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Professor Stephen Quake's research has helped countless patients avoid the pain and suffering that can come with invasive diagnostic testing. Russ and Stephen discuss his work to develop a number of noninvasive blood tests to help detect preterm births, genetic disorders like Down Syndrome, cancer, and organ transplant rejection. It's an episode that reminds us of the power of good science. We hope you'll take another listen and enjoy.Links:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads or Twitter/XConnect with School of Engineering >>> Twitter/XChapters:(00:00:00) IntroductionHost Russ Altman introduces the episode featuring Dr. Stephen Quake, highlighting his contributions to non-invasive blood tests. (00:00:46) Understanding DNA in DiagnosticsIntroduction to the revelation of detecting DNA in the bloodstream, shedding light on various bodily processes.(00:02:24) The Beginning of Dr. Quake's work with Cell Free DNADr. Quake tells the story of his journey into research with cell free DNA beginning with searching for a less risky alternative to an amniocentesis(00:05:11) Impact on Prenatal TestingThe transformation in prenatal diagnostics, replacing invasive tests & understanding the detection capabilities for prenatal genetic disorders like using cell-free DNA.(00:06:39) Transplant Rejection MonitoringThe discovery of cell free DNA & it's use in heart & lung transplant patients detecting early rejection & the real-life implications of this technology.(00:10:35) Unveiling Infectious AgentsThe detection of infectious agents in blood & the real life applications of this discovery(00:14:52) Advances in Cancer DetectionDiscussion shifts to cancer detection using cell-free DNA, emphasizing the important application of monitoring cancer progression and treatment efficacy. (00:17:18) Predicting Preterm BirthDr. Quake delves into the groundbreaking research predicting preterm births using cell-free RNA and DNA, sharing insights into discoveries indicating preterm birth risks and gestational age predictions and the significance of this.(00:21:42) The Chan Zuckerberg Biohub's MissionThe origins and bold mission of Steve Quake's current work at the Chan Zuckerberg Biohub, to cure, treat, or prevent all human diseases by the end of the century and the feasibility of such an ambitious goal. (00:24:03) Biohub's Research StrategyBiohub's strategy focusing on cell biology and infectious diseases internally, while funding nearly a hundred faculty across diverse areas in Bay Area Universities.(00:26:26) Conclusion LINKS:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads or Twitter/XConnect with School of Engineering >>> Twitter/X
The CZ Biohub's inspiring story began when Priscilla Chan asked Stephen Quake a seemingly impossible question: “Is it possible to cure, prevent, and manage disease in our children's lifetime?”. In 2016, the Chan Zuckerberg Initiative, founded by Priscilla and Mark Zuckerberg, set out to answer that question with a bold new mission. On the final installment of our CZ Biohub series, Priscilla and Stephen join Nate to talk about the work being done at Biohub, and how understanding human biology is the key to unlocking powerful medical treatments and cures. Through their commitment to the cause, they are showing that anything is possible. Priscilla Chan is co-founder and co-CEO of the Chan Zuckerberg Initiative (CZI). Stephen Quake is Head of Science at the Chan Zuckerberg Initiative, where he oversees CZI's science grant programs, technology development, and the CZ Biohub Network. Stephen is also a professor at Stanford University. Learn more about CZ Biohub: https://www.czbiohub.org/about/#history-amp-mission Listen to more episodes from our CZ Biohub series: https://theshowaboutscience.com/2023/02/12/099-accelerating-science-to-eradicate-disease-with-priscilla-chan-and-stephen-quake/ Connect with The Show About Science: Instagram: https://www.instagram.com/showaboutscience Facebook: https://www.facebook.com/theshowaboutscience YouTube: https://www.youtube.com/showaboutscience Twitter: https://www.twitter.com/natepodcasts LinkedIn: https://www.linkedin.com/ Loved this episode? Leave us a review and rating wherever you listen to podcasts!
Dr. Stephen Quake, President of the Chan Zuckerberg Biohub Network, spoke to CANCER BUZZ about the application of liquid biopsies across multiple cancer stages and their potential to improve patient outcomes, minimize financial toxicity, and create health equity through greater testing access and lower cost. He identified trends that are shaping the future of cancer research, including the amazing developments in new cancer screens for diseases where they don't currently exist. Hear about the hydroxymethylation measurement techniques pioneered by his lab, which is the exact science now being used by many investigational multi-cancer early detection (MCED) assays to screen for cancers which don't have guideline-approved tests, like pancreatic and ovarian cancer. Guest: Stephen Quake, PhD Professor of Bioengineering and Applied Physics, Stanford University Co-President, Chan Zuckerberg Biohub Network Resources: Stanford Quake Lab Chan Zuckerberg Biohub Network New Chan Zuckerberg Biohub awards foster research collaborations Transforming Complex to Clear: Precision Medicine Resources [Blog] Barriers to Liquid Biopsy [Podcast] What You Need to Know about Liquid Biopsy Improving the Timeliness of Biomarker Testing by Using Liquid Biopsy When Tissue Samples are Insufficient for Testing [Podcast] Financial Barriers to Biomarker Testing Biomarker Testing: Cost and Coverage Bluestar Genomics | Liquid Biopsy Cancer Detection
CZ Biohub Network president Stephen Quake reveals that they are looking to expand across the United States. Apply to become the next Biohub at czbiohub.org. This podcast is intended for US healthcare professionals only.
