George Church on the revolution in and future of dna editing (22-04-2016)

Geneticist and bio-engineer George Church interviewed in his office talking about what motivates him, the current revolution in dna editing and the implications for the future of mankind.

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00:00:00 Speaker 1: I told [INAUDIBLE] you were in the player.
00:00:02 Speaker 2: Right.
00:00:03 Speaker 1: Do you think you fit in that one?
00:00:05 Speaker 2: Yeah, I think we have a very creative laboratory,
00:00:11 and I like pushing the boundaries into what's sort of called disruptive or transformative technology.
00:00:19 And we have artists in the lab. And yeah, I think player would fit.
00:00:26 Speaker 1: But also, I think the importance of the fun of playing with DNA, with just the science [CROSSTALK]
00:00:34 Speaker 2: Right, yeah, I mean, we don't take ourselves too seriously.
00:00:38 We try to do experiments that are both important for something societal, but they're also very playful
00:00:48 and illustrate an interesting way of looking at things. It usually makes people smile and surprised, yeah.
00:00:55 Speaker 1: And how come? Why is that, do you think?
00:00:57 Speaker 2: Why do we do that? [CROSSTALK] Why do they smile?
00:00:59 Speaker 1: Yeah.
00:01:00 Speaker 2: Well some of them are funny, like making 70 billion copies of my book.
00:01:07 That's more than all the most well purchased books in history. And it's kind of a funny idea.
00:01:17 And the idea that the DNA could last for 700,000 years or maybe a million years is fun.
00:01:23 And making a woolly mammoth, you can have a serious reason like the survival of the Asian elephant,
00:01:35 but also it just makes you smile to think that an old animal that's extinct comes back.
00:01:42 Speaker 1: That's one of the projects.
00:01:44 Speaker 2: Yes, right.
00:01:45 Speaker 1: That you're working with?
00:01:45 Speaker 2: Yes.
00:01:46 Speaker 1: And in what way is the personal genome project is part of your work? Can you explain?
00:01:55 Speaker 2: Right, yeah, so in a way, that's very serious in that when we started it ten years ago,
00:02:03 there were all these really scary and crazy rules that didn't really make sense.
00:02:11 That your medical information would never escape from the lab, even though there are multiple examples,
00:02:20 like WikiLeaks and so forth.
00:02:22 And then once it escaped, it would never be re-identified, even though it was a very rich data set,
00:02:26 and we know we can re-identify.
00:02:29 That if we'd learned something about you that could save your life,
00:02:33 we couldn't tell you because we couldn't give data back to you, just all sorts of crazy things like this.
00:02:40 And so we wanted to, again, be a little more playful and say, well,
00:02:45 what if we did just the opposite of all of those things?
00:02:48 If they sound a little crazy, let's do the opposite, maybe it will be either playful or super sane.
00:02:54 So it's the only project in the world now for ten years, where you can actually have free access to human biology,
00:03:04 genomes, environments, and traits. It's kind of like Wikipedia for human beings. So it's revolutionary and playful.
00:03:11 Speaker 1: And can you explain what it exactly is?
00:03:14 Speaker 2: It's a collection of big data of each individual person.
00:03:21 So it's not just big because there are a lot of people, it's big for each person.
00:03:25 And it's the way we think that medicine will be practiced in the future.
00:03:28 But we collect medical records, a whole variety of measurements that we do every year on DNA Day,
00:03:38 where the people come back every year and get a update.
00:03:41 Sometimes all sorts of new tests, and then the genomic sequence, and a number of other omics, microbiomics,
00:03:53 and viral sequences. The things in your environment that can greatly influence your health.
00:04:00 So we get this big collection and then we make it publicly available, so that anybody in the world can help analyze
00:04:08 and interpret and understand your genome, everybody's genome that's in the project.
00:04:14 Speaker 1: And what would that mean for future if the database is getting bigger and then better?
00:04:19 Speaker 2: Yeah, so, it's not intended to be a production project so much as an inspirational one.
00:04:26 Where we show people said you can't do this, it's impossible. And we showed well, it's actually not so hard to do it.
00:04:34 And so now, it changes the conversation.
00:04:37 And so many of the things that we thought were crazy,
00:04:39 now people agree that maybe we should be sharing data back with the individual, getting them properly educated upfront.
00:04:50 Admitting that we can't keep the data from getting out in any project anywhere in the world.
00:04:55 In fact, even medical records in a hospital, which have nothing to do with research, are extremely valuable now.
00:05:02 They're 20 times the value of your credit card on the black market.
00:05:06 So many of these things that we're talking about ten years ago are now accepted,
00:05:12 so that was the main thing we were going for.
00:05:16 But what will happen is once it's widely accepted, we may eventually have 7 billion people's genomes
00:05:22 and medical records available. And then you can find all kinds of correlations and what causes diseases and cures.
00:05:30 Speaker 1: And then you can almost personalize the medication and the solution, is that right?
00:05:35 Speaker 2: Yeah, not only personalized based on your DNA, but personalized based on your environment, as well.
00:05:45 And most importantly, I think, is prevention.
00:05:49 So, an awful lot of medicine is you wait until it's kind of too late where you've already got DNA,
00:05:54 that's where you get damage to your body or you've got cancer.
00:05:59 And even if you try to catch the cancer very, very early, it's really already too late because it's already start.
00:06:05 It's got its mechanism revved up to make more mutations.
00:06:11 Speaker 1: So basically, when you explain what you are doing to somebody that doesn't know, could you explain it?
00:06:22 Speaker 2: Sure, our lab develops radical technologies for reading and writing DNA, the same way you'd read
00:06:30 and write a book. We can do that with DNA, and we've brought the price down by about over a million-fold.
00:06:37 Speaker 1: And the consequence, when you look back the last ten years and
00:06:44 when you look further in the coming ten years, what do you foresee in the near future in ten years?
00:06:50 Speaker 2: Right.
00:06:51 Speaker 1: How would it look like?
00:06:52 Speaker 2: Yeah, well, we don't know if we can sustain this incredible, exponential speed, where it gets faster
00:06:59 and faster every year. But if we can, in ten years, we'll be unrecognizable in terms of the technologies we can do.
