send me a friend request and your comments to facebook where I'm Tim Drury and look like this http://www.flickr.com/photos/tdrury/3711029536/in/set-72157621161239599/ in case you were wondering. You can see my photos of Dalek Day here http://www.flickr.com/photos/tdrury/sets/72157633722396728/ video of Ray Brooks here http://www.youtube.com/watch?v=IzOag8_v9P8 and of Kevin Davies here http://www.youtube.com/watch?v=juEkIlVfqXw

IntroductionRichard Saunders 0:04:17Maynard's Spooky Action.. An interview with Dr Krissy Wilson about talking to the... dead? 0:25:10 Danger 5Just for fun, Richard Saunders checks in with Maynard as he hosts a public Q & A with the cast of this Australian TV show. 0:27:50 Skeptical BBQRichard Saunders travels to Canberra for a screening of "Here be Dragons" by Brian Dunning and enjoys a chat with Kevin Davies, the president of Canberra Skeptics. 0:34:18 The Think TankJoin a host of Canberra Skeptics as they chat about Conspiracy Theories.

Don't forget to show your support for the only club who's season never ends! Click Here to renew your yearly subscription by clicking on the link. On the "My Account" page, click on the "Extend WFD Membership" under the Account tab and follow the prompts. Welcome to the Tuesday edition of World Football Daily. Steven and Kenny will go over the weekend of the leagues they didn't quite get to yesterday: La Liga, Serie A, and the Bundesliga, as well as cover the top stories from around the globe. Top football news of the day goes to Bolton striker, Kevin Davies, who was called up for England's game against Montenegro next Tuesday - and he thought it was a wind up from BBC Radio Five Live, no joke Kevin, you're in. More locker room troubles at Manchester City, as it is reported that Manager Roberto Mancini and striker Carlos Tevez have had a row. Kris Voakes will join us to talk about the big game of the Italian weekend, Inter v.Juventus, and why the game did not live up to the hype. Tim Vickery will join the boys for an update on things South American football. Phil Ball from ESPN Soccernet will join us to discuss all things Spanish football. For more on Spanish football, and specifically Real Madrid, Pablo Oolo from Marca will join us for a discussion.

Genetic sequencing once was a prohibitively costly endeavor costing billions of dollars and untold number of man-hours. Yet, the price for sequencing has plummeted rapidly such that personalized genomic sequencing may soon be available. On this program, Kevin Davies discussed the thousand dollar genome.