Stephen Quake is the Lee Otterson Professor of Bioengineering & Professor of Applied Physics @ Stanford University & Co-President of the Chan Zuckerberg Biohub. Quake has invented many measurement tools for biology, including new DNA sequencing technologies that have enabled rapid analysis of the human genome and microfluidic automation that allows scientists to efficiently isolate individual cells and decipher their genetic code. Quake is also well known for inventing new diagnostic tools, including the first non-invasive prenatal test for Down syndrome and other aneuploidies. His test is rapidly replacing risky invasive approaches such as amniocentesis, and millions of women each year now benefit from this approach. His innovations have helped to radically accelerate the pace of biology and have made medicine safer by replacing invasive biopsies with simple blood tests.Quake was elected a member of the National Academy of Engineering in 2013 for achievements in single-cell analysis and large-scale integration of microfluidic devices. He has also been elected to the National Academy of Sciences, the Institute of Medicine, the American Physical Society, the American Institute for Medical and Biological Engineering and the American Academy of Arts and Sciences. He is the recipient of numerous international awards, including the Human Frontiers of Science Nakasone Prize, the Jacob Heskel Gabbay Award, the MIT-Lemelson Prize for Innovation, the Raymond and Beverly Sackler International Prize in Biophysics, the NIH Director's Pioneer Award, the American Society of Microbiology's Promega Biotechnology Award, and the Royal Society of Chemistry Publishing's Pioneer of Miniaturization Award. He has founded or co-founded several companies, including Fluidigm, Helicos Biosciences, Verinata Health, Quanticel Pharmaceuticals, Moleculo, Cellular Research, Immumetrix, and Karius.Quake received a B.S. in Physics and M.S. in Mathematics from Stanford University in 1991 and a doctorate in Theoretical Physics from the University of Oxford in 1994 as a Marshall Scholar. He did his postdoctoral work at Stanford in single molecule biophysics with Steven Chu. Quake joined the faculty of the California Institute of Technology at the age of 26, where he rose through the ranks and was ultimately appointed the Thomas and Doris Everhart Professor of Applied Physics and Physics. From 2006 to 2016 he was an Investigator of the Howard Hughes Medical Institute.Thank you for listening!BIOS (@BIOS_Community) unites a community of Life Science innovators dedicated to driving patient impact. Alix Ventures (@AlixVentures) is a San Francisco based venture capital firm supporting early stage Life Science startups engineering biology to create radical advances in human health.Music: Danger Storm by Kevin MacLeod (link & license)
This marks the 150th episode of DNA Today! Our guests to celebrate this landmark episode of DNA Today are Dr. Euan Ashley, a medical geneticist and cardiologist. And Dr. Stephen Quake, a physics professor, bioengineer and pioneer in microfluidics. A Scotland native, Dr. Euan Ashley graduated with degrees in Physiology and Medicine from the University of Glasgow. He completed medical residency and a PhD in molecular physiology at the University of Oxford before moving to Stanford University where he trained in cardiology and advanced heart failure, joining the faculty in 2006. In 2010, he led the team that carried out the first clinical interpretation of a human genome. The paper published in the Lancet was the focus of over 300 news stories, and became one of the most cited articles in clinical medicine that year. The team extended the approach in 2011 to a family of four and now routinely applies genome sequencing to the diagnosis of patients at Stanford hospital where Dr. Ashley directs the Clinical Genome Service and the Center for Inherited Cardiovascular Disease. In 2014, Dr Ashley became co-chair of the steering committee of the NIH Undiagnosed Diseases Network. Stephen Quake is a professor of bioengineering and applied physics at Stanford University and is co-President of the Chan Zuckerberg Biohub. He holds a B.S. in Physics and M.S. in Mathematics from Stanford University and a doctorate in Theoretical Physics from the University of Oxford. Dr. Quake has invented many measurement tools for biology, including new DNA sequencing technologies that have enabled rapid analysis of the human genome and microfluidic automation that allows scientists to efficiently isolate individual cells and decipher their genetic code. Dr. Quake is also well known for inventing new diagnostic tools, including the first non-invasive prenatal test for Down syndrome and other aneuploidies. His test is rapidly replacing risky invasive approaches such as amniocentesis, and millions of women each year now benefit from this approach. He was also the fifth person in the world to have their genome sequences and his genome was the subject of clinical annotation by a large team at Stanford Hospital led by Dr. Ashley. On This Episode We Discuss:The first clinical interpretation of a human genomeGenome sequencing technologiesThe cost of sequencing a genome Understanding the genomic codeThe future of precision medicineDr. Ashley's book, The Genome OdysseyWant to read the Genome Odyssey? Enter to win your own copy! Head over to our Twitter, Instagram, Facebook, and LinkedIn to enter to win a free book!Be sure to follow Dr. Ashley and Dr. Quake on Twitter! How do you keep research articles organized? We have struggled with this for years, but have finally found a solution that is simple and easy. It's called Paperpile! It radically simplifies the workflow of collecting, managing and writing papers. Paperpile allows you to highlight and annotate papers, manage references, share and collaborate and even cite directly in Google Docs and Microsoft Word. Paperpile's new mobile apps allows you to sync your library to all your devices so you can read and annotate on your iPad, iPhone, or Android device. Start your free 30 day trial today at paperpile.com with promo code “DNATODAY”. Paperpile costs only $36 per year, but with code “DNATODAY” you save 20%! Want to become a genetic counselor? Looking for ways to engage with the field and boost your resume for grad school applications? Then you should check out Sarah Lawrence's “Why Genetic Counseling Wednesday Summer Series”! Every Wednesday this June Sarah Lawrence is hosting this series where you can interact through Zoom with genetic counselors from different specialties for an hour and a half. You can sign up at SLC.edu/DNAtoday to register to level up your resume for applications in the fall. Stay tuned for the next new episode of DNA Today on July 2nd, 2021! We'll be joined by Dr. Richard Michelmore and Dr. Brad Pollock who will be discussing COVID-19 variants. New episodes are released on the first and third Friday of the month. In the meantime, you can binge over 150 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. All episodes in 2021 are also recorded with video which you can watch on our YouTube channel. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com.
The Future of Everything with Russ Altman "Stephen Quake: What can the DNA in your blood reveal about your health?" In our 100th episode, we meet the scientist who answered this question and revolutionized everything from detecting Down syndrome to cancer. In The Future of Everything’s 100th episode, bioengineer, physicist and inventor Stephen Quake recounts a personal experience. When Quake’s wife was pregnant with their first child, doctors performed a common but risky procedure known as an amniocentesis. Using a long needle, they pierced his wife’s uterus through her abdomen to grab a few cells from the amniotic fluid surrounding the fetus to test for genetic diseases and abnormalities. The child was fine, but to Quake and his wife the test felt like an invasion. So Quake, a renowned bioengineer and physicist at Stanford, decided to do something about it. He invented a blood test to replace amniocentesis. It turns out that a small percentage of the DNA floating around in every mother’s bloodstream comes from the fetus. And that cell-free DNA, as it’s known, can be tested for the same diseases and abnormalities that amniocentesis can reveal, all without risk to the mother or child. Today, 4 million expectant mothers each year get Quake’s blood test, and use of amniocentesis is quickly fading as a diagnostic tool. Little did Quake understand at the time that his lab would set off a revolution of sorts, leading to a remarkable array of similar blood tests that can detect everything from cancer to hidden infections to tissue rejection in transplant patients to premature birth – all weeks or months earlier and less invasively than existing techniques can. Join host Russ Altman and Stephen Quake for The Future of Everything radio show’s 100th episode. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine.