00:07:09 We'll be able to change agriculture, medicine, forensics, you name it.
00:07:19 Even information handling that you normally think is the realm of electronics will be molecular.
00:07:24 Speaker 1: Even networking.
00:07:25 Speaker 2: Yeah.
00:07:26 Speaker 1: And in what sense I understand crisp, what is crisp, first?
00:07:34 Speaker 2: Crisper?
00:07:34 Speaker 1: Yeah, crisper.
00:07:35 Speaker 2: So crisper is a buzz word that really is capturing the imagination,
00:07:47 but it represents a much broader set of tools. So we've had for a few years To engineer genomes.
00:07:56 So, in addition to the new ability to read genomes, CRISPR represents a way of editing genomes.
00:08:02 It's not the only way, but it's something that captures people's imagination.
00:08:07 And we helped invent that about three years ago now, and many people have improved on it.
00:08:15 About 70 labs have contributed to an open non-profit resource called Addgene
00:08:25 and then re-distributed it into 30,000 laboratories.
00:08:28 Speaker 1: What is CRISPR?
00:08:29 Speaker 2: Sorry.
00:08:32 So, CRISPR is the latest in a series of ways of manipulating a genome where the computer, the science,
00:08:41 define 20 base pairs- As, Cs, Gs and Ts in a particular order, chosen to be specific for one place in your genome,
00:08:49 in your DNA, and not anywhere else in your genome. So it's both positive and negative computer selection.
00:08:56 And then it will cut, it will search through the genome randomly and find the right place and make a,
00:09:02 cut both strands of the DNA, and then that either eliminates the gene that it just cut in
00:09:09 or it helps repair to whatever you want.
00:09:13 So that's precise gene editing is what people are so excited about, where you can change it into whatever you want.
00:09:19 And we were the first lab to do that in human stem cells, and those can be turned into almost any cell,
00:09:26 and it can be done in a whole variety of different organisms now. Almost every organism that's been tried, it works in.
00:09:31 Speaker 1: Yeah. And then because you use in the text that you are able to-
00:09:41 Speaker 2: Right.
00:09:44 So some people call editing just making a mess, making a break,
00:09:48 but I think that's like saying that ripping a page out of your journal is editing, and it's not really.
00:09:57 But this allows you very precise editing.,
00:09:59 Speaker 1: And the possibilities that it give, is that you really can prevent a lot, when [INAUDIBLE] is that correct?
00:10:06 Speaker 2: Right, right so you can now engineer agricultural species, wild species,
00:10:14 and you can do preventative medicine.
00:10:16 Speaker 1: It's not students, it's now really in a, this year it's really, also really growing, this technique.
00:10:24 It's developing hard,
00:10:25 Speaker 2: So it's a three year old technique, but it's been growing exponentially.
00:10:33 And the number of people adopting it is huge, and every new person that adopts it helps also make it work better.
00:10:42 Speaker 1: Yeah.
00:10:43 Speaker 2: Yeah.
00:10:43 Speaker 1: Then the consequences are endless, because you can prevent diseases, you can create, you can,
00:10:50 because of course people with this diseases that are very strong, you can help those people as well.
00:10:56 Speaker 2: Right.
00:10:57 So it's particular valuable for so-called rare diseases that are individually rare
00:11:04 but collectively there's a large number of them
00:11:07 and so you might have maybe 3-5% of the population is affected by these,
00:11:12 even though each one only affects 1 in 100,000, together there.
00:11:16 And, so if you have two parents that are carriers, and they have no
00:11:22 Speaker 2: They will have 25% of their children will be severely affected, very deterministic.
00:11:29 It's not really probabilistic. It's almost guaranteed.
00:11:33 And that means that the only real way that protects the family, including the children and family are healthy,
00:11:46 is abortion, which is not acceptable to many people in the world.
00:11:51 And so gene editing gives us the opportunity of changing the sperm, so that you don't have to affect the embryos.
00:11:58 You can do it without hurting or putting embryos at any risk.
00:12:02 So that's a new possibility that has yet to be demonstrated.
00:12:06 Speaker 1: Yeah.
00:12:07 That will also see an incredible future when this is further on developing because you can do a lot with it.
00:12:16 Speaker 2: Yeah, you can reduce disease without eliminating the gene variants..
00:12:22 Speaker 1: Okay, but you can also make viruses or bacteria that are with synthetic [INAUDIBLE]
00:12:28 Speaker 2: Right, right.
00:12:29 Speaker 1: [INAUDIBLE]
00:12:30 Speaker 2: So we've made biocontainment versions of bacteria that are stuck in the lab. They have very low escape rates.
00:12:44 And this is particularly important, if you put things into the bacteria that would give them an advantage in the wild,
00:12:49 like for example virus resistance, that could be very productive in an industrial setting
00:12:55 but you don't want it to get out of the wild.
00:12:57 So you have to have both the viral, anti-viral strategy and the biocontainment together.
00:13:04 That was actually done without CRISPR.
00:13:06 Quite a bit of the genome editing and genome engineering we do in our lab does not involve CRISPR.
00:13:11 And that's a perfect example of one where we've done probably the most radical
00:13:15 and extensive engineering of 4 million base pairs without CRISPR. Yeah.
00:13:22 Speaker 1: Where comes this energy that you have in your work? Where is it coming from? What's your source?
00:13:31 Speaker 2: The source of our industry
00:13:36 and enthusiasm is just knowing that you can answer very basic scientific questions at the same time you push,
00:13:46 you drive down the price of technology, democratizing it, making it available to many people.
00:13:51 And then the product, the applications of the technology,
00:13:56 can be even more societally impactful than the technology itself, such as transplantation,
00:14:04 solving the transplantation crisis, the malaria crisis, and aging crisis.
00:14:10 These are all things that are highly motivational, where millions of people are dying every year.
00:14:14 Speaker 1: Your personal source, your personal energy, where does it come from? [CROSSTALK]
00:14:17 Speaker 2: My personal energy comes from the threat, that all these people are going to die every year
00:14:26 and the curiosity, playfulness of the science that, so you could simultaneously play
00:14:32 and do something were serious which is saving millions of people.
