Cracking the Longevity Code: J. Craig Venter PhD #182

[Music] we were talking about who was going to introduce you and I thought you know does anyone actually need dr. Venter to be introduced and I think we could talk about you know the fact that you've been a fire starter and a renegade for your whole career you've done things people you know have said could not be done and you've inspired a whole generation of geneticists and biologists and physicists and health entrepreneurs doctors with your science and your ability to harness technology to understand the potential of our DNA so my first question is where are we in terms of collecting and parsing the data that will be required to really understand the human genome that's a good question so not as far along as most people think it's still extremely early we're somewhere still around 1% of the knowledge that will be ultimately obtained and work that's sort of the basis of why we started human longevity is that we could collect hopefully tens of millions of genomes but in conjunction having phenotype and clinical records on every person and we're using machine learning to make correlations between them so it's the way discoveries are being made in the genome as the way genetics has been done for the last century and it's very slow tedious and I would say at least half if not 80 to 90% of the papers published in this field are wrong well and we made a fundamental decision when we started hli well we would we use the literature to validate our data or would we use our database to validate the literature and we were glad we chose the latter because our team has found as much of a third of clinvar which is the reference everybody uses for annotating their genomes is just riddled with false data so if that's what diagnoses are being made on you know that's why the genome is struggling right now and people to accept it you can't get the same results from two different places so we hope the next couple years will start to change that as we get more and more people going through the health nucleus it gives us a huge phenotype data set and we can talk more about that if you want so I want to talk a lot more about everything you just said let's start with some of those numbers so 1% you say we understand we so we know or we understand 1% of the human genus a we understand 1% and is that a sort of educated guess or is that based on something it's more based on discovering how much we don't know every day it means we know very little it's not a precise number or it's just we have a very long way to go so the percentage that's classified currently as junk DNA that's not junk right I would classify some of the scientific literature as junk ok ok so there is no junk in the genome there's a famous paper that said you know something like 60% of all research is subsequently proven wrong you're quoting 80 to 90 percent so yeah most of these papers don't even get quoted once but even by the author unless they get quoted to say that they're wrong oh yeah or their mom's quote them ok so it does kind of do a boil down to databases though doesn't it I mean there's a lot of companies and projects both public and private that are collecting genomes and publishing literature and then deciding which literature to use to interpret the genome it starts with a fundamental quality of the data so we hired Bill Biggs to build out our sequencing facility three and a half years ago and various groups have validated that our data is the most accurate data out there so it's not a banner of mine a machine it's the whole process and we've been doing this for well over 25 years now it makes a big difference whether it's a rare variant used to diagnose a trait or a disease or a sequencing error and each of us have around four or five thousand rare variants some have more some have less rare variants means ones that we don't find in any database at this stage so certainly you know lleol frequencies of less than one and 20,000 so when you're at that level or lower you and you're attributed something to it you want to know that it's real and not just some sloppy lab work what is an acceptable degree of error in a genome what do you guys strive for it hli so when you're using it to give people predictive information I say there's no acceptable level of error the trouble is we're finding with various genetic disorders for example what triplet repeats there were never really broad population surveys done people sort of look under the lamppost so they look at people with that disease we're finding now looking at a much broader population that for example with Huntington's disease we're finding people with that numbers of triplet repeats that greatly exceed what would be used for clinical diagnosis but these people clearly do not have Huntington's disease they have no family history of it no symptoms of it and maybe they'll get extremely late onset disease or something but what was classified by looking at people with Frank disease doesn't kind of extend when you see the whole population and we have another thing with heterozygotes for a bovie for which puts them at very high risk for Alzheimer's no exact way but one individual from all the genetic scores you'd be sure this guy would get Alzheimer's disease he's 74 right now and he had almost a perfect brain skin more like a 40 year old so the challenges the the lack of correlation at a hundred percent level between genetics and what we attribute to it bracket 1 and bracket 2 or another example it's actually 50% risk factor for a woman to get breast ovarian cancer having the well-known genetic changes in those genes unless