Russ Altman: Today on The Future of Everything, the future of detecting DNA in your blood.Now DNA is the building block of life. It is a relatively simple long molecule or polymer made out of four components or DNA bases which have one letter abbreviations, the famous ATCG, which stand for their chemical names. It's like a string of beans, beads, beads, but it is long. A human genome is made of about three billion DNA bases, divided into 23 chromosomes. So if you add up the beads in each chromosome, you get about three billion. You get a genome from mom and you get one from dad. So you have two copies of the genome, mostly the same but obviously not identical, or six billion total.Now DNA contains the blueprints for how your cells live, how they grow, how they interact with other cells, and like a computer program, it allows the cell to perform simple computations to make decisions about when and where things happen.If this goes wrong, you can get cancer. Mutations in the DNA cause the computations and decisions to go wrong.Other things can happen too. In the last ten years, researchers have learned that they can detect DNA in the blood. Now we knew that the cells in the blood had DNA, so that was not surprising, but what was surprising is that there is sometimes DNA from other cells in the body, often cells that have died and just released their DNA into the bloodstream. This is sometimes called cell-free DNA because it is floating in the blood and it's not really part of a cell. Although this may seem like it's junk, it offers evidence of lots of other processes going on in the body, processes diverse as cancer, pregnancy, stress on organs, or even death and many others.Dr. Stephen Quake is a professor of Bioengineering, Applied Physics and Physics and Stanford University. Steve pioneered the detection of DNA in the blood and some its first applications.Steve, what drove your interest in detecting DNA, and what was the first demonstration that this would actually be useful?Stephen Quake: Well, my interest came actually when I became a father. My wife and I were in to see the doctor, and the doctor says you guys should think about getting amniocentesis. And it was seemed like a theoretical question and something we have time to think about. We said yeah, okay, that sounds like the right thing if recommending it.Russ Altman: And this is a super risky procedure in many ways. A needle goes into the uterus near the baby to extract fluids.Stephen Quake: Big needle right in the mom's belly, right next to the fetus to try to grab a few cells, and so to do genetic testing. And we said yeah, it sounds like a good idea, thinking we schedule another appointment for it. Next thing we knew, the guy was turning around with a giant needle, plunges it right into my wife's belly,Russ Altman: Whoa.Stephen Quake: Yeah, whoa, exactly. That was our response. And it's the response of many people who undergo that certain invasive testing. And not surprisingly, there's risk associated with doing that testing. Sometimes, you lose the baby and other health problems that might happen.Russ Altman: How far into the pregnancy were you?Stephen Quake: That's typically done, I don't know, around 14 weeks, something like that, 15 weeks, somewhere around there. And so that sensitized me to holy cow, there's a problem here that you're asking a diagnostic question, and there's a lot of risk associated with it. And so I began to think are there ways to ask these genetic questions and do diagnostics without adding risk? And I eventually stumbled upon this old scientific literature about this cell-free DNA that you were mentioning, which, as it turns out, was first discovered as a phenomenon in 1948.Russ Altman: That's before Watson and Crick even articulated the importance of DNA for genetics.Stephen Quake: It's before the structure, and it's before people knew. It's roughly contemporary people first realized that DNA was the molecule of inheritance.Russ Altman: Right.Stephen Quake: Oswald Avery just that same year was working that out. So it was blood chemistry to those guys who did it. But the field stayed alive, and it was mostly people doing cancer research. And eventually, it was figured out that when you're pregnant, some of the DNA in your blood comes from the fetus, and that was worked out in the late 1970s. And –Russ Altman: And so this is not a large amount, I'm guessing.Stephen Quake: It's not much, just a few percent of what's there, so it's a very challenging measurement problem and the decade-long search to try to figure out how to really use that to build a diagnostic that would allow you to understand the genetics of the baby without having to risk the baby's life. And we saw that at Stanford, and it was through the work of a really terrific graduate student in my lab when the bioengineering department was young, Christina Fan. And that has now been the first real clinical application of cell-free DNA in diagnostics, and that's how I got into it, to answer your question.Russ Altman: So in that initial demonstration or in your first industrial translation, what are the things that we can actually detect from the DNA of a fetus in the mom's blood?Stephen Quake: Well, when we published the paper on this, started getting press inquiries. When is this gonna be available in the clinic? I said, I don't know, decades, something like that.Russ Altman: That's usually the answer.Stephen Quake: It takes a long time, right. It turns out people jumped on like you wouldn't believe. Clinical trials were launched immediately. Within three years, the first real commercial diagnostic products had been launched, and now it's four million women a year, something like that, get the test, and the use of amniocentesis has plummeted.Russ Altman: And so now you do this as a screening before you make the decision about the amnio. Is that the general use of it?Stephen Quake: That was the initial indication, and it's very quickly moving to replacing amnio completely.Russ Altman: Completely, yeah. And what kind of things can we diagnose in the fetus these days?Stephen Quake: So the major genetic disorders you have for live births are things like Down syndrome; that's number one. And it's an aneuploidy is what it's called technically, means the extra copy of a chromosome. And there's a few other disorders, which are extra copies of chromosomes that are also detected with this approach.Russ Altman: Awesome. So that has had big-time market impact, and it's changing people's lives. I think it's on the street now. People know you can get this blood test instead of the amnio, so it didn't stop there. Now you had this hammer, and it worked. You hit one nail. What was the next nail you guys turned your attention to?Stephen Quake: Well, after we published that, word got around Stanford that I was interested in non-invasive diagnostics. And I got a call one day from Hannah Valantine, who's a cardiologist –Russ Altman: Great cardiologist.Stephen Quake: Yep, and she says, well Steve, we got a similar problem in heart transplants. We give people a new heart, and after the operation, we then go biopsy that new heart and rip out pieces of the tissue to make sure it's not being rejected by the body. And we're doing that every couple of months. And so is there a blood test that could replace that? Same sort of problem, patients were having this painful, risky procedure, and there was a question of whether it could be replaced by a simple blood test. And so we thought about that a bit, and –Russ Altman: The key opportunity here is that the DNA and the heart that belongs to the donor is not gonna match the DNA of the person who received the heart, and, like the baby and the mom, because those are different DNAs, you have a chance of picking it up.Stephen Quake: Yeah, the key there is that the DNA is different. A little different with the baby and the mom because we don't use