YouSaid · the spoken record

Jeffrey H. Cohen

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34

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2017-02-22

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2017-02-22

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1

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1. “Yeah, a standard sort of Mendelian disorder would be cystic fibrosis, where you have basically issues in the lung, and it really is driven by mutations in a chlorime channel. In the case of sort of complex disorders, we're talking about things, you know, things related to sort of metabolism, where you have lots of genes contributing. Those are definitely controlled by lots of different variables. And genetics plays a role in both of those. And I think it's really important that we remember which type of disorder we're talking about when we think about how we're applying AI. And we think very carefully like, okay, what is the features and types of data that we're correlating with these?”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

2. “Here, I think there's a really important distinction to make in genetics, which is there are Mendelian disorders where the phenotype is correlated with single genes, and there's estimates are that there's at least 7,000 of them, and we know like 3,500 of them. And then there's complex sort of phenotypes. Maybe give examples of what”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

3. “You need to really think about that and realize there is an optimum for you in terms of what kind of food you eat, how you exercise, how much you sleep, things along those lines that really minimize those kinds of events. Right now, patients have zero idea how what they do in their lives actually correlates to any kind of changes in that space. That is a huge big data problem that's just starting to get deconvoluted and that's where the machine learning can really step in and figure out those kinds of interactions and correlations for us so that we can provide it to the consumer.”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

4. “Yeah, and just adding to that, because I completely agree with that. From the patient's perspective and the consumer's perspective, what the learning engine can really provide is a way to make sense of all of that data in a way that pertains to them. These kinds of things, Apple watches, Fitbits, and things like that, phenomenal at gathering data, right? Very bad at telling you what that actually does for you or what that means for you, right? On average, an average human being makes 12 cancer cells every minute. Sorry to freak out people in the audience.”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

5. “To add to that, when you think about really what I mean, AI is it just lets us combine a lot of different variables. Make predictions, but we live in a world where Google and Facebook use millions of variables to predict which ad we're going to click on or whether or not we can repay a loan. But we try and reduce disease to single variables, and that's happening in genetics right now with a single nucleotide variant. We want to say if you're going to get breast cancer, that's crazy, honestly. Human body is an extremely complicated system to build predictive models based on a single variable, which is exactly what clinical studies do, because what they're designed to do, really, is pretty asinine. And I think we have to think about why it's true in one place and not the other part of society. And I think that applying machine learning is really just applying a tool that lets us look at far more information. I mean, can you imagine somebody in real time trying to figure out which ad you're going to click on better than Google? It's just things to look at.”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

6. “We see that as a fantastic place for machine learning. And in fact, the American College of Medical Genetics has guidelines for the use of computational tools in this space. And so that's really one of the key places where we're focusing on entering because we know that today we can make those tools 35% better and that we're happy to distribute these tools as a horizontal across lots of different genetic test providers and not in”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

7. “So we at Jungla have sort of realized that in this explosion of genomics entering more and more of the clinic, what you see is that there is this really large growth in the amount of uncertainty around genetic tests. And it's kind of ironic that when you look at even some of the most abundant, larger volume, genetic tests, these are cancer gene panel tests for basically hereditary risk of developing cancer. Those tests will basically find 95 mutations that they have absolutely no clue of what the effects of those mutations are in these important cancer-associated genes per each mutation that is known to cause disease. So when you can only interpret basically one out of 96 mutations in this space, it's kind of ironic that we call it precision medicine.”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

8. “Actually, as you talk about that, in order for us to get to that, well, we do definitely need to have better diagnostic tests, higher quality, lower cost. And we're very long AI in Silicon Valley. We think AI plus any industry leads to a giant company in that industry generally. AI plus cars, AI plus radiology. What is AI plus genomics look like?”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

9. “So it really needs patient and consumer buy in, but that's partly on them, partly also on the technology companies making it easier for them or enabling them or certainly motivating them in certain ways.”