there's family history if every woman in your family has breast ovarian cancer then plus those markers it goes up into the high 90% so that means there's other genetic elements that we simply don't understand yet and once we do understand that we'll be able to tell women whether their risk is zero or close to a hundred percent right now it's 50/50 because the most important risk factors only come from knowing your family history mm-hmm so let's go back to some more numbers I think the last time we checked in HL I had about 2000 is that right genome complete genomic and phenotypic information yeah we've had a little over 2,000 people go through the health nucleus and does that include like the full-body MRIs and yes it testing in fact we have a new definition of it February at first we're rolling out a new product but we're handing out brochures on it because there's there's a special on it here for people four thousand nine hundred and fifty dollars okay that's a big discount off of 25 yes okay so but are we not getting and it's the the whole body MRI the quantitative brain analysis quantitative vascular analysis the new Siemens MRI actually does a pretty extensive cardiac analysis in 12 minutes and the report is done by the time you get out of the MRI perhaps the most important thing we're finding because it's such a huge percent of the population is a greatly elevated organ fat primarily liver fat normal is four percent or less we've had people as high as 38 percent without knowing it and so we're trying to estimate how many of those go on for fibrosis and would need liver transplants we found a correlation between a microbiome and fatty liver so I think that's important and what the special deal is is you get a free microbiome analysis if you do things that start up health it was a partner with us but so it's the full genome a number of lab values particularly we use a thing called the cuantos that measures insulin sensitivity it's with metabolome we do cardiac CT for people over a certain age and what we're finding there is the age groups were finding calcium and the heart keeps going down recently we had a 45 year old woman that was clearly not obese no history of heart disease she was in the 99th percentile for four different coronary vessels which means she's extremely high chance of having a major cardiac event and next decade she did have elevated blood lipids but these unusual cases give us you know fodder to go back and look at the genome of these individuals as well but we're finding a shift in all diseases to younger and younger cohorts cancer as well but as you probably know cancer has been replaced by heart disease and women as the number one killer and most women don't consider heart disease a woman's disease most physicians don't and so it's it's getting neglected but the kinds of tests that we do make it very clear whether you have it or not so $25,000 I think going down to do the full monty on yourself as a healthy person yeah was a bit of an indulgence and it was for you know the leading edge people who had lots of money and curiosity and we didn't know what to charge initially we still have so the new version is called hnx we still have hnx platinum that people still ask for and it's a full either/or one this takes two and a half hours to go through everything so it it's a big difference in time and uh and dollar commitment and you can use health savings plans to pay for this well we're trying to get enough data where it makes sense for third-party payers to pay for it but preventive medicine is is hard to sell but we just did a study on 25 people for a pharma company sort of average age so out of 25 people we found one with a very serious cancer that they didn't know they had a couple with serious heart disease and a spectrum of other diseases so all which would have you know their self-insured so they would have had to pay for these once they revealed themselves so we're finding one percent of the population have brain aneurysms and our MRI is nice because it's no contrast so you can have an MRI everyday with no risk in brain aneurysms most people know somebody that's died from one they can generally be treated as an outpatient just writing up a coil to put in them mm-hmm five percent of people over 50 we're finding a major tumor that they didn't know they had the good news is we're finding these at stage zero stage one and somewhat stage two thus far they've all been successfully treated all the diagnoses were confirmed by the pathology so we're doing really well with diagnosing things in the MRI and we now have a machine learning algorithm that's as good as the best pathologists for scoring high-grade prostate cancer straight from the MRI and we think in a year we will have the same thing for breast cancer switching from doing rafi a to MRI for breast cancer which will be a major shift particularly with no contrast media so mammography has a huge false positive and a false negative rate so we think getting this data with machine learning is really changing what can happen so so it's a fantastic thing to do just on a preventive basis to find out what may be lurking in your body a little time bomb or something that you could do something about what about discoveries so have you been able to discover some correlations that were previously unknown have you so we don't view what we do is diagnostic or you know because everybody that comes in is by their definition healthy so so that's that's the question I'm getting at - so as a consumer $5,000 is still you know a fair amount of money I'm not sure I would come unless there was something wrong with me