differences in their DNA. But in the case of the transplant, absolutely. The whole principle is based on there being different genomes of every cell in the heart compared to other cells in the recipient's body. And we monitor those so-called polymorphisms, those changes.Russ Altman: And so you went after this, and you were indeed able to show that people who were in rejection were spilling, so to speak, the heart DNA into the blood, and maybe we can avoid some of those biopsies.Stephen Quake: Absolutely. So we did a proof of principle study with some bank samples she had, and then we wrote a grant together and were able to do a very large study on both heart and lung transplants where pretty much every transplant patient at Stanford for those two organs was enrolled in our study over a period of three years, and were able to validate it. It was amazing. One of my kids was in elementary school at the time, and there was a new family who was in the class that year. And at the end of the year, we got a note around saying that, well, there's a family that's in town because they were at the Ronald McDonald House. One of their kids was in the hospital and very ill, and would anyone wanna put them up for the last couple of months because their time had run out there. And so we invited them –Russ Altman: Took them in.Stephen Quake: to our house, yeah, and very interesting family. They were immigrants from Africa. The father had been a nurse there, had some medical training and knew that when his son was infant and very ill that needed serious help and eventually got him to Stanford where the son had had a heart transplant.Russ Altman: Whoa.Stephen Quake: And we were talking around the dinner table one night, and the dad says well, and we're just so proud to be part of this study where people are trying to figure out if they can replace the biopsies. And we enrolled our son in it and drew the blood. I said that's my study. It was amazing and felt very good about it.Russ Altman: Of course, of course.Stephen Quake: And now that's available. So there's now tens of thousands of people every year who are getting that test, and it's saving a lot of pain and suffering for those patients.Russ Altman: This is The Future of Everything. I'm Russ Altman. I'm speaking with Dr. Steve Quake about detecting DNA, and at this moment, detecting DNA in transplant, hoping to detect rejection. So does the test detect rejection potentially earlier than the old-fashioned biopsy approach would?Stephen Quake: It does, and we've proved that, absolutely. You see rejection weeks, if not a month, earlier than the biopsy.Russ Altman: And then presumably, that gives the docs more option for changing the immunosuppression.Stephen Quake: Oh, absolutely because yeah, as you mention, all these patients are immunosuppressed to try to prevent rejection, and too much of that, and they'll get an infectious disease. Too little of that, you have rejection. So they can dial up the immunosuppressants a little bit and try to avoid the rejection event, and that's much better for the patients. Once they hit rejection, all sorts of bad things happen, and so the whole thing is trying to keep them properly suppressed.Russ Altman: And just to flesh it out a little bit, how frequently are they getting these blood draws? Is this every six months or every three months or –Stephen Quake: The standard of care for the invasive biopsies was every two months, and that's where they initially matched it. But this is the sort of thing that can and should be done more frequently, and I think it's gonna change the way people treat the patients over time.Russ Altman: I know that there are more applications, and I'm interested to know which ones you wanna talk about, but let's talk about one that fascinates me, which is the detection of infectious agents in the blood. Can you tell me how this technology has been used in that regard and what's the future look like?Stephen Quake: Yeah, so when we were doing the large transplant study, my post doc at the time, Ian De Vlaming, was looking at all the sequencing data very carefully and realized that not all of the sequence reads off the sequence that were mapping to the human genome. And he said maybe 98% of it's mapping; there's one or 2% that aren't. And I said that's great. It means we're not having a lot of contamination and it's all good, and he didn't let it go with that, thank goodness. And he started looking at those things that weren't mapping, and he realized it wasn't contamination, and they actually were not human, and it was part of the microbiome of these individuals. So the bacteria and the viruses and funguses that live in our body also release cell-free DNA, and we were measuring that as well. And he realized that we could use that to monitor things like what happens to your microbiome when your immune system gets turned offRuss Altman: Right, because a lot of folks —Stephen Quake: Because a lot of patients are immunosuppressed, exactly.Russ Altman: Right.Stephen Quake: And then we realized ‘cause some of them are getting infectious disease, we could also see infectious disease. And so that has evolved into a new kind of infectious disease diagnostic, which is hypothesis free. You don't have to test for a particular thing. You're essentially testing for a thousand infections all at once, and it's just now reached commercial development. We're seeing the first peer-reviewed studies showing how to use it, and it's a very exciting innovation for infectious disease.Russ Altman: People might find this surprising so let's just unpack this a little bit. We know that there are some bacteria that live in our gut, and we've always expected to see them there. Many of us have assumed that my blood should be pretty much infection free. That's not where the bacteria and the viruses live. I guess the first question is how much of a surprise, what do you see in normal people who are not immunosuppressed, and how do we interpret this? Do we know that these are diseases? Are these pathogens causing problems, or might they be part of some ecosystem of health?Stephen Quake: Yeah, all good questions. So a fun way to think about it is to do an order of magnitude calculation. Could we talk about calculations here?Russ Altman: Yes, this is something that physicists do, folks.Stephen Quake: So there's a statistic going around by the microbiome people. You've got 10 times more bacterial cells in your body than you do human cells. If you take that at face value and you say well, the human genome is 1,000 times longer. You said three billion base pairs, then the typical bacterial genome, which about three million base pairs. You do the math on that, and you say by mass, all the DNA in our body is 99% human, 1% bacterial. And so if you were to mush this all up in a blender, purify the DNA out, that's what would come out.Russ Altman: And that matches what your post doc found.Stephen Quake: Yes, exactly.Russ Altman: So are these normal signs? Are these normal organisms, or are these things that we have to run to the doctor and get treated for?Stephen Quake: The vast majority of it, the vast majority of is our normal microbiome, bugs that live with us commensally and happy, equilibrium, with us as humans.Russ Altman: I'm guessing you saw viruses or bacteria that were either entirely novel or not appreciated as living in humans?Stephen Quake: Absolutely, we have discovered traces of novel organisms that is an area of ongoing research in the group to try to understand what they are and where they fit into the tree of life.Russ Altman: This is The Future of Everything. I'm Russ Altman. I'm speaking with Dr. Steve Quake, and now we're talking about infectious disease detection.As a doctor, I know that we have patients come into the emergency room or into the clinic with what we call FUO, fever of unknown origin. They look sick, they have a fever, it's not