 next speaker is chief medical officer for the Intel corporation. You might have heard of them. And I was surprised that Intel had a chief medical officer and I am personally really excited to hear what Dr. John is going to share with us. So please join me in welcoming to the DEFCON stage, Dr. John Soto. Thanks, I will. Thank you very much. Did somebody say break? I'm a cardiologist. I'm not going to destroy brain cells. It's against my professional ethics. So it's an honor to be here today. I hope you get something out of the talk, at least something to think about. But first of course I have to start with disclaimers. What I'm going to talk is not necessarily the official position of Intel or the department of defense. I've got a department of defense affiliation too, which I'll go over. So anyway, with that let's get going. I'm going to use my pointer over on this side. I hope everybody. Okay. Well, here we go. So first let's go back to 1978 when I was a college student in about this part of the country. And I got sick. Really sick. I was sick as crap. I was laying in bed shivering. Excuse me. My teeth were actually chattering and every muscle in my body hurt. It wasn't just me. It was everybody it seemed like. Well, almost. The professors didn't get sick. Just the students. And it wasn't just my college. At the Air Force Academy, 77% of the recruits got sick. The cadets, sorry. It wasn't until 30 years later I found out what had happened. In 1918, that's when the story starts, a virus got from a bird into humans. And that killed about 1% of the entire world's population in 1918. And that virus and its descendants stayed circulating in the population for another 40 years or so. And you know how there's an influenza every winter and there's a different shot. You get every winter. The virus changes little by little. So over the next 40 years that virus hung around. And then in 1957 it went away. It was replaced by another influenza virus, an H2 virus. And then in 1968 another virus replaced that. So far all is normal. In 1977 though, H1 came back. And in fact it just wasn't a random H1. It was almost exactly identical to the H1 from 1948. And that's why the professors didn't get sick. The professors had all gotten sick in 1948 because they were older. It was only the students who had never seen this virus that got sick in 1977. So how did that happen? Because these viruses change. You can't get a 30-year span in time when an influenza virus doesn't change. And so, the common consensus is the reemergence of this virus in 1977 is unexplained and probably represents reintroduction to humans from a laboratory source. What does that mean? It means something got out of a lab. It got out of a lab and it came halfway across the world and it got me. This is where this virus first appeared in the wild somewhere in northeast Asia. We don't know if it was a Soviet union or China. But it went worldwide. And it didn't affect the old and the infirm. It affected the healthiest people, the college students. So you're affected by this too. Because ever since then the descendants of this H1 virus have stuck around. And this H3 virus has stuck around too. So every year when you get your flu shot, and I hope you do, you're getting immunized against something like this and something like this. So, that's one of the motivations for this talk. Stuff that happens in labs can have worldwide reach. And we know that engineering of microorganisms is happening every day today in laboratories. The question is, what is the potential when malicious engineering of organisms starts? And how do we defend against it? And I would claim that only massive preemptive development of counter hacking biotechnologies can save the world. Because I think the threat is that grave. So who am I? As I mentioned, I'm a cardiologist who doesn't drink much. I work for Intel. I've been in the Air National Guard for 30 years, mostly as a rescue flight surgeon. I've been programming since 1970. I don't get to do much of it at Intel, unfortunately. That was my first computer that I ever programmed there. And am I a hacker? Do I deserve to be here? Well, I wouldn't presume on the computer side. But I have an interest in what you might call diagnostic hacking. Hacking the diagnostic process. And I wrote a book on that. And I was a professor for a long time. But you probably know me, if at all, for my work on house for six years where I was a consultant. And also on Torchwood Miracle Day. And I'll be consulting for a new show this fall on ABC called The Good Doctor. So tune in Monday nights. So today I want to talk about epidemics and bio weapons. Talk about digital biology. Show how exploits, where they'll come from. And then conclude with a few reflections. So bio weapons are actually amazingly effective. And they date from ancient times. The Hippocratic oath that all us physicians take, that started because it was a doctor who told his military commander how to poison a village and overrun it. So in the middle ages, the black plague killed about 25% of Europe's population. Smallpox killed about 95% of the Aztecs. That's why