The Bioinformatics CRO Podcast

Episode 55 with Mo Jain

Mo Jain, Founder and CEO of Sapient, discusses the importance of small molecule biomarkers and his approach to biomarker discovery research.

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen on Spotify, Apple Podcasts, Google Podcasts, Amazon, and Pandora.

Mo Jain

Mo Jain is the Founder and CEO of Sapient, a biomarker discovery CRO using next-generation mass spectrometry technology.

Transcript of Episode 55: Mo Jain

Disclaimer: Transcripts may contain some errors.

Grant Belgard: [00:00:00] Welcome to The Bioinformatics CRO Podcast. I’m Grant Belgard and joining me today is Mo Jain of Sapient. Welcome.

Mo Jain: [00:00:07] Thank you so much, Grant. Pleasure to be here today.

Grant Belgard: [00:00:10] So tell us about Sapient.

Mo Jain: [00:00:12] Absolutely, Grant. So Sapient is a discovery CRO organization which is really focused on biomarker discovery. And the way we operate is through leveraging novel technologies, particularly in the mass spectrometry sector in order to enhance human discovery. And we primarily serve as a partner for large pharma, early biotech, and even some foundations to help them in their biomarker discovery efforts as part of their drug discovery work.

Grant Belgard: [00:00:39] Can you tell us about the history of the company?

Mo Jain: [00:00:41] Yeah, absolutely. The concept of Sapient admittedly dates back almost two decades now. I’m trained as a physician, and one of the common questions that one receives when treating patients is, why did I get this disease? How do I know next time if this is going to happen to me? How can I protect my loved ones and family members? What are the diagnostic tests that I can use to know if I’m going to respond to this drug? And one of the really humbling aspects of medicine is, despite the massive amount of knowledge that’s been gained over the last several hundred years, really what we still understand and know represents a very, very small fraction of all the knowledge there is to know. And for most of these very insightful questions, the answer typically is I really don’t know the answer. And at this time, when I was in the midst of training, the human genome was really coming to fruition in the early 2000, when the initial draft of the human genome was reported, and genomics was going to revolutionize the world as we know it. And the basic idea behind this was by understanding the basic blueprints of human life. We could leverage that information to understand how healthy or not healthy you may be over the course of your existence, what diseases you were going to develop or predispose to, what drugs you were going to respond to, and essentially we would be able to transform the way we think about diagnosing and treating human disease.

Mo Jain: [00:02:06] The challenge has to do with the fact that however the amount of information and the type of information that’s encoded in the genome doesn’t actually enable that to happen in most cases. And at the time when I was in the midst of training and I apologize for the long answer, you’ll see where I’m going in a moment. But at the time of this, we were doing a thought exercise, and that is well if we could parallelize sequencing to the nth degree, and if we essentially could line up every single human on the planet, and we knew everything about everyone and we sequenced everyone’s genome, how much of human disease could we explain? And the hope would be 80, 90, 95, 98%. In actuality, when you look at the numbers and there’s many ways you can calculate this as a heritability index, population attributable risk index, etcetera. But the true answer is probably somewhere in the 10 to 15% range. And that’s a theoretical upper limit. If you really look in actuality, the numbers probably in the single digits for how much of human disease we can truly explain through sequence. And perhaps that’s not surprising that we know the way in which you live your life. Your genome is set from the moment to conception and the way you live your life. Everything you eat, drink, smell, smoke, where you live, how you live, we know is massively important in how healthy or not healthy you’re going to be over the course of your existence.

[00:03:25] And none of that information is captured in your underlying genome. And so I became very interested in that 85% of population attributable risk that’s not encoded in genetic sequence, understanding once again, diet, lifestyle, environmental factors, how one organ system may communicate with another organ system, how the microbiome that’s part of our gut and skin and saliva influences human disease. Again, none of that information is encoded in genetic sequence. But it turns out that that’s encoded in small molecule chemistry. So when you ate something for breakfast or lunch or dinner depending upon where in the world you are and what time it is, that gets broken down at your gut into small molecules. Those small molecules enter it into your bloodstream. And because we all eat only healthy things, they do good things in our organ systems and allow us to be healthy over time. And the basic premise is that well if we could capture that information, if we could take human blood and probe the thousands of markers that are floating around in human blood, we can begin to understand how humans interact with their environment both internally as well as externally, and leverage that information now in the way the genome was supposed to in understanding and predicting who’s going to develop what diseases over time, how long someone may live, whether or not I’m going to respond to a particular drug A versus drug B et cetera.

[00:03:25] So that was the basic premise. Now this is not a new idea. Every year you go to the doctor. They draw two tubes of blood, typically about 20ml of blood. And in that, we measure somewhere in the order of 12 things to 20 things depending upon the test you get. Half of those are small molecule biomarkers, creatinine and cholesterol levels, glucose etcetera. The challenge is that there’s tens of thousands of things floating around in your blood, and we’re literally capturing less than 0.1% of them. And so how do we develop technologies that allow us to very rapidly measure these thousands of things in blood, and to do this at scale across tens of thousands of people in a manner that allows us to discover, well, what are the next 12 most important tests? What are the next 12 after that? And how do we leverage this information at scale to to really predict and understand the human condition at its earliest disease points? And so that was the basic premise of Sapient. It was born out of academia, where we spent the last decade prototyping and developing these bioanalytical technologies. And as these were coming to fruition, we spun them out to form Sapient and that’s how we came to be today in.

Grant Belgard: [00:05:47] The work you’ve done at Sapient, have you seen a large number of complex, non-linear, non-additive interactions among factors, or are you finding the major signals are things that can be reduced to more simple and straightforward guidelines looking at LDL and HDL, new markers along those lines?

Mo Jain: [00:06:11] Yeah. The simple answer is both, which I recognize is not all that helpful. But it comes down to what type of predictive analytic you require, what’s the threshold that you require for actual diagnosis. Now often times for virtually all cases, you can reduce down information to a single marker or at least what I would say is a practical number of markers, somewhere below half a dozen that we can measure under the most stringent of laboratory methods clinically in hospitals around the world, and provides us the information we need to know. That works well. You can imagine in the same way, cholesterol is highly predictive of those individuals who are at risk for heart disease. Developing simple tests like that for cancer, Alzheimer’s disease, liver disease, lung disease, GI illnesses, pregnancy related complications, etcetera, etcetera is oftentimes quite functional. And that’s where we spend most of our time at Sapient. At the same time though, as you’re suggesting Grant, much of human disease is non-linear in its etiology. It’s rarely a single case or an additive case of two events that cause disease, but rather it’s a much more complex interaction of many, many different [inciting] etiologies. It may be a genetic predisposition, which increases risk somewhere in the order of several percentile. Added on with an environmental exposure, together with a particular initial acute insult that collectively results in a disease process cascading and starting. And so this is where we’ve become much more interested in taking these very complex data sources, where we’re measuring tens of thousands of things in human blood, and using much more advanced AI based statistic modeling now to be able to much more holistically predict and understand these complex interactions.

Grant Belgard: [00:07:48] How much added power do you see from that?

Mo Jain: [00:07:50] Yeah, quite a bit, which is both an incredible opportunity and is incredibly challenging. As you can imagine, in the same way if you look at a picture, a painting, oftentimes with a very small reductionist view of that painting where you’re looking at only several pixels, you can oftentimes tell something about the painting. This is a blue painting. It’s of the ocean or something to that extent, but with a very, very small snapshot. But as you took a much more global view of the underlying image, that’s where the real granularity begins to emerge. And as we go from simply saying, well, your risk of disease X is Y percentile or it’s increased in this manner to a much, much more holistic view of across these 100 different diseases, this is your sort of combinatorial risk. This is how you want to optimize life and diet. This is how you want to optimize medications specifically for you. This is how we want to develop new drugs. This is where allowing for that complexity is absolutely critical.

Grant Belgard: [00:08:52] Would you say this approach is more powerful for risk of onset of a disease that hasn’t yet occurred or for prognosis?

Mo Jain: [00:09:04] Yeah, it very much depends upon the disease and the biological question. And you can break these down into diagnosis, meaning early diagnosis prior to disease onset or at the earliest stages. Prognosis meaning once disease has become clinically apparent, understanding long term outcomes and then prediction regarding response to therapeutics, which is really the third component of this. And as you can imagine, the added value of more complex modeling versus reductionist testing of single molecules partially depends upon which of those three question baskets you’re in. And then also the specific disease and the complexity and heterogeneity of the underlying disease state. Now the good and bad is we do a relatively poor job of this today. And when you think about a complex disease, whether it be heart disease or diabetes, this probably represents half a dozen or more diseases, all of which have a common end phenotypic variable of metabolic insufficiency or hardening of your coronary arteries that were lumping all together, even though they have very different mechanisms of action that allowed someone to go from a normal stage to an abnormal stage. So even for these very heterogeneous, complex multi-organ systemic diseases, even being able to break it down into those broad categories, what are the four types of subgroups? What are the five types of subgroups can be extremely valuable? But now being able to take that even further and using more complex modeling, these AI based nonlinear approaches where you can be able to say well I’m not interested in the five subgroups, I’m interested in the 100 subgroups and understanding which one of these specific subgroups is going to be optimal for a particular therapeutic. This is where adding complexity and nuance becomes critical.

Grant Belgard: [00:10:43] What is the path to clinic look like for what you do?

Mo Jain: [00:10:45] So this is where it becomes really, really important. And this is absolutely an evolving area that’s changing literally week over week. It used to very much be five years ago that clinical translation had to be dependent upon a single test, a single molecule that was well measured that we could enter into what we call a CALEA Accredited Laboratory. And that was a one test, one diagnosis. That modality and that way of operating has completely changed over the last half decade. And we’ve seen this now. There’s something on the over 100 different tests that are at the FDA that use much more complex ML based algorithms or AI based algorithms for diagnostic purposes. We’ve already seen this in early pathology and histopathology and in radiology, and I wholly expect that the inflection is only starting now. So I suspect that over the near future here, I’m literally talking about the next several years, much more complex, nuanced, blood based testing is going to become the norm. We already see this in a number of conditions, whether it be diagnostic tests, whether it be Cologuard, for instance for colon cancer, whether it be a genetic testing for particular chemotherapeutics in the setting of cancer. We’re already seeing this evolution happening in real time, and I suspect that’s going to not spill over, but extend to virtually every single human disease.

Grant Belgard: [00:12:07] How much of the work you do is brought to you by clients or sponsored by partners versus internal R&D to develop these tests?