normal to have a fever, and they look infected, but we can't find an infection. And so I'm guessing that one of the key applications of this technology would be, well, what DNA are we seeing in the bloodstream, ‘cause that might point us to the infectious agent. Is that how the infectious disease community —Stephen Quake: Absolutely, yep.Russ Altman: — is taking this up?Stephen Quake: Absolutely. That's a major application. There's a bunch of others that are really interesting. And to come back to the earlier point you raised about blood infections being a different thing, the point is that the blood is like the septic system of the body, and it's exploring all the tissues and organs. And when cells are dying and they're releasing their DNA, it picks it up and carries it. So even if the infection is not in the blood, you see the remnants of the infection in the blood from that cell-free DNA.Russ Altman: Yes, and so the final area that I wanted to get into, of course, is cancer. And, in fact, you mentioned cancer in your initial comments. Where are we with the detection of cancer from cell-free DNA?Stephen Quake: Yeah, that's been an area of intense interest for decades. That's the one that was primarily driving the field before the prenatal work and because tumors have different genomes than the normal body does. And so people would monitor those differences in the blood and try to understand how the disease was progressing and to try to do detection. And that's been a little later into the clinic than the prenatal stuff, but it's happening now. And it's an area of intense interest. There's a bunch of companies out there that have launched tests or about to launch tests, and it's gonna be very important for helping monitor course of treatment, and that's the first clinical application that's out there.Russ Altman: That's what I was gonna ask. Is this about detection or about monitoring? And it sounds like the monitoring.Stephen Quake: That's the first one. It's the easiest one ‘cause you're in such a high risk group and it makes it an easier technical task.Russ Altman: And you know the cancer, so you've been able to characterize what you're expecting to find if the cancer comes back.Stephen Quake: Correct. But the big thing to go after is early detection, and that would help a lot of people and save a lot of lives. And that's something that is gonna be coming. Maybe it's five years, maybe it's sooner, but there'll be some very valuable tools for that coming down the pike; I'm pretty confident about that.Russ Altman: Yeah, so let's just think about that for a moment because one of the things that I know is an issue is when these new technologies arise, they often move up the time of detection. You could get the cancer detection earlier, you get the rejection. In general, that's a good thing. But in cancer, it's a little tricky because there is some, if I understand the literature, there's some indication that some cancers arise, and it's the body's own immune system suppresses the cancer effectively before it can grow. Have people worked out what actions you should actually take if you see a very early indication of cancer? Is it definite that we're gonna hit the patient very hard with chemotherapy and radiation and whatnot, or might we still have to figure out what to do about that?Stephen Quake: Yeah, that's a really good question and important issue, and I think we're so early on that that's being worked out in the clinical community. But the initial thought is not that you would go right to treatment with chemotherapy but that you would reflex to other testing methods that are more expensive and more sophisticated and are not the sort of thing you use to screen people broadly but if you got a hint that something's wrong, you'd use them, things like imaging techniques and such forth.Russ Altman: Makes sense. This is The Future of Everything. I'm Russ Altman. More with Dr. Stephen Quake about DNA, the future of health and biology and bioengineering, next on Sirius XM Insight 121.Welcome back to The Future of Everything. I'm Russ Altman. I'm speaking with Dr. Stephen Quake about the fabulous uses of DNA that's floating around in our cells. Now Steve, we just went through a bunch of really killer apps, but I know that there's yet another one, which is looking at pre-term birth. And that's a funny one to me because it's not immediately obvious how detecting DNA would have anything to do with a pre-term birth. So tell us that story.Stephen Quake: Yeah, so pre-term birth ends up being number one cause of neonatal mortality and complications later in life. It's a huge problem, and there's been, despite decades of effort, no real progress on creating a meaningful diagnostic that tells people who's at risk. And there's been a lot of effort put into –Russ Altman: So the goal would be very early, say this looks like a pregnancy that might have some pre-term problems.Stephen Quake: Exactly. And more generally, when is the baby gonna be due? Even if it's not early, can you predict the due date? And there's been a lot of effort put into understanding the genetics of that, the DNA base part, that has not really had a lot of predictive power or success. And so we turned to looking at RNA, which is carries the message from the genome and tells you about not the inheritance but the state of the cell and body at any given point. And it turns out same guys who discovered cell-free DNA in 1948 also discovered cell-free RNA.Russ Altman: They have a good year.Stephen Quake: They did.Russ Altman: Same year?Stephen Quake: Same paper!Russ Altman: Same paper!Stephen Quake: And so we began looking at cell-free RNA as a way to measure what's going on in the mom's body and with the baby and the placenta at any given point in time and how are things changing and can that signal to us when the baby's gonna be born and if the baby's gonna be born early. And we were able, after a long effort, it took seven or eight years of work by a very large group of people, a number of collaborators here at Stanford, including David Stevenson and Gary Shaw and Yair Blumenfeld, bunch of the MFM docs.Russ Altman: MFM is maternal fetal medicine.Stephen Quake: Fetal medicine, thank you.Russ Altman: It's okay, it's my job.Stephen Quake: But we managed to, we managed to figure it out. And we published a paper last year showing that there's a handful of transcripts which indicate when the mom is gonna give pre-term birth, about two months in advance of that.Russ Altman: Wow, so these are like canaries in the coal mine.Stephen Quake: Exactly. And we found another set of transcripts which were predict gestational age, so you can tell how old the baby is and predict when it's gonna be born. And that turns out to be a really interesting problem as well.Russ Altman: I was gonna say, I thought that good old-fashioned subtract nine months from the date of birth gets you a pretty, and in fact, I must say, I'm born on November 5th, and that's important because if you go back nine months, that gets you to February 14th, Valentine's Day. So that's a side story.Stephen Quake: Okay, I got a couple of stories there for you.Russ Altman: But tell me about this.Stephen Quake: All let me give you a couple of stories.Russ Altman: Tell me about this.Stephen Quake: So when we were having our first kid, the one with the amnio, right, I asked the doctor what's the due date, tells us the due date. I said what's the error of your measurement, your estimate? And he got very offended ‘cause he thought I was questioning his ability as a doctor.Russ Altman: Of course, of course.Stephen Quake: We had a very tense discussion. Finally, I manage to communicate I was asking about the uncertainty in the estimate ‘cause I wanted to know when to adjust the travel schedule to make sure I didn't miss it. And he couldn't tell me the uncertainty, but he told me a number that I could use to derive