that I was trying to figure out in which case I might come to you instead of going on a Mayo Clinic but that's that's the wrong way to think about preventive medicine it's like you're not going to ever change the oil on your car until all the oil drains out in your engine freezes because then you know something's wrong yeah with these cancers with the early detection as I said we've been a hundred percent successful thus far in treating them all the individuals are cancer-free we have a cancer exome program we're dealing with four women and their 30s with stage four colon cancer when you detect cancer from symptoms the outcome is totally different so getting pre-symptomatic early discoveries so yeah your odds are pretty high if over 55% of people having a cancer they didn't know they had is pretty stunning and in fact it's we're having to re-educate the the medical system so we diagnosed one men in the 70s as having a high-grade renal tumor because we use our algorithm as post processing with no contrast media he went to a clinic up here in the Bay Area and was told they put him through a standard MRI and it was told he just had cysts and to ignore odd so we found somebody here in San Francisco that knew how to read this new technique and confirmed that he actually had renal cancer and was operated on a week later and it was confirmed that it was a high-grade tumor not yet metastasized so most the medical communities not even aware of these new techniques that you can do non contrast MRI with all this post processing algorithms so but you'd be smart to go through because then you become a baseline you're your own control level for things mm-hmm and I give you an example with with myself I was discovered to have high-grade prostate cancer last December and this was after a long period of having elevated PSA having biopsies being told they didn't have prostate cancer also one of my blood tests showed that I had extremely low testosterone levels which is bizarre cuz nobody's ever accused me of being low on testosterone and what turned out trying to understand my tumor we went back through my genome and looked at the androgen receptor and so there's a it's a triplet repeat phenomenon so if you have a 21 or more triplet repeats you have a very low incidence of prostate cancer the fewer repeats you have the higher your odds go I had only six repeats that's one of the lowest numbers and what that causes is the over expression of the androgen receptor which explains why my testosterone levels were so low it took only a tiny bit to maximally activate the receptors everywhere so the production was down regulated so compared to the average population there were low compared to my own personal baseline had I known that was the situation I wouldn't have gone on a testosterone supplement which probably aggravated the tumor and made it grow extremely fast so getting a baseline and then you can detect differences annually in yourself so we're we're setting up these new programs as membership programs so once you have some of the tests you can come back annually for example if you have a higher risk for cancer and just get the the whole MRI so and I think you're also increasing your outreach to other organizations to help yes have this not just be localized in San Diego in fact where we're trying to get several dozen set up and then next year to around the country some our partnerships some are being done as franchises so how many genomes would you like to sequence by the end of let's say 2018 well our goal is as soon as possible to get 10,000 individuals through the health nucleus because that gives us a really good starting data set for the machine learning of comparing all the traits back to the genome so what can you discover with 10,000 versus a hundred thousand versus a million so the higher that numbers go the better chance of finding things with the really rare alleles so one of the interesting things is we saturated the common alleles in the human population at about 8,000 genomes the common alleles is what most people use on gene chips to measure things so by the definition be common alleles that are not the cause of disease the ones you want to measure in yourself are the extremely rare alleles and so with each person we actually give a ranking we have a really nice tool that looks at your entire genome in 200 milliseconds and it gives the allele frequency for that variant and there are population data set so when you're looking for things of significance if seventy-five percent of the population has it we just ignore it if one out of twenty thousand have it we pay a lot of attention pay attention to it we've also mapped the genome so we know sites that are very susceptible to mutation and ones that aren't there's places that if you have a variant at that site it's incompatible with life so those are probably associated with early spontaneous abortions for example just mapping transmembrane receptors if a change occurs in the transmembrane section that usually leads to a loss of function mutation so from just mapping the genome to combine unit with this data it's pretty exciting every day there what we're finding so you wrote and an iPad last month talking about the risks of gene editing and you've been very vociferous about sort of your concern that we are so excited by the potential that we are liable to get ahead of ourselves and start editing the genome prematurely with unintended consequences and you were not alone in that obviously there's no fun CERN and that's actually kind of unusual for you I expected you to be out on the the French of that debate but how much do we have