00:14:35 Speaker 1: Yeah. And when did this start? When you were young? Do you still remember when you're-
00:14:39 Speaker 2: Yeah. I remember when I was a boy in Florida living on the water, in the mud.
00:14:50 I would play in the mud and I would pull the creatures out of the mud and wonder how they worked.
00:14:57 And I would look at my father's medical bag. It was full of drugs and instruments. And I said.
00:15:05 That was an inch, so one was very natural and was very artificial and I was in awe in both of them and then,
00:15:12 and then I went to a World's Fair in New York cCity.
00:15:15 From, all the way from Florida to New York city when I was ten years old and and they have created a simulated future.
00:15:23 They had gone really,
00:15:25 really far out on making a pretend world where they had robots that looked just like a human being.
00:15:34 And then, from that day, I could never go back to the past.
00:15:40 Even though they didn't have a real future, it was a fake future, I could not adjust any more.
00:15:45 Once I had seen the future, I had to work on it to make it happen because it seemed very attractive.
00:15:52 Speaker 1: It's exactly what my daughter also said.
00:15:54 Speaker 2: Yeah.
00:15:55 Speaker 1: Last week, when it was in the Scientific Museum in Amsterdam.
00:15:58 Speaker 2: Yeah.
00:15:59 Speaker 1: She saw-
00:15:59 Speaker 2: It's dangerous and very hopeful to create a fictitious future in such graphic terms,
00:16:11 where you can walk around, that you can taste it, you can feel it, you can see it.
00:16:15 They had touch pads in 1965 where you could draw something and then, it would print out the whatever you drew.
00:16:24 Not on paper, but in fabric you could actually make a scarf of a butterfly you would draw with a pen.
00:16:32 That took like forty years before there was anything even similar to that, that the average person could use.
00:16:39 Speaker 1: Where you would organize a museum or a fair where you would show the future of us in 40 years,
00:16:55 what would I see?
00:16:58 Speaker 2: Well, to some extent it doesn't have to be entirely accurate,
00:17:04 obviously it can't be because you can't see the future, but it just needs to be inspiring.
00:17:07 And to a 10 year old, is particularly easy to inspire.
00:17:12 So, you might see space colonies, I think, with humans that are adapted to space.
00:17:19 Right now, our biology is particularly, I mean,
00:17:22 it was not designed for space travel in terms of radiation resistance and the bone loss that happens at low gravity.
00:17:29 So, there might be some of that, there might be either conquering our microbiome, or completely eliminating it,
00:17:39 or getting to the point where we are resistant to everything, so we didn't eliminate it,
00:17:45 we just got better at vaccination, or something like that.
00:17:50 I mean, so, that you can, you can now go back to doing surgery without hygiene, you just doesn't even clean your hands.
00:17:56 Speaker 2: I think there are many things like this that would seem like science fiction,
00:18:06 but if you created it in a realistic enough-
00:18:08 Speaker 2: Fictional universe, kids especially will dream about it and make it happen.
00:18:20 Speaker 1: And there's already coming, information out that you didn't expect, as your own data?,
00:18:25 Speaker 2: Well, I expect everything [LAUGH] so it's fun. And I wouldn't say there's anything gigantically in it.
00:18:41 Well, my family was very concerned, because my father had died of senile dementia
00:18:48 and they were worried that I would have risk factors, and so far it looks like I have the opposite,
00:18:54 I have no risk factors. So, maybe that's suprising, maybe it's false assurance.
00:19:01 Speaker 1: It's good to have you now working in the lab for the future.
00:19:06 Because somehow the lab feels like you're on the fringes of knowledge. Do I see that right?
00:19:10 Speaker 2: It certainly feels that way to me.
00:19:14 Every day somebody walks in and gives me something that shocks me and it's not easy to shock me.
00:19:20 But it's very common that they'll come up with something that,
00:19:23 that really changes the way we approach biological research.
00:19:31 Speaker 1: Yeah, so could you give us example when [INAUDIBLE] kind of short.
00:19:34 Speaker 2: Well, for example, getting nanopol sequencing that was some,
00:19:40 it's a way of you got a handheld device that it's capable of sequencing DNA.
00:19:46 Speaker 2: Engineering mosquitos,
00:19:52 so that they can spread really good genes through the environment that would make them resistant to a malaria parasite.
00:20:04 Every little breakthrough in each of those two projects is remarkable.
00:20:10 Speaker 1: Yeah, and what do you think about the criticism that you also hear of course that it's not secure.
00:20:12 And that you can create also the other side with it. What do you think of that? How do you see that?
00:20:18 Speaker 2: I'm one of the biggest critics of it.
00:20:25 I try to raise consciousness and make people concerned,
00:20:29 because if you're not concerned things can be unintended consequences.
00:20:35 If you are concerned it helps you plan for alternatives.
00:20:42 But in particular, I suggested over the last 11 years, that 12 years,
00:20:50 that we should have a surveillance mechanism in place where anybody that participates in these powerful technologies
00:20:59 and all the ordering that they do of supplies should be monitored by the companies
00:21:07 and ideally by the governments as well.
00:21:09 Speaker 1: Why?
00:21:10 Speaker 2: I mean, you wouldn't want surveillance on your everyday activities,
00:21:14 but if you're dealing with synthetic DNA, that's not everyday activity.
00:21:17 And nobody forcing you to work on synthetic DNA, but if you choose to work on synthetic DNA then,
00:21:23 you need to be under surveillance because we're in a time where you don't know how powerful it is.
00:21:32 And so, it's better to just have everything under surveillance.
00:21:36 And a particular why I proposed, was looking for people synthesizing things that are extremely hazardous.
00:21:42 Things like smallpox, and polio, and anthrax, toxin, and things like that. Cuz there's no reason.
00:21:51 They should only be ordering that if they have permission from the government to order it and a very good reason.
00:21:57 Speaker 1: Because that's all possible.
00:21:59 Speaker 2: It's very easy.
00:22:02 And so, you not only have to monitor how they order it as DNA, but you need to monitor the machines
00:22:08 and the chemicals that they could use to do it themselves.