nobody in this room knows any Aztecs. Influenza, as I mentioned, killed 1% of the world's population. And it went everywhere. There were only two places on earth that didn't go. And even today, we have an epidemic of small headed babies. I mean, who would have thought such a thing is possible? It turns out the Zika virus can do that. And no less than Bill Gates says of all the things that could kill more than 10 million people around the world, the most likely is an epidemic. So we haven't even started to see unnatural epidemics, just the natural epidemics. So this I saw an exhibit in Oxford, England. This is from a book published in 1625. And when the black plague came through. And so here you have obviously death. And the population of the town, we fly. They try to get out of the town. You can see soldiers stop them. But even though they try to flee, death follows them. And then we die and hear the coffins. So that's what we're up against. And the effect of bio weapons can be long lasting. The Brits tested some anthrax in World War II and the island where they tested it was uninhabitable for 50 years. Malaria has affected the evolution of multiple human genes. I've got a gene that I have only because my ancestors survived malaria and they were good at it. And about 8% of your genome started out in viruses. So the problem or the reason you haven't heard much about bio weapons when we talk about warfare is they've been held back by a pretty severe limitation, which is the potential for blowback. If I use a bio weapon on some adversary across a border, that epidemic is probably going to spread back and get me too. So that doesn't make it a great weapon. There are international treaties that outlaw bio weapons, but you know, treaties are easily broken. So let's get now into the exploits and how they might work and how to think about them. The first thing to realize is what's called the central dogma of biology. You start with DNA and you make RNA out of that and then you make a protein. And the proteins are the real work horses of life. They do various jobs. Now if you want to make a medicine today, you're usually making a medicine that attacks the protein. And for, you know, just convenience, we can call that analog therapy. You know, you design a chemical that fits into the protein or does something to it. And this is pretty difficult and it's imprecise. There's lots of cross reactivities across different proteins and that makes it hard to design safe and effective new medications. It's why drug companies spend so much money developing drugs because it's so difficult. So tomorrow, though, I think we're going to see digital medicines and we're starting to see a few. Remember RNA and DNA are digital programs. They're written not in binary but in a quaternary code, A-C-T-G-A. And they're amenable to digital manipulation, which means you can reprogram them. And so this is going to allow an algorithmic or a digital design of medications. And the cancer moonshot, which Vice President Biden, of course, pushed, is going to really drive these new technologies to manipulate DNA because cancer really is a disease of DNA. And if we get a good cancer mechanism to combat cancer going using this route, it's going to be exquisitely specific because cancer cells are not that different from normal cells. Okay. And just some of the catch words you might have heard, some of these digital DNA technologies are something called RNA interference, which won a Nobel Prize in 2006. You've probably heard about CRISPR-Cas9 and for sure there will be a Nobel Prize for that someday. There are things called gene drives. Spreading these DNA programs can be done through measles, virus, let's say. It's unbelievably contagious. And even nanodiamonds can be used to get viruses or DNA into you. So what you can do with this sort of digital approach to DNA and RNA is you can do things like program in an if-then statement. And this has already happened. In fact, somebody programmed a five part predicate in here for the if statement. So far, nobody I don't think is working too hard on the, or is succeeded in the deploy payload part, but the if part is very well along the road. And this sort of construct is going to be the key to biohacking. So I'm from Intel. We talk a lot about Moore's law, but biotechnology is blowing Moore's law out of the water. This graph here shows how much it cost to sequence a human genome going back to, I guess that's about 2,000. I can't read it. And this line, this straight line is Moore's law and this is the cost of genome sequencing and you can see it is dropping way faster than Moore's law. So in 10 years we might be talking about a $10 genome sequence. And you know, these sort of if-then statements are going to continue to get better and better. And so this whole talk was prompted by the question, with this kind of exponential increase in biotechnology, with new things like CRISPR, where is biotechnology going to be in five years or 15 years? And it's kind of scary because defensive technology always lags, offensive technology. So, you know, the cancer moonshot I would propose