Mo Jain: [00:12:17] Yeah, it’s a great question Grant. We’re somewhat multi-personality if you will, let’s say, and that we’re a front facing CRO. So a good portion of what we do over 80% of our time and attention is really based upon servicing large pharma and early biotech and their drug development efforts and simply put there. We’re engaging these sponsors. They’re bringing biological samples to us. We’re analyzing them on our proprietary mass spec technologies, generating that data, doing the statistical analysis, making the discovery, and returning that discovery to them for commercialization as part of their drug development efforts. The other 20%, as you suggested is really based upon our internal R&D efforts. And so at the same time, because we have such ultra high throughput mass spectrometry systems that are capable of generating data faster than any other technology worldwide, we’ve also at the same time been able to go around the world and collect hundreds of thousands of biological specimens internally as part of our R&D efforts, analyze those samples, generate now what is the world’s largest human chemical database. And amalgamate that information in a centralized repository internally here at sapient that we now are subsequently mining for novel diagnostic purposes.

Grant Belgard: [00:13:28] What are the biggest challenges you face doing that?

Mo Jain: [00:13:30] Yeah, it’s a really good question. Up until several years ago, this would have been a simple technology issue. How do we actually generate the data? And I’m very glad to say that the efforts of Sapient have enabled us to generate now and handle data very, very quickly, meaning handling 100,000 to several million biological specimens for mass spectrometry analysis now is no longer a dream effort, but is very practical. It’s a daily ongoing here. So you can imagine that bucket now has been or that can has been kicked down a little bit of the road where it’s no longer a data generation issue. It comes down to a data understanding interpretation issue, whereby how do we take this complex data now and really commercialize it in a way that for the betterment of society. How do we develop the diagnostic tests that are going to be most meaningful. In many ways Grant, it becomes the kid in the candy store problem. If you have massive amounts of data, you can theoretically answer hundreds of questions simultaneously. And so what are the most high yield, high impact questions for different populations that we want to answer first and bring to clinical testing as quickly as possible? And that’s very much a personal sort of question.

[00:14:42] Obviously there’s a business use case behind it. But you can imagine, if you ask a particular foundation that operates in the rare disease space, they may have a particular preference. If you look across prevalence of disease across large populations of adults in the developed world, it’s a very different answer, may be heart disease and cancer, may be basic aging. And if you ask foundations that are operating in low to medium income countries, whereby there’s arguably the greatest need for human health and development, it’s obviously a very different set of questions around early childhood development, pregnancy nutrition and optimisation of in-field testing. So that’s one of the largest challenges that we face on a day to day basis. Now, certainly that’s a good problem to have. It’s very much a “first world problem” as to where you want to go first, and how do you want to operationalize and commercialize a very large data? But it’s a very real problem that I think many organizations that operate in this space are facing every day.

Grant Belgard: [00:15:40] Is there a system you use to make those decisions?

Mo Jain: [00:15:44] Yes, there is. And like the best of systems, you can imagine Grant that it oftentimes goes out of the window within the first three sentences of a discussion. So there’s certainly a lot of business use cases that we think through understanding what’s the addressable markets, what is reimbursed look like, these things that point us in particular directions. But at the same time, we’re fortunate enough just given how we operate, to have a little bit of leeway and the other questions that may be of equal if not greater importance, but may be of slightly less commercial value. And thinking through some programs that we have in understanding maternal nutrition in the developing world, programs that can have massive impact in large numbers of people that can move needles but may not have the same commercial relevance as coming up with a diagnostic test that tells us if we’re going to develop cancer in the next several years. Equally important, just slightly different commercial market.

Grant Belgard: [00:16:37] How do you think about causality or do you think about causality? Are you just really focused on strong associations? What’s the most predictive regardless of causal relationships?

Mo Jain: [00:16:46] It’s a fantastic question, and I’m happy to provide an answer. But ask me tomorrow and I’m sure I’ll give you a different answer. And as you can imagine, this is one of those things that fluctuates quite a bit. In the end, it depends upon what you’re using that information for. So let me give you an example, HDL is an extremely strong predictor, stronger than any other predictor for heart disease over time. But it’s still very questionable whether HDL itself is causal for coronary disease. We call it the good cholesterol, but likely what the evidence really points to is that HDL is reading out some other phenomenon that’s actually the causal agent. Now if I want to understand what my heart disease risk is over time, I just need a valid correlation that we know is specific and is statistically rigorous over time. And so HDL serves that purpose for me. Now, if I want to develop a drug and I want to use as a marker of drug efficacy HDL, well then having a causal association becomes much, much more important. And we spend quite a bit of time thinking through this process, because our goal is not only to come up with diagnostic markers, but to develop new drug targets and to validate those targets to develop new nutraceutical and natural product based therapeutics et cetera, et cetera.

[00:18:01] There’s a lot we can do with this type of data. And part of this has to do with understanding that causal question. And this is where we do quite a bit of multidimensional data integration, particularly with genomics information together with these small molecule biomarkers. In essence, doing a Mendelian randomization type of approach from which we may be able to infer causal relationships. And as you’re well aware having worked for many years in this space, MRI based analyses particularly MR bidirectional is very useful when it works, but in the absence of information, doesn’t necessarily negate causality. And so this is the way we certainly think about it. Again, it all has to do with how you want to use that data and what’s the objective function. In the end for a diagnostic test, it just a matter if it accurately diagnoses and predicts people who are at risk of a disease state.

Grant Belgard: [00:18:51] How important is longitudinal data for what you do?

Mo Jain: [00:18:54] Very, very important. And I think one of the lessons that we learned from the genomic revolution, well there’s several things that we learned. One, the genome as I suggested earlier on, really imparts a minority risk of human disease, who our parents are, what occurs at that moment of conception when a human is formed, that really provides only a very small amount of predictive capacity for what’s going to happen to us over the next 100 years of our existence. That’s the first lesson. The other lesson that we’ve learned is that human disease is a very dynamic process. Health is ever fluctuating. On different time scales certainly on a decade long time scale, but even on a day to day basis, in an hour to hour basis, when you really dive into the nuance, if I slept last night versus if I slept one hour last night, I probably have a different health state today. Now, the impact of that may not be relevant over many, many years, but certainly you could argue that I’m healthier because I slept or didn’t sleep, or if I ate correctly versus didn’t eat correctly. And anyone who’s ever gone out and had an interesting night and woke up with a hangover can agree with that. And so being able to understand that dynamic nature is critical. Now your genome for the most part, your somatic genome is fixed from the time of conception and doesn’t change over life. And this is where diving into dynamic market, particularly these small molecule dynamic markers that read out communication channels between our internal organ systems, between the external world and the world, and our internal sort of physiology between things like diet, lifestyle, microbiome, toxicants, etcetera, etcetera. This is where small molecule biomarkers are particularly important. And because of their dynamic nature, they have the ability to change quite quickly, which can read out almost in a real time fashion particular health and disease states.

Grant Belgard: [00:20:41] What challenges have you run into collecting longitudinal data and integrating that with clinical data? And I guess I’m going to ask a multi-pronged question here. Have you done this in health systems outside the US? And do you have and experience comparing and contrasting the data you get from different systems?

Mo Jain: [00:21:04] Yeah, as you can imagine, there’s a couple of different parts to the question, all of which are really important. I’m going to answer the final part first. I firmly believe that humans are all equal, but not identical. And one of the core components is where geographically in the world in which we live. And you know the famous quote that best summarizes this is that it’s not your genetic code, but it’s your zip code that’s a better predictor of disease. And statistically, that’s absolutely true. Based upon your geographic zip code, we typically have a better handle on your underlying long term risk of disease than anything else. And so certainly geography plays a huge role in this. It’s one of the core aspects of our interaction with the world. And you can imagine geography feeds into everything from the degree of sunlight, the type of water, the type of diet, toxicants that are local to that environment, socioeconomic state and access to health care. There are so many aspects that are fed into underlying geography. And so this is where our ability to broadly biological samples as well as individuals from around the world has been critical. And so as you can imagine, there’s value in identification of universal diagnostic tests that work independently of where you are. If you’re in Sub-Saharan Africa, if you’re in sunny San Diego, if you’re in Western Europe, it doesn’t matter. The test reads out what it should read out.

[00:22:19] And there’s also secondarily value in having localized or population specific tests, not something that traditionally in medicine we’ve done. But if it’s the case that there’s particular exposures that are unique to a given environment, those are a key determinant of a given disease in a particular location. To not sample that information and use it is silly to me. And so we oftentimes are looking for both of these. What you can find is there’s certainly universal realities and universal markers that denote health and disease states over time or drug response. But there’s also geographically localized markers that may be unique in specific populations, owing once again to diet or whatnot that may be unique to that environment. And I think both of them have the value in understanding the human condition. There’s certainly some practical issues and considerations. We’ve been very fortunate to have a number of relationships with top academic medical centers around the world. And the simple answer is that there’s more biological specimens and there’s more data available in the world than people are using. So it’s there if you’re willing to work within the constraints of the legal constraints of accessing it and whatnot. The real challenge is one that I suspect you’re alluding to, that everyone who works in the large data analytics space has learned one way or the other over the last decade, and that is garbage in, garbage out. I don’t care how good your metrics are. If the data is fundamentally not clean, and if you’re not conditioning on high quality data then you’re just leading yourself astray.

[00:23:53] Now, that doesn’t mean data has to be pristine. I’m actually quite a bit of a fan of using real world data because you want there to be noise. When you see signal emerging from that noise, you have much more confidence that that signal is real, as opposed to pristine data that may be present only in a phase three clinical trial. And then when you extend those same markers to the real world, you see that they have less of an effect that they should, simply because there’s now other confounding factors. But in the end, as much as I’m a fan of our technologies and the type of data we generate, having clean phenotype data is absolutely essential. And so we spend quite a bit of time internally here at Sapient, thinking through ways in which we can clean human data. We can QC that data, we can sanity check it. And ensure it’s of the highest quality otherwise you’re just leading yourself astray. And certainly there’s very, very large data assets out there and data sets out there that are of less than stellar quality. And oftentimes those don’t result in any real meaningful discovery.

Grant Belgard: [00:24:52] Are there any go to external datasets that you’ll look to for validation of what you’re seeing at Sapient?

Mo Jain: [00:25:01] Yeah, it’s a really good question Grant. And this is one I’ve been in the challenges from an R&D perspective for us personally in that when you think about the molecules that are floating around in your blood right now. There’s tens of thousands of these molecules floating around in you Grant. Somewhere in the order of less than 5% of these have ever been measured, analyzed, structurally elucidated, or understood in any meaningful way, which means more than 95% of what’s in your blood right now is a black box. And so this is where I have challenged sometimes using external sources for validation, because they’re very much couched within that 5%. This is the same as the light pole, if you will effect where everyone is looking under that same light shade or lamppost at the same several dozen to several hundred molecules, whether it be genetic factors or small molecule biomarkers or protein biomarkers when the real signal lies outside of that initial light. And I’m a big fan of jumping into the dark, even if it’s sometimes a little bit challenging. And so what this ultimately ends up meaning is that we end up doing quite a bit of validation ourselves, simply because the current publicly available data assets, or even proprietary private data assets are really not of a nature that allows us to adequately validate or not simply powered for true discovery in this space.