00:22:11 But if you monitor everything, then it greatly reduces the probability they could do it themselves.
00:22:15 Speaker 1: That's also the other side of CRISPR, you're able to on not a very simple way,
00:22:19 but you can in a way you can do anything.
00:22:22 Speaker 2: Yeah, CRISPR has a lot of power, but it's probably not the most dangerous, I mean,
00:22:33 I'm not trying to reassure people.
00:22:35 I'm just saying if you're going to worry,
00:22:36 worry about the right thing which is worry about ordinary pathogens that you can find all over the world because those
00:22:48 are much more powerful that anything you can do with CRISPR today.
00:22:51 CRISPR and all of our amazing technology for reading and writing DNA, is now you can use for better surveillance.
00:23:03 I mean, if its a million times cheaper, you can have it distributed work of surveillance.
00:23:08 You can make faster and better vaccines, that are very responsive to emerging threats for the natural and unnatural
00:23:15 and so forth.
00:23:15 I think that revolution in reading and writing DNA is much more easily used for protection
00:23:24 and prevention than it is for misuse.
00:23:26 With misuse you just go out and get somebody who's got some serious disease and weaponize them with ordinary methods,
00:23:36 not modern molecular biology.
00:23:38 Speaker 1: And so, in the way by making it cheap, by making it possible-
00:23:51 Speaker 2: Yeah.
00:23:52 Speaker 1: Millions of people use, it's like the internet in a way. Is this correct?
00:23:55 It's like you see that the date on the Internet is like it exploded. And then, it doesn't mean [CROSSTALK]
00:23:57 Speaker 2: Well a slight difference between this and the Internet,
00:24:00 I think is we have the opportunity of having a higher security, and safety.
00:24:05 And I think in the Internet early days, it wasn't a top priority,
00:24:12 and it ended up with kind of a culture that includes hackers, and computer viruses, and credit card,
00:24:21 or just identity theft, and stalking, and so forth.
00:24:28 I think if you had the equivalent thing in biology, it'd be much more serious.
00:24:33 So if you have a computer virus, that might cause billions of dollars of damage.
00:24:37 But a real virus could cause billions of dollars of damage and millions of lives.
00:24:42 So I think we need to create a culture of surveillance and good deeds.
00:24:48 Speaker 1: And that's happening now? What you're saying?
00:24:52 Speaker 2: Yes it is. But we need to keep raising consciousness and keep that motivation going. Yeah.
00:25:01 Speaker 1: It is good to stay critical also.
00:25:04 Speaker 2: Yes, right.
00:25:06 Speaker 1: And when you look at the future of, well,
00:25:15 I actually once said that the universe is getting conscious by itself, which of itself, and the past and future,
00:25:26 via the humans. What do you think of that idea?
00:25:30 Speaker 2: That was definitely the case that one of the distinguishing features of human beings is our ability to think
00:25:38 very deeply about the past and predict the future, and thereby avoid future existential risk to ourselves, our family,
00:25:48 and to in fact the entire planet.
00:25:52 So in particular, asteroids, and super volcanoes could destroy all of civilization, or, at least,
00:26:02 throw it back into the dark ages by eliminating the social fabric and cooperation.
00:26:12 That's even if we do nothing wrong at all, if we just don't create some killer virus, we don't pollute our atmosphere,
00:26:21 we don't create global warming. If we do everything right, we could still die as a species.
00:26:27 I think the antidote to that is to get us off the planet as a sort of a space genetics planetary species.
00:26:36 And we have to start spreading outside of the planet.
00:26:41 Speaker 1: Yeah there's also one of your goals I understand, is that correct?
00:26:45 Speaker 2: Yeah, and I think we have a consortium for space genetics centered here at Harvard, but international.
00:26:54 And if one is to raise consciousness about the needs, the special needs that you have,
00:27:02 that have to do with genetics in getting off the planet.
00:27:06 Speaker 1: Yeah, that's really the beauty of the human genome.
00:27:10 Speaker 2: The beauty of the human genome?
00:27:13 Speaker 1: Can you explain it?
00:27:15 Speaker 2: Well it's beautiful awe inspiring because it is in a certain sense very simple and very complicated.
00:27:25 There's parts of it we don't understand. There's parts of it amazingly predictive and we understand well enough.
00:27:32 It's beautiful, and it's a simple set of four letters, G, A, T, and C.
00:27:39 So, in a way, once you get a little education, you can read it just by looking at it. It didn't have to be that simple.
00:27:49 Everybody talks about how complicated it is
00:27:51 but really once you have a little bit of training it's amazing how much you can get out of human and other genomes.
00:27:58 It's a beautiful structure. It's very elegant in the two strands and the way it replicates by separating.
00:28:08 They're many things about DNA that's beautiful. You can build machines out of it. You can-
00:28:13 Speaker 1: Print books?
00:28:14 Speaker 2: And you can print books.
00:28:16 Speaker 1: But you and your team somehow are astronauts because you say it's very simple
00:28:23 but you are getting into the universe of the genome.
00:28:26 Speaker 2: Right, yeah.
00:28:27 Speaker 1: Everything that comes with it.
00:28:29 Speaker 2: Right.
00:28:30 Speaker 1: As an astronaut traveling through it, you discovering it-
00:28:32 Speaker 2: Right.
00:28:32 Speaker 1: More and more and more. So we are, it must be, how is that to be-
00:28:41 Speaker 2: Right.
00:28:42 Speaker 1: That far ahead?
00:28:42 Speaker 2: Right, yeah, so when I say it's simple, I'm doing it from an unusual standpoint.
00:28:47 It would be like an astronaut saying, it's simple to walk on the moon. Well maybe for you it is.
00:28:54 And what happens is once you get a certain number of technologies working with nobody else in the world can use not
00:28:59 because we've kept it a secret. I mean, we shared it openly it's a we're very interested and open asset.
00:29:06 It's just that nobody, even though it's open they can't necessarily practice it that easily or they don't trust it
00:29:13 or to be as easy as it looks.
00:29:16 And so then we have the opportunity of using it for a couple of years
00:29:20 and putting together another layer of invention and another on top of that.