   2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

10. “I think it's important to remember to patients and the consumer's role in this because it's really not going to work without the patients and consumers opting into these kinds of behavioral changes. Effectively, we're asking people to look at your health in a different way. Because Jeff brought up the dentist example, we brush our teeth every day, and hopefully every day. Twice a day. usually have annual checkups and things like that and we don't really expect to go to the dentist after 20 years of not brushing our teeth and expecting them to you know make our teeth perfect right but that's exactly what we ask of our doctors today yeah it's like people treat their bodies terribly and then when they are you know on the verge of death they go to doctors and then say you know make me perfect”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

11. “To get you as a customer because they know eventually you're going to need a root canal, right? And that's when you pay. And so they take the preventative approach saying it's inevitable, we're all going to get sick, we're all going to die, and that's when we should get paid. We're going to try and keep you healthy until then. Very fundamentally different approach, but healthcare nonetheless.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

12. “Well, think about dental care in the United States. That's actually a preventative, I would argue that that's the one of the best preventative healthcare systems in the world. How does it work? Twice a year, you go get the same set of things basically measured about your body, and we develop hundreds of millions of longitudinal medical dental records tied to outcomes. So there's this positive feedback loop in the dental industry where actually if you look at the cost of dental care over time, it's flat or down in inflation adjusted dollars, and the quality of the care has gone up. If you look at the exact same period of time in healthcare, it's the exact opposite trend. Care in a lot of ways is getting worse. Costs are skyrocketing. And so I think it's worth kind of asking, what is the difference? And in the dental care system, there are dentists who give away checkups.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

13. “Fair point. I think there's a really good opportunity. As you bring down the cost of these tests and you have consumers able to directly pay for them or sometimes actually go outside the US, there's a lot of countries where it's either single pair or it's very much self-pay and consumers are used to paying for themselves like in India.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

14. “I think fundamentally the point that I bring up is that if you think about who the pairs are in healthcare right now and you think about the actuarial models that have been built, they're completely reactive and backwards looking. And all of these new technologies which genomics, transcriptomics, proteomics, metabolomics, microbiomics, all this stuff is really much more powerful as a preventative tool. And so how do you convince an entire industry that looks as spending a dollar as a dollar lost that when you have these tools that you say can in the long run save money but they're preventative? It's not like we don't want to spend money when somebody's already sick and that's the fundamental problem that any of these new technologies have when you're trying to find who the payer is. And so I think it's not clear to me that the existing payers will actually ever come around to that.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

15. “And so one of the things that we're really working on is how can we empower the patient with the right essentially genomic thermometer, if you will, to give them a sense of what kind of things can they eat and how much should they exercise for that particular individual to maximize their wellness and avoid chances of getting these kinds of diseases? I like that model because we don't have to talk to peers. We don't have to deal with a lot of people. All we have to do is make sure that that test gets to a price point that's affordable for the vast majority of people.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

16. “That's why we spend 80% of the money on right now. That's really unacceptable. And the fact that it's such a high percentage really in some ways makes my argument is if we create an accurate enough cancer test that detects the disease early enough when it's actually treatable, we save that 80% of the money. And so when dealing with the payers, it's really about listening to them and for them, what kind of evidence do they need to really show that we can save that 80% for them that they're reimbursing? And then, of course, we already talked about the wellness angle is if and when I do get fed up with the payers, which maybe sometimes soon, there are other opportunities to explore, especially because FDA has released guidelines around a wellness space and they basically said that patients have the right to choose their own lifestyle choices, their diet and exercise, and how that can potentially affect their wellness.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

17. “Sure, one thing I always like to point out is 80% of all the money that we spend on treating and dealing with cancer in the healthcare system in the United States is something about between 75 and $100 billion a year is to help people die.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

18. “I want to chime in on this on the challenges for commercialization because they are really important to all of us. And I completely agree. There's challenges in the regulation side. There are challenges in the reimbursement side, which are coupled to that. And there's challenges also in showing value to customers, showing clear, understandable value of the products that they're buying in genomics. And I think that kind of couples to what Gabe was saying earlier, that we need more phenotypic data, more clinical data, for example, to support the value of decisions or guidance that we can get out of genetic information. Now it stands to reason that we didn't have hundreds of thousands of genomes a few years ago. And so we didn't have hundreds of thousands of genomes coupled to EHR systems. But that's definitely the way that a lot of this is moving. And being able to access that information is going to be able to test how well do different models distinguish between different outcomes on the basis.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