Grant Belgard: [00:26:22] What is the future hold for Sapient?

Mo Jain: [00:26:24] Yeah, it’s a great question. The simple answer is I frankly don’t know. There’s obviously many things that we’re hoping to do. I very much believe in our service orientation and really accelerating the drug development process and pipeline together with our sponsors, whether they be large pharma organizations, small medium biotech foundations or governmental organizations. There’s tremendous value in that work that we see. And if we can help bring drugs to fruition, well, we’ve had a good day. At the same time as I mentioned earlier Grant, we’ve already generated the world’s largest human chemical databases, and they’re growing exponentially month over month. That provides some very, very unique opportunities that we have an obligation to bring to clinical translation, whether it be around new diagnostic tests, whether it be around better development and designing of clinical trials, whether it be an understanding and bringing means forward whereby we can predict who’s going to respond to particular therapeutics, whether it be developing natural pharmaceuticals, natural product pharmaceuticals themselves de novo. There’s a tremendous amount that we can do with these data assets. And that’s where I think Sapient is certainly going to continue to grow into the future. Now I hope as someone who’s aging hourly, today is actually my birthday Grant. So I’m aging more than [overlap]

Grant Belgard: [00:27:43] Happy birthday.

Mo Jain: [00:27:44] Well thank you, sir. Thank you. I just was alerted to that this morning. I forgot so I’m actually aging faster than I care to admit. But you know, I hope within the next several years to decade, diagnostic testing is completely different than where it is today. We’re no longer measuring two dozen molecules in human blood, but we’re measuring 20,000 molecules in human blood. And from that, being able to provide much, much more nuanced diagnostic information, prognostic information and therapeutic information regarding what’s the ideal way that I need to live my life, what’s the ideal diet, lifestyle and drug regimen that maximizes my personal health over time. And I’m hoping we’re moving to that position very quickly.

Grant Belgard: [00:28:27] So changing topics a bit, can you tell us about your own history, what in your background ultimately led to what you’re doing now? What prepared you for this? What maybe didn’t prepare you for this?

Mo Jain: [00:28:40] I wish I could say it was all very well planned out and deliberate, but you and I know that’s absolutely not the case. And so I trained as an MD-PhD. I was dual trained in medicine and science. My PhD degrees in molecular physiology. And I absolutely loved, loved, loved clinical medicine. It was a privilege to take care of patients. I very much enjoyed my patients. Those personal interactions and being able to help people in their own personal journey was something I was very passionate about as a cardiologist. I was also very frustrated by it, simply because much of clinical medicine is really about regressing to a common denominator or a common mean, whereby everyone with a given disease be treated with a given drug, even though we know that’s just not the way human medicine works, but it’s the best we can do. I was very frustrated by not being able to answer simple questions. When someone asks, well, why did I develop a heart attack at age 40? And what’s going to happen to my kids? And how do I test them for this? And there’s a lot of hemming and hawing that happens from the physician, simply because the real answer is, I have no idea. And there’s simply no testing we have for you. That, to me is very unacceptable.

[00:29:45] As I mentioned, I was training at the dawn of the genomic revolution and I was very much excited by this idea that parallelized sequencing and genomics were going to transform the universe in a meaningful way that this was all going to change. And at the same time, I was frustrated when saw that that wasn’t going to actually happen. When we really got down to brass tacks and did the calculations, it didn’t make sense how this was going to work. And so I trained initially in clinical medicine. I spent quite a bit of time in Boston at the Broad Institute, at MIT, at Harvard Medical School, and at Brigham and Women’s. In my scientific pursuits, that’s where I started working in mass spectrometry and large data handling. I spent the better part of the last decade as a professor in the University of California system here in San Diego as a professor, where I was privileged to work with really, really bright students and postdocs and faculty members to develop some of these technologies. And now I’ve lost track. I don’t know if it’s the third or fourth career, but this next phase or next adventure whereby we spun out the technology and now I have the privilege of leading this organization and thinking through how we begin to commercialize these technologies and these types of data. So it’s a very wandering path. This is oftentimes the case. I’m excited by big questions. I’m excited by solutions that bring about real change. And I’m still charting that path, if you will.

Grant Belgard: [00:31:08] And what have been the biggest surprises to you personally on your founder’s journey?

Mo Jain: [00:31:14] Oh, boy. How much time do you have Grant? I think there’s some universal surprises that I think anyone who goes through this process learns. You learn how hard it is. You learn that no matter how great your technology is, no matter how unique your data is, this is a people business in the end. And having the right people around the table is really the key to everything. Virtually all questions can be answered if you have the right people. You learn that it’s absolutely an emotional roller coaster. This is something that a number of founders had warned me about, but never really made sense to me that this is something that you’re going to have days where you’re flying high, and then literally an hour later, you’re on the ground in the fetal position, and that high frequency fluctuation is maddening. This is a hard business, if you will. There’s a lot less risky pursuits in life than being a founder and being an entrepreneur. But in the end, there’s frankly nothing more rewarding in my mind. And oftentimes these two things go together. I’m not necessarily a risk taker by nature, but I feel this is what I was meant to do so it makes sense to me in some crazy way that I can’t quite explain.

Grant Belgard: [00:32:27] If you could go back to early 2021 around the founding of Sapient and give yourself some advice, maybe three bits of advice, what would they be?

Mo Jain: [00:32:37] Yeah. Wow. That’s tough. I hope it’s not don’t do this, but I was incredibly naive when we founded Sapient. And I think that’s a good thing. I think sometimes knowing too much prevents people from taking a leap, and leaps require faith, and they require oftentimes blinders. You can’t see the pool if you’re going to jump into it.

Grant Belgard: [00:32:57] You need a bit of irrational optimism, right?

Mo Jain: [00:32:59] That’s exactly right. Anyone who knows me knows I suffer from massive doses of optimism and so I’m not sure if I knew everything I know today. Certainly we would do things differently and whatnot, but I like the fact that I was naive. I think that was really an important aspect of our development, certainly of my own personal growth, but also for the company. Oftentimes coming into an enterprise with bias means you’re just going to do the same thing that the person before you did by the very nature of bias. And not having that experience forces you to question from a very first principle basis, every problem and come up with oftentimes solutions that may not be traditional in many ways more efficient. I think I would warn myself, if you will, just to answer the question about how difficult this is emotionally and psychologically, not something I appreciated. My job was to take care of people who are dying in the ICU. So I said, well, how hard can this be? And I was incredibly naive and ignorant to just how hard it is. But again, that’s not a bad thing. That’s a good thing. And lots of people had given me the advice of make sure you surround yourself with other founders, other CEOs, people going through this. You’ll need more “emotional support” than you’ve ever needed at any point in your life. And I’ve always liked to believe I was highly resilient and had strong emotional backbone, but that absolutely turned out to be true and in many ways has been the difference maker. And so I’ve certainly sort that out over the last year and have some incredible friends who are in this space who are in very, very different fields, who help me every day. I wish I had done that a little bit earlier. I think that would have saved a little bit of sanity and probably some gray hairs.

Grant Belgard: [00:34:43] I noticed just before recording that you’re a YPO member.

Mo Jain: [00:34:47] Yeah, that’s exactly right. I’m a true convert. And when I first heard about YPO, I said this sounds nuts. I don’t need another networking event. And it was honestly a very dear friend of mine who we were having dinner with in the early days of Sapient, who just was a biotech entrepreneur himself and very successful, who looked over at me and said, hey, I’ve got something you need. And I said, oh man. He explained it to me and it sounds like a mix of a cult and a networking event, neither of which have the time or energy for. And my wife certainly at the time was like, wow, do you really want to get involved in something else? But I would honestly say, and again I know I sound like a true believer, but it’s been one of the most important things I’ve done for myself personally over the 40 years of my existence. And so it’s been incredibly helpful to learn from people who are very talented and successful at different phases of their life in a very open and honest way. And so it’s had massive impact on me, not only professionally, but personally.

Grant Belgard: [00:35:43] Yeah, I just went to a Vistage event this morning, so I know exactly what you’re talking about. Fantastic. Maybe third piece of advice. I think we’re on three.

Mo Jain: [00:35:53] Yeah, a third piece of advice would be to ground yourself. And what I mean by that, it’s really, really important. As life becomes more chaotic and crazy and I never thought it could get any crazier than it was previously, but somehow we’ve been able to pack more in. It’s really important to understand what your North Star is. It’s important to have those people in your life that you’re present for, whether it be family and children, whether it be spouses and friends, parents, whatever the case may be. It’s really, really important selfishly to have those grounding mechanisms. And again, I always understood how important it was, but not something I appreciated how important it is professionally. I’m a better professional individual and I think I’m a better founder and a better CEO because I take the time now for those individuals in my life and I ground myself, and that’s really important for me personally.

Grant Belgard: [00:36:46] I think it’s fantastic advice. Thank you so much for your time. I really enjoyed speaking with you. I think it’s been a fun discussion.

Mo Jain: [00:36:54] Thank you so much, Grant. I really appreciate the invitation and I equally had a lot of fun today. So looking forward to this again at some point in the future.

Grant Belgard: [00:37:01] Thanks.

The Bioinformatics CRO Podcast

Our Inaugural Episode with Razib Khan

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen onSpotify, Apple Podcasts, and Google Podcasts, with Pandora coming soon.

In the first episode of The Bioinformatics CRO Podcast (Recorded August 24, 2020), our founder and CEO Grant Belgard talks with Razib Khan, geneticist, science communicator and director of science at the Insitome Institute, about consumer genomics, SARS-CoV-2, and academia. 

Transcript of Episode 1: Razib Khan

Grant: Welcome to the inaugural episode of The Bioinformatics CRO podcast. I’m your host Grant Belgard and joining me today is Razib Khan. Razib would you like to introduce yourself? 

Razib: Yeah sure Grant. I am the director of science at the Insitome Institute. I run a few blogs. I do a lot of random things. I run a blog called Gene Expression I run a blog called Brown Pundits.  I run a podcast for the Insitome Institute called The Insight so just check on Stitcher, iTunes, whatever. And I also run a podcast called Brown Pundits and that’s just like a fun project on the side. I have a Twitter, Razib Khan. That’s basically it. I do some other things. I do some consulting. You know, Grant and I have a conflict of interest, maybe we should just disclose: I did some work for Grant in the past. And yeah so I have my fingers in a lot of different things. 

Grant: Yeah I love your blogs. I highly recommend your blogs. I’ve kept up with them for a long time and a lot of other people have as well. So, what made Razib Razib? 

