Podcast appearances and mentions of larry gold

A recent Fifth Circuit holding in Memorial Hermann has caught the attention of lawyers in our space, with some wondering if the tax law rules on how 501(c)(4)s operate may change. But what did the court really say, and how should 501(c)(4) advocacy organizations react? On this special holiday edition of the pod, we are joined by Larry Gold of Trister Ross Schadler and Gold to understand what this case says and what it means for (c)(4)s in 2025 and beyond.  Attorneys for this episode  Tim Mooney  Susan Finkle Sourlis  Larry Gold, Trister Ross Schadler and Gold   Show notes  What is Memorial Hermann?  Very basics of the case  Basics of the holding  Where does this court's ruling apply?  501(c)(4) organizations must exclusively operate for the social welfare,  how is that interpreted to mean primarily, and the limit on items that do not as social welfare as secondary activity. We frequently talk about one of those secondary activities a lot – partisan political work. But this case focuses on another thing – can you explain why commercial activity does not promote social welfare?   The concern raised by some is the court's move to a smaller insubstantial standard for commercial activity may also apply to political activity, limiting the amount advocacy groups can engage in. How does the law treat commercial activity and political activity differently, and does that distinction matter here for other courts that may be addressing this?  Do (c)(4)s in the Fifth Circuit that engage in partisan political advocacy need to change what they're doing or how much they're doing? What about (c)(4)s outside of the Fifth Circuit?  There's another layer to all of this with (c)(4)s that have filed Form 1024s accepted by the IRS – can you explain what that is and why filing a 1024 now may be a good idea for some (c)(4)s that haven't yet?  What's happening next with this case?  What's your take on how various media outlets have presented this case – do you think they've helped or muddied the waters?  On a scale of 1 to 10 where 1 is a yawn and 10 is metaphysical crisis, where are we now with Memorial Hermann for (c)(4)s?     Resources - Tim  The Rules of the Game     