00:29:25 And recombining them in various ways to get hybrid inventions.
00:29:29 And it just keeps in this positive feedback loop keeps going. And it's a very funny experience..
00:29:41 It's like diving off a cliff [LAUGH] You get faster and faster as you hit the water. Yeah.
00:29:46 Speaker 1: But you're not in the water yet..
00:29:48 Speaker 2: Yeah, there may not be any water [LAUGH] It may just be free fall, yeah.
00:29:54 Speaker 1: Yeah, and with the free fall, with a few people with you in a free fall cuz you're one of the few in a way,
00:30:07 still.
00:30:07 Speaker 2: Yeah, there's a large research community, but within that, as a smaller set that do technology,
00:30:16 and there's a even smaller set that does radical, basic enabling technology.
00:30:20 So some of the technology developers might develop a particular drug for a particular disease,
00:30:26 but then there's a tiny set that develop technology which can be applied to almost anything.
00:30:32 So, reading and writing DNA can be applied to any organism, and can be applied even to things that are not biological.
00:30:40 And those tools can be applied to themselves which is what creates this exponential of just grow, growing faster
00:30:48 and faster.
00:30:49 Is it the tools that you use to engineer DNA can be use to engineer the tools that you used to engineer DNA.
00:30:55 It is very cyclic and the, it's just that's playful.
00:31:04 Speaker 1: Yeah, and then exponentially growing means that, well, it grows very fast.
00:31:11 Speaker 2: And what, yeah, what will it bring us in few years?
00:31:15 Well, hopefully, what it'll bring us is higher safety, rather than less safety.
00:31:22 And that requires that we talk about it a lot and be very thoughtful about it
00:31:27 and encourage the new generation to be focused on safety security and modeling and extensive testing.
00:31:40 But other than that I mean it will bring us whatever we want. It's unlimited.
00:31:47 The question is not so much what it will do, it's what are the few things that it won't do.
00:31:52 For example, even computers, which currently now, are not biological. Those could easily be biological in the future.
00:31:58 The most amazing computer in the world, is the human mind.
00:32:05 And if the human mind starts modifying itself, then it becomes even more amazing.
00:32:11 Than a human trying to make a computer that can't yet think the way a human can.
00:32:18 Speaker 1: So we think everything can be created. It's like a parallel universe that can be made.
00:32:29 Speaker 2: Yeah, it could be revolutionary in terms of how unrecognizable it is a few years from now.
00:32:37 Speaker 1: Yeah, so organized to inspire ten-year-old kids.
00:32:40 That it's quite difficult to put to show what it will bring us.
00:32:51 Speaker 2: Right, yeah, I mean, it's much easier to illustrate the revolutions in mechanical and electrical engineering.
00:32:57 You can build like in the days of Edison, you could build a crude prototype for a motion picture camera and projector.
00:33:08 And you can touch that, you can feel that, you can understand how it works.
00:33:14 If you were to create a futuristic [INAUDIBLE] vision today, most of the mechanisms would be invisible.
00:33:21 They'd be so small that there's no real way of observing them directly.
00:33:28 And even if you could observe them it's hard to understand what they're doing.
00:33:31 Because we're not used to thinking the way that a molecule thinks.
00:33:36 A crisper molecule in order to cut it might jump around to 6 billion different places.
00:33:43 Randomly knocking on the same wrong door until it finally finds the right place and then it will act.
00:33:50 I mean that's very different from how you would build a cuckoo clock where it does exactly what you want it to do right?
00:33:57 Speaker 1: Yeah.
00:33:57 Speaker 2: So, I think people are not used to thinking molecularly
00:34:01 but I try to encourage my lab to think like a molecule.
00:34:04 Speaker 1: And how does a molecule think?
00:34:07 Speaker 2: Well, they don't. They're very random and they're fast.
00:34:15 And so you might try 400 times a second to do something
00:34:22 and only get it right about once in 20 like making proteins in ribosomes.
00:34:30 Speaker 1: Random is important.
00:34:34 Speaker 2: Random, yeah, but also the randomness at the atomic molecular scale.
00:34:41 But then all of the evolved machinery of life that overcomes that randomness and makes it very non random.
00:34:50 So for example when your chromosomes separate, when your daughter cells replicate.
00:34:56 It's almost perfect, it's not random.
00:34:59 And so what you're doing is you're using the random noise of the energy of the cell.
00:35:05 To make nearly perfect decisions that should be random.
00:35:09 Speaker 1: Yeah, and then going back to the idea of the different techniques that we have now.
00:35:15 The possibilities that it gives, is you really can create all kinds of, at the start, the sperm and the egg.
00:35:23 So there, you can already change things, or prepare, for [CROSSTALK]
00:35:28 Speaker 2: Well you can change it even before the sperm and the egg get together,
00:35:31 you can change it in the sperm itself.
00:35:33 Speaker 1: Yeah, but that's gonna create a human 2.0. You can create new-
00:35:41 Speaker 2: Right, I mean, you can alter, well, we are already altering adult humans with gene therapy.
00:35:52 Not just in ways that correct something that's wrong, that correct an inborn, inherited mutation.
00:36:00 There are even some where we augment them as adults. For example, making them resistant to HIV.
00:36:08 I mean, it's still medicine, because they might be at risk or already have AIDS.
00:36:14 But the way you do it is not by a chemical that kills the AIDS virus.
00:36:22 It's changing the human body so it no longer has the receptor for the HIV virus particles.
00:36:33 Speaker 1: Incredible.
00:36:34 Speaker 2: Yeah.
00:36:35 Speaker 1: It's like being [INAUDIBLE]
00:36:39 because we are now in the phase that you are in the middle of this scientific revolution.
00:36:52 Speaker 2: Yep.
00:36:52 Speaker 1: It must be incredible. Wow. I mean it's like-
00:36:57 Speaker 2: It's not hard to stay motivated when you have a lot of people in the lab that are enjoying themselves.
00:37:05 And making revolutionary breakthroughs on a regular basis. Very easy to get everybody motivated..