Razib: So yeah, a combination of genes and environment. If I want to think like a behavior geneticist. I do have a pedigree, I have three siblings. And I can tell you that there’s much more concordance between my youngest brother and myself. We didn’t really grow up together because I’m way older than him so that does suggest that there’s a strong heritable component of some of my tendencies. But in terms of growing up, I grew up in Eastern Oregon. So I think that gives me a very different perspective than a lot of people that I’ve met in academia who grew up in, say, upper middle-class suburbs. 

Razib: I grew up in “cowboy country”. There were literal cowboys at my high school in terms of that’s what they did after school as their job. So I have kind of a different cultural perspective. I consider myself a northwesterner, but I’ve lived in urban areas in my adult life. So, you know, I’ve seen the start-up scene in the Bay Area, I’ve lived in Austin. So what made me me is kind of like having this life background, I think, where I lived in rural areas, my dad was a college professor, and I lived in urban areas and I saw the global economy and I see the global economy. My family’s from Bangladesh but obviously I’m an American. 

Razib: In terms of my intellectual interests, I started biochemistry as an undergraduate because my family’s Asian American and if you’re going to do biology it has to be biochemistry or biomed but they don’t really understand it. But I was always attracted to genetics. I actually did a fair amount of molecular genetics as electives for the biochemistry which as you know biochemistry was in the chemistry department; it wasn’t in the biology department. 

Grant: A respectable degree.

Razib: Basically what we always say is we had to take physical chemistry, which is like. You know, at my university physical chemistry was a very difficult course so it was like we took physical chemistry. We are legit chemists okay? 

Razib: So that’s where I started but eventually, I faded back towards genetics and genomics. I’m not really good with my hands in terms of pipetting and stuff like that, so benchwork was never my thing. I worked in IT for a while and then eventually I went to grad school at UC Davis. I did not finish. I am still everything but a dissertation. And I worked in evolutionary genomics mostly with mammals and I do a lot of work with humans. I’ve worked for personal genomics companies. 

Razib: I have a lot of interest in history that gives me a unique skill set in being able to do the data science, you know, doing some algorithm writing as well as knowing basically what outputs or intelligible to the end-user, which can be kind of difficult if you’re a technical science person. Anyone who has ever seen an error output on a computer understands that that can be a problem with the technical person because error output does not tell a normal person anything except it scares them. So that is a skill being able to figure out what the consumer needs definitely that I think I bring to the table.

Grant: And where do you think you’re heading in the future? I mean obviously you have very broad-based interests and you found your way to science communication platforms and is that something you’re planning on doubling down on?

Razib: Yeah I don’t know, I mean it depends on, and I’m using a start up word here, what your bandwidth is. Right? I still do write for various publications when I get the chance. I don’t do it really for the money. There’s not that much money in it but who else is going to speak about what I speak about? If there is another Razib Khan I’ll give them my notes and I’ll just move on, because you know I’ve got three kids. I’m a busy guy–you know what I’m saying? 

Razib: I do it partly because you know who else is going to do that? But the Insitome Institute purview is to do science communication. And that’s what Spencer Wells and I do, my boss who is the director, we do the Insitome podcast. And so yeah there’s still a lot of science communication to be done and that I do expect to be doing, but I also do work in consumer genomics as you know. I do a fair amount of contracting and consulting with people and I do have some experience in that space that I would like to provide. I am trying to actually finish some papers, which I don’t know if I should talk about, but I’ll just put it out there. I am trying to finish some papers on some topics that nobody else seems to be really interested in and get that out there. So I’m trying to do a bunch of different things, so I’m not in a situation where I  have a straightforward “what am I going to do with my next 20 years”. The past 20 years have been pretty surprising to me. I mean who knew what genomics-based data science was 20 years ago? It wasn’t a thing. So what’s going to be a thing 20 years from now? And I think a lot of people feel this way. So my goal is to be nimble and you know just go with the punches and try to survive in this world because it’s pretty tough right now. 

Grant: You’ll find your way. So speaking of consumer genomics companies, what’s your take on what’s been happening in that space in the last couple of years, and where do you think things are heading?

Razib: I did a podcast with Libby Copland, Lost Families, and we talked a little about the Insitome in April, if listeners want to look that up type Libby Copeland, she has a book out, Lost Families. She asked me that and we had a discussion a little back-and-forth because she’s done all of this research in consumer genomics. 

Razib: I have friends who work in 23 and Me, friends who work in industry, my boss founded the  Genographic Project . I actually have consulted for Linda Avey, the founder of 23 and Me. I consider her a friend. She is a really good person by the way. I’m just gonna put that out there. I have nothing bad to say about her. So, I’ve had a lot of discussions. 

Razib: It seems like there’s a leveling off of growth in that field. And some people say oh it’s because of privacy concerns. Other people say it’s kind of market-saturated for the initial wave of consumers. I suspect it’s both.  I do think the privacy concerns are starting to spook a lot of people. But who they are speaking is the next marginal consumer. So the initial consumers that were going to get it, they were going to get it no matter what. You could say, “oh we are going to use your DNA and we are actually going to release it out to the cloud in a tarball and everyone can access it.” And there’s just a core group of people that don’t care. They are still going to do it. So those people are insensitive to that. As you get further and further out through word-of-mouth because these are Christmas gifts, you know things people talk about over Thanksgiving in terms of their results a lot of awkward results sometimes.

Grant: I will just interject here that Grace, who is helping us out with this podcast, got as a Christmas gift from me: an Insitome ancestry kit. 

Razib:  Okay okay, so you know eat your own dog food. I’ve been on all of the platforms. So there’s ups and downs to all of them and it’s an interpretation service so they are all interpretation services. The killer app of the last decade that just went by was Genealogy and Ancestry to a great extent. 

Razib: The medical aspect has not really become unlocked yet. I do think it will be. So right now we have about 10% of Americans on these platforms okay? 30 million people. Probably a little bit more than 30 now. But it’s really leveled off so that’s about 10% of Americans. I don’t believe by 2030 we are going to be any lower than 75%. Okay? I think a lot of kids will be genotyped, you know low coverage and various coverage sequencing. Grant you work in the medical genetics phase, medical genomics, you know the gain that can be had by detecting novel variants, you know variants of unknown significance in young children if they have an idiopathic condition. And these are not most children but there’s enough with them that a lot of hospitals are already doing this with “mystery conditions” for newborns because newborns cannot give you any feedback about what’s going on with them. So these are the niche cases. They’re little segments but the segments keep on expanding. 

Razib: So those of us who remember the Internet in the 1990s, which Grace probably does not remember, but it was super exciting for a lot of us. And we had no idea what people were going to do with it. We had fantasies. I will tell you Grant, I think I’m a little older than you. I remember getting a gopher, which is like a pre-web thing, and it was a text interface. I remember reading about Ethiopia on the CIA gopher page for Ethiopia. And I was super excited because I could read about Ethiopia without opening an encyclopedia or going to the library. That’s what I thought the Internet was. That’s what the Internet was in 1993. And now the Internet is a lot different. The Internet is podcasts, Twitter, a lot of stuff that is good and also considerably bad stuff, but different than I was expecting. But this is you know 25 years since I got on the Internet and I couldn’t have guessed what we see around. Like some things I could’ve guessed but like a lot of it is super surprising to me. 

Razib: So think in genomics 2010 is the same as 1995. Like that’s when 23 and Me really came out with a big marketing push and people started talking about personal genomics. It was pretty low boil I think for the first five years. And then it really jumped up right before 2019. A lot of this is marketing spend. If you look at Ancestry‘s marketing spend, as it increased there was a linear response with purchasing. I know through the grapevine that the former CEO of ancestry–he kind of admitted this–basically they did not expect that there was going to be a linear response to their marketing spend. I think it was a little bit more than linear because word-of-mouth triggered and kicked in at some point. And so it just became one of those gifts like $100 price point $99 $79.

Grant: Black Friday sales.

Razib: Yeah and so it just became a thing and like YouTube unboxings of Ancestry kits became a thing. So it’s become part of our culture but it hasn’t become ubiquitous. And so I think that’s the next step. I think medical is going to help make it ubiquitous. The problem with medical and consumer is you don’t want to buy a kit that tells your mom that she’s going to develop breast cancer by the time she’s 60. Telling people that they have a health risk is not a feel good gift. So they need to figure that out. I’m not a marketing person. It’s not my job. I think probably some sort of distribution deals with hospitals is the way to go. I think that’s the future. 

Razib: And also I wouldn’t be surprised if some European country with socialist or semi socialist medicine it’s just like “You know instead of building our own genomics service for our citizens and let’s just contract with Ancestry or 23 and Me and have them build something for us”, turn the key, and then maybe the data is stored in those countries with some bureaucrat somewhere. I know for example Estonia is trying to do things to provide genetic kits and services to its people just as part of its national health. Because I know a scientist who is on the Government board and at a conference he came up to me and started asking questions about it. Because they’re like “We are serious. We are a small country and we can scale it.” And they have really really good distribution and fluency with information technology. That is what it is. Genomics is information technology.

Grant: So speaking of data protection and distribution where do you think those Genomes will be housed? I know there are ideas about this and many of them are in conflict with one another. 

Razib: Yeah. Well I think it depends on the country. In China they’re going to be housed where the government wants them to be housed and the government is going to know everything about your genome. Like they’re already sampling males because they want to get genetic profiles of potential criminals because 90% of violent crimes are committed by men. So that’s why they’re targeting males. So in China it’s going to be like that. 

Razib: In Europe they have the GDPR, which is like the data protection law. That’s what genetic data is under. And different countries have ways of enforcing this. Like in France genetic testing of the sort that we do in the United States for consumers is banned. Like they have to ship it to Belgium, drive to Belgium, and pick it up if they’re a French genealogy fanatic. There are some. Germans have a fraught relationship with genetic science, So if it’s anything relating to human genetics, they are really terrified of it. So that’s not really a good market. Other European countries like Scandinavia are much more open and much more enthusiastic. 

Razib: So how do they deal with privacy? One idea that Spencer and I have been kicking around is some sort of encryption key where you’re the only one that can unlock it, which is the kind of thing that is relatively common. And now with block chain and all of these crypto companies we could just cryptify your genome. So you are the only one who is able to unlock it that way. Of course the problem is if you lose the key, it’s gone. But then sequencing is pretty cheap too. So you could just do it again, so that’s one solution. 

Razib: The issue with genomics is, aside from somatic mutations, your sequence does not change. Your germ line mostly doesn’t change, there’s a few mutations over time whatever. Anyways so if someone has it, it’s there, they have it forever. So my genotype and a GCF Of my whole genome sequence is actually publicly searchable, if anyone wants to search Razib Khan genotype, you can find them. I’m not scared personally because I’m not an important enough person, where someone would design a bio weapon to come after me. I mean it would be way cheaper to hire a hitman.