In this podcast, Thomas Czech, Distinguished Professor at the University of Colorado, Boulder, with a lineage of remarkable contributions on RNA, ribozyme, and telomeres, discuss why RNA is so incredibly versatile.Video snippet from our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to the audio and external linksEric Topol (00:07):Well, hello, this is Eric Topol from Ground Truths, and it's really a delight for me to welcome Tom Cech who just wrote a book, the Catalyst, and who is a Nobel laureate for his work in RNA. And is at the University of Colorado Boulder as an extraordinary chemist and welcome Tom.Tom Cech (00:32):Eric, I'm really pleased to be here.The RNA GuyEric Topol (00:35):Well, I just thoroughly enjoyed your book, and I wanted to start out, if I could, with a quote, which gets us right off the story here, and let me just get to it here. You say, “the DNA guy would need to become an RNA guy. Though I didn't realize it at the time, jumping ship would turn out to be the most momentous decision in my life.” Can you elaborate a bit on that?Tom Cech (01:09):As a graduate student at Berkeley, I was studying DNA and chromosomes. I thought that DNA was king and really somewhat belittled the people in the lab next door who were working on RNA, I thought it was real sort of second fiddle material. Of course, when RNA is acting just as a message, which is an important function, a critical function in all life on earth, but still, it's a function that's subservient to DNA. It's just copying the message that's already written in the playbook of DNA. But little did I know that the wonders of RNA were going to excite me and really the whole world in unimaginable ways.Eric Topol (02:00):Well, they sure have, and you've lit up the world well before you had your Nobel Prize in 1989 was Sid Altman with ribozyme. And I think one of the things that struck me, which are so compelling in the book as I think people might know, it's divided in two sections. The first is much more on the biology, and the second is much more on the applications and how it's changing the world. We'll get into it particularly in medicine, but the interesting differentiation from DNA, which is the one trick pony, as you said, all it does is store stuff. And then the incredible versatility of RNA as you discovered as a catalyst, that challenging dogma, that proteins are supposed to be the only enzymes. And here you found RNA was one, but also so much more with respect to genome editing and what we're going to get into here. So I thought what we might get into is the fact that you kind of went into the scum of the pond with this organism, which by the way, you make a great case for the importance of basic science towards the end of the book. But can you tell us about how you, and then of course, many others got into the Tetrahymena thermophila, which I don't know that much about that organism.Tom Cech (03:34):Yeah, it's related to Tetrahymena is related to paramecium, which is probably more commonly known because it's an even larger single celled animal. And therefore, in an inexpensive grade school microscope, kids can look through and see these ciliated protozoa swimming around on a glass slide. But I first learned about them when I was a postdoc at MIT and I would drive down to Joe Gall's lab at Yale University where Liz Blackburn was a postdoc at the time, and they were all studying Tetrahymena. It has the remarkable feature that it has 10,000 identical copies of a particular gene and for a higher organism, one that has its DNA in the nucleus and does its protein synthesis in the cytoplasm. Typically, each gene's present in two copies, one from mom, one from dad. And if you're a biochemist, which I am having lots of stuff is a real advantage. So 10,000 copies of a particular gene pumping out RNA copies all the time was a huge experimental advantage. And that's what I started working on when I started my own lab at Boulder.Eric Topol (04:59):Well, and that's where, I guess the title of the book, the Catalyst ultimately, that grew into your discovery, right?Tom Cech (05:08):Well, at one level, yes, but I also think that the catalyst in a more general conversational sense means just facilitating life in this case. So RNA does much more than just serve as a biocatalyst or a message, and we'll get into that with genome editing and with telomerase as well.The Big Bang and 11 Nobel Prizes on RNA since 2000Eric Topol (05:32):Yes, and I should note that as you did early in the book, that there's been an 11 Nobel prize awardees since 2000 for RNA work. And in fact, we just had Venki who I know you know very well as our last podcast. And prior to that, Kati Karikó, Jennifer Doudna who worked in your lab, and the long list of people working RNA in the younger crowd like David Liu and Fyodor Urnov and just so many others, we need to have an RNA series because it's just exploding. And that one makes me take you back for a moment to 2007. And when I was reading the book, it came back to me about the Economist cover. You may recall almost exactly 17 years ago. It was called the Biology's Big Bang – Unravelling the secrets of RNA. And in that, there was a notable quote from that article. Let me just get to that. And it says, “it is probably no exaggeration to say that biology is now undergoing its neutron moment.”(06:52):This is 17 years ago. “For more than half a century the fundamental story of living things has been a tale of the interplay between genes, in the form of DNA, and proteins, which is genes encode and which do the donkey work of keeping living organisms living. The past couple of years, 17 years ago, however, has seen the rise and rise of a third type of molecule, called RNA.” Okay, so that was 2007. It's pretty extraordinary. And now of course we're talking about the century of biology. So can you kind of put these last 17 years in perspective and where we're headed?Tom Cech (07:34):Well, Eric, of course, this didn't all happen in one moment. It wasn't just one big bang. And the scientific community has been really entranced with the wonders of RNA since the 1960s when everyone was trying to figure out how messenger RNA stored the genetic code. But the general public has been really kept in the dark about this, I think. And as scientists, were partially to blame for not reaching out and sharing what we have found with them in a way that's more understandable. The DNA, the general public's very comfortable with, it's the stuff of our heredity. We know about genetic diseases, about tracing our ancestry, about solving crimes with DNA evidence. We even say things like it's in my DNA to mean that it's really fundamental to us. But I think that RNA has been sort of kept in the closet, and now with the mRNA vaccines against Covid-19, at least everyone's heard of RNA. And I think that that sort of allowed me to put my foot in the door and say, hey, if you were curious about the mRNA vaccines, I have some more stories for you that you might be really interested in.RNA vs RNAEric Topol (09:02):Yeah, well, we'll get to that. Maybe we should get to that now because it is so striking the RNA versus RNA chapter in your book, and basically the story of how this RNA virus SARS-CoV-2 led to a pandemic and it was fought largely through the first at scale mRNA nanoparticle vaccine package. Now, that takes us back to some seminal work of being able to find, giving an mRNA to a person without inciting massive amount of inflammation and the substitution of pseudouridine or uridine in order to do that. Does that really get rid of all the inflammation? Because obviously, as you know, there's been some negativism about mRNA vaccines for that and also for the potential of not having as much immune cell long term activation. Maybe you could speak to that.Tom Cech (10:03):Sure. So the discovery by Kati Karikó and Drew Weissman of the pseudouridine substitution certainly went a long way towards damping down the immune response, the inflammatory response that one naturally gets with an RNA injection. And the reason for that is that our bodies are tuned to be on the lookout for foreign RNA because so many viruses don't even mess with DNA at all. They just have a genome made of RNA. And so, RNA replicating itself is a danger sign. It means that our immune system should be on the lookout for this. And so, in the case of the vaccination, it's really very useful to dampen this down. A lot of people thought that this might make the mRNA vaccines strange or foreign or sort of a drug rather than a natural substance. But in fact, modified nucleotides, nucleotides being the building blocks of RNA, so these modified building blocks such as pseudoU, are in fact found in natural RNAs more in some than in others. And there are about 200 modified versions of the RNA building blocks found in cells. So it's really not an unusual modification or something that's all that foreign, but it was very useful for the vaccines. Now your other question Eric had to do with the, what was your other question, Eric?Eric Topol (11:51):No, when you use mRNA, which is such an extraordinary way to get the spike protein in a controlled way, exposed without the virus to people, and it saved millions of lives throughout the pandemic. But the other question is compared to other vaccine constructs, there's a question of does it give us long term protective immunity, particularly with T cells, both CD8 cytotoxic, maybe also CD4, as I know immunology is not your main area of interest, but that's been a rub that's been put out there, that it isn't just a weaning of immunity from the virus, but also perhaps that the vaccines themselves are not as good for that purpose. Any thoughts on that?Tom Cech (12:43):Well, so my main thought on that is that this is a property of the virus more than of the vaccine. And respiratory viruses are notoriously hard to get long-term immunity. I mean, look at the flu virus. We have to have annual flu shots. If this were like measles, which is a very different kind of virus, one flu shot would protect you against at least that strain of flu for the rest of your life. So I think the bad rap here is not the vaccine's fault nearly as much as it's the nature of respiratory viruses.RNA And Aging Eric Topol (13:27):No, that's extremely helpful. Now, let me switch to an area that's really fascinating, and you've worked quite a bit on the telomerase story because this is, as you know, being pursued quite a bit, has thought, not just because telomeres might indicate something about biologic aging, but maybe they could help us get to an anti-aging remedy or whatever you want to call it. I'm not sure if you call it a treatment, but tell us about this important enzyme, the role of the RNA building telomeres. And maybe you could also connect that with what a lot of people might not be familiar with, at least from years ago when they learned about it, the Hayflick limit.Tom Cech (14:22):Yes. Well, Liz Blackburn and Carol Greider got the Nobel Prize for the discovery of telomerase along with Jack Szostak who did important initial work on that system. And what it does is, is it uses an RNA as a template to extend the ends of human chromosomes, and this allows the cell to keep dividing without end. It gives the cell immortality. Now, when I say immortality, people get very excited, but I'm talking about immortality at the cellular level, not for the whole organism. And in the absence of a mechanism to build out the ends of our chromosomes, the telomeres being the end of the chromosome are incompletely replicated with each cell division. And so, they shrink over time, and when they get critically short, they signal the cell to stop dividing. This is what is called the Hayflick limit, first discovered by Leonard Hayflick in Philadelphia.(15:43):And he, through his careful observations on cells, growing human cells growing in Petri dishes, saw that they could divide about 50 times and then they wouldn't die. They would just enter a state called senescence. They would change shape, they would change their metabolism, but they would importantly quit dividing. And so, we now see this as a useful feature of human biology that this protects us from getting cancer because one of the hallmarks of cancer is immortality of the tumor cells. And so, if you're wishing for your telomeres to be long and your cells to keep dividing, you have to a little bit be careful what you wish for because this is one foot in the door for cancer formation.Eric Topol (16:45):Yeah, I mean, the point is that it seems like the body and the cell is smart to put these cells into the senescent state so they can't divide anymore. And one of the points you made in the book that I think is worth noting is that 90% of cancers have the telomerase, how do you say it?Tom Cech (17:07):Telomerase.Eric Topol (17:08):Yeah, reactivate.Tom Cech (17:09):Right.Eric Topol (17:10):That's not a good sign.Tom Cech (17:12):Right. And there are efforts to try to target telomerase enzyme for therapeutic purposes, although again, it's tricky because we do have stem cells in our bodies, which are the exception to the Hayflick limit rule. They do still have telomerase, they still have to keep dividing, maybe not as rapidly as a cancer cell, but they still keep dividing. And this is critical for the replenishment of certain worn out tissues in our such as skin cells, such as many of our blood cells, which may live only 30 days before they poop out. That's a scientific term for needing to be replenished, right?Eric Topol (18:07):Yeah. Well, that gets me to the everybody's, now I got the buzz about anti-aging, and whether it's senolytics to get rid of these senescent cells or whether it's to rejuvenate the stem cells that are exhausted or work on telomeres, all of these seem to connect with a potential or higher risk of cancer. I wonder what your thoughts are as we go forward using these various biologic constructs to be able to influence the whole organism, the whole human body aging process.Tom Cech (18:47):Yes. My view, and others may disagree is that aging is not an affliction. It's not a disease. It's not something that we should try to cure, but what we should work on is having a healthy life into our senior years. And perhaps you and I are two examples of people who are at that stage of our life. And what we would really like is to achieve, is to be able to be active and useful to society and to our families for a long period of time. So using the information about telomerase, for example, to help our stem cells stay healthy until we are, until we're ready to cash it in. And for that matter on the other side of the coin, to try to inhibit the telomerase in cancer because cancer, as we all know, is a disease of aging, right? There are young people who get cancer, but if you look at the statistics, it's really heavily weighted towards people who've been around a long time because mutations accumulate and other damage to cells that would normally protect against cancer accumulates. And so, we have to target both the degradation of our stem cells, but also the occurrence of cancer, particularly in the more senior population. And knowing more about RNA is really helpful in that regard.RNA DrugsEric Topol (20:29):Yeah. Well, one of the things that comes across throughout the book is versatility of RNA. In fact, you only I think, mentioned somewhere around 12 or 14 of these different RNAs that have a million different shapes, and there's so many other names of different types of RNAs. It's really quite extraordinary. But one of the big classes of RNAs has really hit it. In fact, this week there are two new interfering RNAs that are having extraordinary effects reported in the New England Journal on all the lipids, abnormal triglycerides and LDL cholesterol, APOC3. And can you talk to us about this interfering the small interfering RNAs and how they become, you've mentioned in the book over 400 RNAs are in the clinic now.Tom Cech (21:21):Yeah, so the 400 of course is beyond just the siRNAs, but these, again, a wonderful story about how fundamental science done just to understand how nature works without any particular expectation of a medical spinoff, often can have the most phenomenal and transformative effects on medicine. And this is one of those examples. It came from a roundworm, which is about the size of an eyelash, which a scientist named Sydney Brenner in England had suggested would be a great experimental organism because the entire animal has only about a thousand cells, and it's transparent so we can look at, see where the cells are, we can watch the worm develop. And what Andy Fire and Craig Mello found in this experimental worm was that double-stranded RNA, you think about DNA is being double-stranded and RNA as being single stranded. But in this case, it was an unusual case where the RNA was forming a double helix, and these little pieces of double helical RNA could turn off the expression of genes in the worm.(22:54):And that seemed remarkable and powerful. But as often happens in biology, at least for those of us who believe in evolution, what goes for the worm goes for the human as well. So a number of scientists quickly found that the same process was going on in the human body as a natural way of regulating the expression of our genes, which means how much of a particular gene product is actually going to be made in a particular cell. But not only was it a natural process, but you could introduce chemically synthesized double helical RNAs. There are only 23 base pairs, 23 units of RNA long, so they're pretty easy to chemically synthesize. And that once these are introduced into a human, the machinery that's already there grabs hold of them and can be used to turn off the expression of a disease causing RNA or the gene makes a messenger RNA, and then this double-stranded RNA can suppress its action. So this has become the main company that is known for doing this is Alnylam in Boston, Cambridge. And they have made quite a few successful products based on this technology.Eric Topol (24:33):Oh, absolutely. Not just for amyloidosis, but as I mentioned these, they even have a drug that's being tested now, as you know that you could take once or twice a year to manage your blood pressure. Wouldn't that be something instead of a pill every day? And then of course, all these others that are not just from Alnylam, but other companies I wasn't even familiar with for managing lipids, which is taking us well beyond statins and these, so-called PCSK9 monoclonal antibodies, so it's really blossoming. Now, the other group of RNA drugs are antisense drugs, and it seemed like they took forever to warm up, and then finally they hit. And can you distinguish the antisense versus the siRNA therapeutics?Tom Cech (25:21):Yes, in a real general sense, there's some similarity as well as some differences, but the antisense, what are called oligonucleotides, whoa, that's a big word, but oligo just means a few, right? And nucleotides is just the building blocks of nucleic acid. So you have a string of a few of these. And again, it's the power of RNA that it is so good at specifically base pairing only with matching sequences. So if you want to match with a G in a target messenger RNA, you put a C in the antisense because G pairs with C, if you want to put an A, if want to match with an A, you put a U in the antisense because A and U form a base pair U is the RNA equivalent of T and DNA, but they have the same coding capacity. So any school kid can write out on a notepad or on their laptop what the sequence would have to be of an antisense RNA to specifically pair with a particular mRNA.(26:43):And this has been, there's a company in your neck of the woods in the San Diego area. It started out with the name Isis that turned out to be the wrong Egyptian God to name your company after, so they're now known as Ionis. Hopefully that name will be around for a while. But they've been very successful in modifying these antisense RNAs or nucleic acids so that they are stable in the body long enough so that they can pair with and thereby inhibit the expression of particular target RNAs. So it has both similarities and differences from the siRNAs, but the common denominator is RNA is great stuff.RNA and Genome EditingEric Topol (27:39):Well, you have taken that to in catalyst, the catalyst, you've proven that without a doubt and you and so many other extraordinary scientists over the years, cumulatively. Now, another way to interfere with genes is editing. And of course, you have a whole chapter devoted to not just well CRISPR, but the whole genome editing field. And by the way, I should note that I forgot because I had read the Codebreaker and we recently spoke Jennifer Doudna and I, that she was in your lab as a postdoc and you made some wonderful comments about her. I don't know if you want to reflect about having Jennifer, did you know that she was going to do some great things in her career?Tom Cech (28:24):Oh, there was no question about it, Eric. She had been a star graduate student at Harvard, had published a series of breathtaking papers in magazines such as Science and Nature already as a graduate student. She won a Markey fellowship to come to Colorado. She chose a very ambitious project trying to determine the molecular structures of folded RNA molecules. We only had one example at the time, and that was the transfer RNA, which is involved in protein synthesis. And here she was trying these catalytic RNAs, which we had discovered, which were much larger than tRNA and was making great progress, which she finished off as an assistant professor at Yale. So what the general public may not know was that in scientific, in the scientific realm, she was already highly appreciated and much awarded before she even heard anything about CRISPR.Eric Topol (29:38):Right. No, it was a great line you have describing her, “she had an uncanny talent for designing just the right experiment to test any hypothesis, and she possessed more energy and drive than any scientist I'd ever met.” That's pretty powerful. Now getting into CRISPR, the one thing, it's amazing in just a decade to see basically the discovery of this natural system to then be approved by FDA for sickle cell disease and beta thalassemia. However, the way it exists today, it's very primitive. It's not actually fixing the gene that's responsible, it's doing a workaround plan. It's got double strand breaks in the DNA. And obviously there's better ways of editing, which are going to obviously involve RNA epigenetic editing, if you will as well. What is your sense about the future of genome editing?Tom Cech (30:36):Yeah, absolutely, Eric. It is primitive right now. These initial therapies are way too expensive as well to make them broadly applicable to the entire, even in a relatively wealthy country like the United States, we need to drive the cost down. We need to get them to work, we need to get the process of introducing them into the CRISPR machinery into the human body to be less tedious and less time consuming. But you've got to start somewhere. And considering that the Charpentier and Doudna Nobel Prize winning discovery was in 2012, which is only a dozen years ago, this is remarkable progress. More typically, it takes 30 years from a basic science discovery to get a medical product with about a 1% chance of it ever happening. And so, this is clearly a robust RNA driven machine. And so, I think the future is bright. We can talk about that some more, but I don't want to leave RNA out of this conversation, Eric. So what's cool about CRISPR is its incredible specificity. Think of the human genome as a million pages of text file on your computer, a million page PDF, and now CRISPR can find one sentence out of that million pages that matches, and that's because it's using RNA, again, the power of RNA to form AU and GC base pairs to locate just one site in our whole DNA, sit down there and direct this Cas9 enzyme to cut the DNA at that site and start the repair process that actually does the gene editing.Eric Topol (32:41):Yeah, it's pretty remarkable. And the fact that it can be so precise and it's going to get even more precise over time in terms of the repair efforts that are needed to get it back to an ideal state. Now, the other thing I wanted to get into with you a bit is on the ribosome, because that applies to antibiotics and as you call it, the mothership. And I love this metaphor that you had about the ribosome, and in the book, “the ribosome is your turntable, the mRNA is the vinyl LP record, and the protein is the music you hear when you lower the needle.” Tell us more about the ribosome and the role of antibiotics.Tom Cech (33:35):So do you think today's young people will understand that metaphor?Eric Topol (33:40):Oh, they probably will. They're making a comeback. These records are making a comeback.Tom Cech (33:44):Okay. Yes, so this is a good analogy in that the ribosome is so versatile it's able to play any music that you feed at the right messenger RNA to make the music being the protein. So you can have in the human body, we have tens of thousands of different messenger RNAs. Each one threads through the same ribosome and spills out the production of whatever protein matches that mRNA. And so that's pretty remarkable. And what Harry Noller at UC Santa Cruz and later the crystallographers Venki Ramakrishnan, Tom Steitz, Ada Yonath proved really through their studies was that this is an RNA machine. It was hard to figure that out because the ribosome has three RNAs and it has dozens of proteins as well. So for a long time people thought it must be one of those proteins that was the heart and soul of the record player, so to speak.RNA and Antibiotics(34:57):And it turned out that it was the RNA. And so, when therefore these scientists, including Venki who you just talked to, looked at where these antibiotics docked on the ribosome, they found that they were blocking the key functional parts of the RNA. So it was really, the antibiotics knew what they were doing long before we knew what they were doing. They were talking to and obstructing the action of the ribosomal RNA. Why is this a good thing for us? Because bacterial ribosomes are just enough different from human ribosomes that there are drugs that will dock to the bacterial ribosomal RNA, throw a monkey wrench into the machine, prevent it from working, but the human ribosomes go on pretty much unfazed.Eric Topol (36:00):Yeah, no, the backbone of our antibiotics relies on this. So I think people need to understand about the two subunits, the large and the small and this mothership, and you illuminate that so really well in the book. That also brings me to phage bacteria phage, and we haven't seen that really enter the clinic in a significant way, but there seems to be a great opportunity. What's your view about that?Tom Cech (36:30):This is an idea that goes way back because since bacteria have their own viruses which do not infect human cells, why not repurpose those into little therapeutic entities that could kill, for example, what would we want to kill? Well, maybe tuberculosis has been very resistant to drugs, right? There are drug resistant strains of TB, yes, of TB, tuberculosis, and especially in immunocompromised individuals, this bug runs rampant. And so, I don't know the status of that. It's been challenging, and this is the way that biomedicine works, is that for every 10 good ideas, and I would say phage therapy for bacterial disease is a good idea. For every 10 such ideas, one of them ends up being practical. And the other nine, maybe somebody else will come along and find a way to make it work, but it hasn't been a big breakthrough yet.RNA, Aptamers and ProteinsEric Topol (37:54):Yeah, no, it's really interesting. And we'll see. It may still be in store. What about aptamers? Tell us a little bit more about those, because they have been getting used a lot in sorting out the important plasma proteins as therapies. What are aptamers and what do you see as the future in that regard?Tom Cech (38:17):Right. Well, in fact, aptamers are a big deal in Boulder because Larry Gold in town was one of the discoverers has a company making aptamers to recognize proteins. Jack Szostak now at University of Chicago has played a big role. And also at your own institution, Jerry Joyce, your president is a big aptamer guy. And you can evolution, normally we think about it as happening out in the environment, but it turns out you can also make it work in the laboratory. You can make it work much faster in the laboratory because you can set up test tube experiments where molecules are being challenged to perform a particular task, like for example, binding to a protein to inactivate it. And if you make a large community of RNA molecules randomly, 99.999% of them aren't going to know how to do this. What are the odds? Very low.(39:30):But just by luck, there will be an occasional molecule of RNA that folds up into a shape that actually fits into the proteins active sighting throws a monkey wrench into the works. Okay, so now that's one in a billion. How are you going to find that guy? Well, this is where the polymerase chain reaction, the same one we use for the COVID-19 tests for infection comes into play. Because if you can now isolate this needle in a haystack and use PCR to amplify it and make a whole handful of it, now you've got a whole handful of molecules which are much better at binding this protein than the starting molecule. And now you can go through this cycle several times to enrich for these, maybe mutagen it a little bit more to give it a little more diversity. We all know diversity is good, so you put a little more diversity into the population and now you find some guy that's really good at recognizing some disease causing protein. So this is the, so-called aptamer story, and they have been used therapeutically with some success, but diagnostically certainly they are extremely useful. And it's another area where we've had success and the future could hold even more success.Eric Topol (41:06):I think what you're bringing up is so important because the ability to screen that tens of thousands of plasma proteins in a person and coming up with as Tony Wyss-Coray did with the organ clocks, and this is using the SomaLogic technology, and so much is going on now to get us not just the polygenic risk scores, but also these proteomic scores to compliment that at our orthogonal, if you will, to understand risk of people for diseases so we can prevent them, which is fulfilling a dream we've never actually achieved so far.Tom Cech (41:44):Eric, just for full disclosure, I'm on the scientific advisory board of SomaLogic in Boulder. I should disclose that.Eric Topol (41:50):Well, that was smart. They needed to have you, so thank you for mentioning that. Now, before I wrap up, well, another area that is a favorite of mine is citizen science. And you mentioned in the book a project because the million shapes of RNA and how it can fold with all hairpin terms turns and double stranded and whatever you name it, that there was this project eteRNA that was using citizen scientists to characterize and understand folding of RNA. Can you tell us about that?RNA Folding and Citizen ScienceTom Cech (42:27):So my friend Rhiju Das, who's a professor at Stanford University, sort of adopted what had been done with protein folding by one of his former mentors, David Baker in Seattle, and had repurposed this for RNA folding. So the idea is to come up with a goal, a target for the community. Can you design an RNA that will fold up to look like a four pointed cross or a five pointed star? And it turned out that, so they made it into a contest and they had tens of thousands of people playing these games and coming up with some remarkable solutions. But then they got a little bit more practical, said, okay, that was fun, but can we have the community design something like a mRNA for the SARS-CoV-2 spike protein to make maybe a more stable vaccine? And quite remarkably, the community of many of whom are just gamers who really don't know much about what RNA does, were able to find some solutions. They weren't enormous breakthroughs, but they got a several fold, several hundred percent increase in stability of the RNA by making it fold more tightly. So I just find it to be a fascinating approach to science. Somebody of my generation would never think of this, but I think for today's generation, it's great when citizens can become involved in research at that level.Eric Topol (44:19):Oh, I think it's extraordinary. And of course, there are other projects folded and others that have exemplified this ability for people with no background in science to contribute in a meaningful way, and they really enjoy, it's like solving a puzzle. The last point is kind of the beginning, the origin of life, and you make a pretty strong case, Tom, that it was RNA. You don't say it definitively, but maybe you can say it here.RNA and the Origin of LifeTom Cech (44:50):Well, Eric, the origin of life happening almost 4 billion years ago on our primitive planet is sort of a historical question. I mean, if you really want to know what happened then, well, we don't have any video surveillance of those moments. So scientists hate to ever say never, but it's hard to sort of believe how we would ever know for sure. So what Leslie Orgel at the Salk Institute next to you taught me when I was a starting assistant professor is even though we'll never know for sure, if we can recapitulate in the laboratory plausible events that could have happened, and if they make sense chemically and biologically, then that's pretty satisfying, even if we can never be absolutely sure. That's what a number of scientists have done in this field is to show that RNA is sort of a, that all the chemistry sort of points to RNA as being something that could have been made under prebiotic conditions and could have folded up into a way that could solve the greatest of all chicken and egg problems, which came first, the informational molecule to pass down to the next generation or the active molecule that could copy that information.(46:32):So now that we know that RNA has both of those abilities, maybe at the beginning there was just this RNA world RNA copying itself, and then proteins came along later, and then DNA probably much more recently as a useful but a little bit boring of genetic information, right?Eric Topol (46:59):Yeah. Well, that goes back to that cover of the Economist 17 years ago, the Big Bang, and you got me convinced that this is a pretty strong story and candidate. Now what a fun chance to discuss all this with you in an extraordinary book, Tom. Did I miss anything that you want to bring up?Tom Cech (47:21):Eric, I just wanted to say that I not only appreciate our conversation, but I also appreciate all you are doing to bring science to the non-scientist public. I think people like me who have taught a lot of freshmen in chemistry, general chemistry, sort of think that that's the level that we need to aim at. But I think that those kids have had science in high school year after year. We need to aim at the parents of those college freshmen who are intelligent, who are intellectually curious, but have not had science courses in a long time. And so, I'm really joining with you in trying to avoid jargon as much as possible. Use simple language, use analogies and metaphors, and try to share the excitement of what we're doing in the laboratory with the populace.Eric Topol (48:25):Well, you sure did that it was palpable. And I thought about it when I read the book about how lucky it would be to be a freshman at the University of Boulder and be having you as the professor. My goodness. Well, thank you so much. This has been so much fun, Tom, and I hope everybody's going to get out there and read the Catalyst to get all the things that we didn't even get a chance to dive into. But this has been great and look forward to future interactions with you.Tom Cech (48:53):Take care, Eric.*********************Thanks for listening or reading this edition of Ground Truths.Please share this podcast with your friends and network. That tells me you found it informative and makes the effort in doing these worthwhile.All Ground Truths newsletters and podcast are free. Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Gold Lab Symposium on Science and Health.  (starts 6:40) Boulder scientist and entrepreneur, Larry Gold, shares a sneak preview of this year's Gold Lab Symposium at CU-Boulder Muenzinger Auditorium this Thursday and Friday.  This year's symposium focuses on Pain, Culture and Intelligence. The symposium includes discussion of the paper, Organ aging signatures in the plasma … Continue reading "Gold Lab Symposium – 2024 – Health, Intelligence & Culture"