is dual use. Just like nuclear weapons and nuclear power, two sides of the same coin. The ideal cancer treatment someday is going to be, the doctor is going to biopsy your tumor, get a sample, send it down to the lab. The lab will figure out the genetic syndrome or the signature of your exact cancer tumor. Then somebody will build a virus that using that if-then statement only targets the cancer cells in you. They'll put that virus inside you. You'll feel like you have a cold for a few days. And then that virus will go to work. And that's because the virus is going to work destroying your cancer. And then you'll wake up cancer free. That's a pretty good deal. We all want that to happen. But notice this exquisite targeting overcomes that big drawback against bioweapons. So, the new technology is going to allow incredibly targeted bioweapons. So, think about three different axes. Who might you target? A specific tissue? That's what cancer does if that cancer therapy. And if you wanted to edit an embryo, as is just starting now, that will certainly come along too. But you could also target a family, like the royal family. You could target a whole group of people. You could target an entire species. So that's the who. Then there's the what. You know, if you're doing cures, that's great. But you know, you might be making life inconvenient for somebody. You might be giving them a disease or you might be killing them. And then there's the when. And there's a very important factor here I'll talk about later too. So if you were going to cause death in an individual, well, we call that assassination or murder. If you were going to cause death in an identifiable group of people, we'd call that genocide. And you might say, well, why would we ever want to kill off an entire species if that species is the malaria parasite or if it's the mosquito that carries Zika virus or Yellow Fever? You'd want to kill those off too. So certainly this part of the graph is in the sites of scientists working today. And so this talk is about what happens in this part of the graph. The technology is inevitable. Let's remember that. Everybody wants that cure for cancer. And so they're going to be, you know, I think thousands of people down in the basement of hospitals doing these viral manipulations, this genetic program. And that's a lot of power to put into those people. So what could happen? Let's talk about that. So first, let's talk about that what access, the damage that people can do. So I'm going to use genetic diseases as a guidebook for exploits. And here I define disease as any kind of abnormal function in your body. So an exploit is anything that includes a genetic that induces a genetic disease. So here's an example. Here's a rare genetic disease called Xeroderma pigmentosum. And this little girl has it. And it's a defect of DNA repair that arises from a variant in the XPA gene, one of the 25,000 genes that you have in your body. And these people are intolerant of sunlight. Every time sunlight hits your skin, it damages DNA. But your body repairs it. These people don't have that repair capability. So when they go out in the sun, they will blister after a few minutes. Okay, now if you're hackers and you could deploy something like this worldwide, you know, why might you want to do it? Think about that for a few minutes and I'll come back and give you a suggestion. So there's lots of potential in our human genomes to cause this kind of problem. This is my mentor at Johns Hopkins. He was a terrific guy. And back in the 1960s, he started collecting every inherited trait that the profession of medicine could identify in humans. And this is my copy of his book in 1990. That's the 1990 version. And if you've read Moby Dick, you know, you can see that it's way bigger than Moby Dick. And that was in 1990. And since then, the book got so big, they couldn't publish it in hard copy anymore. And this only goes up to 2004. And you know, I think they just gave up counting at that point. So we know a lot about what happens in people's bodies. So within this book, this big book of genetic susceptibilities in human beings, there's a lot of stuff. And in fact, there's some stuff worse than dying. And I call that hell. And you don't want to know what that is, what could happen. So the question is really what happens in these two places. So let's give some examples. So let's say you were a passionate animal rights person. And you didn't want people eating animals. You might be a passionate vegetarian as well. Well, there is a disease called Ornithine Transcarbamelase Deficiency, which is in that big book. And it arises from a variant in the OTC gene. So if you could spread, if you could mess up everybody's OTC gene across the world, all of a sudden almost nobody in the world could eat meat. That's something that is an extreme vegetarian you might want to have happen. Let's say you believed in sexual chastity. And you really wanted to punish people who were a little profligate. You could make everybody in the world hyper susceptible to gonorrhea by messing with the C5 or the C6, 7, 8 or 9 genes. It caused lots