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.

More videos with George Church



No video? Please use the latest version of Safari, Chrome or Firefox. Internet Explorer might cause problems.
Why is a playful attitude in science important? (00:00:00)
Why start the Personal Genome Project? (00:01:46)
What is the Personal Genome Project? (00:03:11)
What is the future of the Personal Genome Project? (00:04:14)
What does your scientific work entail? (00:06:11)
How will your work transform the future? (00:06:37)
What is CRISPR gene technology and what are its (future) possibilities? (00:07:33)
What drives you? (00:13:22)
What inspired you as a child? (00:14:35)
What if you had to curate an exhibition about the future? (00:16:39)
Can you name some mind boggling new ideas from your lab? (00:18:21)
What are the dangers of gene editing and how to handle? (00:20:11)
Why should humans colonize space? (00:25:13)
What beauty lies in the human genome? (00:27:07)
How come your research is a pioneering piece of work? (00:28:17)
What more will the future bring? (00:31:05)
How to illustrate the future of the revolution in biology? (00:32:38)
What can gene editing mean for curing diseases like hiv? (00:35:10)
"It's not hard to stay motivated" (00:36:57)
How does your average working day look like? (00:37:23)
When do you have your best ideas? (00:38:51)
What is needed to anchor your discipline in society? (00:40:49)
Why are some dna techniques harder to adopt than others?  (00:42:48)
What do these new dna techniques mean for the future? (00:47:02)
How are you involved in age reversal research? (00:50:21)
What projects are you most excited about? (00:54:05)
What's the story behind the mammoth resurrection? (00:56:54)
automatically generated captions
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.
TV Get inspired and watch tv episodes of The Mind of the Universe, made by Dutch public broadcaster VPRO
  • Browse through over 30 hours of interviews
  • Download the interviews, including subtitles
  • Remix, re-use and edit under CC-BY-SA license
  • Start exploring