00:37:13 Speaker 1: Yeah, yeah because [INAUDIBLE]
00:37:16 Speaker 2: Right so the bleeding cutting edge of science and technology.
00:37:23 Speaker 1: Yeah so could you explain to me how your work?
00:37:28 Could you explain to me a working day in your [INAUDIBLE] cuz that's a very busy day.
00:37:31 Speaker 2: Right yeah.
00:37:33 Speaker 1: How do you work?
00:37:34 Speaker 2: It wasn't that different from regular days.
00:37:40 I usually get up around four o'clock in the morning without an alarm on my own, then I work until my wife and I walk in.
00:37:52 Together, we work on the same department in the same floor. It's just a short walk.
00:37:59 And so from about four in the morning till about nine, I get to do, I get to think
00:38:07 and work on without any interruptions.
00:38:11 And then my day is packed with talking some science with my students and post doctoral fellows.
00:38:20 And looking at their experiments designing and interpreting.
00:38:25 And then I usually don't take a break for lunch or anything. Then at the end of the day I walk back home with my wife.
00:38:36 And sometimes I get to visit with my daughter and granddaughter who live next door. And that's it.
00:38:50 Speaker 1: I understood that you need sleep?
00:38:52 Speaker 2: Yes.
00:38:54 Speaker 1: But that you dream your experiments or you dream your experience and can you elaborate on that?
00:39:02 Speaker 2: Well I'm narcoleptic, I have some kind of genetic problem that makes me fall asleep all the time.
00:39:09 And, during the day, even though I get a totally normal night's sleep, it's dark, it's quiet,
00:39:18 I fall asleep quickly at night. And I don't wake up in the middle of the night.
00:39:24 But nevertheless, during the day I fall asleep. And what happens is I superimpose the dream state on the reality.
00:39:31 And I can't always tell the difference, and I'll talk in my sleep. But sometimes it's very helpful.
00:39:43 Usually it's a nuisance, but sometimes it helps me solve problems,
00:39:47 and makes me look at things differently But you've seen it already? I've seen alternative ways of looking at it.
00:39:58 The dream state is very unusual and creative, and it allows you to get out of a rut,
00:40:07 what thinking about things the same way you've thought about them before.
00:40:11 Almost always look at them differently in dreams.
00:40:15 Speaker 1: Do you write them then afterwards? Are you writing them [CROSSTALK]
00:40:17 Speaker 2: No, no, no, it's just sometimes if I have a really difficult problem, I'll just shut down.
00:40:26 And then when I wake up, I have the answer. I don't have to write it down. I now know the answer.
00:40:34 In other cases, something strange will happen, I might write the few notes, but I'll just forget about it.
00:40:41 And then, a month later, I'll realize, yeah, that was actually something that was useful.
00:40:45 Speaker 1: Good, and when you look in the scientific field, what do you expect how your work
00:40:55 or field will develop itself,
00:40:57 Speaker 1: Or your scientific world?
00:40:59 Speaker 2: Yeah, our scientific world, I mean, it doesn't really develop itself.
00:41:04 It needs funding, it needs educated population to support it, and to add to join as the next generation.
00:41:17 So, it's very far from self-renewing.
00:41:24 But there is a component of it where we might inspire some of the other things that we need.
00:41:29 We might inspire people to fund this and we might inspire youth to join.
00:41:36 But a lot of it is a very unusual set of motivations and skills that not everybody has,
00:41:44 not everybody reacts to a statement as I'm gonna look that up.
00:41:51 Most people they say, I don't believe it or I do believe and I don't care. But they don't say I wanna look it up.
00:41:58 I'm gonna research it. Prove or disprove it, yeah. But that's almost, that's the natural response that we have.
00:42:06 And even if you look it up and you see evidence for it, online or in the literature, you say no,
00:42:13 I still need to check it.
00:42:15 I need to do a controlled double blind study to make sure that it's really,
00:42:19 there wasn't any research are bias that sort of thing. So science is a very unusual breed in that sense.
00:42:26 It really, some of them they don't need reminders that this is how they, this is really deep in their body
00:42:36 and their soul. It's how they think about the world with deep curiosity, playfulness, but this rigor of inquiry.
00:42:47 Speaker 1: Were you surprised that the techniques in a way are easy as you said? [INAUDIBLE] Research and understanding-
00:42:55 Speaker 2: Right.
00:42:56 Speaker 1: That it wasn't broadly picked up then.
00:43:00 That everybody was using it because in a way it was successful for everyone to use, other scientists,
00:43:08 were you surprised by that?
00:43:09 Speaker 2: Well, most of the technologies are not useable until a technologist makes them useable.
00:43:17 They may be derived from nature.
00:43:19 I mean in fact they may be very sophisticated machines so, for example, DNA polymerase, CRISPR.
00:43:25 These are all very, very complicated machines. It would be very hard to make from scratch.
00:43:32 From first principles on a drawing board and then manufacturing it. Once you see them you can make variations on them.
00:43:39 But making the first one without a hint would be very hard.
00:43:45 But then the technologist is needed to change that from a natural form into something that's useful.
00:43:51 And then to improve it and improve it until finally, it's usable by non-technologists.
00:43:57 And the usual reason they don't pick it up is because the technologist either hasn't really made it work.
00:44:02 I mean that sort of kind of works, works fall enough to polish but not enough for you to or someone else to use.
00:44:08 Or it works but it's not very well documented, not very user friendly.
00:44:15 So it's kind of a like you got to have a computer that works but it doesn't have any graphics,
00:44:19 it doesn't have any real way that on ordinary person could interface with it.
00:44:27 So it's not totally surprising when people don't pick up a technology.
00:44:31 What's more surprising is when you don't even have to give it a nudge.
00:44:35 It's like CRISPR, you just basically publish a paper and put some plasmids in Addgene
00:44:41 and suddenly everybody gets it to work.
00:44:46 That's the more unusual situation, out of maybe a couple of dozen of technologies I've developed,
00:44:53 maybe five of them are that easy for people to adopt.
00:44:56 Speaker 1: Why it come that CRISPR is that easy to be adopted?