19. “I agree with everything Gabe just said, but I think there's also kind of a societal and ethical question of what rights do we have as patients to have information about our bodies? Because there are regulatory bodies that say, if you look what happened to 23andMe, effectively the argument for shutting them down was, well, if you say I have an increased risk of breast cancer and then I go home and cut off my own breasts and die, then twenty-three and me is liable. Now, that seems a little strange to me considering we live in a world where there's like a surgeon general's warning on alcohol and cigarettes and we know that's just bad for you. So we have to ask ourselves, is it reasonable that we have access to this information and can we be responsible as patients for having access to that information rather than someone telling us it's dangerous for you to have access to that information? And I think that's a big question that I don't think”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

20. “Save me money now, not 10 years from now, not five years from now when this person is dying of cancer, but like, is it going to save me money now? So I think from a business model perspective, there's a lot of opportunities to really work in, I guess, what's broadly known as the wellness space. And as our technology improves and we can start detecting diseases so early that we can affect even lifestyle changes to potentially avoid certain types of diseases, I think that's really the future that we need to head towards because consumers are getting screwed over by this sort of old style mentality of is this has really going to save money for the payers or not. I think most people in this room can agree that detecting cancer earlier rather than later is probably a good thing. So I don't think there's an argument from a consumer perspective. It's really the pairs and some of the clinicians that are being the inhibitors to this progress.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

21. “You do point out at a really interesting point, which is when I talk to clinicians, when I talk to pears, it's often an argument about whether detecting cancer is a good thing or not, whether that will lead to what they care about, which is sort of savings on the medical system. I think the really interesting thing is we've been used to doing things a certain way. Like in the field of cancer screening, cancer diagnostics, we're used to really, really bad tests. So PSA for prostate cancer detection, mammography for breast cancer detection, these things have false positive rates of anywhere from 50 to 75%. You're literally better off flipping a coin than taking one of these tests from a false positive perspective. And so, yes, of course, if our tests are that inaccurate, it's going to lead to all sorts of downstream unnecessary procedures that adds burden. But so many people have that mentality where they basically say, we're not going to reimburse this unless your test”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

22. “Part of the challenges I think diagnostics field, genomics field has had our healthcare system, which is you need to convince a payer, an insurance company, to reimburse you, then you need to also convince a doctor to prescribe that test. And only once you get both those parties on board can you actually go to market. That's a lot of people to convince. And really, the only person you should be convincing is the patient who is nowhere in that equation at all. So are there other ways to get to market that are compelling? Maybe you could that could break past those barriers”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

23. “I think that the most immediate or obvious places, and I think Russ Altman at Sanford is doing really interesting things here, is using genetics to determine which drugs you're most likely to respond to. I think that that is the lowest hanging fruit. I think in order for genomics to be used in diagnostics or predictive models, are you going to get sick, I think it has to be combined with actual time series biomarker data, which is a longer potential discussion.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

24. “Sure, is it a tool that we use to determine if you're sick, or is it a tool that we use to help you heal if you are sick? And I think that if you look at just a single shot whole genome sequencing, I think there's another question to ask if you want it to use it diagnostically, which is at what point is a prediction a diagnostic? And I think that's a little bit of a question like saying if I keep taking a grain of sand off of a pile of sand, at what point is it no longer a pile of sand? Because if you think about the expectations in healthcare, a doctor really most of the time is expected to give a binary decision of are you sick or are you not? Looking at a whole genome sequence for the vast majority of cases, it's just going to give you a statistical likelihood of diseases you may be more predisposed to than another person. But it will be almost entirely environmental factors that determines whether that's expressed.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

25. “So, you know, a simple example is when you get blood sample and I'm extracting DNA from that to try to understand the genomics behind whether this person has cancer or not, I need to know whether that person had cancer or not. I need to know whether that person was male or female, what age, some kind of background information about that person so that I can properly annotate that the physical characteristics. Yeah, exactly. It's a physical characteristics. And what's been severely lacking is a deeper understanding of the phenotypic information that we can associate back to genomic information, something that almost everyone that's doing research in genomics would agree it's really hard information to get and it's really hard to get really clean information around that even when you get information.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