the uncertainty, and so I did that. Worked out to two sigma three sigma. I had three sigma baby. So the baby was premature by three and a half weeks, and it was fortunate –Russ Altman: Oh, it was at the border of the plus minus.Stephen Quake: Yeah, I was fortunately in town, and fortunately, she turned out fine. But this got me aware of the importance of not only pre-term birth but also understanding, trying to understand when the baby's gonna be born and prediction of due date.Russ Altman: Okay, so you sold me. This is actually an impactful question.Stephen Quake: Yes, exactly.Russ Altman: So what can you guys do?Stephen Quake: Well, it's early still. Our first paper was a small number of women, few dozen women, and yet it seems very promising, and we've now been able to reproduce it in a different cohort that we can predict pre-term birth and gestational age and, from gestational age, hopefully predict when the normal baby's gonna be born. But it's all now going into much larger clinical trials to validate it. It's very much the beginning of the story, but it's an exciting one.Russ Altman: So, great. This is a new molecule for our discussion, this RNA molecule, also from the baby or the placenta or both and a combination of maternal and fetal factors gives you the data you need and a big data mining approach, not to overuse that, to actually draw inferences that might be very impactful both for the actual due date but, more importantly, for uh oh, we have a woman who might be having a pre-term birth, let's do what we can, and again, the ability of doctors to intervene is probably much better if they have two-month warning.Stephen Quake: Correct, correct.Russ Altman: Well, so this has been an amazing ride, and I wanna turn our attention a little bit now to a separate thing but very excited that you're involved with. A few years ago, I think three years ago, the Chan and Zuckerberg Foundation announced the creation of a big biomedical research institute with you and a colleague from UCSF, Joe DeRisi, as co-presidents, and it had a very bold mission. The mission was to, I believe, cure or manage all disease by the end of the century, something like that; you can correct me if I'm wrong.Stephen Quake: Cure, treat, or prevent all human disease by the end of the century.Russ Altman: Bingo. So you agreed to that charge. You've now been doing it for three years. Can you tell us a little bit about how it was set up and why it was set up, and is it really even possible to imagine that level of progress in the next century?Stephen Quake: Yeah. So since we've been talking about becoming parents, and Mark and Priscilla began to turn their attention to philanthropy in a pretty large way when they became parents. And they wrote an open letter before their first daughter was born that launched the Chan Zuckerberg Initiative and ultimately the Biohub with this idea of trying to create a better world.Russ Altman: It's called the Chan Zuckerberg –Stephen Quake: Chan Zuckerberg Biohub.Russ Altman: Biohub, mm-hmm.Stephen Quake: And so in their children's lifetime, so broadly in this hundred-year span, they wanted to see if they could fund scientific research that would help make the world a healthier place for their kids and everyone else, which is a lovely mission. And it sounds crazy, right?Russ Altman: Sounds crazy.Stephen Quake: It sounds absolutely absurd, and for awhile, I couldn't say it even to them with a straight face.Russ Altman: And yet a few moments ago, you said it forcefully and convincingly, so wait to go.Stephen Quake: In, well –Russ Altman: What turned you?Stephen Quake: Well, you think about it for awhile, and it helps to think backwards in time and think about how far medicine has advanced in the last 100 years. And in this country, mortality has been cut in half. And the things that kill us now are very different than the things that killed us 100 years ago. Primarily, it was infectious disease then. Now it's things like heart disease and such forth. And so we've eliminated entire classes of diseases, effectively, and cut mortality in half. So you can project forward another 100 years and say if we don't do anything, we should get another factor of two. And with some really serious effort, maybe we can do better than that. It's just very hard for people to think on century-long timescales. We're thinking when's our next grand proposal or something like that or when's our next student gonna graduate, and it's not often that we have the opportunity to think on that sort of timescale.Russ Altman: This is The Future of Everything. I'm Russ Altman. I'm speaking with Steve Quake, now about curing, managing, treating, and what was the other verb?Stephen Quake: Prevent.Russ Altman: Preventing all disease. Do you take a portfolio approach? It sounds like you were talking about the causes of death 100 years ago, so you have to look at the causes of death now. And I guess you have to pick the low-hanging fruit to say how do we make progress. So how have you decided to deploy the assets of the Biohub for the next five to 10 years?Stephen Quake: Yeah, well, a two-fold approach. One approach is to pick a couple of areas that capture a large part of the global burden of disease, and we've chosen two that we focus on in our internal research. One is cell biology, and a lot of diseases are a consequence of disorders of cell biology, cancer, heart disease, pulmonary disease, a number of neurological diseases. And so better understanding how cells work will lead to new therapies and treatments.Russ Altman: Could be a platform of discoveries that will have multiple applications.Stephen Quake: Right, exactly, and that covers a large part of the global burden, as you work out the numbers of that. The other big part is infectious disease.Russ Altman: So it's still a problem.Stephen Quake: Still a problem worldwide, absolutely. There's a bunch of open areas, malaria, HIV. There's a bunch of other ones, TB, number of viral infections. So that's our other big internal effort. And at the Biohub, our researchers have been hired to focus on those two areas. Now the other, all the rest, what we've done is we've partnered with the Bay Area University, to Stanford, UCSF, and Berkeley, and we fund research of nearly 100 faculty at those universities across everything else. We have an open competition. We've committed roughly $100 million to those faculty over the next five years, and we'll do it again for the second five years. And we're encouraging them to work on the riskiest, most exciting ideas, whether they're basic science, technological, or more disease focused, to cover the span of where we think a lot of the great innovations are gonna come over the next decades.Russ Altman: So that does sound compelling. So basically, a two-fold strategy with some top-down projects that you know are gonna be impactful, and then you spread your bets by giving money to a bunch of smart people and say just do what you think is right. And the hope is that that will lead to the next set of challenges that you guys can perhaps adopt as top-down challenges.Stephen Quake: That's right.Russ Altman: So how is it going?Stephen Quake: Well, as you mentioned, we just celebrated our third birthday three weeks ago. Joe and I have been working really hard, but it feels great. I feel like we're at full steam, and great science is happening, and the people we're funding are doing great work, and the future is bright.Russ Altman: And I guess are the donors satisfied? Are the people who put up the funds, are they starting to see their fruits of their vision?Stephen Quake: Well, you'll have to ask them that. It's not my place to say. But they haven't fired us yet, and so we take that as a good sign.Russ Altman: Thank you for listening to The Future of Everything. I'm Russ Altman. If you missed any of this episode, listen anytime on demand with the Sirius XM app.