CU-Boulder's 14th annual Gold Lab Symposium on the Science of Health takes place this Thursday and Friday at CU-Boulder's Muenzinger Auditorium and on line.   You can sign up for the symposium  here.   In today's show, Larry Gold, founder, scientist and entrepreneur, talks about some key scientific discoveries being discussed at this year's symposium, along … Continue reading "Gold Lab Symposium on Science and Health"

Gold Lab Symposium and DeepMind's Alpha Fold  (starts 1:00) We continue our discussion with Boulder scientist and entrepreneur, Larry Gold, about the Gold Lab Symposium on the science of Health, taking place this Thursday and Friday.  You can sign up here. Off-Target Drug Effect (starts 5:48 – ends at 10:00)  A local Boulder man recounts … Continue reading "Gold Lab Symposium and DeepMind/Alphafold"

Genomics is just one branch in the burgeoning field of science informally known as -omics. The data points flowing from various branches of omics can be pieced together to build a sharper picture of how disease takes root and develops. The technology has the potential to deliver new biomarkers for earlier diagnosis of disease, faster and more successful clinical trials, and the ability to predict and prevent disease before it becomes more grievous and costly. In this episode, we talk to Larry Gold, founder of SomaLogic, a company with technology that provides more coverage of the proteome than any other platform. This technology is based on aptamers—nucleic acid molecules that bind to precise targets. Prior to SomaLogic, Gold founded and was chairman of NeXagen, which later became NeXstar Pharmaceuticals. To dive further into this topic, please join Amgen scientists at the DNA Unlocked Q&A webinar discussion on September 8, 2021. Register for this event here: DNA Unlocked Q&A   DNA Unlocked is a special edition podcast series produced by The Scientist's Creative services Team. This series is brought to you by Amgen, which is a pioneer in the science of using living cells to make biologic medicines. They helped invent the processes and tools that built the global biotech industry, and have since reached millions of patients suffering from serious illnesses around the world with their medicines. Since the initial sequencing of the human genome almost twenty years ago, researchers have been enticed by an explosion of DNA data. These sequences hold the promise of understanding human biology, transforming drug research and development, and curing diseases. However, the quest to generate insights from human genetics and -omics research has been full of twists, turns, and roadblocks. In DNA UNLOCKED, Ray Deshaies, senior vice president of Global Research at Amgen, explores the ever-evolving perception of human biology and disease processes thanks to a growing mountain of genetics and omics data. Through discussions with colleagues and other leading research experts, Deshaies unpacks how drug developers decode human genetics to solve some of the most challenging diseases.  

We get a report from last night’s Boulder City Council meeting on plans to revise the city code to further prevent homeless individuals from camping in urban parks. Then, we hear from Boulder health science entrepreneur Larry Gold who says […]

(Entire Show)  Larry Gold, Boulder entrepreneur and scientist, invites listeners to register on line for the 12th annual GoldLab symposium.  Due to COVID, it's a virtual symposium this year, Thursday and Friday, May 13-14.   Extended version coming soon.   Executive Producer: Joel Parker Show Producer & Host: Shelley Schlender

Larry Gold is the founder and former CEO of SomaLogic, a company which aims to revolutionize healthcare by measuring protein biomarkers, allowing for breakthroughs in personalized medicine and the early detection of diseases and risk factors. He first moved to Boulder to be a professor of molecular biology at the University of Colorado in 1971. Larry founded his first company, Synergen, in 1981. Then, in 1989, he and his PhD student, Craig Tuerk, created SELEX, which launched Larry into the biotech world, founding NeXstar in 1992 and SomaLogic in 2000. In 2010, he created the Gold Lab Symposium, an annual event that tackles big questions on healthcare in a human way. Larry is also Emily's father! We talk about his life as a scientist and entrepreneur, the future of personalized medicine, and what books he's reading right now. Larry also discusses alcohol intake, moderation, and how to stay fit while traveling for work. Todd Dorfman Tom Cech SELEX Jax Massimo Catalani Mesa Trail De West Yoga Gold Lab Symposium Craig Mundie 23andMe Ancestry.com The Book of Joy Doing Nothing Jill Blakeway Interview Energy Medicine: The Science and Mystery of Healing Sponsored Promotions: 15 % off at checkout at Haven using the code FINELINE15 Donate to The Fine Line Here --- Support this podcast: https://anchor.fm/finelinepodcast/support