of other problems, but you could, you could make people really susceptible to gonorrhea. Let's say I didn't want anybody at DEF CON to do a shot. And I wanted to make them intolerant to alcohol. I could screw with their ALDH2 gene. Or to go back to Zeroderma pigmentosum, if I wanted all women to be veiled when they went outside, I could design something that would mess up the XPA gene only in women. Or if I wanted to blur some of the distinctions between races, I could distribute genes or vectors that would cause skin color to change. If I'm a pharmaceutical company and I have a drug that treats some genetic illness, how great would it be if everybody in the world had that genetic illness? That would do wonders for sales. And let's say you were once turned down for the astronaut program because you were color blind. I don't know who that might be, but you're looking at them. And let's say you wanted everybody in the world to be color blind. Then they couldn't turn you down. So there's more. Let's say I just don't want to hurt people, but I want to target national economies. I have an enemy, an adversary, and I know that it would bankrupt their economy to take care of epidemic-expensive diseases. So there are ways that I could give people cancer, Parkinson's disease, Alzheimer's disease, cystic fibrosis. I could give everybody pain all the time or I could make them insensitive to pain, which trust me causes a lot of problems. I could immunocompromise people or I could accelerate aging. Let's say I just wanted to do things to impair workers. I could give everybody narcolepsy syndrome. The face blindness syndrome is probably genetically mediated. No one's discovered the gene yet. Or if I wanted to give a whole generation of children learning disabilities so some country couldn't compete against me, I could do that. Let's say I just objected to a lifestyle. You know, I could make everybody deaf or blind. And look at this. There are 540 genes that go into our hearing process and 600 genes that go into vision. It could make everybody night blind, interfere with taste and smell and destroy a big industry right from that. There are genetically mediated diseases that make you die from excitement. These are cardiology diseases actually. And then there are diseases of physical fragility. Okay, we've got a few more. Epidemic micro penis. Epidemic erectile dysfunction. Or you could make everybody hyper libidness. You could, I think, I couldn't quite find the gene but I'm sure this is genetically determined somehow. You could fix it so a nation just became a nation of sons or a nation of daughters. There were reports that certain organizations were looking to try and change the sexual preference of their adversaries. And you could sterilize an entire population. Let's say I just wanted to mess with some politicians. And, you know, I could make somebody go totally bald or I could give them a really bad fishy odor. And that is actually an incredibly tough disease to have. It's caused by this TMAU gene because there's no treatment for it and it's impossible to disguise the odor. And those people have a very difficult time socially. I could give somebody intractable diarrhea, cause a massive weight gain or, you know, in some forms of Tourette's syndrome, which is mediated by this gene, people involuntarily emit obscenities. So that would be interesting in a politician. I put this in before Mr. Scaramucci started his work. So we might have to cross it off the list. Okay, that's the what. We talked a little bit about the population. I would recommend keeping your genome secret. So, you know, we talked about the royal family. And, you know, you could get just DNA from one member of the royal family and you could then target the whole family. You know, this word race is very squishy. But if you use it to mean any observable physical characteristic defines a race, then, you know, it becomes possible to think about it in a sort of rigorous way. So for instance, there's a gene called EDAR. And 87% of Asians have that. And you can exclude Asian descent to nearly 100% of Europeans and Africans by looking at this one gene. So if you wanted to do racial elimination, EDAR is a good place to start if this is your target. So obviously, this is very dangerous if used by hate groups. And then there are easy ways to identify genetic males and genetic females, which of course is genetic. You know, identifying ethnic groups is a little tougher. You know, Tay-Sachs disease tends to run in the Ashkenazi Jewish group. But even there, it's not very good, quote unquote, if you're using it to target them. So that may be sort of a blessing. You know, inter breeding is helpful. And we talked about species. You know, if you're a dog person and you want to wipe out cats, you can do that or vice versa. You could wipe out food sources. And you know, if you wanted to kill a wine crop, if you're from Napa and you wanted to kill the French wine industry, you might be able to do that. So let's talk about time. You know, I think it's possible to build binary weapons. So you insert one thing, but the bad thing doesn't