Mark sits down with Dr. Joe DeRisi and Dr. Stephen Quake, who lead the Chan Zuckerberg Biohub, a nonprofit research center that brings together scientists and engineers from Stanford, Berkeley, and UCSF. They talk about how technology is accelerating health research, the new advancements they’re most excited about, how to restore faith in science and what wearables will mean for the future of health.
Em 2018, um relatório da Organização Mundial da Saúde revelou que cerca de 30 milhões de bebês nasceram prematuros no mundo. Por ano, aproximadamente 1 milhão de recém-nascidos com baixo peso e infecções sobrevivem ao início de suas vidas, mas com algum tipo de deficiência, incluindo paralisia cerebral e problemas cognitivos. De acordo com Lilian Sadeck, neonatologista do Centro Neonatal do Instituto da Criança e do Adolescente do Hospital das Clínicas da Faculdade de Medicina da USP, “temos uma tendência a aumentar o nascimento de partos prematuros”. Conforme a especialista, atualmente no Brasil os bebês prematuros, ou seja, nascidos vivos abaixo de 37 semanas, compõem 12% dos partos. Essas crianças precisam de cuidados especiais não apenas durante o parto, mas nos meses seguintes, em especial. Na tentativa de combater essa estatística, a tecnologia que envolve os exames médicos tem avançado. Em especial, uma técnica criada pelo bioengenheiro Stephen Quake, da Universidade de Stanford, nos Estados Unidos, que envolve um exame capaz de fazer a medição de fragmentos de RNA no sangue de uma mulher grávida e, partir daí, fornece uma estimativa confiável da data de nascimento do bebê, prevendo se ele vai ou não nascer prematuramente. Para Lilian, o impacto desse tipo de técnica se dará principalmente na rotina das gestantes, que poderão ser encaminhadas imediatamente para serviços com UTI neonatal. “Sabemos que a melhor incubadora de transporte ainda é o útero materno, então o conhecimento do risco do seu bebê nascer prematuro vai melhorar muito o prognóstico dessa criança.” Ouça a matéria completa acima. Para receber atualizações com novos episódios, assine o feed do podcast Momento Tecnologia. Estamos também no Spotify, no iTunes, Google Podcasts, entre outros apps.
Stephen Quake discusses rapid DNA sequencing and treating medical patients based on their genomes.
You heard it here first, folks; Stephen Quake is coming for the colonoscopy. The scientist has made a career of replacing invasive, painful, and dangerous procedures with simple, cheap tests that can be performed almost anywhere. Just this year, a blood panel he developed to detect genetic birth defects has been taken by more than three million women, replacing the need for amniocentesis and giant, uterus-puncturing needles.
Stephen Quake is a professor in the department of bioengineering at Stanford University and a serial founder of biotech companies. His talk with Nature Biotechnology covers launching Fluidigm, being chosen as copresident of the Chan Zuckerberg Biohub, and what it was like to be one of the first people to have their genome sequenced. See acast.com/privacy for privacy and opt-out information.
When Lee Herzenberg remembers the day her son Michael was born, she laughs and calls it a “cool birth.” Her obstetrician was a friend, and she describes it almost like a party -- “a little bit painful, but that you forget very quickly.” Lee even got a kick out of the fact that a resident learned to do an episiotomy on her. It was November 1961, and she was at the newly christened Palo Alto-Stanford Hospital Center; her husband Len was a biology professor on campus. Like most fathers at the time, he didn’t attend the birth -- which meant he wasn’t there when their new child, Michael, started turning blue. The nurses whisked the newborn off to the nursery without telling Lee anything was wrong. It was then that a doctor noticed the characteristic features of Down syndrome: floppy muscles, eyes that slanted upward. They got Michael breathing again, but doctors thought his prognosis was grim. They gave Michael just a few months to live. A daisy chain of physicians was called, and Lee says it was a pediatrics professor who told her husband what had happened. Then Len was dispatched to tell Lee. She remembers the moment with uncharacteristic emotion. “We hugged each other, and it was a terrible conversation to realize that you’d lost the baby, but the baby was lost,” Lee says now. “We knew immediately what we’d do – we had already made the decision that it was not a good thing to take the baby home, and so we didn’t.” In the 1960’s -- an era before neurodiversity movements and early intervention programs -- many people still called people with Down Syndrome “mongoloids.” Playwright Arthur Miller institutionalized his son, Daniel, in 1966; a few years later, an article in The Atlantic Monthly argued that “a Down’s is not a person.” Lee and Len Herzenberg had seen friends struggle with the birth of a child with Down syndrome and even gone with a colleague to an institution, where he dropped off his own infant daughter. So, they made a choice: Michael would never come home. But Michael wasn’t lost. Michael’s birth sparked their search for a blood test that has revolutionized prenatal care in this country. Lee Herzenberg with her son, Michael. (Mary Harris) --- I made the mistake of telling one scientist I was reporting about “Len Herzenberg’s lab.” He corrected me instantly: “Len and Lee’s lab”. Because Lee Herzenberg was “leaning in” decades before Sheryl Sandberg coined the phrase. At 81, Lee, a professor of genetics, is still running the lab she and her husband founded more than 50 years ago. Len died in 2013. The lab is a quirky place, even by Stanford standards. Lee rarely sits on chairs, preferring cushions on the floor. She’s often accompanied by her bichon frise, Gigi. Researchers can often be found working in this basement office well into the night. But Lee Herzenberg isn’t just quirky: she’s one of the few -- possibly the only -- professor at Stanford never to have officially graduated from college. Instead, she trained by her husband’s side, auditing courses while he got his Ph.D. at Cal Tech (women weren’t allowed to attend at the time), and working at his labs at the Pasteur Institute in Paris and the NIH. And the science that’s done here has changed the course of medicine. The Herzenbergs are best known as the creators of the modern-day fluorescence-activated flow cytometer, or FACS. It was a machine born out of frustration: Len couldn’t stand squinting down a microscope looking at cells. Before the FACS, a biologist looking at slides could feel like he was playing a really intense round of “Where’s Waldo”, staring at crowds of all kinds of cells, trying to pinpoint the exact one he was looking for. Not only was it annoying, Len Herzenberg worried it wasn’t particularly scientific. He wanted a way to find and describe cells that didn’t rely on his worn out eyes. The FACS was used to diagnose AIDS - because it can quickly and easily sort out