Grant: Did you already buy life insurance?

Razib: I do have life insurance. So you know but if I was the head of state somewhere there would be a concern. Maybe. Maybe. Bioweapons are expensive and not very effective. I’m not super worried about that. There will be a point where sequencing is so cheap and so many people have done it in so many different places, that I do wonder if privacy concerns will just disappear. You know we share a lot on social media about ourselves and nobody seems super stressed about it even though if you had talked to people like a couple of decades ago they would be like “that’s creepy.” I wonder if people will be more chill about it in the future. One of the weak points is hospitals. They are not very good about data protection. Like there have been traditionally problems with a lot of hospitals. And they usually just pay a fine and they’re like whatever. The issue is if you do your genome and they release it by mistake…

Grant: Once and done. 

Razib: Yeah it’s out there. It’s out in the wild. And so I don’t really know the long-term prospects for privacy. I think in the short term privacy is feasible if you care. I don’t care, but if you care, there are services you can go to that are very bespoke, where you can be sure and trust that they are deleting your data and stuff like that, but that’s not going to be the thousand dollars genome or $300 genome. That’s going to be people that will charge you a premium because they are going to validate everything in a way that you know that they are deleting everything. They are sending you a physical copy. There are things you can do like that. I think in the short term, we don’t know for sure, but I strongly suspect that a lot of consumers are going to be okay with a lot less privacy than you would think.

Grant: Yeah it seems to be. I am on 23 and Me under a pseudonym. I paid cash for a prepaid card. I had the kit shipped to another state and address that was completely unconnected to me and through a series of coordinated happenings, I got the kit in my own hands, but of course these things can be triangulated through family members and what not, so it’s not foolproof. 

Razib: Yeah I think if you are a white American, it is highly likely that you are easy to identify. Like it’s 95% likely now just because there’s enough people in there. Like if you’re adopted and you don’t want to know who your relatives are, do not do this because you’ll automatically get a match. And maybe you’ll delete it from your mind, but that’s going to give you information automatically. So when you have 10% penetration that’s penetration for almost all the pedigrees for Americans. There’s still some gaps for black Americans although that’s closing and other groups. But really the way the statistics of this works is you don’t really need to sample that much to get all the pedigrees.

Grant: Right. Interesting. So based on the mumbling so you hear what things do you expect to transpire in the coming years that you think relatively few people are expecting.

Razib: I don’t know. It’s difficult because I don’t talk to normal people about genetics so anyone I know, they know everything because I talk about it like yeah this is going to happen. So for example I talked to my friend Rob Henderson and he’s a prominent person. He’s a writer he happens to be from kind of a lower class background and he went to Yale. He didn’t know who his biological father was. He’s getting his PhD in social psychology I think at Oxford. He’s a smart guy. He was shocked when I told him “don’t do a DNA test if you don’t want to know who your dad’s family is because you’ll automatically know.” And he was like “really?” And I was like “yeah if your dad is a generic white American it’s in there. You’ll automatically know.” If you’re ambivalent, which he was, you shouldn’t do that. 

Razib: I think I told Grant the story I don’t know if I did, it’s a really weird story. One of my friends had heard that his dad had had an affair and he had a half-sister. And he was like “Should I use one of these tests to find his half siblings. What are the chances?” And I was like “You’re going to find something, not necessarily the half sibling but you could figure things out of who’s related to who and all the stuff.” He did get a match of someone who looked like a half sibling, but it turned out it wasn’t a half sibling it was his stepdad sister. So he found out that his stepdad is his biological dad. He said he’s not gonna tell his mom, and he’s not gonna tell his stepdad, who he hates. And so these are the things that are going to come out. And I don’t even know that his stepdad knows because I think his mom probably, you know. His mom might not even know about his parentage. But my friend’s problem is he saw the match with his stuff and so she probably saw the match with him. So don’t open some things that you don’t know how to deal with. It’s like a Jack-in-the-Box coming at you. Don’t be surprised. 

Razib: And sometimes it’s funny and silly works like I had a friend and she’s like classic southern California blonde and her husband who is 100% Irish American but she’s like “I think he’s part black because of his features“ OK I was like “well you know you guys should just do the test” because you know they wanted to have kids. It turns out they both were hemachromatosis carriers or something, but it’s not a big deal. It’s whatever. But here’s the funny thing: he turned out to be 100% Irish, and she was 2% African. And so we figured out that there is a blank spot and her mom’s genealogy from the early 19th century. This is not a shocking thing. It’s just a big laugh, that she was looking for black ancestry and her husband, and it turned out that she herself had had an ancestor who passed from black to white in the early 19th century, which is not super over the top. And so that’s silly. That doesn’t affect a lot of people. 

Razib: But with the genealogy thing you might think it’s silly, but for a lot of people it shakes them in weird ways. I didn’t find anything super shocking. I found some surprising things, but nothing that was super shocking, so I can’t relate to that personally. And honestly who really cares who your ancestors were. That’s just my personal opinion about me, but to a lot of people it’s a much deeper thing. And there’s all these stories that go along with it. 

Razib: I consult on Skip Gates’ show. I didn’t mention that at the beginning, but I consult on his DNA show on PBS. And so George RR Martin he has a thing where his paternal grandfather is Italian and he’s from Jersey and he’s got this Italian background, but actually it turns out that his paternal grandfather was not his biological paternal grandfather. His paternal grandmother was a secretary for a Jewish guy and that’s his biological grandfather. So when he found that out through the genetic testing, that he’s 25% Jewish not 25% Italian. Now I’m only bringing this up because— I didn’t watch the episode and I don’t know how he reacted but— he always had this schtick that he would talk about how he was like Martino or something and he’s Italian and he’s from Jersey. And he can kind of keep the story because that’s how you’re raised but his understanding of being Italian… I don’t know if he wants to bring up the fact that “Well I’m also part Jewish” you know, there’s a lot of things like that that change family stories and that’s not super significant. 

Razib: The disease stuff can be super significant. I’ve had to talk to friends about stuff they found that was surprising, which was sobering because the disease stuff is never “it turns out I am superman and I have super powers.” There’s no gain of function mutations that give you a secret invisibility power that you didn’t know about. So it’s never positive really. I mean for some people it’s positive where they didn’t have the risk for something that was autosomal dominant but really mostly it’s a bad thing. 

Grant: And of course something like that wouldn’t be shocking right? You kind of just do a punnett square or something and you know.

Razib: Yeah, so for other people I have found out things that a lot of people don’t connect you into so I’m not always aware of things that are or aren’t genetic. So I’ll give you a concrete example of this. A friend of mine is at high risk for cataracts. Very high risk to go blind early in the probably have to do surgery and hopefully they’ll have a correction. But his family is from India And one of his parents went blind, but that’s just very common in India because of my infections and stuff. And so that’s what he assumed it was. Because that parent had an eye infection of some sort and so the doctor said “oh it’s probably because you have the eye infection and that’s causing the blindness” and all the stuff. And so that’s when my friend knew. And I mean he’s a college educated person he has a science degree and so he just assumed that that was what it was, but they got his parents tested. And they both have some sort of autosomal dominant trait where you have a 50% chance of getting cataracts by the time you’re 50. And he’s 37 now. So you know, it’s just something that’s on his mind. He has a 90% chance of getting cataracts by the time he’s 65. And I haven’t kept up with the surgeries that he might have to do to not go totally blind. But that was an awkward conversation because when he got the testing I was like “oh there’s only a small probability that there’s going to be anything that’s going to be a problem”, which is true. Your prior is that you’re not going to discover anything new, but there’s going to be a minority of people who are going to discover the new thing. And it’s not going to be a little new thing. 

Razib: If it’s a disease thing, it’s going to be a big thing if it’s going to add value. Because knowing you have a 1.5 greater odds of developing type 2 diabetes is not that big a deal. That’s not really actionable, and that’s not gonna change you very much. But knowing that you have 25 times the odds of getting cataracts by the time you’re 20 or by the time you’re 50 is a big deal. And I felt kind of crappy because I told him honestly “Don’t worry bro you’re not going to find anything. You don’t know anything from your family background“. That’s literally what I said. But there are things like this that happen. And I think this sort of stuff is going to affect our lives in the next decade. And how that’s going to affect consumer purchasing decisions, I don’t know. That’s just an awkward sell. But the kits and the tests are going to get from the people that are deploying them to the people that are going to use them, and that’s going to go back to the doctors. It’s got to go back to the healthcare system. That needs to happen so that people can make better decisions with their lives. Now I kind of sound like an infomercial here, but that’s what it is. It needs to be informational to people about why you want to do this. Some people want to put it off as long as possible, and that’s a choice. 

Razib: In some countries they’re not going to give you the choice. I’m 90% sure that in Britain they’re not going to give you the choice. Because the healthcare system is soup to nuts. They take care of you top to bottom so they are invested in you. They can make the decision for you. And they’re going to nudge you. And they’re already nudging people. And they really want to nudge you hard. So if they find out that you have certain risks or dispositions, they don’t want you to make life decisions that get you really ill because then they’re on the hook for it. 

Grant: And certain HMOs might be the same way.

Razib: Yeah. The issue with HMOs in the United States is they are very sensitive and vulnerable to bad public relations. When you have a government monopoly, they are much less sensitive to bad public relations. As long as the government doesn’t cut their funding, they are fine. That’s the downside of a monopoly. That’s the downside of socialized medicine run by the government. There is no way you have leverage against it aside from through the government itself. The upside is that they can make some unilateral decisions. I do think a lot of innovation might actually happen in Europe because it’s a monopoly and people are scared in the United States. People are scared across the whole world of genetic science partly because of GATACA and the Nazis and all that stuff. Now, use correctly it can make your life better. 

Razib: And so how do you get people over the hump? Well in a system where the government has socialized the cost we as the individual don’t have the final choice on everything. And I think that might allow certain innovation to happen and then it eventually will come back to the United States as people see “oh they’re not using it to round up the genetically unfit“. And if they are using it to round up the genetically unfit then we’re not going to do that. So I’m just saying that we are going to see some experimentation across the whole world with this sort of science and with this sort of technology and we’re going to see what works and what doesn’t and how things work differently.

Grant: Yeah it’ll be interesting to see what happens in China in this space.

Razib: That’s a word for it. Interesting yeah.

Grant: So where do you think science is going and the ways that we do science will change over the next 1 to 2 decades? Tech and all the knock on social effects of tech are kind of revolutionizing everything. What do think this impact and the broader political impact will be in science and in the context of science? 