happen until a second agent is exposed. But the really interesting thing about time is, yeah, I could do something to everybody who's living here and make some of you sick or whatever. But if we can get that gene change into the cells that make sperm and ova, then it's in human beings in perpetuity until somehow they all get fixed. So this is just the RNA and the DNA part. You know, there's a whole other field called epigenetics. And epigenetics is where the environment, signals in the environment are transmitted to your genome. So for example, if you move to Denver where the air is thin, where there's not much oxygen, somehow that signal has to get from the oxygen in the air into your genome so that you can make more red blood cells. So they're gonna be, I think, a whole host of epigenetics exploits that I really haven't started to think about too much. And then targeting based on the microbiome would also be possible. So to summarize, you know, a lot of this is possible now, some of these engineering angles, but it's very difficult. And so not many people can do it. But with the progress that we all hope the cancer moonshot will make, it's gonna get easier and easier to do these kind of things. And then once to the point that thousands of people can do this sort of stuff, we have a real problem. So my first statement to you is don't do this stuff. There's just no point in doing that. Yeah, we know it can be done. You're not showing anybody you're smart if you do this. But if you have a chance to talk about this problem with policymakers, do that. You know, if this group gets scared, because not much scares this group, but if this group gets scared, I think that will get their attention. Or get involved more directly, go into bioscience yourself and try and put your digital way of thinking to work and trying to build the defensive technology for this. I don't have all the answers, that's for sure. So we need a lot of help. What I would tell the policymakers to do is to, and this is very difficult for them, it's essentially saying you have to start working on defensive technology for an offensive technology that isn't here yet. But the goals are really quite laudatory in the sense that the first step is to figure out how to cure every infectious disease known to science. And you'd want to do that using some sort of digital technology. And that alone would create the largest amount of wealth that I think the world will have ever seen when you think about how much infectious disease costs mankind and how much people would pay not to get infected. But that's only the first step because there are going to be unnatural infectious diseases that people will build. And so we're going to have to develop an infrastructure that will be able to detect new agents and then characterize the infection, devise a countermeasure, produce the countermeasure, produce the countermeasure in millions or billions of doses, and then distribute it across the world. And oh yeah, probably within a month or a couple weeks of the time the disease is detected because that's how long it takes. You know, a disease that we get here could go everywhere in a couple weeks. And you know, not too long ago infections were of a magnitude that we can hardly believe today. In 1947, New York vaccinated six million people in four weeks against smallpox. So I don't think this is necessarily impossible. I think it's harder than a moonshot. It's like a Mars shot, though. If you're interested in this and you want to get more motivated, or maybe I should say if you're not interested and you think is this guy up here talking crazy, this is a novel that was published in the 1990s. And it is a terrific novel just on its own merits. But in the introduction the author says all the science in this novel is true except for three things. And I'm not gonna tell you what they are. That's what the author said. So read it and have a good time and think about it. And then finally, thanks for sticking around today toward the end of the conference and hearing. Remember that as we leave the conference we're gonna go back all over the world. So it's a pretty good thing that we're not carrying any bad bugs with us. Thank you very much. John, do I have time for questions? Where's John? Okay. Do they go to the mics? What's the routine here? Thanks. So I think one of your colleagues just tweeted that you said don't share your genome. And I'm wondering how you see reconciling that with doing the research that's needed to better understand genomic medicine and also to treat people genomically. Presumably for me to get that precise treatment I'm gonna have to share my genomic information. Yeah, if you've got a genetic disorder you have a proximate threat to your existence and to your life. And so there the balance would tip toward sharing the genome. So thank you for asking that. That's worth a clarification. Everything in life is a risk benefit balance. And so I would say don't share your genome without reason. Without good reason. Hey, so attribution is a famously challenging problem in computer security, determining the origins of malicious