A bioscience industry pioneer and entrepreneur, Dr. Larry Gold has been involved in several biotech companies over the years, most recently SomaLogicin Boulder, CO, an organization with the goal of improving the quality of life of every individual by transforming how health is assessed and managed, based on the precise measurement of changes in the body's proteins. In addition to his work as a scientist, Dr. Gold, with the help of his wife and their friends, created Friends School, a top-rated independent school in Boulder focused on creating life-long learners. On this episode of The Boulderista, we share Larry's journey from Schenectady, NY to Boulder, CO and the meaningful impact he has made on our local and global community. --- Support this podcast: https://anchor.fm/the-boulderista/support

For the last 30 years, Larry Gold has spent most of his working life as the CEO of numerous different hospitals throughout the world. He's helped brand new ones start from scratch and helped struggling ones grow and become huge parts of their communities and at times he's managed over 3000 people. Nowadays he's a consultant to executives who work within healthcare.   This episode is split into two sections: the first 15 minutes is about Covid-19 and how to effectively lead through this and the section after is all about Larry's career, leadership, managing people and building relationships.        Timestamps: [03.20] - The difference between a manager and a leader [06.00] - The three critical leadership components that must be present during times like this [10.59] - What don't you want to do as a leader during times of disaster? [13.34] - Dealing with the uncertainty that Covid has brought everyone [17.02] - Larry sums up his career and tells us what he's doing just now [18.20] - How he got started in healthcare [28.10] - How he's approached growing within each new job he's done [30.45] - How he managed to get 3000+ staff all on the same page working as a CEO in a hospital [36.40] - Why every single person in an organisation needs to know why what they do is important [40.25] - Why he used to walk the halls in his hospital every single day to connect with his employees [43.25] - Why building relationships has been so important to his leadership style [45.05] - How to approach challenging staff situations [46.25] - Giving tough feedback and saying the things that need to be said [52.15] - How he's approached building up his weaknesses [54.52] - Revealing personal aspects of himself to his colleagues and employees [62.25] - Making the whole community proud of his hospital and what you can learn from it [66.28] - What he wishes he could go back tell his younger self   Find Out More About Larry: LinkedIn Profile   Find Out More About LTB: Website Instagram Facebook

DJ and owner of Unique Musique, Larry Gold, joins the podcast today to talk about these 4C's: From Poly-Sci to DJ extraordinaire, The DJ Business, Saturday Night Fever, and we do a Disco Quiz. Poor Neil. 

Philadelphia native Larry Gold has worked on countless hits over the past four decades. He was a member of MFSB, helping shape “The Sound of Philadelphia" via classic recordings on Philadelphia International. By the late ’90s, Gold was the go-to string arranger of the modern R&B and hip-hop era, working with the likes Brandy & Monica, the Roots, Erykah Badu and Kanye West. Here, Gold discusses learning and making music in Philadelphia, creating emotional depth with string arrangements and more.

Chasing New Horizons  (starts 1:00) brings the reader Inside the Epic First Mission to Pluto to  hear the details and meet the personalities behind building, launching, and flying this audacious mission.  How on Earth's Joel Parker (also an astrophysicist on the New Horizons mission) speaks with authors and fellow scientists Alan Stern and David Grinspoon. (Booktalks at Boulder Bookstore and Tattered Cover). You can also listen to the full extended interview. GoldLab Symposium (starts 13:00) This year's symposium theme is Complexity:  The Intersections Between Health and Policy. Boulder Entrepreneur and symposium founder Larry Gold speaks with How on Earth's Shelley Schlender about this year's annual symposium that explores the frontiers of science and health with an eye toward ideas that will inspire even the greatest world expert, with an ear toward being understandable to anyone in the room. Host/Producer/Engineer:  Shelley Schlender Add'l Contributions/Executive Producer: Joel Parker

Tracklist : -Craig David feat. Mos Def & Nate Dogg : Seven days (Dj Premier remix) (2000) -Bobby Brown : Every little step (1988) -TLC : Girl talk (2002) -Mariah Carey : My all (1997) -Aaliyah : I care 4 u (2001) -Ashanti : Leaving (Always on time, Part II) (2002) -Jennifer Lopez : Baby, I love u (2002) -Christina Milian feat. Young Jeezy : Say I (2006) -Mary J. Blige feat. Jay-Z : Can’t hide from luv (2005) -112 : Dance with me (2001) -SWV feat. Puff Daddy : Someone (1997) -Mis-Teeq : B with me (2001) -Whitney Houston : Whatchulookinat (2002) -Jonell feat. Method Man : Round and round (remix) (2001) -Larry Gold presents Don Cello feat. Gerald Levert : Dance (2003)

Voilà maintenant quinze ans que Justin Timberlake a sorti cet album hybride de pop et de R’n’B, produit par The Neptunes et Timbaland à leur pic de créativité, qui se réinventent après le son épuré et bouncy de la fin des années 90. Malgré sa cible très mainstream, Justify n’est pas un album facile, mais à l’inverse, assume des vrais partis pris, très modernes pour l’époque, avec une fibre très hip-hop héritée de la large culture rap de Justin Timberlake et de ses envies d’expérimentations dans la pop. Sans jamais parler d’amour ou de sexe, l’album slalome avec légèreté entre flirt, innocence, séduction, parade, et rupture (avec Britney en l’occurrence). Des thématiques estivales, pour un album de saison qui n’a pas vieilli.Podcast animé par Mehdi Maïzi avec Raphaël Da Cruz, Aurélien Chapuis, Nicolas Pellion et Brice Bossavie RÉFÉRENCES CITÉES DANS L’ÉMISSION Justified (Justin Timberlake, 2002), NSYNC, Backstreet Boys, Johnny Cash, Al Green, Earth Wind and Fire, Gone (N’Sync, Celebrity, 2001), Stevie Wonder, Pharrell Williams, Surrounded By Idiots (Timbaland, Pharrell Williams, Magoo), Larry Gold, N.E.R.D, FutureSex/LoveSounds (Justin Timberlake, 2006), The 20/20 Experience (Justin Timberlake, 2013), Max Martin, Clipse, Bubba Sparxxx, LL Cool J, DJ Paul, Three 6 Mafia, CRÉDITSEnregistré le 4 juillet 2017 à l’Antenne Paris (10, rue la Vacquerie 11ème). Production : Binge Audio. Direction de production : Joël Ronez. Chargé de production et d’édition : Camille Regache. Direction générale : Gabrielle Boeri-Charles. Moyens techniques : Binge Audio / L’Antenne Paris. Réalisation : Sébastien Salis. Générique : extrait de "Tyra Banks" de Nodey (Atrahasis EP) par Nodey. NoFun est une production du réseau Binge Audio www.binge.audioPOUR ASSISTER AUX ENREGISTREMENTSPour assister à notre prochain enregistrement en public à L'Antenne Paris, rendez-vous sur notre page bingeaudio.eventbrite.com See acast.com/privacy for privacy and opt-out information.

((Starts 00:00)) Today we speak with Larry Gold, founder of the GoldLab Symposium that brings scientists and thinkers from around the world to share their perspectives about health and healthcare.  The theme of this year’s symposium is: Standing Together—Health Care for Our Common Good Host / Producer / Engineer: Shelley Schlender Executive Producer: Shelley Schlender

  GOLD LAB SYMPOSIUM (start time: 4:26) We talk with Larry Gold, Founder of the Gold Lab Symposium, about this Friday/Saturday, free symposium at CU Boulder.  (check the website for previous talks, or to register for this weekend's seminar).             MAPPING CHRONIC PAIN   (start time: 15:56)  We visit a Chronic Pain Support group led by Boulder therapist Charles Horowitz, and we talk about "mapping pain" with Harvard Scientist Clas Linnman and CU-Boulder Scientist Tor Wager, who are uncovering new techniques for mapping pain in the brain that are helping to validate chronic pain and might someday guide better treatment.     HEADLINES   (start time: 1:00)  Bats use "telephoto" sound, new pathway for blocking malaria, Fiske Planetarium Events, CU Boulder Tree Walk, Intel Science Finalist from Boulder's Fairview High. Hosts: Beth Bennett, Kendra Krueger Producer: Shelley Schlender Engineer: Shelley Schlender Executive Producer: Susan Moran Headline contributions: Daniel Strain, Beth Bennet  

We review last Saturday's Draft which Scott and Mike both participated in. Here's the Draft Board.  Tonight's Special Guests: It's The Expert vs The Executive!  Larry Gold @TwoRedDucks and Corey Parson @FantasyExec  We pit them in 1 on 1 confrontations where each must represent a side in our new game show Yes Please or No Thanks Josh Gordon - Is he draftable now?  Question: He wasn't drafted in this draft, however he was drafted last night in the 8th round. Yes Please or No Thanks Rueben Randle - Were we a year too early on the kid? He's entering pivotal year three. Might he be undervalued right now? Question: Mike Drafted this guy at 7.12. Yes Please or No Thanks Ben Tate - So the kid has always had potential and he had to sit behind Arian Foster. Now he has a starting job and all of a sudden, he's garbage and yesterday's news? 6.5 - Yes Please or No Thanks To take a TE early or Not? - Last night, Scott drafted in a high roller league and took Julius Thomas in the 3rd and came back and grabbed Bishop Sankey in the 5th. Looking back he could have had Andre Ellington in the 3rd and Jordan Cameron in the 5th. Juilius and Sankey Yes Please or No Thanks Should Sammy Watkins (a rookie) be drafted BEFORE Golden Tate? Last night he was, but what do you say? Yes Please or No Thanks Draft tonight in a $35 Scout Draft-Only! 10pm EDT

Join Scott Atkins & Michael Trent as their joined by the FFWC Commissioner Emil Kadlec who will announce draft slots for the Fantasy Football World Championship III.  We'll discuss various draft strategies with the pros at Scout Fantasy like Dr. Roto, Larry Gold, Micah James and more...  Tune in tomorrow night, 9pm EDT. Show may go over the 1 hour limit as we announce the draft slots for all the teams paid in full. 