T-cells. The FACS was used to find the first stem cells. When Len Herzenberg died, one colleague told The New York Times that “without Len, tens of thousands of people now alive would not be.” But in the 1970s, the Herzenbergs were still proving the value of this machine. That’s when they started thinking about using it to create a blood test for Down syndrome. Len Herzenberg had seen research from Finland claiming it was possible to see a fetus’ cells in a mother’s blood. It was hard to believe. But he knew that the FACS, with its nearly magical sorting capabilities, could figure it out. So he took on a medical student named Diana Bianchi as a research associate and made sorting out these cells her project. If they isolate these cells, he could know a lot about the developing fetus, including whether the fetus had chromosomal abnormalities. “They had a very personal reason for doing this, because of their son, Michael,” Bianchi says now. “They wanted to have a test that could be offered to any pregnant woman – that would be noninvasive and would allow them to know if child had Down syndrome. The first step, however, was to show that you could pull out fetal cells.” Scientists now estimate that for every 200 billion cells in a mother’s bloodstream - about 10 of those are fetal cells. Bianchi was one of the first people to see them. The New York Times quoted Len Herzenberg saying it was a “first step” towards a blood test for Down syndrome for all pregnant women. But it would take thirty years for a practical test to become a reality. As it turned out, Len Herzenberg's FACS wasn't the right tool for prenatal diagnosis. There weren’t very many fetal cells to be sorted, and if a pregnant woman already had children, scientists couldn’t be sure if the cells in her blood came from the current fetus or one of her older kids. But in 2008, Len helped ensure the right tool was found. A researcher named Stephen Quake had discovered a way to sequence chunks of fetal DNA floating in expectant mothers' blood. As a member of the National Academy of Sciences, Len made sure the paper was published in the academy's journal. Another researcher, Dennis Lo, confirmed Quake’s findings. Three years later, the tests were on the market. Now, at just 10 weeks into a pregnancy, a whole range of things can be revealed with this test. Not just Down syndrome, but a host of other chromosomal abnormalities as well as the sex of the child to be. Until this test, doctors had to rely on amniocentesis, an invasive procedure that involves-- inserting a needle in the womb to sample amniotic fluid, or biopsying the placenta -- to tell them with any reliability whether a fetus had a chromosomal abnormality. These tests aren’t just uncomfortable, they come with a risk of miscarriage. By some estimates, in the last five years the number of these procedures performed in this country have plummeted by more than 50 percent. To some parents, this knowledge can be alarming. Advocates in Ohio are trying to pass a law preventing abortions if Down syndrome is the reason (North Dakota and Indiana have already passed similar laws). Lee Herzenberg is honest about what she would have done if she’d known early on in her pregnancy that Michael had Down syndrome. “I’d say if I had the choice of not pushing Michael into this life – if I at that time would know I was carrying a Down syndrome child -- I would have aborted the child,” she says. “I see no reason Michael has to live the life he leads. The fact that we’ve made it very happy for him or that he’s made it very happy for us -- all of that is adapting to a situation, but I don’t think it’s fair or proper.” But Lee Herzenberg is alarmed that these tests are now being used to determine the sex of unborn babies. She worries about parents choosing to abort girls. -- Diana Bianchi, that medical student from the Herzenberg lab, is now a professor at Tufts, where she founded the Mother Infant Research Institute. She’s still working in prenatal testing. In fact, perfecting these tests has become her life’s work. But her focus has shifted. Now that she can detect Down syndrome so early, she wants to treat it early, too: in the womb. Because finding this chromosomal abnormality at 10 weeks means there’s a window of opportunity: The brain changes associated with Down syndrome don’t occur until a month or so later. Theoretically, you could treat a fetus before some brain changes occur at all. Bianchi’s work is still early. She’s experimenting with mice, giving them existing drugs in utero to see if she can forestall brain damage. There’s an often-quoted statistic, that 90 percent of parents who find out that their fetus has Down syndrome will abort. But that statistic is from a study done in the United Kingdom. In the US, far fewer women terminate. “We have to unpack this connection between prenatal testing and abortion,” she says. “We have good data to suggest that approximately 40 plus percent of women who know their fetus has Down syndrome continue their pregnancy. There are many women who speak very highly of the fact that this allows them to prepare.” -- The photos that Michael keeps in his room. (Mary Harris) The Down syndrome baby who kicked off the search for this blood test is now a 54-year-old man. He lives in a squat house in Redwood City, Calif., just a 30 minute drive from his birth mother’s home. For years, Michael lived with a local woman named Barbara Jennings, who raised a number of children with developmental challenges. The Herzenberg’s pediatrician helped them find her when Michael was a newborn. The Herzenbergs would visit Michael every month or so, but they never felt they should bring him home. When Barbara died, Michael moved to this group home. It’s hard to know how much Michael understands when I talked to him, though he’s learned to read and use a cell phone. And he’s stubborn. A lot like his mother, actually. “Michael has the hardest head in the whole world,” says Janet Thomas, the caretaker who runs this house. “He does whatever he wants to do. He does not care whatever you say. He’s going to do whatever it is he wants to do -- that’s Michael.” I asked Lee if she ever regretted not raising Michael, and she said no. “It was a decision that was selfish if you like, because we had things we wanted to do. In retrospect, a lot of things would never have gotten done. There would be no FACS had we decided to do this. Because it would have been a very intensive kind of upbringing.” As for Michael, he clearly loves his mother, no matter what she decided. In Michael’s room, there are photos on almost every surface, with snapshots of his biological and adopted families. In the corner is a huge poster of his father, celebrating when he won the Kyoto Prize for his contributions to biotechnology. And deep in one album, there’s a picture of Len and Lee together. The caption reads “Michael’s other mom + dad.”
Stephen Quake discusses rapid DNA sequencing and treating medical patients based on their genomes.