software. I was wondering if there's any current work that you know of going on around watermarking these modifications to genomes or other techniques that could be used to trace their source and their progress. I couldn't understand that question. I mean talk a little slower. Sorry. So attribution is this famous problem in computer security? Like when malware spreads around the world, where did it come from? Was it Russia? Was it China? You know. And so I was wondering is there any current work happening in genomics that you know of around developing ways to watermark or otherwise annotate these modifications so that you can determine where they came from and how? That's an interesting question. So no I haven't heard of that. You know the whole science of epidemiology focuses on where did things, where did infections come from? How did they spread? And that's been very difficult over the hundreds of years that epidemiology has been a science. And even when we look in genomes we can get some help. So but not the kind of help that you want. So I can, if I gave you influenza, the match between our two viruses would be like 100% minus epsilon, some really small number. But if he got influenza from somebody in Portugal, it would still be influenza A and H1 or whatever. But his difference between your two influences would be bigger. So you can do some sort, you can do tracing that way. But you can't go and say oh it started in you know the Amazon jungle or anything like that. So the questions about encoding, signing modifications that you put into the genome, sure. There's lots of room in the cell. You can add a few more DNA base pairs that you know somehow you would claim or something like that and put a signature in there. So I'm thinking a little bit about data archiving. In long term data archiving, large amounts of data, one of our primary concerns is bit rot. And so we so we check that frequently and then readjust it from available sources. I'm wondering if it would be reasonable to think about the DNA in an archiving. Maybe personal archiving, sort of like backing it up. Where then with frequent checking you could find something that had gone awry and then essentially restore it. But doing it. Yeah. Do you have an identical twin? No. Too bad. So yeah identical twins are great for that kind of backup. Well you know for cancer you know there's another way which is cord blood. So you know when babies are born they have the umbilical cord and nowadays you can snip that umbilical cord and put it in a freezer and that thing is that cord, the blood in that cord is loaded with stem cells. And you know if you get a leukemia later you can go back to the cord blood and you have a sample of blood there that is essentially the backup you're talking about. There's no leukemic cells in it. Um you know that was sort of the rage a few years ago. I don't even know. Technology may have passed that by I can't say. But you know just from a um from a sort of IT perspective if you put your entire genome in some digital format and put it on a hard drive or something um the question is how do you restore from that backup? So you know there are several trillion cells in you and that's the worst case scenario is you need to get that backup into every one of those cells. But if it was a sort of thing where you got leukemia and they were saying hey we can't find any non leukemic cells in your blood to do a transplant, a bone marrow transplant on you. Maybe someday in the future you could go back to that digital backup, build some cells with your correct DNA and then infuse those into you. Regarding your uh advice to work on contra measures um working on contra measures mean to go through the same technology because if we need to fix the and actually it's easier to break than to fix. So the whole genetic therapy it's a bit old and but it's really declined because it's very difficult to fix stuff to break this. Yeah that's that's why defensive technology tends to lag behind offensive technology. But I would say there there's still ways you could do it. So let's say CRISPR turns out to be the former director of national intelligence for the United States called CRISPR a weapon of mass destruction. So if just working on anti CRISPR technology for instance might be a way to go. So that you know whatever program is embedded in some sort of CRISPR implementation if you had a way to kill the CRISPR part um that would be potentially in some situations useful. Um and the same you know but I think CRISPR might be kind of easy. Other things like RNA interference that might be really hard to develop counter measures for that. But that that's what I was thinking when I made that statement. So I've noticed a recent rise in popularity of these service. Talk slower. Oh my apologies. So I've noticed a recent rise in popularity of these services where say they'll send you a vial uh you spit in it you send it back they give you information on your genome. I've seen uh a lot of uh educational channels on YouTube encouraging people to go out and do this uh and it seems like quite an interesting thing to do if not