00:45:00 Speaker 2: Well, some things require a new instrument, and new instruments require software,
00:45:10 and so you've got all the engineering, conventional, mechanical, electrical, and software engineering,
00:45:15 that you need to get that. So that takes about five years from the concept to something that people can use.
00:45:23 When you have something that's basically what you found in the wild,
00:45:28 then things that you find in nature tend to be highly evolved. It's as if an engineer made them.
00:45:34 But whether they were evolved or however they got that way, they're got a good user interface sometimes.
00:45:41 They do what you expect them to do.
00:45:43 Speaker 1: And so why was CRISPR then, so it was also the general public picked it up?
00:45:52 Speaker 2: Yeah, the general public, I mean, we know scientists picked it up because it's easy to program.
00:45:58 The GSATs and Cs I think the general public they're a little strange.
00:46:04 It's like the name is very cute name which wasn't nobody really intentionally made it a cute name recently anyway.
00:46:14 Part of it is because there was some odd patent issues having to do with it that got some people's attention.
00:46:26 I think part of it is just there was like it's like there was a,
00:46:30 Speaker 2: A pent-up, it's kind of an overdue slot machine. Or it's a tsunami that's coming off the shore.
00:46:40 And just before it is a whole bunch of technologies, that just before they hit shore, you blame it on one of them,
00:46:48 but it's really the whole collection.
00:46:49 And so I think it's a combination of those things, the name, the patents,
00:46:57 and a lot of other things that have been building up for decades.
00:47:00 Speaker 1: And CRISPR will revolutionize, or is revolutionizing the way we can work with the DNA?
00:47:12 Speaker 2: Well, what I think, yeah I think its ability to read and write DNA and some of it's editing
00:47:19 and some of it's rewriting DNA from scratch.
00:47:21 There is a whole collection of technologies,
00:47:24 there is suddenly many factors of ten maybe a million times easier to use more accurate and less expensive.
00:47:34 And CRISPR gets most of the credit but there's this whole other thing sometimes called next generation sequencing.
00:47:41 There are ways of synthesizing DNA on chips,
00:47:44 these things if you didn't have all these things CRISPR would be much less interested.
00:47:49 Speaker 1: Yeah now
00:47:50 when all these developments all coming together I still don't completely understand what it means now.
00:47:55 Speaker 2: Yeah.
00:47:56 Speaker 1: Cuz it's such a revolution that I can't.
00:48:04 Can you share what it means that this is happening now, and what it will mean for me and my family, and my daughter?
00:48:10 Speaker 2: Well, nobody really knows what it means.
00:48:13 In the same sense that if you asked even the greatest visionary in computer science in the 1950s what the computer
00:48:22 revolution meant, he or she would probably not guess right.
00:48:27 They probably would not guess Facebook, or maybe not even Google or search engines, or Google Maps.
00:48:37 They might have said, it will be used for calculating logarithms for rockets, so you can do warfare better.
00:48:46 Or you can do accounting better, so that you don't have to have human calculators. So I think the same thing.
00:48:55 Well, for what society will do with its enhanced ability to read and write DNA is we will modify ourselves
00:49:04 and our environment and the way we obtain food and [COUGH] all the materials that we use,
00:49:12 including very smart materials like computers.
00:49:15 All these things will be altered beyond recognition in a fairly short period of time.
00:49:21 Speaker 1: We'll all live that time or is it?
00:49:26 Speaker 2: Well, I was alive in the 1950s, so yeah, we might be in the equivalent time.
00:49:37 But everything's moving faster now and one of the things that's moving faster is our ability to reverse aging.
00:49:43 So if we can reverse aging, then yes, you will definitely be around to see all sorts of things,
00:49:49 because there's no law of physics that we know of that requires vision.
00:49:56 We know that there's a continuity of life that goes back 3 billion years, so there's no particular reason why,
00:50:05 Speaker 2: Humans or animals in general have to senesce and get old and break,
00:50:15 because some of the cells in the body keep on living in the next generation.
00:50:21 Speaker 1: That's also where your lab is, also active [INAUDIBLE]
00:50:25 Speaker 2: Yes, right, we have very active projects, plural, on aging reversal.
00:50:34 Not so much on longevity, where you don't wanna prolong the end of life, which is unpleasant and expensive.
00:50:41 And where you become a less productive member of society, less engaged.
00:50:48 What you wanna do is reverse it back to a time where you were at your optimum performance,
00:50:55 a young person like 65 years old. [LAUGH]
00:50:58 Speaker 1: And do you think that's possible?
00:51:01 Speaker 2: Well, it's not only possible, it's been done in animals.
00:51:08 Now those animals may or may not be good models for human.
00:51:12 But certainly the time is ripe for testing things that either cause longevity in animals or aging reversal in animals.
00:51:20 And then test to see if they can cause aging reversal in larger animals and humans.
00:51:25 Speaker 1: How can you do the aging-
00:51:27 Speaker 2: Well,
00:51:29 there are many things that have been shown to increase animal lifespan by a factor of two to a factor of ten.
00:51:37 There are things that involve, I mean, not to get too technical, but mitochondria, the tips of chromosomes,
00:51:44 the telomeres, the growth factors and muscle related proteins, like myostatin pathway.
00:51:53 So there's all these pathways that are pretty well understood.
00:51:56 And if you harness a little of each for gene therapy, then you could try them separately and in combinations.
00:52:02 Gene therapy is particularly easy to go from an idea to a test of it.
00:52:08 You don't have to take a side route where you randomly screen through millions of pharmaceutical compounds.
00:52:16 And we talk about reverse aging, how does that affect the fact that you are able to, how far are we in that?
00:52:23 Speaker 1: You have gene therapy for that?
00:52:25 Speaker 2: Well, we have lots of demonstrations in animals, both in extreme extensional longevity,
00:52:31 and reversal in some cases. Many different ways of doing that.
00:52:36 And so we're collecting all those that are known for small animals and we're applying them to large animals
00:52:42 and to humans. Coming off the gene therapy trials is much easier, but we're still just beginning on that.
00:52:51 It's looking very promising, but it's too early to say.
00:52:55 And something that might even work for large animals may still not work for humans.