Dr. Ames is a Senior Scientist at Children's Hospital Oakland Research Institute, director of their Nutrition & Metabolism Center, and a Professor Emeritus of Biochemistry and Molecular Biology, at the University of California, Berkeley. Rhonda Patrick has a Ph.D. in biomedical science. Dr. Patrick is currently a postdoctoral fellow at Children's Hospital Oakland Research Institute with Dr. Ames. Bruce Ames Sr Scientist at CHORI, and Prof Emeritus of Biochem and Molecular Bio, at UC Berkeley. Rhonda Patrick Ph.D. biomedical science, postdoc at CHORI in Dr. Ames lab. The effects of micronutrients on metabolism, inflammation, DNA damage, and aging.TranscriptSpeaker 1: Spectrum's next. Speaker 2: Mm mm mm Speaker 3: [inaudible].Speaker 1: Welcome to spectrum the science and technology show on k a l x [00:00:30] Berkeley, a biweekly 30 minute program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news [inaudible]. Speaker 4: Good afternoon. My name is Rick Karnofsky. I'm the host of today's show. This week on spectrum we present part one of a two part interview with our guests, Bruce Ames and Rhonda Patrick. Dr Ames is a senior scientist at Children's Hospital, [00:01:00] Oakland Research Institute, director of their nutrition and metabolism center and a professor Ameritas of biochemistry and molecular biology at UC Berkeley. Rhonda Patrick has a phd in biomedical science. Dr. Patrick is currently a postdoctoral fellow at Children's Hospital, Oakland Research Institute in Dr Ames. His lab, she currently conducts clinical trials looking at the effects of [00:01:30] micronutrients on metabolism, inflammation, DNA damage and aging. Here's Brad swift and interviewing doctors, aims and Patrick Bruce Speaker 5: Ames and Rhonda Patrick, welcome to spectrum. Thank you very much. Sue, can you help us understand the term micronutrient and briefly explain what they do? Sure. Speaker 6: About 40 substances you need in your diet and [00:02:00] you get it from eating a really well balanced style, get them more about eight or 10 of them are essential amino acids. So they're required for making your all your protein. And then there are about 30 vitamins and minerals, roughly 15 minerals in 15 five minutes. So you need the minerals, you need iron and zinc and calcium and magnesium and all these things, you know, and the vitamins [00:02:30] and minerals are coenzymes. So you have 20,000 genes in your body that make proteins, which are enzymes that do bio or Kimiko transformations. And some of them require coenzymes, maybe a quarter of them. So some require magnesium and they don't work unless there's a magnesium attached to the particular pace in the enzyme. And some of them require vitamin B six which is something called [00:03:00] paradoxal, goes through a coenzyme paradox of phosphate. Speaker 6: And that's an a few hundred and enzymes and they make your neurotransmitters and other things. And if you don't get any one of these 40 substances, you'd die. But how much we need is, I think there's a lot of guesswork in there and we have a new idea I can talk about later that shakes a lot up puppet. And so when your research, you're trying to measure these [00:03:30] micronutrients obviously, well people can measure them in various ways. Somebody can just measure in blood and say, ah, you have enough vitamin D or you don't have enough vitamin D. But some, for example, calcium and magnesium marine, your bones, but they're also used for all kinds of enzymes and if you get low, the tissue might get low, but you keep your plasma up because you're taking it out of the bone. So just measuring [00:04:00] plasma isn't useful in that case. Speaker 6: But anyway, there, uh, each one is a little different. Do you want to talk about the triage theory? Okay, I could talk to about that. Now. Some years ago we kept on finding when we had human cells in culture or mice, that when we left out various vitamins and minerals or didn't have enough, we got DNA damage. I'm an expert in DNA damage and we're interested in how [00:04:30] to prevent DNA damage. We sat leads to cancer and so I kept on wondering why is nature doing this when you're not getting enough of magnesium or iron or zinc, you getting DNA damage and then one day it hit me. I, that's just what nature wants to do. Through all of evolution, we'd been running out of vitamins and minerals. The minerals aren't spread evenly through the soil. The red soils with a lot of iron and the souls that have very little iron. Speaker 6: [00:05:00] Selenium is a required mineral, but there's soils with too much saline and we get poisoned. And then the areas where it, you don't have enough selenium so you get poisoned. So it's a little tricky. Back in 2006 I had this idea that nature must do a rationing when you start getting low on any vitamin or mineral, and how would you ration it? The proteins that are essential for survival get it first and the ones that are preventing [00:05:30] some insidious damage that shows up as cancer in 10 years or calcification in the arteries. That's the [inaudible] papers, those proteins lucid. And I call this triage ship. It's a French word for dividing up those wounded soldiers that the doctors can make a difference on. So anyway, I publish this with what data? That wasn't the literature, but it wasn't completely satisfactory. We didn't, hadn't really nailed it, but it was an idea. Speaker 6: And then Joyce McCain [00:06:00] in my lab wrote two beautiful reviews, one on selenium and one on vitaminK , and they both fit beautifully. And people who work in these fields had shown that the clotting factors get it first because you don't get your blood clotting and you cut yourself every week or two, you'd just bleed to death. But the price you pay is you don't make the protein that prevents calcification of the arteries so [00:06:30] people can die of calcification the arteries. But that takes 10 years. So when nature has to face keeping alive now so you can reproduce or you're getting calcification arteries in 10 years, it does this tradeoff. And also you don't have enough vitamin K. My ptosis doesn't work quite as accurately. So you'll lose the chromosome here or there and you get cancer in 10 years. But again, it's the trade off between short term survival and longterm health. Speaker 6: It all [00:07:00] makes perfect sense. It was a very plausible theory. That's why I came out with it. But it's true for vitaminK and the mechanism used in vitaminK is different than the mechanism and sleeping. So each system has developed a different mechanism for doing this racially. And so that changes our view of vitamins and minerals base. You're paying a price every time. You're a little low on one with them. So it's the disease of aging. So basically when you should have any vitamin or mineral, [00:07:30] it accelerates your aging in some way. You can accelerate some kind of insidious damage. And we're talking about huge numbers of people. 70% of the population is low in vitamin D and we're talking about magnesium, what we said the third 45% 45% these are big numbers and they're cheap boldly saying Speaker 7: [inaudible]Speaker 8: [00:08:00] you are listening to spectrum on a l x, Berkeley. Today's guests are Dr. Bruce Ames and Dr Rhonda Patrick Speaker 9: with the micronutrients and the activity of DNA, RNA. Talk about the effect there, the impact, is there more to talk about that? Absolutely. So there are many different micronutrients [00:08:30] that are required for functions in your body that involve DNA replication involved DNA repair, preventing DNA damage. Things are all very important because we're making 100 billion new cells every day to make a new cell, we have to replicate the entire genome of that cell to make the daughter cell. And that requires a whole holster of enzymes. So if you don't have enough magnesium for those DNA polymerase to work properly, when ends up happening is that their fidelity is [00:09:00] lessen, meaning they don't work as well and they're gonna likely make more errors in that DNA replication that they're performing. And if they can't repair that error, then when ends up happening is that you can get every rotation and depending on whether that mutation has any functional consequences, sort of random, but the more times as occurs, then the more chances you're having of getting a mutation that can, you know, something that's not good and can either cause cell death or it can also [00:09:30] be something that causes dysregulation of the way your genes are expressed. Speaker 9: So it's very important to make sure you have the right co factors such as magnesium for DNA replication, also in your mitochondria and your mitochondrial DNA. When you make new Mitochondria, this is called mitochondrial biogenesis. It's an important mechanism to boost the number of mitochondria per cell. And this can occur during things like exercise when your mitochondria also have their own genome and they have to replicate this genome. Well guess what? Those mitochondrial [00:10:00] DNA were preliminaries. This also require magnesium. And so if there's not enough magnesium around, you're not making your mitochondria as optimal as you could be in Mitochondria. Play an important role in every single process in your body, including, you know, neuronal function. So that's really important to make sure that your Mitochondria Hobby. Also, this is very relevant for things like aging. These micronutrients like vitamin D gets converted into a steroid hormone that regulates the expression of over a thousand genes in [00:10:30] your body and some of those genes are involved in DNA repair and also in preventing DNA damage. So these micronutrients are extremely important for a variety of different physiological properties that are going on in your body every single day. Things that you can't see when you look in the mirror, we're talking about something that's not an acute deficiency that's going to lead to a clinical symptom like scurvy. Speaker 6: We think bad nutrition is the main thing, accelerating all these degenerative diseases of aging and contributing to these huge medical costs and [00:11:00] all of that. And it's something you can do something about because they're all very cheap minerals that are cheap. So the sourcing of the minerals and vitamins, it's not crucial at this point you think? I don't think so. Yeah. Getting them is the the really the key factor think and I think to really reform people's diet, we're going to need the numbers and we're working to try and show that there's some vulnerable protein that goes first when you're short of McNeese. I [00:11:30] mean you should measure that and then you'll know you're not getting enough and all the consequences or you're disabling all your DNA repair fronts. I'm so whatever. Speaker 9: It is ideal to try and get as many of these micronutrients essential vitamins and minerals that you can from your diet. For example, I personally make a smoothie for breakfast every morning, which consists of Kale, spinach, Swiss carrots, tomato, avocado, berries, and I'm getting a broad spectrum of vegetables and fruits [00:12:00] just from that one smoothie. And I think in addition to these essential vitamins and minerals that we know are in these various plants and fruits, I think there's also a lot of micronutrients in there that we have yet to discover that also may be doing important things. However, it's extremely difficult for people to get all of these micronutrients from their diet. And I think in that instance, supplementation can help fill those nutritional gaps. And we've actually shown that Speaker 6: in general, people in nutrition don't like the idea of pills, but people [00:12:30] are learning about all this. But you shouldn't overdo it. Mae West said too much of a good thing is wonderful, but she was saying about sex, not micronutrients, and particularly for minerals in minerals, there's a sweet spot. Too much can hurt you into little canary, Speaker 5: and that's what you're hoping these next generation devices would help people understand where they are situated within, right? The class of vitamins and minerals. What are they up in? What are they down? Speaker 6: So this may be a decades [00:13:00] worth of science to do this, but we're trying to frame the ideas and say, look, this is where we're going. And it isn't drugs that are gonna help you. It's getting your diet tuned up, your metabolism [inaudible] Speaker 9: your doctor can look at a few different nutrients and vitamin D is one test that they do. But there's a couple of companies that are out there right now such as something called wellness effects. They're measuring a variety of different micronutrients in people's blood, including omega [00:13:30] three fatty acids, vitamin D, magnesium, potassium, calcium. So looking at all these different vitamins and minerals and people are quantifying. It's called the quantified self movement where people are getting their vitamins and minerals and essential fatty acids measured. They're making dietary changes. If they find out they're low in vitamin D or they're low in mega three or they have low magnesium, they're making dietary changes and then about three months later they go back and they'd quantify the levels again so they can physically measure and quantify this, this change that they're making in their diet. And I think really that's the direction [00:14:00] to go. Speaker 6: Yeah, and analytical methods of Guinea. So wonderful that you can do it on a finger prick of blood. I have two entrepreneurs, scientist friends. One of them has put a machine in every hospital in China and he measures couple of dozen proteins of medical importance and the Chinese are subsidizing this. They think it's going to save money. And another friend of mine from Boulder, first one is built routed. The second one is Larry Gold. And he developed [00:14:30] an alternative to monoclonal antibodies and he can measure 1500 different proteins in one fingerprint compliant. I mean, it's fantastic and he's working to get them all right now it's a discovery system, but we're going to discover what protein tells you. You're low in magnesium and what protein tells you you're low in vitaminK or protein tells you low in paradox and then it's all going to go to your iPhone and you'll get the diagnosis. Speaker 6: We'll cut out the doctors [00:15:00] because they don't know much about Olis anyway, and they're too expensive. So it's not drugs you need for all of this. It's tuning up limit tap of the drugs that youthful. I'm not saying that not and for some things that are absolutely essential, but this area of getting your metabolism tuned up, see, people are worried about a pot Papillion a pesticide and it's all irrelevant. We, we published a hundred papers on that in that era, just saying, look, it's all a distraction from the important thing and important thing [00:15:30] is all these bad diets where eating and obesity isn't just calories in, exercise out a beach. People are starving and what this starving for vitamins and minerals because they're eating sugar and carbohydrate and every possible disease of aging is accelerated and hippies and plus huge costs, years of expensive diabetes and heart disease and cancer, you name it, it's been linked to obesity. So I think it's a big [00:16:00] opportunity to tune people up. Speaker 8: Spectrum is a public affairs show on k a l x Berkeley [00:16:30] is this part one of a two part interview with Bruce Ames and Rhonda Patrick. Speaker 9: So Rhonda, the recent paper you published on vitamin D explain that. So vitamin D gets converted into a steroid hormone in your body and the steroid hormone can regulate this expression [00:17:00] of between 900 and a thousand different genes. And the way it does that is that there's a little telltale sequence in your gene and it's basically a six nucleotide sequence repeat that's separated by three nucleotides. And this nucleotide sequence itself can determine whether or not vitamin D will turn on a gene or turn off aging. And so vitamin D can do both of these where it turns on genes and turns off genes. Well, what we found is that there's two different genes that encode for Tryptophan hydroxylase, [00:17:30] which is the rate limiting enzyme that converts trip to fan into Serotonin. There's one that's in the brain called Tryptophan hydroxylase too, and there's one that's outside of the blood brain barrier in tissues like Mosley got also in your t cells and your Peniel gland and placenta tissue if you're woman, and this is called Tryptophan hydroxylase one and what we found is that both of these genes have what's called a vitamin D response element that tell a sequence I was telling you about. Speaker 9: However, they had [00:18:00] completely opposite vitamin D response elements. One, the one in your brain had an activation sequence turn on and the one in the gut had a repression sequence. The turnoff sequence, which suggested that vitamin D hormone was controlling the expression of these two different genes in opposite directions. Vitamin D's important to turn on Tryptophan hydroxylase and two and your brain so you can make serotonin and it's important to turn it off and your gut to blunt the production of Serotonin in your gut. Serotonin in your gut. Too Much of it causes GI inflammation. [00:18:30] This was a really cool finding because there was a recent paper where they found that autistic individuals, 90% of them had some abnormal tryptophan metabolism and they didn't really identify what it was, but sort of like an Aha moment where it was like trick to fan metabolism. Well, chuck did fan, you need to make Serotonin, and so I started doing some reading and sure enough, there's a whole literature connecting Serotonin to autism. Speaker 9: Serotonin is made in your brain. It's an important neurotransmitter, but during early, early brain development, [00:19:00] it is a brain morphogenic meaning it actually is a growth factor that guides the neuronal proliferation, the development, the migration of neurons to different regions in the brain. It plays an essential role in shaping the structure and the wiring of the early developing brain. And so not having enough serotonin in early, early brain development in Utero can lead to very aberrant brain morphological and functional consequences. You know, this was kind of like, wow, well what if you're not getting enough vitamin D during that critical [00:19:30] period, which is important to activate that gene that converts Tryptophan into Serotonin? Is it possible then that you wouldn't be making enough serotonin in that early brain and therefore you wouldn't have a normal brain development? Also, the Serotonin in the gut can cause a lot of GI inflammation and also quite a few autistics have high GI inflammation. Speaker 9: Also, they have high levels of Serotonin in their blood. There's something that we call the Serotonin anomaly where they've measured brain levels of Serotonin autistics from SMRI and have also measured blood levels [00:20:00] of Serotonin. And there was sort of this weird dichotomy where autistics had high levels of Serotonin in their blood, but they had low levels in their brain and so it was like, well, why is that? Why would they have high levels in their blood, the low levels in the brain and we think we found a mechanism why if you're low in vitamin D, your vitamin D won't be turning on the one in your brain and you won't be making enough Serotonin in your brain and it won't be repressing the one you've got and you'll be making too much and you've got this sort of a a really cool finding. We also in our paper discuss how estrogen can [00:20:30] activate Tryptofan hydroxylase to in the brain pretty much the same way vitamin D does also a steroid hormone and the sequences, the receptors bind to a somewhat similar under dug out of the literature that people showed. Estrogen can turn Speaker 6: on the Messenger RNA for the brain enzyme making serotonin in girls, but it's not doing it in boys, which explains why five times as many boys get autism as girls. [00:21:00] Anyway, she worked out all this mechanism. We kept on explaining one thing after another render would come in every week, hopping up and down. Look what I found and look what I found and I think she walks on water, but she did this wonderful scholarship, which is a good metaphor, but she used to be a surfing instructor when she was incentive. Speaker 9: It's pretty exciting. It was largely theoretical work where we did find a underlying mechanism to connect these dots. So we're hoping now that people in the field are going to continue on and look even deeper. Speaker 6: So [00:21:30] what we think we know is how to prevent autism. But what we are not sure of is whether you can give vitamin D to people who have autism and help some of the symptoms. Uh, biggest people need to do clinical trials on all of this and they haven't done them right. But now that we have the mechanism, you can do them right. The trouble is drug companies aren't going to make money with vitamin D and they know that. And so [00:22:00] they're trying to develop a new drug. But we're hoping that these biochemicals trip to fain and vitamin D and nowhere to tone and and may get threes, which are all seem to be involved, which you can find out by reading Ramdas paper that that is going to at least give him mechanisms so we can do more focused clinical trials. Speaker 8: [inaudible] [00:22:30] to learn more about the work and Patrick are doing visit their websites, Bruce ames.org and found my fitness.com Speaker 7: oh Speaker 6: papers take a lot of polishing. Basically we're going into all these fields [00:23:00] that we don't know an awful lot about us and that requires a lot of double checking and sending it to experts and getting criticism. Speaker 9: First you have to learn everything and then you'd have to put, make the connections together and then you have to write it and then there's a whole process. It's very, it's a lot of work. Personally, my favorite part of it is the creative part where you just make all the connections and you find things and you start fitting things together and it's like, oh yeah, you know, it's just, it's almost like awesome rush, but then once you've make all those connections and you do that creative work, then you really have to [00:23:30] do all the tedious, hard digging and working diligence. Yes and that it's not as much fun. Then once you have a good theory Speaker 6: you assume no. Is it explaining new things that you didn't expect and right away this idea explains so many things and it was all really lying on the ground and round it just picked it up and put it together. Speaker 9: People like Bruce and I who liked to make those connections. I think that we play an important role in science as well. Like this paper that we published recently, [00:24:00] while we didn't physically do any experiments, we didn't test our theoretical work. We made a very interesting connection with a mechanism for other people to test. And I think that every once in awhile science needs that because there's so much data out there and now with Google we have access to all this data. So I think that taking people that are familiar with the fields and can put things together like pieces of a puzzle, I think that also advanced the science in a very creative way. Speaker 6: Biology's so complicated that there hasn't been much room for people [00:24:30] who just sit in their office and do theoretical work. And we do a lot of experimental work in lab and Rhonda is carrying on an experimental problem while she's doing all this. But I like to get it in between fields. I was always half a geneticist and half a biochemist and it was wonderful because I saw all these problems. The geneticists turned up and the biochemists didn't know existed and the geneticists didn't know how to tackle this was before Watson and crick and all of that. Uh, I'm pretty [00:25:00] old anyway. I think science is so competitive, but if you know two fields in this an interface, you have a big advantage on everybody else and we like to have people in the lab with many different expertise and put things together. Speaker 10: [inaudible]Speaker 4: you can tune into the rest of Brad's interview with Bruce Ames and Rhonda Patrick [00:25:30] two weeks from now. Speaker 7: [inaudible]Speaker 4: irregular feature of spectrum is a calendar of the science and technology related events happening in the bay area over the next two weeks. On Thursday, July 10th the bay area skeptics will host a free lecture by Glenn Branch. The deputy director of the National Center for Science Education Branch will present untold stories from the scopes trial. [00:26:00] If you thought that you knew everything about the scopes monkey trial. Thank you again to commemorate the 89th anniversary of this seminal episode in the long contentious history of evolution. Education in the United States branch will tell the story of the scopes trial as it has never been told before. Focusing on obscure under appreciated and amusing details. The event will be at the La Pena Cultural Center, three one zero five Shattuck avenue in Berkeley [00:26:30] and it will start@seventhirtypleasevisitwwwdotbaskeptics.org for more info and here's the new story we think you'll find interesting in a paper published in nature neuroscience on June eight University of Minnesota researchers at B Steiner and a David Reddish report that they have made behavioral and neuro physiological observations of regret [00:27:00] in rats to regret is to recognize that taking an alternative action would have produced a more valued outcome than the action one took. Speaker 4: The research team created a circular runway with four spokes and feeding machines at the end of each spoke that contained different flavors of food pellets. The feeding was preceded by a tone that indicated how long the rat would wait at a particular machine for food if the rat left one of these restaurants with waiting time below [00:27:30] its threshold only. Do you find an even longer waiting time at the next spoke? The team hypothesized that the rat may regret the choice. Indeed, the rats that fit this description were more likely than control rats to look toward the spoke. They just left and electrodes indicated that neurons in the orbital frontal cortex fired at the same time. Science news talk to cold Spring Harbor Neuro scientist Alex Vaughan about the paper. He [00:28:00] said, the researchers did a great job of designing a task that can discriminate between the regret of making a poor decision and the disappointment that results when one is punished despite making all the right choices. Speaker 8: [inaudible] spectrum shows are archived on iTunes university. [00:28:30] We have created a symbolic for you. The link is tiny, url.com/calix spectrum. Speaker 7: Oh Speaker 3: [inaudible]. The music [00:29:00] heard during the show was written and produced by Alex diamond. Thank you for listening to spectrum. If you have comments about the show, please send them to us via email. Email address is Doug KLX. Hey, young com. Speaker 8: [inaudible]. Hosted on Acast. See acast.com/privacy for more information.