something uh information that would be good to know. However I worry about the security of these sort of uh of these sort of organizations. Are they selling my data? Um what government organizations uh what would what would your advice be for the security of these? Where do you think uh how do you think we could make sure that uh our data isn't being sent out? Uh should we discourage family members and friends from using these that sort of thing? Yeah I think it comes back to a bit of what the first questioner asked was the risk benefit trade off. So if you have a medical condition where you think your care could be improved if the full genome were known. Okay I could see that but if you're trying to figure out whether you're Lithuanian or Greek or something else you know who cares? Um so and you know I had a friend do that and he found out that his father wasn't his father. So you know you really can't get great news from it. But you know uh what I worry about is a physician is let's say they're 5,000 diseases that are mediated by genetics. They're probably more but let's say they're 5,000 and let's say someday you get a report back that lists your risk for all those diseases. Well you're gonna be at above average risk for 2,500 diseases just statistically. And so if you come in to see me and I'm your doctor and you start talking about 2,500 diseases that you're at risk for I have no time to talk to you about anything else. You know I know that getting your blood pressure down by 10 points is gonna extend your life by so many years or helping you to quit cigarette smoking is gonna extend your life by 10 years. So you crowd all of that out for this information that really isn't helpful. So uh that's that's what I would think about. Medicine is very aggressive in the sense that you know if if we have a way to decrease your risk of disease um we'll develop screening technologies around that. But if we don't have any way to decrease we don't have a way to decrease your risk of rheumatoid arthritis or your risk of psorias or any anything like that. So there's no point um in a preventive way of coming of getting tested for that and coming to talk to me about it. Thank you. So the topic has come up a couple times now. Slower because the echoes bother. Yeah. That it's easier to crash a human than fix it. The number one problem with gene therapy that we've observed from our historical data is random insertions into the genome that lead to different errors that are actually much more catastrophic than the area you were trying to fix. So is anyone working on how you would be able to have a defensive strategy to not have that happen because in its current state gene therapy is kind of like playing Russian roulette. So um let's go back to that big thick book that I showed a picture of. Most of the diseases in there are single gene diseases. Uh like that zero dreamer pigmentosa. That's one gene. But if you look at what humans tend to suffer from, obesity, Alzheimer's disease, atherosclerotic heart disease, you know the common stuff, those are multiple gene diseases. And so um it's they're almost like two different sets of targets. The single gene diseases we understand how to find them and we understand how repair would occur theoretically. The multiple gene diseases and I think this is what you're saying are much more mysterious. You know if there are 640 genes that go toward making your visual system work correctly, and that's a bad example. If there are 50 genes that are involved in um atherosclerosis, you know when you start tweaking one it's gonna have a bunch of other effects and you're not gonna maybe find a big effect from any one gene. So now you're talking about diddling with multiple genes. And so that's really hard and that's gonna be quite a ways in the future. Is that what you were asking about? Because you mentioned like stop codons and things like that. That's sort of the single gene disease. Yeah it doesn't matter how many genes are involved in the disease. If you introduce something into the code that was external so you downloaded information and it went to the wrong file and it caused an error that was significantly worse than the original error. The best case was a single gene, gene therapy approach. The genes randomly inserted into the genome and caused leukemia in most of the patients in that population. Yeah so that's gonna be part of the safety and efficacy evaluation of any new therapeutic that comes out. So you know the first gene therapy efforts didn't work. You know it it caused harm. But lessons were learned from that and so it's getting better. So like an earlier questioner says it's always easy to break something than to fix something. And any attempt to fix, every attempt to fix something you know you have to be prepared for unintended consequences. And so it's just gonna be a matter of refining techniques. Your point is well taken. But medicine is is pretty accustomed to trying to work out what the adverse effects of any therapy are. Do you think it would be a bit more responsible to target something that's not the equivalent to the source code? Well