Razib: I mean it’s weird. Science has had multiple phases. Science and technology have had multiple phases of enthusiasm. Sputnik era: enthusiasm. 1970s: Environmentalist movement etc. etc. and then I think like in the 80s and then into the early Internet era–I mean not to be the old guy but I remembered 1995 to 2000–oh my god we were so optimistic about the Internet. We didn’t realize at the time. 

Grant: Democratize the world right?

Razib: Yeah it’s like “oh I can talk to somebody in Ecuador.” I specifically remember having a chat with someone in Ecuador, and I told my friends the next day “I talked to somebody in Ecuador” it was so amazing. And now it turns out that I didn’t anticipate how toxic Twitter would be, how social media would be used to destroy people. All of these things you can go back and read about it, people did not anticipate that. We didn’t understand the human capacity for depravity. And I’m using that in a very broad broad sense. Like Facebook has been used to coordinate ethnic cleansing in some countries. Like we didn’t anticipate that. We thought it would bring people together, and today I think that a lot of people when they’re not on the web. When they’re not on the Internet, they are happier. Like being disconnected is a thing when I get an email it’s a “now what?” sort of situation. Whereas 25 years ago or even 20 years ago I was like “who emailed me!?”

Grant: “You’ve got mail”

Razib: Yeah it was exciting. Like “oh my girlfriends emailing me”. Like I remember that was a big thing “oh well she emailed me today”. Even though we saw each other every day. So that was like an exciting thing and now today I just don’t want to be bothered. I get a lot of requests because I am a “public person” and so I get a lot of direct messages and sometimes I try to respond. I can’t respond. All these questions and I just can’t deal with it. And it’s made the whole world accessible to me but now I’m accessible to the whole world. And that’s a downside of information technology that we couldn’t anticipate. 

Razib: So what about genetics? I don’t think that we know all of the consequences of knowing all of your relatives. We’ve talked for decades and genetic science about how this is going to affect dating. So I have never done anything like Internet dating. I’ve been non-single since the year 2003. So this is all abstract for me, but I could see there being a situation, where it’s like in the Jewish community where everyone know is a Tay Sachs carrier. You don’t wanna marry somebody with that. Well it’s just like automatically with your dating profiles you might do an intersection with carriers so that you know. A lot of people if you’re just on Tinder you’re not thinking that far into the future but if you’re a match.com you might be. So depending on your level of seriousness you might want to exchange the information ahead of time. 

Grant: It’s more efficient unless you want to go through IVF. 

Razib: Yeah you just could get it out of the way. Some people don’t care but if you want to anticipate having to do a pre-implantation diagnosis which some people might have to do. Maybe just get that out-of-the-way. I don’t have it be a surprise. And they’re all sorts of weird things like some people have bad credit I mean do you ask people immediately? Probably not. The questions about people that you don’t ask immediately and there’s other things that you do. I don’t know if the genetic thing is going to be one that you were asking mediately. 

Razib: The issue with genetics that I tell people is genetics is also something that you see on someone’s face. So you see me and you automatically know kind of where my ancestors are from. My risk of being a cystic fibrosis carrier is is quite well. You just know that as a prior. It’s not like genetics is a total mystery to people. It’s like you kind of know how much money someone makes by the car they drive the way they’re dressed. There’s always information you can get from people and it’s how much you want to put out there. 

Razib: The thing with genetics though is you could fake a sequence, but your genes are your genes. I’m just being honest about it and at some point we’re probably going to have to do some validation services, where you provide the SSL of the sequence. Because what if someone sends you a fake sequence? Because they don’t want to tell you that they have some autosomal dominant trait. It’s common and dating services. What if you carry the dominant for Huntington’s. Even if people are interested in a serious relationship they just don’t want to deal with it. Because that’s kind of heavy. 

Razib: I know people–well I don’t know them personally–but I know a woman whose sister has Huntington’s. And her nephew won’t get tested because he has a 50% chance of being a carrier. You know, she tells him that he should be super serious about protection then. Because she basically said he’s not the most responsible kid. Well, what if that’s on dating profiles? What if you can check it? It’s just like when you, when you blackball people for employment because their credit rating is bad. That’s kind of unfair in a way.

Razib: So is it unfair to not want to date somebody seriously that has Huntington’s? Cause they’re going to develop Huntington’s if they carry the autosomal dominant. Right? So, I mean, these are social questions that we don’t have to confront today because most people haven’t gotten sequenced. And Huntington’s as, as you guys know, it’s a repeat. And so I’m not sure if it’s going to be on a genotype array, like you’d have to do some sort of tagging. So it’s not even trivial to just have it with your 23 and Me. Even if they could provide it, it has to be like whole genome sequencing. So the technology is a little bit in the future, but it’s going to be something we confront.

Razib: Like if you are a person that has an autosomal dominant disease, that’s going to present later in life. That’s pretty, that’s pretty heavy. That’s pretty heavy. And this is why a DNA test for Huntington’s disease is not a feel-good consumer product. Like this is a problem. 

Grant: Yeah. So where do you think academic science is headed?

Razib: So basically COVID-19 has accelerated certain things and the financial crisis in academia that was going to happen because of demographics because Zoomers are a much smaller generation than millennials. What was going to happen is happening now.  

Razib: There are some departments that are laying off. Mostly not in science. STEM is not predominantly dependent on tuition money or liberal arts colleges are when universities get NIH and NSF.  So academic science is special in certain ways where there are certain types of innovation, certain creativity that occurs there that is really difficult to happen, or really does not happen in industry because industry is more siloed.  Just the way sociology works, right? You don’t get the cross-fertilization in the seminars just doesn’t happen. So there’s a reason academic science is there. 

Razib: I do think academic science is getting too politicized.  What’s the next consequence?  One consequence is when people are looking for what to allocate resources to. The national science foundation, NSF funds, non practical things. That’s its goal.  It will have practical implications, a lot of the time, way down the line, but NSF is where you go if you’re an ecology lab and you’re not going to get funded by the NIH, which you’re not. I mean, there’s different ways, you know? So I think that will be cut. 

Razib: I think, I think trust in academia and faith in academia is declining. That means public academia, public academics will have problems because if you’re in a red state, when they go to allocate budgets, they’re going to cut.

Razib: Now. I know universities get a lot of funding from various sources. I don’t really know how comfortable a lot of academic scientists are going to be with public private partnerships, but that’s probably going to be a thing just to survive. There’s some universities, agricultural universities, where I went to UC Davis. They were actually very happy with that. And that’s part of the tradition. Monsanto, or whatever the company is called now, has a lot of projects there. But a lot of academic scientists and universities are not happy with this.

Grant: Hopefully Nassim Taleb is not listening to this podcast. 

Razib: Well, if he is, he’ll say we’re morons and idiots. But Berkeley for example is very, very anti Monsanto. Anti-public private. I’ve had friends, who were discouraged from ever looking into that because it would be seen badly kinda by their department, but I think they need to look at that because the funding is going to be an issue. There’s also overproduction of scientists.  They’re not all going to land in academic spots. There’s going to be a reduction in R2 universities, research 2 universities, liberal arts colleges that absorb some people. That means everyone’s going to be competing for the same few spots. They’re already having, you know, a thousand applicants for one job, so it kind of seems a bit like a hellscape.

Razib: A lot of people are going to be really stressed and anxious. You know, in a way academics are actually quite privileged.  When I was a grad student at UC Davis, I got the best health insurance I ever had by the way, because the UC system is part of Cal, the California buying system. And so they buy gold plated insurance for everybody, at least for graduate students and above. And so, there’s a lot of good perks that come with it, even though people complain, and that’s not a law of the universe. It’s the way our American society works today to give people the leisure to study things that they love and that they’re passionate about. 

Razib: Like I talked to some people on the Senate staff who were prominent Republicans, I’m not gonna name who, but you’d recognize the name. And they were like, “yeah, we can’t defund the universities cause they would say that we were like primitive barbarians, but the first chance we really get without the media saying that, we will do it.”  

Grant: Well, I mean, it’s been quite interesting, as you mentioned, the broad based support has fallen apart in relatively recent times and in just recent years. And this politicization is nothing new in the humanities and so on. It is newer in terms of the kind of openness of the contempt and things like this in the sciences.

Razib:  The whole atmosphere is very, very hot-housed and hot houses, uh, they eventually burn out and so it will. You know, what cannot be sustained won’t be. And I feel like that’s going to be the issue in academia, which might be good for industry.  More people with abilities and skills and talent will go into the private sector, but we’re going to be losing something. We’re going to be losing some really curious creative people who might’ve gone in some impractical directions that would give us some real innovation. 

Grant: Do you think there’ll be a decoupling between traditional universities and funded research? 

Razib: I think there will be more, there’ll be more or diversity of think tank research institutes. And also I think we seriously need to consider the European technical university. Technical universities exist to further technical knowledge. Period. Right? And that’s fine. People would fund that. I mean, you can be a communist who cares. If you’re working in solid state physics, and you’re building a better microchip, nobody cares. That’s your business what your politics are. 

Grant: So I want to make sure we have some, some time to talk about the elephant in the room before we wrap up: COVID.  What the hell happened? How did we end up here? And where do you think things are going? 

Razib: Yeah. I wrote an article in City Journal in April where I simply said it was elite. So people can Google “Razib Khan City Journal.” But basically I said the elite systematic failure. I should have probably emphasized Trump more if I was going to be totally honest, but I didn’t probably because everything when it becomes about Trump, it goes crazy.  So I didn’t say much about Trump in the piece. So my thesis is the American society as a whole is obsessed with symbolic, you know, like, postmodernist stuff where it’s about the word you use and the representation and the symbol. And that is actually what Trump is good at. He’s good at these nicknames, but what will we really need to lead us right now as an engineer? Like some of them I can do the cost versus benefit that can do the math. That’s not our political elite right now. In fact, our political elite right now is mostly lawyers. They’re mostly talkers. 

Razib: So as listeners know, you can’t debate COVID away. You can’t beat them by out-arguing them, by redefining them. Trump has kind of tried to do that a couple of times. Even into the middle of February, you were crazy. Like all the cool kids, all the blue checks on Twitter said you were crazy. If you expressed worry–and I’m not talking about Q Anon and Maga Twitter, I’m talking about Vox and you know, like, Huffington post people–and they were saying like, “Oh, these Silicon Valley guys are just weird, and it’s only like anti-Chinese racism.”

Razib: And so they were more preoccupied about whether we were racist against Chinese people, than whether there was a pandemic happening. Right? COVID doesn’t care about our categorizations. It doesn’t care about our borders. It’s just a force of nature.  It’s like a typhoon, it’s like a tornado. It’s like an earthquake. 