to understand about the genome before editing it editing dating the germline would make sense well if we're at 1% now you know does 50% increase your comfort does 90 percent increase your comfort or do we have to know everything about the genome the metabolomic audio mix everything before you would be comfortable so we need tools that are really precise tools so crispers have off-target effects and usually people just measure the effect they want to they don't resequenced the whole genome and see what else was changed on this latest day the paper just came that's very interesting something like 2/3 of the population have had a body's too crisper and probably won't be very effective obviously for germline that's different but you want to know that you're making changes that are you know that are unique and important I think getting rid of tay-sachs disease or ataxia telangiectasia wouldn't be bad ideas in the population KJ must do that with frozen embryos don't we kind of get around that once you start down this road that's a very slippery slope and all the poles most young parents want to change fairly trivial traits in their children you know eye color hair color types of muscles versus disease risk and Kay Jamison that was at Hopkins I think she's still there has written several books about manic-depressive illness and creativity and so if we treat manic depression as a disease and we find the genetic links for it I'm gonna interrupt you because we're now running short on time and we'll wipe out all the creativity in the human population by editing that out so we need to know all the consequences of making changes for future generations absolutely okay so so you've signed on as a sponsor for start-up health longevity moonshot and the definition of the moonshot was to increase average lifespan by 50 years so you know we can prevent a lot of aging through lifestyle choices tobacco sugar alcohol eliminate the poisons diet exercise sleep stress but we have no means of clearing the senescence cells or repairing the mutated DNA or what have you so what do you think are the most promising avenues of research to pursue so in the quest for longevity yeah about 30% of people that reach the age of 50 will die before the age of 74 right now so when you're talking about increasing lifespan finding a tumor in a 50 year old that can be completely cured probably changed their life span by 30 or 40 years if they were gonna die from metastatic cancer so you're just you're saying early diagnosis gonna get worse so if we had a twenty-something that we found that she had changes with insulin sensitivity increased oregon fat a pear-shape peripheral fat distribution and elevated lipids she can go one course we're developed into diabetes you get cardiac complications with that but cardiac complications you get early brain damage and dementia or you can totally prevent that pathway into developing diabetes in the first place and the same thing with heart disease the same thing with early detection of cancer so early detection buys us twenty five of the 50 years that were going for some people could buy them 90 years right when we look at the total distribution so where we started an in of one program at the Venter Institute with a 16 year old girl whose younger brother died at age 12 from her neuroblastoma on sequencing her genome she had multiple oncogenes that were mutated the same as her younger brother and their parents were sure that she was going to develop cancer so we set up a program she's now 18 the student at UCSD she comes to hli every six months for a whole body MRI with the goal knowing she's at risk for cancer of detecting it at stage zero stage one so it's like doing the preventative maintenance the more you know early on the better the chance of detecting things early enough we're finding cancers just happenstance and when people come in my colleague ham Smith at age 84 because we we set up at the ventures to do for all the senior scientists to go through the health nucleus mm-hmm so only by going through the health nucleus we found a a fist-sized tumor in his lungs turned out to be a very rapidly join lymphoma had he not come in that day he would have died in six weeks he responded extremely well the chemotherapy and radiation he his hairs grown back he works every day in the lab now and he's totally back to normal so if his appointment was six weeks later so timing is everything and if you know you have risk you can just have repeated visits as a non-invasive checkup so we know we we interviewed you actually Neil life interviewed you last year and asked you just quick questions about what your personal longevity strategy is and in addition to avoiding toxins as much as possible and diet and exercise sleep and stress reduction you mentioned that you take metformin mm-hmm are there so do you think that's making a difference and are there other pharmaceuticals or other ingestible --zz of some sort that you think I take statins and they've changed my cholesterol level substantially metformin and a combination but diet changes my a1c is now in normal levels so it does have an impact I do believe in preventive medicine even I do risky behaviors like drive motorcycles really fast so I I now have one of these paths that if you fly off your motorcycle inflates instantly see you bounce down the highway I haven't tried it yet this to see if it worth it there's some great videos of it but so you know I try to mitigate risk even with risky behavior mm-hmm okay so you you probably have the most studied genome in the world in human history and I'm just curious how long do you expect to live