00:52:59 Speaker 1: Yeah, what is in the line of work you're now which really thing, or in research project,
00:53:08 or your project where you're working where you really feel like I hope this will develop as soon as possible?
00:53:17 Speaker 2: Well, I mean, top priority, I guess, would be transplantation of organs, malaria for developing countries,
00:53:30 and aging reversal for industrialized nations, and preventative medicine in general is the strategy.
00:53:39 And then right behind all of those, once those are all working and we improve our basic human condition,
00:53:49 then space genetics.
00:53:51 Speaker 1: One second. [INAUDIBLE]
00:53:53 Speaker 2: Sure, yeah.
00:54:04 Speaker 1: So when you looked at the projects, what were you-
00:54:10 Speaker 2: So the projects that I find most compelling and exciting, in terms of applications,
00:54:14 are transplantation of organs. There's a gigantic need for that.
00:54:21 Speaker 2: Gene drives to eliminate malaria, and then for developing nations.
00:54:28 And then aging reversal for industrialized nations where most of the morbidity
00:54:34 and mortality is due to diseases of aging.
00:54:38 You want to get at the core of that, and then once you have all those things which are drains on our economy,
00:54:44 if you can solve all those, then you can reduce.
00:54:47 Then you have more money available for things like space where we really need to get off the planet to avoid super
00:54:53 volcanoes and asteroids. And that has a genetic component as well.
00:54:58 Speaker 1: Okay, in what way? What's the genetic component?
00:54:58 Speaker 2: Well, we have radiation sensitivity, and our bones rot at low gravity.
00:55:11 And so even, not only in traveling, let's say, to Mars, but even once you arrive there, its gravity is 38% of Earth's.
00:55:23 And so our body was designed for normal gravity.
00:55:27 And as soon as you don't have normal gravity, you have muscle
00:55:31 and bone wasting because the body thinks it's doing a physiological feedback loop to keep everything right.
00:55:39 But you need to have muscles and bones even in low gravity because when you touch something with weak bones,
00:55:49 you'll crush your bones and And you need muscles to move things around.
00:55:54 So, anyway, those are some of the things that are problematic.
00:56:01 And also, there's questions like what do we bring with us? Do we bring all the species of the Earth?
00:56:07 Or do we leave out the giant sequoia, and the bowhead whale, and smallpox. Do we [COUGH].
00:56:13 Speaker 1: We can create that again on Mars [INAUDIBLE]
00:56:16 Speaker 2: We could, yeah, but we haven't done that yet. We have not really recreated.
00:56:27 And so it's a big decision, is whether you take it with you.
00:56:29 In fact, some of them, it could be that their ecosystem is fragile enough,
00:56:34 that you can't really make it with our current knowledge.
00:56:37 So having the complete DNA sequence of everything in the planet may not be enough to recreate some of the more complex
00:56:43 ecosystems.
00:56:43 Speaker 1: Yeah, but when you create it [INAUDIBLE]
00:56:46 Speaker 2: Yes, that's correct. Yeah, yes, we're big on double two sides on,
00:56:52 Speaker 1: [INAUDIBLE]
00:56:53 Speaker 2: Yeah, the story?
00:56:55 Speaker 1: Yeah what's the story [CROSSTALK]
00:56:59 Speaker 2: So a nine year old girl sent us two copies of that poster and we put it on the wall.
00:57:10 But it's based on our, she had read about our project in the news.
00:57:15 It's small project
00:57:16 and it mainly benefits from the technology that we've developed for other projects like human medical research.
00:57:24 But these things, we bring the price down a million-fold, and then, you can use it for reading
00:57:29 and writing DNA from ancient samples.
00:57:32 And [INAUDIBLE] mammoth is that the Asian elephant is the closest relative to the mammoth.
00:57:39 And it's so close in fact they're both closer to each other than they are to the African elephant.
00:57:44 And the Asian elephant can breed and make offspring children with African elephants.
00:57:48 So probably, the Asian elephant and the mammoth are basically very close to being interfertile.
00:57:55 And so, one way of focusing on modern day species is to extend the range of the Asian Elephant.
00:58:03 It will already play in the snow.
00:58:05 But you could extend it all the way out to -40 degrees in the tundra of Canada, Russia, and Alaska.
00:58:14 And furthermore, so you get a benefit to the elephant.
00:58:16 But you also get a benefit to the tundra, because the tundra is melting.
00:58:21 And there's experiments
00:58:23 and field studies that indicate that a mammoth-like creature could keep the temperature colder by up to 20 degrees in
00:58:33 temperature.
00:58:34 Speaker 1: [INAUDIBLE]
00:58:35 Speaker 2: So the experiments for the idea followed by experiments is that trees absorb about twice as much light
00:58:45 and so that's a warming effect and the grasses have roots that protect from erosion and then punching down the snow.
00:58:57 The big fluffy insulating layer of snow in the winter time,
00:59:00 if you punch that down you can get penetration of the cold winter air.
00:59:06 And these three things put the mammoths or sorry the elephants or mammoths will knock down trees
00:59:11 and replace them with grass A, much richer ecosystem full of some small animals.
00:59:17 Anyway, we did the experiment replacing mammoths with a combination of caribou, which is one of the biggest mammals,
00:59:26 and tanks, Soviet tanks, that would knock down the trees cuz carabao can't knock down trees but elephants, [INAUDIBLE].
00:59:32 Anyway, it was about 15 to 20 degrees, it's the difference between the experimental and the control site.
00:59:40 Speaker 1: Well, there's a variety of projects we are talking about here.
00:59:43 Speaker 2: Yes, right. Yes, yeah.
00:59:46 Speaker 1: Or working.
00:59:46 Speaker 2: Well, we haven't scratched the surface yet.
00:59:48 Speaker 1: Can you-
00:59:49 Speaker 2: Keep going?
00:59:50 Speaker 1: [INAUDIBLE]
00:59:51 Are there any particular things that you would like to share with the- I think we've covered a good sampling of it.
01:00:00 Speaker 2: We covered the personal genome project, data incorporation in the DNA-
01:00:09 Speaker 1: The future.
01:00:11 Speaker 2: The future. Yeah, I think we covered it.
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