Dr. Ames is a Senior Scientist at Children’s Hospital Oakland Research Institute, director of their Nutrition & Metabolism Center, and a Professor Emeritus of Biochemistry and Molecular Biology, at the University of California, Berkeley. Rhonda Patrick has a Ph.D. in biomedical science. Dr. Patrick is currently a postdoctoral fellow at Children’s Hospital Oakland Research Institute with Dr. Ames. Bruce Ames Sr Scientist at CHORI, and Prof Emeritus of Biochem and Molecular Bio, at UC Berkeley. Rhonda Patrick Ph.D. biomedical science, postdoc at CHORI in Dr. Ames lab. The effects of micronutrients on metabolism, inflammation, DNA damage, and aging.TranscriptSpeaker 1: Spectrum's next. Speaker 2: Mm mm mm Speaker 3: [inaudible].Speaker 1: Welcome to spectrum the science and technology show on k a l x [00:00:30] Berkeley, a biweekly 30 minute program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news [inaudible]. Speaker 4: Good afternoon. My name is Rick Karnofsky. I'm the host of today's show. This week on spectrum we present part one of a two part interview with our guests, Bruce Ames and Rhonda Patrick. Dr Ames is a senior scientist at Children's Hospital, [00:01:00] Oakland Research Institute, director of their nutrition and metabolism center and a professor Ameritas of biochemistry and molecular biology at UC Berkeley. Rhonda Patrick has a phd in biomedical science. Dr. Patrick is currently a postdoctoral fellow at Children's Hospital, Oakland Research Institute in Dr Ames. His lab, she currently conducts clinical trials looking at the effects of [00:01:30] micronutrients on metabolism, inflammation, DNA damage and aging. Here's Brad swift and interviewing doctors, aims and Patrick Bruce Speaker 5: Ames and Rhonda Patrick, welcome to spectrum. Thank you very much. Sue, can you help us understand the term micronutrient and briefly explain what they do? Sure. Speaker 6: About 40 substances you need in your diet and [00:02:00] you get it from eating a really well balanced style, get them more about eight or 10 of them are essential amino acids. So they're required for making your all your protein. And then there are about 30 vitamins and minerals, roughly 15 minerals in 15 five minutes. So you need the minerals, you need iron and zinc and calcium and magnesium and all these things, you know, and the vitamins [00:02:30] and minerals are coenzymes. So you have 20,000 genes in your body that make proteins, which are enzymes that do bio or Kimiko transformations. And some of them require coenzymes, maybe a quarter of them. So some require magnesium and they don't work unless there's a magnesium attached to the particular pace in the enzyme. And some of them require vitamin B six which is something called [00:03:00] paradoxal, goes through a coenzyme paradox of phosphate. Speaker 6: And that's an a few hundred and enzymes and they make your neurotransmitters and other things. And if you don't get any one of these 40 substances, you'd die. But how much we need is, I think there's a lot of guesswork in there and we have a new idea I can talk about later that shakes a lot up puppet. And so when your research, you're trying to measure these [00:03:30] micronutrients obviously, well people can measure them in various ways. Somebody can just measure in blood and say, ah, you have enough vitamin D or you don't have enough vitamin D. But some, for example, calcium and magnesium marine, your bones, but they're also used for all kinds of enzymes and if you get low, the tissue might get low, but you keep your plasma up because you're taking it out of the bone. So just measuring [00:04:00] plasma isn't useful in that case. Speaker 6: But anyway, there, uh, each one is a little different. Do you want to talk about the triage theory? Okay, I could talk to about that. Now. Some years ago we kept on finding when we had human cells in culture or mice, that when we left out various vitamins and minerals or didn't have enough, we got DNA damage. I'm an expert in DNA damage and we're interested in how [00:04:30] to prevent DNA damage. We sat leads to cancer and so I kept on wondering why is nature doing this when you're not getting enough of magnesium or iron or zinc, you getting DNA damage and then one day it hit me. I, that's just what nature wants to do. Through all of evolution, we'd been running out of vitamins and minerals. The minerals aren't spread evenly through the soil. The red soils with a lot of iron and the souls that have very little iron. Speaker 6: [00:05:00] Selenium is a required mineral, but there's soils with too much saline and we get poisoned. And then the areas where it, you don't have enough selenium so you get poisoned. So it's a little tricky. Back in 2006 I had this idea that nature must do a rationing when you start getting low on any vitamin or mineral, and how would you ration it? The proteins that are essential for survival get it first and the ones that are preventing [00:05:30] some insidious damage that shows up as cancer in 10 years or calcification in the arteries. That's the [inaudible] papers, those proteins lucid. And I call this triage ship. It's a French word for dividing up those wounded soldiers that the doctors can make a difference on. So anyway, I publish this with what data? That wasn't the literature, but it wasn't completely satisfactory. We didn't, hadn't really nailed it, but it was an idea. Speaker 6: And then Joyce McCain [00:06:00] in my lab wrote two beautiful reviews, one on selenium and one on vitaminK , and they both fit beautifully. And people who work in these fields had shown that the clotting factors get it first because you don't get your blood clotting and you cut yourself every week or two, you'd just bleed to death. But the price you pay is you don't make the protein that prevents calcification of the arteries so [00:06:30] people can die of calcification the arteries. But that takes 10 years. So when nature has to face keeping alive now so you can reproduce or you're getting calcification arteries in 10 years, it does this tradeoff. And also you don't have enough vitamin K. My ptosis doesn't work quite as accurately. So you'll lose the chromosome here or there and you get cancer in 10 years. But again, it's the trade off between short term survival and longterm health. Speaker 6: It all [00:07:00] makes perfect sense. It was a very plausible theory. That's why I came out with it. But it's true for vitaminK and the mechanism used in vitaminK is different than the mechanism and sleeping. So each system has developed a different mechanism for doing this racially. And so that changes our view of vitamins and minerals base. You're paying a price every time. You're a little low on one with them. So it's the disease of aging. So basically when you should have any vitamin or mineral, [00:07:30] it accelerates your aging in some way. You can accelerate some kind of insidious damage. And we're talking about huge numbers of people. 70% of the population is low in vitamin D and we're talking about magnesium, what we said the third 45% 45% these are big numbers and they're cheap boldly saying Speaker 7: [inaudible]Speaker 8: [00:08:00] you are listening to spectrum on a l x, Berkeley. Today's guests are Dr. Bruce Ames and Dr Rhonda Patrick Speaker 9: with the micronutrients and the activity of DNA, RNA. Talk about the effect there, the impact, is there more to talk about that? Absolutely. So there are many different micronutrients [00:08:30] that are required for functions in your body that involve DNA replication involved DNA repair, preventing DNA damage. Things are all very important because we're making 100 billion new cells every day to make a new cell, we have to replicate the entire genome of that cell to make the daughter cell. And that requires a whole holster of enzymes. So if you don't have enough magnesium for those DNA polymerase to work properly, when ends up happening is that their fidelity is [00:09:00] lessen, meaning they don't work as well and they're gonna likely make more errors in that DNA replication that they're performing. And if they can't repair that error, then when ends up happening is that you can get every rotation and depending on whether that mutation has any functional consequences, sort of random, but the more times as occurs, then the more chances you're having of getting a mutation that can, you know, something that's not good and can either cause cell death or it can also [00:09:30] be something that causes dysregulation of the way your genes are expressed. Speaker 9: So it's very important to make sure you have the right co factors such as magnesium for DNA replication, also in your mitochondria and your mitochondrial DNA. When you make new Mitochondria, this is called mitochondrial biogenesis. It's an important mechanism to boost the number of mitochondria per cell. And this can occur during things like exercise when your mitochondria also have their own genome and they have to replicate this genome. Well guess what? Those mitochondrial [00:10:00] DNA were preliminaries. This also require magnesium. And so if there's not enough magnesium around, you're not making your mitochondria as optimal as you could be in Mitochondria. Play an important role in every single process in your body, including, you know, neuronal function. So that's really important to make sure that your Mitochondria Hobby. Also, this is very relevant for things like aging. These micronutrients like vitamin D gets converted into a steroid hormone that regulates the expression of over a thousand genes in [00:10:30] your body and some of those genes are involved in DNA repair and also in preventing DNA damage. So these micronutrients are extremely important for a variety of different physiological properties that are going on in your body every single day. Things that you can't see when you look in the mirror, we're talking about something that's not an acute deficiency that's going to lead to a clinical symptom like scurvy. Speaker 6: We think bad nutrition is the main thing, accelerating all these degenerative diseases of aging and contributing to these huge medical costs and [00:11:00] all of that. And it's something you can do something about because they're all very cheap minerals that are cheap. So the sourcing of the minerals and vitamins, it's not crucial at this point you think? I don't think so. Yeah. Getting them is the the really the key factor think and I think to really reform people's diet, we're going to need the numbers and we're working to try and show that there's some vulnerable protein that goes first when you're short of McNeese. I [00:11:30] mean you should measure that and then you'll know you're not getting enough and all the consequences or you're disabling all your DNA repair fronts. I'm so whatever. Speaker 9: It is ideal to try and get as many of these micronutrients essential vitamins and minerals that you can from your diet. For example, I personally make a smoothie for breakfast every morning, which consists of Kale, spinach, Swiss carrots, tomato, avocado, berries, and I'm getting a broad spectrum of vegetables and fruits [00:12:00] just from that one smoothie. And I think in addition to these essential vitamins and minerals that we know are in these various plants and fruits, I think there's also a lot of micronutrients in there that we have yet to discover that also may be doing important things. However, it's extremely difficult for people to get all of these micronutrients from their diet. And I think in that instance, supplementation can help fill those nutritional gaps. And we've actually shown that Speaker 6: in general, people in nutrition don't like the idea of pills, but people [00:12:30] are learning about all this. But you shouldn't overdo it. Mae West said too much of a good thing is wonderful, but she was saying about sex, not micronutrients, and particularly for minerals in minerals, there's a sweet spot. Too much can hurt you into little canary, Speaker 5: and that's what you're hoping these next generation devices would help people understand where they are situated within, right? The class of vitamins and minerals. What are they up in? What are they down? Speaker 6: So this may be a decades [00:13:00] worth of science to do this, but we're trying to frame the ideas and say, look, this is where we're going. And it isn't drugs that are gonna help you. It's getting your diet tuned up, your metabolism [inaudible] Speaker 9: your doctor can look at a few different nutrients and vitamin D is one test that they do. But there's a couple of companies that are out there right now such as something called wellness effects. They're measuring a variety of different micronutrients in people's blood, including omega [00:13:30] three fatty acids, vitamin D, magnesium, potassium, calcium. So looking at all these different vitamins and minerals and people are quantifying. It's called the quantified self movement where people are getting their vitamins and minerals and essential fatty acids measured. They're making dietary changes. If they find out they're low in vitamin D or they're low in mega three or they have low magnesium, they're making dietary changes and then about three months later they go back and they'd quantify the levels again so they can physically measure and quantify this, this change that they're making in their diet. And I think really that's the direction [00:14:00] to go. Speaker 6: Yeah, and analytical methods of Guinea. So wonderful that you can do it on a finger prick of blood. I have two entrepreneurs, scientist friends. One of them has put a machine in every hospital in China and he measures couple of dozen proteins of medical importance and the Chinese are subsidizing this. They think it's going to save money. And another friend of mine from Boulder, first one is built routed. The second one is Larry Gold. And he developed [00:14:30] an alternative to monoclonal antibodies and he can measure 1500 different proteins in one fingerprint compliant. I mean, it's fantastic and he's working to get them all right now it's a discovery system, but we're going to discover what protein tells you. You're low in magnesium and what protein tells you you're low in vitaminK or protein tells you low in paradox and then it's all going to go to your iPhone and you'll get the diagnosis. Speaker 6: We'll cut out the doctors [00:15:00] because they don't know much about Olis anyway, and they're too expensive. So it's not drugs you need for all of this. It's tuning up limit tap of the drugs that youthful. I'm not saying that not and for some things that are absolutely essential, but this area of getting your metabolism tuned up, see, people are worried about a pot Papillion a pesticide and it's all irrelevant. We, we published a hundred papers on that in that era, just saying, look, it's all a distraction from the important thing and important thing [00:15:30] is all these bad diets where eating and obesity isn't just calories in, exercise out a beach. People are starving and what this starving for vitamins and minerals because they're eating sugar and carbohydrate and every possible disease of aging is accelerated and hippies and plus huge costs, years of expensive diabetes and heart disease and cancer, you name it, it's been linked to obesity. So I think it's a big [00:16:00] opportunity to tune people up. Speaker 8: Spectrum is a public affairs show on k a l x Berkeley [00:16:30] is this part one of a two part interview with Bruce Ames and Rhonda Patrick. Speaker 9: So Rhonda, the recent paper you published on vitamin D explain that. So vitamin D gets converted into a steroid hormone in your body and the steroid hormone can regulate this expression [00:17:00] of between 900 and a thousand different genes. And the way it does that is that there's a little telltale sequence in your gene and it's basically a six nucleotide sequence repeat that's separated by three nucleotides. And this nucleotide sequence itself can determine whether or not vitamin D will turn on a gene or turn off aging. And so vitamin D can do both of these where it turns on genes and turns off genes. Well, what we found is that there's two different genes that encode for Tryptophan hydroxylase, [00:17:30] which is the rate limiting enzyme that converts trip to fan into Serotonin. There's one that's in the brain called Tryptophan hydroxylase too, and there's one that's outside of the blood brain barrier in tissues like Mosley got also in your t cells and your Peniel gland and placenta tissue if you're woman, and this is called Tryptophan hydroxylase one and what we found is that both of these genes have what's called a vitamin D response element that tell a sequence I was telling you about. Speaker 9: However, they had [00:18:00] completely opposite vitamin D response elements. One, the one in your brain had an activation sequence turn on and the one in the gut had a repression sequence. The turnoff sequence, which suggested that vitamin D hormone was controlling the expression of these two different genes in opposite directions. Vitamin D's important to turn on Tryptophan hydroxylase and two and your brain so you can make serotonin and it's important to turn it off and your gut to blunt the production of Serotonin in your gut. Serotonin in your gut. Too Much of it causes GI inflammation. [00:18:30] This was a really cool finding because there was a recent paper where they found that autistic individuals, 90% of them had some abnormal tryptophan metabolism and they didn't really identify what it was, but sort of like an Aha moment where it was like trick to fan metabolism. Well, chuck did fan, you need to make Serotonin, and so I started doing some reading and sure enough, there's a whole literature connecting Serotonin to autism. Speaker 9: Serotonin is made in your brain. It's an important neurotransmitter, but during early, early brain development, [00:19:00] it is a brain morphogenic meaning it actually is a growth factor that guides the neuronal proliferation, the development, the migration of neurons to different regions in the brain. It plays an essential role in shaping the structure and the wiring of the early developing brain. And so not having enough serotonin in early, early brain development in Utero can lead to very aberrant brain morphological and functional consequences. You know, this was kind of like, wow, well what if you're not getting enough vitamin D during that critical [00:19:30] period, which is important to activate that gene that converts Tryptophan into Serotonin? Is it possible then that you wouldn't be making enough serotonin in that early brain and therefore you wouldn't have a normal brain development? Also, the Serotonin in the gut can cause a lot of GI inflammation and also quite a few autistics have high GI inflammation. Speaker 9: Also, they have high levels of Serotonin in their blood. There's something that we call the Serotonin anomaly where they've measured brain levels of Serotonin autistics from SMRI and have also measured blood levels [00:20:00] of Serotonin. And there was sort of this weird dichotomy where autistics had high levels of Serotonin in their blood, but they had low levels in their brain and so it was like, well, why is that? Why would they have high levels in their blood, the low levels in the brain and we think we found a mechanism why if you're low in vitamin D, your vitamin D won't be turning on the one in your brain and you won't be making enough Serotonin in your brain and it won't be repressing the one you've got and you'll be making too much and you've got this sort of a a really cool finding. We also in our paper discuss how estrogen can [00:20:30] activate Tryptofan hydroxylase to in the brain pretty much the same way vitamin D does also a steroid hormone and the sequences, the receptors bind to a somewhat similar under dug out of the literature that people showed. Estrogen can turn Speaker 6: on the Messenger RNA for the brain enzyme making serotonin in girls, but it's not doing it in boys, which explains why five times as many boys get autism as girls. [00:21:00] Anyway, she worked out all this mechanism. We kept on explaining one thing after another render would come in every week, hopping up and down. Look what I found and look what I found and I think she walks on water, but she did this wonderful scholarship, which is a good metaphor, but she used to be a surfing instructor when she was incentive. Speaker 9: It's pretty exciting. It was largely theoretical work where we did find a underlying mechanism to connect these dots. So we're hoping now that people in the field are going to continue on and look even deeper. Speaker 6: So [00:21:30] what we think we know is how to prevent autism. But what we are not sure of is whether you can give vitamin D to people who have autism and help some of the symptoms. Uh, biggest people need to do clinical trials on all of this and they haven't done them right. But now that we have the mechanism, you can do them right. The trouble is drug companies aren't going to make money with vitamin D and they know that. And so [00:22:00] they're trying to develop a new drug. But we're hoping that these biochemicals trip to fain and vitamin D and nowhere to tone and and may get threes, which are all seem to be involved, which you can find out by reading Ramdas paper that that is going to at least give him mechanisms so we can do more focused clinical trials. Speaker 8: [inaudible] [00:22:30] to learn more about the work and Patrick are doing visit their websites, Bruce ames.org and found my fitness.com Speaker 7: oh Speaker 6: papers take a lot of polishing. Basically we're going into all these fields [00:23:00] that we don't know an awful lot about us and that requires a lot of double checking and sending it to experts and getting criticism. Speaker 9: First you have to learn everything and then you'd have to put, make the connections together and then you have to write it and then there's a whole process. It's very, it's a lot of work. Personally, my favorite part of it is the creative part where you just make all the connections and you find things and you start fitting things together and it's like, oh yeah, you know, it's just, it's almost like awesome rush, but then once you've make all those connections and you do that creative work, then you really have to [00:23:30] do all the tedious, hard digging and working diligence. Yes and that it's not as much fun. Then once you have a good theory Speaker 6: you assume no. Is it explaining new things that you didn't expect and right away this idea explains so many things and it was all really lying on the ground and round it just picked it up and put it together. Speaker 9: People like Bruce and I who liked to make those connections. I think that we play an important role in science as well. Like this paper that we published recently, [00:24:00] while we didn't physically do any experiments, we didn't test our theoretical work. We made a very interesting connection with a mechanism for other people to test. And I think that every once in awhile science needs that because there's so much data out there and now with Google we have access to all this data. So I think that taking people that are familiar with the fields and can put things together like pieces of a puzzle, I think that also advanced the science in a very creative way. Speaker 6: Biology's so complicated that there hasn't been much room for people [00:24:30] who just sit in their office and do theoretical work. And we do a lot of experimental work in lab and Rhonda is carrying on an experimental problem while she's doing all this. But I like to get it in between fields. I was always half a geneticist and half a biochemist and it was wonderful because I saw all these problems. The geneticists turned up and the biochemists didn't know existed and the geneticists didn't know how to tackle this was before Watson and crick and all of that. Uh, I'm pretty [00:25:00] old anyway. I think science is so competitive, but if you know two fields in this an interface, you have a big advantage on everybody else and we like to have people in the lab with many different expertise and put things together. Speaker 10: [inaudible]Speaker 4: you can tune into the rest of Brad's interview with Bruce Ames and Rhonda Patrick [00:25:30] two weeks from now. Speaker 7: [inaudible]Speaker 4: irregular feature of spectrum is a calendar of the science and technology related events happening in the bay area over the next two weeks. On Thursday, July 10th the bay area skeptics will host a free lecture by Glenn Branch. The deputy director of the National Center for Science Education Branch will present untold stories from the scopes trial. [00:26:00] If you thought that you knew everything about the scopes monkey trial. Thank you again to commemorate the 89th anniversary of this seminal episode in the long contentious history of evolution. Education in the United States branch will tell the story of the scopes trial as it has never been told before. Focusing on obscure under appreciated and amusing details. The event will be at the La Pena Cultural Center, three one zero five Shattuck avenue in Berkeley [00:26:30] and it will start@seventhirtypleasevisitwwwdotbaskeptics.org for more info and here's the new story we think you'll find interesting in a paper published in nature neuroscience on June eight University of Minnesota researchers at B Steiner and a David Reddish report that they have made behavioral and neuro physiological observations of regret [00:27:00] in rats to regret is to recognize that taking an alternative action would have produced a more valued outcome than the action one took. Speaker 4: The research team created a circular runway with four spokes and feeding machines at the end of each spoke that contained different flavors of food pellets. The feeding was preceded by a tone that indicated how long the rat would wait at a particular machine for food if the rat left one of these restaurants with waiting time below [00:27:30] its threshold only. Do you find an even longer waiting time at the next spoke? The team hypothesized that the rat may regret the choice. Indeed, the rats that fit this description were more likely than control rats to look toward the spoke. They just left and electrodes indicated that neurons in the orbital frontal cortex fired at the same time. Science news talk to cold Spring Harbor Neuro scientist Alex Vaughan about the paper. He [00:28:00] said, the researchers did a great job of designing a task that can discriminate between the regret of making a poor decision and the disappointment that results when one is punished despite making all the right choices. Speaker 8: [inaudible] spectrum shows are archived on iTunes university. [00:28:30] We have created a symbolic for you. The link is tiny, url.com/calix spectrum. Speaker 7: Oh Speaker 3: [inaudible]. The music [00:29:00] heard during the show was written and produced by Alex diamond. Thank you for listening to spectrum. If you have comments about the show, please send them to us via email. Email address is Doug KLX. Hey, young com. Speaker 8: [inaudible]. See acast.com/privacy for privacy and opt-out information.