26. “The genes do what, and that's really what mutations target. So that's, I think, one fundamental layer that's really missing for a lot of the applications that we pursue of genetic genetic. I think applications have also been extremely limited because one of the things that you need to understand genomic data is also phenotypic information associated with that.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

27. “Okay, so I think we've done a pretty good job at being able to acquire sequence information. Some of the fastest advances in technology in the history of mankind. Actually, only beat by one other technology, which is the clarity of glass improved at a faster rate over a period of time. But getting basically access to this information doesn't mean understanding it. And so I think one of our sort of views is that a critical missing component here is basically the maps of function for how we're going to interpret mutations in here. We're getting large numbers of individual genomes for people that are changing because they change over their somatic tissues. They develop tumors, et cetera. All of that is information that we need to put in context. We need to be able to associate mutations that have similar effects. And unfortunately, the maps that we have today are really maps of function that just say where things that are things like genes, biomolecules, where they are encoded in the genome. But it says really nothing about how they function and which parts of”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

28. “And all the way to sort of clinical diagnosis like what you refer to, noninvasive prenatal testing, for example, where they're doing much more sort of whole genome or certainly whole chromosome-wide sequencing of both the mother and the fetal DNA to essentially figure out the genomic nature of the fetus. So that's more on the diagnostic side. So we really have applications all from sort of germai mutation detection all the way to agnostics and even prognostic methods. So let's get back to”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

29. “You can do things like 23andMe, which looks at less than 1% of the entire genome, looking at specific mutations that you were born with and what that can tell you about who you're going to be. That's largely predictive and very probabilistic.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

30. “It just means that the rate at which your DNA is copied in your body per second is about 500 terabytes. So if you think about the error correction codes, It's kind of an honor to be up here. These guys are biologists. I'm a physics and computer science, so I look at biology as an information theory problem. But going back to what Gabe said, when you think about, all right, well, 500 terabytes per second, what kind of error correction codes do you need in order to make sure that information is copied correctly? And when you think about diseases like cancer, really those are information corruption problems. And when we talk about solving cancer, it's a little bit scary also because that information corruption is what allows us to evolve. So I think when I met Gabe, it was very exciting to me because it was one of the first or the first person on the biology side that really thought of DNA as actually this thing that was much more dynamic than this thing that could be single”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

31. “Agree with that. I think Gab was just referring to the fact that we were talking a little bit earlier this morning and did some back of the envelope calculations. And I think the data transfer rate of somatic DNA in your body is about 500. Terabytes”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

32. “But your genome changes at a ridiculous rate, and the fact that we thought taking one person's genome at one snapshot was going to answer every question about diseases and things like that was just ludicrous in retrospect.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

33. “Is probably one of the largest big data problems out there. There's three billion bases in the genome. And if that was all, we probably would know a lot more about the genomics and what it can tell us. But unfortunately, that's really just the beginning of that whole picture. Not only the way we call, right now, each one of those bases and how we call them is probabilistic, not deterministic in nature because our technology doesn't necessarily allow us for a deterministic call. So there's sort of a confidence interval around calling mutations, but then there's also this idea that your DNA, your genome is not static throughout your lifetime. And in fact, I'll let Jeff talk about this because he did some math this morning around this.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source

34. “Yeah, thank you. The Human Genome Project is really or was really biology's Apollo program. It was the first large-scale biology project that actually took billions of dollars to complete a coordinated effort across a large number of teams. It set out with the mission of providing basically a first draft sequence that was published in 2001 and later refined to a high quality reference genome that we can all view. Now this is a reference x-ray of what a quote unquote normal genome looks like. And although that functions as a foundation for a lot of basically learning about our origins, our biology and health and disease like the Apollo program, a lot of the value from the Human Genome Project isn't just that reference sequence, but it's also the technologies and concepts that were learned and developed therein.”

    2017-02-22 · a16z Podcast · a16z Podcast: When Will Genomics Live Up to the Hype? · IDENTIFIED FROM THE TRANSCRIPT · source