that might be like the microbiome. Because if you screw up your microbiome in some terrible way you can always flesh it out and load and reboot essentially by eating the feces of some other person. And uh you're good to go. Okay I'll put you down for the feces eating. That was the most scientific way I've ever seen somebody put down a question. That was amazing. Closely related to the last question uh would there be a way or is there any research going towards uh basically locking the editing of the genetic sequence? Yeah. Turn evolution into something purely directed. That would be the end the there would be no more natural vectors of evolution if we did that. But it would secure the uh the the whole code. Uh I that that's a very interesting idea. I I don't think there's any work going on that. Uh I wouldn't know how to implement that. Um you know there there's six uh billion uh between the two parents uh contributions there are billions of base pairs. And so you know we have uh the two rungs of the double helix which uh provides some measure of error correction in there. And it is possible to build uh triple helices uh using not DNA but there's now uh new kinds of NAs XNA and you can build triple helices. So you could actually um increase the error correcting capabilities. But then I think you've got something that's not a human at that point because um it's just so different from us. Hi there how are you doing? Uh so I have two questions. One's pretty quick. Um you talked about changing some physical traits about people to target certain groups. But how complex do you think we could uh develop that technology? Such as if someone has a birth defect where their fingers may not grow properly do you think we would be able to correct that? And then through their uh I guess pre-teen years when their bodies are developing more they would be able to grow proper fingers I guess. So uh there are a lot of people working on that um you know there are some malformations that occur not because of problems in the genetic code but because of environmental influences. So if you have an encounter with a chainsaw you know you could end up with a uh an abnormality in your anatomical structure. So um you know I had a friend who um found out that the tips of your fingers the skin on the tips actually regenerates. And so he took this as part of his research to figure out if he could expand that regenerative uh capacity beyond your fingertips to the other parts of your body. Uh he didn't win a Nobel Prize so I guess it didn't quite work as well as we might hope. But there's a tremendous amount of work in that going on. Thank you. We got time for one more question. Okay. Sorry. Hey. Excellent talk. I just wanted to start by thanking you for scaring the ever loving shit out of all of us. Um yeah because frankly that needs to happen if we're going to avoid this terrible future that you've described. CRISPR is the new kit on the block but I think of CRISPR as like a root kit that's just really good at doing advanced things but it's the spreading mechanism that frankly Mother Nature has been giving us for millennia. That's the real problem to address. So my question is um are Intel or the DOD or other organizations that have the resources to tackle this developing the equivalent of biological intrusion detection systems that can sample airborne or or human spreading epidemics through urban population centers to very quickly identify that spreading vehicle? So that's a great question. Um there there's sort of two mechanisms. One is the science of epidemiology which I've already talked about and of course that is limited uh you know it started in the 1700s or 1800s and we still use the basic same mechanisms. Um on the technology side uh the Centers for Disease Control has something called a BioWatch program which is these today. These big carts um so the San Francisco uh San Francisco area hosted the Super Bowl last year and on the sidewalks in San Francisco these carts appeared and they have you know sort of a smoke stack and they basically sniff the air and they bring the air into the business part of the cart and with today's technology it's just deposited there and a human comes by picks up the samples takes them back to the lab and does some PCR some genetic analysis on it. So the CDC tried to develop a second generation of this cart and the program was not successful and so right now it's in hold as to what to do. Um you know my idea is that um when you go into an emergency room and they draw some blood from you and send it to the lab the blood in that tube uh 90 percent of it is thrown away because it's more than they need. So why not take that blood and throw it into a big vat and once a day just sequence the crap out of all that blood that comes in and send that immense amount of data down to the CDC in Atlanta and that would give them really I think a national picture in real time of what's coming into the emergency room at a genetic level. So I think that would be kind of a first step on um a new generation of biosurveillance. One one this is quick. Is it lupus? It's never lupus. Yes.