For our May 13th show we offer two features: Gold Lab Symposium (starts at 3:42): Biotech entrepreneur Larry Gold, a CU Boulder professor at the BioFrontiers Institute, talks with How On Earth's Shelley Schlender about the annual Gold Lab Symposium, which will be held in Boulder May 16th and 17th.  This year's theme is Embracing the Reptile Within: Head, Heart and Healthcare.  The event will focus on research and educational approaches that can potentially help improve the U.S. healthcare system. U.S. Climate Change Report (starts at 11:50) The National Climate Assessment, a sobering new report on the science and impacts of climate change in the U.S., makes it starkly clear that human-induced climate change is already affecting all parts of the country. It is making water more scarce in some regions while bringing torrential rains elsewhere. It is making heat waves more common and severe, and it’s causing more severe and destructive wildfires. How On Earth co-host Susan Moran talks with two guests: Kristen Averyt, PhD, is a lead author of a chapter on Energy, Water and Land. She is associate director for Science at the Cooperative Institute for Research in Environmental Sciences (CIRES) at CU Boulder.  Dan Glick is a journalist who helped edit the report. His company, The Story Group, also produced a series of videos that highlight the report's key findings and how climate change is affecting many people's lives and livelihoods. Hosts: Ted Burnham, Susan Moran Producer: Susan Moran Engineer: Ted Burnham Executive Producer: Joel Parker Listen to the show (click below):