Razib: We shouldn’t be fighting COVID because it’s impacting poor people or people of color. We should be fighting COVID because people are dying. Period. Right? It doesn’t matter–like in my opinion–it doesn’t matter what their race or what their class, what country they’re in, how old they are. One of the elephants in the room of COVID is it really affects old people in nursing homes.

Razib: Um, No offense to Americans or Europeans because there was an article about Belgium.  It’s kind of shocking to me when I think about it, what we do with old people, by packing them into nursing homes and visiting them every now and then. 

Grant: Out of sight, out of mind.

Razib: The mortality rates in some of these nursing nursing homes in New Jersey or in Europe is terrifying. Like large numbers of people are dying. They’re dying miserably. They’re dying horribly. This is why some of us were alarmists. And the fact that we’re not talking more about this says a lot about us as a society and our values. Yeah. It seems to me there’s been very, very little mourning in Paris. They just pushed it out of sight. Out of mind. 

Razib: One of the complaints that I have about the media is they emphasize young attractive… like I believe that every single young, attractive white woman who has died from COVID has been profiled in the media. Okay? I think that the media wants you to think that it could be anybody and it could be, especially these precious people.

Grant: Well, what I found really interesting about the coverage too, is the age range that they look at for that. Right?  I mean, certainly the mortality rate is through the roof if you’re 80 years old and so on. And, in our County, for example, every day, when you have new deaths in that age range, they just list the ages and that’s it. But what’s fascinating to me is that’s also the case for the 55 year-olds, the 60 year-olds, you know, the, the 40 year-olds will get a writeup in the paper. The 20 something year old, certainly will get to write it up. But even the 55 year-olds will get a write up. 

Razib: Yeah. If you’re an old gen X, no. You’ve got to be a young gen X. Now you have to be a millennial. Actually, you just have to be a millennial. If you’re a millennial, you’ll get a write up. It’s generational discrimination. If you’re generation X, no.  If you’re a boomer, no. If you’re silent. Hell no. 

Razib: The thing with the nursing homes is I’ve only read a couple of things because it’s painful to read. We have a sociological problem that I knew intellectually in an abstract way, where the way we in “developed societies” treat our old people is that we rationalize them, just like we rationalize everything in the economy. And so you take your parents, you put them in a nursing home, and they’re taken care of by people who get paid money. What could go wrong? So in normal day to day, that’s fine. You know, even though there are abuses, we all know about it. I’m just saying like, they will take care of them for money, but now there’s a pandemic that they can catch as well from these old people who are miserable, who need extra care and attention.

Razib: What I read sounds like, hell. This is not the way that you would treat your own. Cause you want these people to treat your parents like they would treat their own parents, but they’re never going to. They’re not blood. That’s not how it is. It’s like, we’ve rationalized it. We don’t want to think about it.

Razib: And so the things that I read in the nursing homes, I’m like, “Oh, this makes sense, in a way, because these are people who are probably being paid minimum wage to take care of old people.  and you know, a lot of it’s been really uncomfortable. There’s some gross things and now they’re really sick and they can be contagious to you.”

Grant: You know, what’s been fascinating to me too, is these, these horrific cases, where several bodies were found days after death and it had never been reported and so on, aren’t just happening in, you know, nursing homes in New Jersey, but even in places like Spain, in cultures where that’s not…

Razib: Traditional yeah, but it’s becoming more traditional. And old people, a lot of them, want their freedom. They want to live alone. Sometimes it’s difficult to get them to give up their houses. And I know this personally through my extended family. And that can be a problem. So we have freedom and we have this great economy that provides services to give us this freedom, but I think the problem is we also see the flip side of freedom, where, when push comes to shove, when nature red in tooth and claw comes at us, all of a sudden, you understand why people live in these extended family units, where people can distribute labor and, and things like that. Where it’s not just about the money, but it’s about just the community. And it’s about helping your, you know, relative helping your friend, these sorts of things. I feel like we’ve lost a lot of that. Not everybody. Not every community and not every person, but I know a lot of people who are very alone right now. 

Razib: Quarantine has not been that difficult for me because I’m with my wife and I’m with my kids. I am with my family really as we understand it in the United States, but there are friends that I have who are single, whose lives were socializing with their crew. Sometimes they have to create pods, but it’s whatever. I’m just saying. Those people underwent. Are undergoing or underwent something very different in quarantine than I did. And that’s because of the way we live and arrange our society where people can live alone and have all their conveniences and not be bumped by their parents or roommates or their siblings and all these other things. But the flip side of that is when the water recedes, just you. That’s it. 

Razib: So, I don’t know. I honestly don’t know what to say because I didn’t think we were this society. I didn’t think Europe was that society. Like I read the article in the New York Times about Belgium. The government was quite clearly giving the, go ahead, not explicitly, but through some channels for emergency, that paramedics should not pick up COVID-positive people that were dying in nursing homes in Belgium for a while. Because they wanted to keep the hospitals free for people or more valuable actuarially. They were making the calculation.

Razib: I think that it’s been a good opportunity in some ways for genetic scientists. Some companies have gotten on board with COVID testing and sequencing and doing all sorts of things and there’s been some good research that’s come out of it, but it’s been a horrible indictment about the sociology and political science of this country. Not the science, the science has been okay. I think science has done what it can do. And the primary problem is we had a state capacity issue where–I think, you know, Grant–most people “in-the-know” were starting to get seriously terrified by the middle of February. And then when Iran hit around 20th, I remember screaming at what Donald Trump was doing, going to India right now, when he needed to just like start really turning the ship around February 20th. As it is, it was closer to March 15th. Those three weeks were when New York became what it became. That’s when New York was seated. I think we could have dodged New York. I think we got to dodged that, that horrible thing that happened in New York, New Jersey and to some extent, in Connecticut, if Trump had started on February 20th. I think if he had started on February 1st, I think,  honestly we are society is, I think the resistance would have said he was being insane.

Razib: They would have eventually come around. But I think for a long time that he would have been attacked because he shut down the economy and did this and this, and you know, it’s only some dumb Silicon Valley bros and paranoid people and a couple of epidemiologists. So I think that would be too early.

Razib: Ideally he would have started that early, but it wouldn’t be feasible. But I think by February 14th, I think enough people were sure that he could have done something and he didn’t. But you know what? Cuomo didn’t do anything either, did he? DeBlasio didn’t either. So it’s not just a Republican thing. This is not a left-right thing.

Razib: Actually, there’s a lot of blood on a lot of people’s hands in our society, in our elites. And, I don’t think that they will be held accountable. They weren’t held accountable in 2008.  when the financial crisis happened, when a lot of people made a lot of money and the government as a whole bailed out the system, you know?

Grant: And people are upset and, honestly, it seems like a lot of the anger is directed at the measures as opposed to people mourning the deaths from the virus or people being upset with the incompetence, with which it’s often been handled. 

Razib: Yeah I mean, so I think part of the issue is there’s been weird enforcement and weird fixations, and some of it is ideological. So like Florida people on beaches: bad.  Black lives matter protesters: Good.  That was pretty obvious.  Also remember that party of the Ozarks, that was the first big thing that the media caught, and it’s obviously like, let’s just come out and say it: like rednecks and the Ozarks, these are bad people. They’re doing something bad. Well, it turned out there wasn’t that much transmission at all, from what I know because it was outside. If it’s outside, it’s probably not that bad. BLM, those protests, are probably not that bad.  So the outside stuff: not bad.  Inside stuff: bad.

Razib: Right. So when I hear Biden saying, “we should have masks outside”, I’m like, “eh, you know, mandatory mass outside is probably overkill.” I mean, you don’t want to do so much that people don’t believe you. I think that there is a problem with some credibility there, that people need to be more measured. They also need to talk about the fact that we’re working with the best science we have, and that might change. And we apologize if we lead you wrong. Cause they did. They have, and we will.  

Razib: There needs to be more humility, less screaming.  Also some people are just using it to kind of be self-righteous pricks, you know? That’s not getting us anywhere. Like you need to, you need to persuade people with the facts and also, like, show empathy. You’re trying to persuade someone. Not because you want to be right, but because you want them to live. Sometimes I hear some people talking or I see things written and I feel like you’re kind of just showing off about how you’re right and they’re wrong, instead of actually writing in a way that indicates to me that you actually care that these people survive.

Razib: And some of the stuff that I’ve heard people just in my social circle or the media say about people dying in red States, they’re almost, like, happy that these people are being insane. And I’m like a lot of them are economically the same type of people that are like Latino field workers and Riverside. I mean, they’re working in agriculture or in rural areas. And, this seems really inappropriate to me. Like you’re missing the forest for the trees and what’s important. We have a pandemic in this country. It’s about people dying and it’s not about who’s dying.

Razib: You know on the other side, like I have heard things about when it was happening in New York and New Jersey where people were just like, “wow, it’s a blue state problem.” And the fact that we are hearing things like this, that people even say this out loud shows you the problem we’re in, in this country. Like if you’re saying it’s a blue state problem, it’s a red state problem. You know what Obama would have said in 2004 is “There is no red America or blue America,” but I guess that’s very 2004. Like it’s done. That’s all. 

Razib: Or I don’t know, I’m being very pessimistic here, but I don’t,  I don’t see a unifying vision right now.  I don’t see a society that can stitch itself back together.  Sometimes these sorts of external shocks can bring people together, and I feel people were brought together for kind of like a month or two. And then it just all kind of unwound in May. And a lot of it was just economic pressure, which a lot of people have been under. And that’s difficult. I mean, there’s just a lot of difficult conversations that I feel like people are not having compassionately. And I think that’s been the ultimate problem.  When people are acting out in a crazy way, sometimes there’s a reason, you know? 

Razib: I have friends who are academics. And I’m like, “you have like a tenured job at an R1 university. Your salary is going to keep getting paid indefinitely.” I mean, yeah, the university could lay you off, but that’s very unlikely with the type of job you have. Okay. You can do social distancing. You can stay inside.  There’s a lot of people who are living paycheck to paycheck and they’re not in that situation. And this is why they’re not being as rational as you, not just because they’re stupid. I mean, they’re probably not as intelligent, whatever, but really they have no options. They’re desperate. 

Razib: There’s that survey that showed that like 30% of young adults have thought about suicide in the last six months. And obviously it increased. I think some of it is hysteria and scaremongering because young adults are not at risk of dying of COVID, but some of it is also like they don’t have a job. Where are they going to get a job? What is the future of this country? There’s a lot of hopelessness, you know, and instead of us stepping up or at least stepping up to COVID-19, we’ve kind of fallen down on the job.

Razib: That’s how I’m feeling right now at the end of the summer of 2020. Maybe something will change and turn around and I’ll be smiling and I’ll be happy. But I stopped–you know Grant, we’ve talked about this–I stopped paying close attention to coverage in June, just because. It didn’t seem like we had what it took to really attack it. And so I will continue doing my quarantine as best as I can. And that’s it. I’m not, like, there’s only so many people I can talk to, only so many people I can convince. We convinced our family and friends that we could go to quarantine early. That took a lot of work in March. That’s done. And as far as the rest of society. I’m not one of those people that’s like, “Oh, you don’t wear a mask. You should die.” Okay. I want to convince people that aren’t doing it, why they should. Okay. But I’m also going to express my alarm. I mean, I have friends who are just like, you shouldn’t be alarmed like this isn’t that bad. And you know, it’s just like, when I read about the way people die, it’s bad.  

Razib: The only hope is–this is the positive spin I will put on it. I just actually had another podcast today that I recorded with someone about COVID-19– I do think that herd immunity is probably a little lower than 50% for various reasons. So it will end even if we don’t get a vaccine, and we’ll pick up the pieces and figure out what this means for us. Because I think after it ends, I feel like people can take a breath and kind of take stock. And I don’t know if they’re going to be happy with what they conclude about our society. I don’t think that we’ve fully processed it because it’s not over, we’re still in it. You know, we’re still like waking up every day, checking the news, checking in with our family and our friends. More and more, more and more of my friends have gotten COVID-19. Not that many, but some of them have tested positive and they have the symptoms, and it’s going through my network right now. But,  I don’t know. I’m just kind of on a pause right now. And I feel like our society is on a pause, but COVID-19 is not on a pause. It looks like it’s slowly winding through and we might be incompetent enough that herd immunity is what protects us. So yeah, on a down note, that’s my COVID talk.

Razib: [laughing] I don’t know. I shouldn’t laugh. I mean, it’s just like, what do I do? This is a nervous laugh. 

Grant: Yeah. If I were forced to prognosticate about it…

Razib: Dark times, man.

Grant: I think there’s a good chance. We’re going to hit some kind of a, I don’t know about a real herd immunity, but at least an effective herd immunity, transient herd immunity, under conditions of social distancing before we get to a vaccine.

Razib: Well, so I don’t know. I think this will change. I think coronavirus will change some things.  I don’t know if I’m ever going to shake hands again. It was always one of those things where I kind of did it because of social pressure. I just didn’t really want to touch someone’s hand. I don’t know where they are, what they’ve been doing. And also like in business, when you shake someone’s hand, I’m always thinking, “okay, how many hands has this person shook today? I’m not just shaking your hand, dude.”  I mean, I’m gen X, I went through the HIV training and that took. Okay? I extrapolated. So I’m not going to shake hands. There was some stuff out today about how teens are not having sex and not like interested in it. You know, I think this is going to affect a lot of people with personal contact until we have a vaccine.

Razib: But even after a vaccine, like this is the first big infectious disease that we’ve had, that has hit our public consciousness this way and had this impact since the 1918 flu. I know the 1957 flu was as bad as this in terms of mortality, but our culture was not impacted in the same way.  

Grant: No one talked about it and it’s very strange.

Razib: There are some newspaper reports about it. People died, but the economy did not get hit that badly. 

Grant: It didn’t imprint on people’s consciousness. Right? Sure. It was in the papers and people working in hospitals obviously noticed. People knew some folks who died and so on, but it wasn’t super new. It wasn’t really remarkable at the time. 

Razib: The world is different. And our economy, the downswing was as big as the great depression in some ways. I mean, it’s obviously structurally different, but you know, I mean, okay, like this is worse than 2008. It is worse than anything since World War II, you know? Great leap forward was really bad. There are bad things that happened after WWII locally. But this is I think the biggest global event since WWII.

Razib: So how can it not affect us psychologically? How could it not change us in terms of how we see. Like when I, when I see movies or TV shows where people are in bars, I get the heebie-jeebies.  I think that will eventually fade, but it’s gonna take a long time. And I think there’s going to be a lot of people on the margin who are already germophobic. We’re just going to say, “you know what? I lived through 2020. I don’t want to take the risk. I don’t want to take the risk. I will drink at home.” Or if you’re going to invite me to drink, it’s got to be a patio place.  

Grant: Well and the virus probably isn’t going to disappear. Right?

Razib: It could be endemic.

Grant: We may get control of it, but it’ll still probably crop up here and there.

Razib: It’ll be endemic. Yeah. So that’s what we’re talking about. I mean, that’s what we’re seeing in places like New Zealand that controlled it. Like it just creeps back in. So until it evolves and gets us really.  I think it’s going to be here to stay. Now that does mean work demand for services of biological scientists. So, you know, undertakers did really well during the black death. I’m assuming. I mean there’s work for people even in a time of COVID-19. In a way I feel like the economic and even the mortality impact is going to be dwarfed by the cultural, social, social impact. 

Razib: We have small children, Grant, and they just kind of accept coronavirus. My three-year-old will yell coronavirus at people if they walk too close to him when he’s in the front yard.  My three year old is also really morbid. He thinks all old people die of coronavirus. Someone recently died that we know, and he’s like, “did he die of coronavirus?” And we’re just like, “dude, there’s other diseases” But he doesn’t know any other diseases. All he knows is about coronavirus, people talking about coronavirus. And I don’t know how my kids get the news. My son has kind of Browner skin and he’s scared of the police, you know? Not even joking. He’s just telling me he should be scared of the police. I’m like, don’t worry about it.

Razib: It’s just like, you don’t know how kids find out these sorts of things. As adults, we’re trying to pay the bills and not get sick. And you got these little kids running around, all these little kids and like, what are they thinking? You know?  It’s just really weird for them because I have a sister who has a newborn or infant.  We don’t know if she’s scared of strangers or he’s scared of strangers. He’s never seen a stranger! So he’s seen doctors, seen parents and seen grandparents. That’s it. Those are the only people that that three month old child has ever seen up close. Right. So, I think we need to think of the social impacts. It is the big thing about COVID-19. Cause I think we know what CFR is, you know, 1%, I don’t know, something like that.

Grant: And actually, so, you know, you mentioned one positive thing about the herd immunity threshold, possibly being lower than anticipated. I’m not sure, but we’ll see and time will tell, but, the CFR does seem to be going down. So the mortality in hospitals, the unadjusted apparent mortality is down dramatically. 

Razib: And also the people who are getting it are the less. Unfortunately, the more vulnerable people probably got hit first.

Grant: Even adjusting for the various risk demographics and so on, mortality in the hospital is still down substantially from the beginning of the pandemic and it looks like it’s down about 40%. Treatments like Remdesivir and all these things, right? I mean, seem to be making a difference and maybe people are getting initial viral loads that are a bit lower. Cause they’re  keeping better distance, wearing masks.  You know, if you were sitting right next to someone at a bar in New York City before they really realized what was happening, you probably would’ve gotten a higher initial exposure. 

Razib: So I think, you know, my discussion on COVID-19 has been very pessimistic. I think from the purely biomedical perspective, I’m cautiously optimistic. I do think we, as in the world, are putting a lot of resources into vaccine work, and I understand vaccines are difficult to develop. They’re not trivial. They’re often not very effective. So I don’t want to oversell this, but everyone’s focusing on this. I would not be surprised if we have a good vaccine in two years, perhaps a year. I have heard that China and Russia are already vaccinating people in government and their army. So, We’ll know how those trials work, you know what I’m saying? They can take a few risks that we couldn’t in the United States. So I think treatment’s going to get better.  So I think the mortality will drop. So from a purely biomedical perspective, we will make it through this, just like we did with the ’57 flu or the milder ’67 flu or the ’68 flu. 

Razib: So that’s doable. I think what COVID-19 though has shown is, what is the measure of a society? If I had to bet if we had like Mitt Romney, I think we would be doing considerably better. Okay. I just like slopping out another Republican. I think Trump to be Frank is. Tactical genius, but he has zero strategic division. And so he’s been going from thing to thing. So yeah, like, I mean, I think that’s a problem, but I think we still would have had a problem with compliance with localities doing their own thing. And so, I think that it’s a little disturbing because.

Grant:  It’s like there would have been a lot of impatience. 

Razib: Yeah. Yes, yes, yes. And in China, they’re not going to have impatience because the government will just like put you in prison. So there are issues like that. I do think the positive lesson would be like South Korea. Okay. I mean, South Korea, they say, “Oh, there’s been an outbreak.” But  if you look at the numbers compared to the United States, even adjusting for population, it’s nothing. If we had South Korea’s problems, we would be so happy. They have a test and trace capability in part because of previous scares. 

Razib: So, you know, we are in this biotech space and I do wonder.  Just things get more efficient as the demand increases, the prices go down, it gets better and better. We have great information technology. Why can’t we have spit kits? For everybody in the world, literally for everybody in the world. Yeah, it would be an expense that we have to take every year or so to produce new spit kits and all these things. But, it’ll prevent what we have just gone through as a world. This massive loss of GDP productivity, psychological trauma. Frankly, I don’t know if I should say the word trauma, but I think a lot of people have been traumatized. There have been suicides in third world countries. I mean, Americans are broke, but we’re not broke, broke ever. Even when we’re broke, you know… There’ve been suicides in India. People have starved in India. Okay. So, the outcomes can be quite deleterious. 

Razib: And so if we just invest more in the technology to do what we need to do. What we need to do is test, trace and contain. That seems to be the magic quote solution. If we ever deal with something that’s very similar. Whereas something like SARS, it’s R0 was lower, I think. And the issue with SARS is it wasn’t as asymptomatic. You got it, you got it. You go to the hospital, you didn’t spread it to other people. The problem with COVID is it hit this sweet spot of 50% asymptomatic spreading it. And these are the people that are spreading it all over the place. And they don’t know. So if you had good testing. So if there’s a local outbreak, just tell everyone to test. Mail everyone a kit, just have it there.  

Razib: Why can’t we do it? You know, we have all of these like other things. We have cruise liners. We have these huge industries that are just for consumption. Why can’t we have this one thing to protect us against this tail risk, which is inevitable. There’s going to be another infectious disease outbreak in the next generation or two. So have the facility. Obviously it is going to have to be a different test, but a lot of the other things can be put in place. Look at South Korea. They didn’t have a test for COVID-19. They had to create one, but they have the whole framework set up. And so, if we’re still going to have a World Health Organization, I think that is really marching orders. 

Grant: Are you optimistic? The U S will do that?

Razib: If you can’t say anything. Nice. Don’t say anything at all. Look, I want to be optimistic. I’m optimistic about being optimistic someday. I don’t know. 

Grant: Good stuff. Alright. 

Razib: I think we’re good.  So I guess I would say though, even if I have a lot of pessimism and concern about what’s happening in this country. I am still excited about the world and excited about science and excited about discoveries. Yeah. 

Grant: Yeah. Thanks. Thank you so much for joining us. It’s been a really fun conversation.