I mean you you're in the business of predicting what people's genomes say about no it's interesting because the team is put in a series of algorithms together like we use with the machine learning for predicting Alzheimer's and prostate cancer and we're using it to predict your the age of your brain from the rough studies so I'm 71 they said I have a brain of a 40 year old my wife said no he has a brain of a 17 year old [Laughter] but I've outlived every male except my urine half older brother from my father's side of the family by almost a decade now they all died from heart disease or combination of heart disease and alcoholism so I think statins and the preventative measures that I've taken have presumably had some effect what would you hope to see so let's say that you're 70 now I think correct 71 71 so you want to go another 30 years another 50 years I you you mentioned it in the book John converse book what's your bio strategy you're talking about 300 years yeah so the the key to longevity is not your BMI like a lot of people think it's your muscle mass so the key is trying to maintain strength as people get more and more frail they fall they break bones then they get hospitalized and they sort of start a slippery slope the data shows if you can maintain a strength and activity we all have sort of a fixed decline that's a question you know can we change that slope and the number one risk for almost every disease as your age mm-hmm so our risk goes up so after 50 I plan to go through the health nucleus at least every six months as preventative measures to because of your history with prostate cancer II so you have to go at least five years with negative PSA to really be proven that you didn't have metastasis from the surgery but I've had melanoma I've now had prostate cancer I have a few oncogenes that are activated so you know I'd like to detect things as early as possible the algorithm for predicting what year you're going to get Alzheimer's is really getting pretty accurate I'm pretty far out on the curve on that at least twenty or thirty years out so but you do have an algorithm for predicting that yes okay and that'll be part of the program that we start to offer people in the near future yeah if I could still be writing a motorcycle at 120 miles an hour at age 102 I think I'd be happy is that your expectation I'm gonna try what else we may be my last motorcycle ride what what would your what would you hope to see happen in your fields whether it's genetics longevity synthetic biology in the next 30 years what do you want to see happen before you die so the biggest challenge in its I didn't realize it would be such a huge challenge and in your an example of it because you were hesitant to do these tests is getting people to do preventive medicine the that doesn't sound like a moonshot it's it's a Jupiter shot or something that you know the moon would be easy by comparison if you look okay and feel okay you deem yourself healthy and the medical establishment deems you healthy you can't tell me you're healthy I can tell you whether you're healthier or not after going through the clinic I can tell you whether you have cancer but you're developing early dementia whether you have metabolic disease all of what you could be completely unaware because it's at stages that haven't started yet you know the million-and-a-half people that get diagnosed each year with cancer didn't just get that cancer of the day before some of them have had it for decades so the medical establishment is fighting screaming healthy people mm-hmm and it sort of stems from the 1970s when CT scanning came out CT scanning is just x-ray and it created what we're called incidentalomas you couldn't tell a tumor from the cyst so but give us something bigger to chew on here you know you announced a DNA printer last year right we could email a file to some off-planet colony and print you know humans or at least vaccines or something so you know how far out can you and imagine something outrageous happening between now and the end of your lifespan well if the 40% of men that die before they reach 74 get preventive medicine and don't die that changes the economy that changes productivity what happens to innovation if all the old people hang around longer well it's not working so long the government right now but I think we need some younger people in the government at least at the top but look at the list of top people and you know still in the prime of their lives that die each year we're losing that knowledge and we sort of have to start with each generation and reteach them all the things like vaccinations are actually important to keep disease away and things so I think if we made preventive medicine and using these new tools of science to find out whether you're healthy or not it's actually probably one of the most important things I could accomplish in my life and particularly if the genome makes that predictable as a triage that would be pretty satisfied [Applause]

Channel: StartUp Health

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Keywords: Jane Metcalfe, NEO.LIFE, Craig Venter, Human Longevity, 2018 StartUp Health Festival, Digital Health, J. Craig Venter PhD, Craig Venter PhD, J. Craig Venter, NEOLIFE, NEO LIFE, Human Genome, Human Genomics, Health Moonshot, Health Moonshots, Dr. Venter, Dr Venter, Dr J Craig Venter, Dr. J Craig Venter, Dr. J. Craig Venter, Dr J. Craig Venter, Dr. Craig Venter, Dr Craig Venter, Human Longevity Inc, Human Longevity Inc., anti aging, Anti-aging, HumanLongevity, Genetic, Health

Id: gNtQmpcNge0

Length: 40min 5sec (2405 seconds)

Published: Fri Mar 02 2018