Philadelphia-based singer/songwriter Jaguar Wright's name can be added to the list of such Philly-based neo-soul talents as Grammy award-winning rap band The Roots and multi-platinum hitmakers Jill Scott and Musiq Soulchild. Wright earned rave reviews for her background vocal stint at Jay-Z' MTV Unplugged appearance during December 2001. Around February 2002, she began appearing in a national TV ad for Coca Cola. Her energetic stage shows garnered favorable write-ups in The New York Times, The Washington Post, Newsweek, and Rolling Stone. In a kind of homage to the old-school, Wright covers fellow Philly singer Patti LaBelle's hit "Love, Need and Want You" on her debut album, Denials Delusions and Decisions, which was issued by Motive/MCA on January 29, 2002. With production by members of the Roots, James Poyser, Richard Nichols, Scott Storch, Pino Palladino, Larry Gold, and Vikter Duplaix, the album is a provocative brew of gut-wrenching soul and incisive, life-influenced lyrics. The results spins a "fo' real" autobiographical tint (helped along by salty language on the uncensored version of the album), moving some to drawing comparisons to her contemporary Mary J. Blige and R&B/rap-roots mother Millie Jackson as well as Ella Fitzgerald and Nina Simone. Still, on Denials Delusions and Decisions Wright offers an enticing, unique portrait of a young woman trying to find her way through life, through songs that are mesmerizing whether they're biting or beautiful. T

We talk with Larry Gold about this year's Gold Lab Symposium at CU-Boulder.  It features, "The Biological and Social Evolution of Healthcare: Rube Goldberg and Time.  Friday, May 17th - Saturday, May 18th, 2013, Muenzinger Auditorium, University of Colorado Boulder.  NOTE:  After the conference, speaker presentations will be posted at the Gold Lab Symposium site. Hosts: Joel Parker, Jim Pullen Producer: Shelley Schlender Engineer: Shelley Schlender Executive Producer: Joel Parker Listen to the show:

Why Calories Count (start time 7:10). More than a billion people in the world suffer from too few of them. About the same number suffer from too many. We're talking about calories. They’re vital to human health, indeed our very survival. A new book, called “Why Calories Count: From Science to Politics,” delves into the many dimensions of calories – personal, scientific, and political. How On Earth co-host Susan Moran interviews the book's co-author, Marion Nestle, a molecular biologist and professor at New York University. Her co-author is Malden Nesheim of Cornell University. Gold Lab Symposium (start time: 17:24). This Friday, CU Boulder presents the annual Gold Lab Symposium.  This year’s theme is “Tempus Fugit.”  That means, “Time Flies,” and speakers this year will focus on why scientists and policy makers must remember that real people and real patients need innovations that lead to better healthcare, right now.  For a sneak preview of what “better” might mean, up next, How On Earth's Shelley Schlender talks with Symposium founder, Larry Gold about one of this year’s speakers, Allen Jacobson.  Jacobson has a cure for some, not all, but some children who have the deadly disease, muscular dystrophy. Hosts: Susan Moran and Jim Pullen Producer: Jim Pullen Engineer: Jim Pullen Headline contributions: Breanna Draxler and Joel Parker Feature contribution: Shelley Schlender Executive Producer: Joel Parker Listen to the show:

We learn about new research that indicates that the combination of exercise plus eating high cholesterol foods may help build lean body mass, even in older adults. What's more, eating high cholesterol foods such as cheese, beef fat and eggs, when combined with exercise, also seems more heart safe than most people think, according to new research published by Steve Riechman, in the Journal of Gerontology. And we talk with Larry Gold, founder of the  Gold Lab Symposium.  The 2011 symposium features scientists, researchers and policy makers discussing how health and science can intersect with healthcare policy, and how to make each one  better. The 2011 GoldLab Symposium was held at CU-Boulder's Muenzinger Auditorium May 13 - 14th.  For audio recordings of the sessions, go here.  For videos and powerpoint presentations from the sessions, go to GoldLabColorado.com Producer: Shelley Schlender Co-hosts: Joel Parker, Ted Burnham Engineer: Shelley Schlender Listen to the show: