English subtitles for clip: File:George Church on the revolution in and future of dna editing-VPRO-The Mind of the Universe.ogv

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Speaker 1: I told [INAUDIBLE] you were in the player.

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Speaker 2: Right.

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Speaker 1: Do you think you fit in that one?

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Speaker 2: Yeah, I think we have a very creative laboratory,

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and I like pushing the boundaries into what's sort of called disruptive or transformative technology.

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And we have artists in the lab. And yeah, I think player would fit.

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Speaker 1: But also, I think the importance of the fun of playing with DNA, with just the science [CROSSTALK]

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Speaker 2: Right, yeah, I mean, we don't take ourselves too seriously.

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We try to do experiments that are both important for something societal, but they're also very playful

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and illustrate an interesting way of looking at things. It usually makes people smile and surprised, yeah.

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Speaker 1: And how come? Why is that, do you think?

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Speaker 2: Why do we do that? [CROSSTALK] Why do they smile?

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Speaker 1: Yeah.

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Speaker 2: Well some of them are funny, like making 70 billion copies of my book.

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That's more than all the most well purchased books in history. And it's kind of a funny idea.

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And the idea that the DNA could last for 700,000 years or maybe a million years is fun.

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And making a woolly mammoth, you can have a serious reason like the survival of the Asian elephant,

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but also it just makes you smile to think that an old animal that's extinct comes back.

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Speaker 1: That's one of the projects.

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Speaker 2: Yes, right.

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Speaker 1: That you're working with?

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Speaker 2: Yes.

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Speaker 1: And in what way is the personal genome project is part of your work? Can you explain?

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Speaker 2: Right, yeah, so in a way, that's very serious in that when we started it ten years ago,

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there were all these really scary and crazy rules that didn't really make sense.

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That your medical information would never escape from the lab, even though there are multiple examples,

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like WikiLeaks and so forth.

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And then once it escaped, it would never be re-identified, even though it was a very rich data set,

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and we know we can re-identify.

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That if we'd learned something about you that could save your life,

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we couldn't tell you because we couldn't give data back to you, just all sorts of crazy things like this.

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And so we wanted to, again, be a little more playful and say, well,

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what if we did just the opposite of all of those things?

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If they sound a little crazy, let's do the opposite, maybe it will be either playful or super sane.

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So it's the only project in the world now for ten years, where you can actually have free access to human biology,

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genomes, environments, and traits. It's kind of like Wikipedia for human beings. So it's revolutionary and playful.

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Speaker 1: And can you explain what it exactly is?

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Speaker 2: It's a collection of big data of each individual person.

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So it's not just big because there are a lot of people, it's big for each person.

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And it's the way we think that medicine will be practiced in the future.

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But we collect medical records, a whole variety of measurements that we do every year on DNA Day,

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where the people come back every year and get a update.

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Sometimes all sorts of new tests, and then the genomic sequence, and a number of other omics, microbiomics,

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and viral sequences. The things in your environment that can greatly influence your health.

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So we get this big collection and then we make it publicly available, so that anybody in the world can help analyze

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and interpret and understand your genome, everybody's genome that's in the project.

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Speaker 1: And what would that mean for future if the database is getting bigger and then better?

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Speaker 2: Yeah, so, it's not intended to be a production project so much as an inspirational one.

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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.

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And so now, it changes the conversation.

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And so many of the things that we thought were crazy,

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now people agree that maybe we should be sharing data back with the individual, getting them properly educated upfront.

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Admitting that we can't keep the data from getting out in any project anywhere in the world.

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In fact, even medical records in a hospital, which have nothing to do with research, are extremely valuable now.

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They're 20 times the value of your credit card on the black market.

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So many of these things that we're talking about ten years ago are now accepted,

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so that was the main thing we were going for.

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But what will happen is once it's widely accepted, we may eventually have 7 billion people's genomes

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and medical records available. And then you can find all kinds of correlations and what causes diseases and cures.

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Speaker 1: And then you can almost personalize the medication and the solution, is that right?

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Speaker 2: Yeah, not only personalized based on your DNA, but personalized based on your environment, as well.

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And most importantly, I think, is prevention.

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So, an awful lot of medicine is you wait until it's kind of too late where you've already got DNA,

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that's where you get damage to your body or you've got cancer.

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And even if you try to catch the cancer very, very early, it's really already too late because it's already start.

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It's got its mechanism revved up to make more mutations.

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Speaker 1: So basically, when you explain what you are doing to somebody that doesn't know, could you explain it?

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Speaker 2: Sure, our lab develops radical technologies for reading and writing DNA, the same way you'd read

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and write a book. We can do that with DNA, and we've brought the price down by about over a million-fold.

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Speaker 1: And the consequence, when you look back the last ten years and

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when you look further in the coming ten years, what do you foresee in the near future in ten years?

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Speaker 2: Right.

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Speaker 1: How would it look like?

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Speaker 2: Yeah, well, we don't know if we can sustain this incredible, exponential speed, where it gets faster

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and faster every year. But if we can, in ten years, we'll be unrecognizable in terms of the technologies we can do.

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We'll be able to change agriculture, medicine, forensics, you name it.

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Even information handling that you normally think is the realm of electronics will be molecular.

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Speaker 1: Even networking.

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Speaker 2: Yeah.

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Speaker 1: And in what sense I understand crisp, what is crisp, first?

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Speaker 2: Crisper?

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Speaker 1: Yeah, crisper.

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Speaker 2: So crisper is a buzz word that really is capturing the imagination,

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but it represents a much broader set of tools. So we've had for a few years To engineer genomes.

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So, in addition to the new ability to read genomes, CRISPR represents a way of editing genomes.

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It's not the only way, but it's something that captures people's imagination.

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And we helped invent that about three years ago now, and many people have improved on it.

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About 70 labs have contributed to an open non-profit resource called Addgene

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and then re-distributed it into 30,000 laboratories.

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Speaker 1: What is CRISPR?

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Speaker 2: Sorry.

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So, CRISPR is the latest in a series of ways of manipulating a genome where the computer, the science,

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define 20 base pairs- As, Cs, Gs and Ts in a particular order, chosen to be specific for one place in your genome,

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in your DNA, and not anywhere else in your genome. So it's both positive and negative computer selection.

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And then it will cut, it will search through the genome randomly and find the right place and make a,

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cut both strands of the DNA, and then that either eliminates the gene that it just cut in

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or it helps repair to whatever you want.

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So that's precise gene editing is what people are so excited about, where you can change it into whatever you want.

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And we were the first lab to do that in human stem cells, and those can be turned into almost any cell,

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and it can be done in a whole variety of different organisms now. Almost every organism that's been tried, it works in.

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Speaker 1: Yeah. And then because you use in the text that you are able to-

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Speaker 2: Right.

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So some people call editing just making a mess, making a break,

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but I think that's like saying that ripping a page out of your journal is editing, and it's not really.

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But this allows you very precise editing.,

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Speaker 1: And the possibilities that it give, is that you really can prevent a lot, when [INAUDIBLE] is that correct?

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Speaker 2: Right, right so you can now engineer agricultural species, wild species,

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and you can do preventative medicine.

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Speaker 1: It's not students, it's now really in a, this year it's really, also really growing, this technique.

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It's developing hard,

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Speaker 2: So it's a three year old technique, but it's been growing exponentially.

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And the number of people adopting it is huge, and every new person that adopts it helps also make it work better.

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Speaker 1: Yeah.

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Speaker 2: Yeah.

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Speaker 1: Then the consequences are endless, because you can prevent diseases, you can create, you can,

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because of course people with this diseases that are very strong, you can help those people as well.

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Speaker 2: Right.

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So it's particular valuable for so-called rare diseases that are individually rare

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but collectively there's a large number of them

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and so you might have maybe 3-5% of the population is affected by these,

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even though each one only affects 1 in 100,000, together there.

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And, so if you have two parents that are carriers, and they have no

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Speaker 2: They will have 25% of their children will be severely affected, very deterministic.

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It's not really probabilistic. It's almost guaranteed.

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And that means that the only real way that protects the family, including the children and family are healthy,

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is abortion, which is not acceptable to many people in the world.

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And so gene editing gives us the opportunity of changing the sperm, so that you don't have to affect the embryos.

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You can do it without hurting or putting embryos at any risk.

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So that's a new possibility that has yet to be demonstrated.

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Speaker 1: Yeah.

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That will also see an incredible future when this is further on developing because you can do a lot with it.

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Speaker 2: Yeah, you can reduce disease without eliminating the gene variants..

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Speaker 1: Okay, but you can also make viruses or bacteria that are with synthetic [INAUDIBLE]

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Speaker 2: Right, right.

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Speaker 1: [INAUDIBLE]

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Speaker 2: So we've made biocontainment versions of bacteria that are stuck in the lab. They have very low escape rates.

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And this is particularly important, if you put things into the bacteria that would give them an advantage in the wild,

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like for example virus resistance, that could be very productive in an industrial setting

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but you don't want it to get out of the wild.

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So you have to have both the viral, anti-viral strategy and the biocontainment together.

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That was actually done without CRISPR.

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Quite a bit of the genome editing and genome engineering we do in our lab does not involve CRISPR.

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And that's a perfect example of one where we've done probably the most radical

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and extensive engineering of 4 million base pairs without CRISPR. Yeah.

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Speaker 1: Where comes this energy that you have in your work? Where is it coming from? What's your source?

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Speaker 2: The source of our industry

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and enthusiasm is just knowing that you can answer very basic scientific questions at the same time you push,

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you drive down the price of technology, democratizing it, making it available to many people.

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And then the product, the applications of the technology,

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can be even more societally impactful than the technology itself, such as transplantation,

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solving the transplantation crisis, the malaria crisis, and aging crisis.

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These are all things that are highly motivational, where millions of people are dying every year.

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Speaker 1: Your personal source, your personal energy, where does it come from? [CROSSTALK]

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Speaker 2: My personal energy comes from the threat, that all these people are going to die every year

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and the curiosity, playfulness of the science that, so you could simultaneously play

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and do something were serious which is saving millions of people.

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Speaker 1: Yeah. And when did this start? When you were young? Do you still remember when you're-

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Speaker 2: Yeah. I remember when I was a boy in Florida living on the water, in the mud.

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I would play in the mud and I would pull the creatures out of the mud and wonder how they worked.

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And I would look at my father's medical bag. It was full of drugs and instruments. And I said.

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That was an inch, so one was very natural and was very artificial and I was in awe in both of them and then,

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and then I went to a World's Fair in New York cCity.

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From, all the way from Florida to New York city when I was ten years old and and they have created a simulated future.

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They had gone really,

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really far out on making a pretend world where they had robots that looked just like a human being.

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And then, from that day, I could never go back to the past.

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Even though they didn't have a real future, it was a fake future, I could not adjust any more.

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Once I had seen the future, I had to work on it to make it happen because it seemed very attractive.

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Speaker 1: It's exactly what my daughter also said.

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Speaker 2: Yeah.

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Speaker 1: Last week, when it was in the Scientific Museum in Amsterdam.

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Speaker 2: Yeah.

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Speaker 1: She saw-

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Speaker 2: It's dangerous and very hopeful to create a fictitious future in such graphic terms,

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where you can walk around, that you can taste it, you can feel it, you can see it.

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They had touch pads in 1965 where you could draw something and then, it would print out the whatever you drew.

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Not on paper, but in fabric you could actually make a scarf of a butterfly you would draw with a pen.

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That took like forty years before there was anything even similar to that, that the average person could use.

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Speaker 1: Where you would organize a museum or a fair where you would show the future of us in 40 years,

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what would I see?

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Speaker 2: Well, to some extent it doesn't have to be entirely accurate,

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obviously it can't be because you can't see the future, but it just needs to be inspiring.

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And to a 10 year old, is particularly easy to inspire.

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So, you might see space colonies, I think, with humans that are adapted to space.

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Right now, our biology is particularly, I mean,

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it was not designed for space travel in terms of radiation resistance and the bone loss that happens at low gravity.

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So, there might be some of that, there might be either conquering our microbiome, or completely eliminating it,

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or getting to the point where we are resistant to everything, so we didn't eliminate it,

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we just got better at vaccination, or something like that.

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I mean, so, that you can, you can now go back to doing surgery without hygiene, you just doesn't even clean your hands.

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Speaker 2: I think there are many things like this that would seem like science fiction,

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but if you created it in a realistic enough-

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Speaker 2: Fictional universe, kids especially will dream about it and make it happen.

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Speaker 1: And there's already coming, information out that you didn't expect, as your own data?,

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Speaker 2: Well, I expect everything [LAUGH] so it's fun. And I wouldn't say there's anything gigantically in it.

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Well, my family was very concerned, because my father had died of senile dementia

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and they were worried that I would have risk factors, and so far it looks like I have the opposite,

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I have no risk factors. So, maybe that's suprising, maybe it's false assurance.

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Speaker 1: It's good to have you now working in the lab for the future.

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Because somehow the lab feels like you're on the fringes of knowledge. Do I see that right?

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Speaker 2: It certainly feels that way to me.

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Every day somebody walks in and gives me something that shocks me and it's not easy to shock me.

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But it's very common that they'll come up with something that,

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that really changes the way we approach biological research.

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Speaker 1: Yeah, so could you give us example when [INAUDIBLE] kind of short.

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Speaker 2: Well, for example, getting nanopol sequencing that was some,

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it's a way of you got a handheld device that it's capable of sequencing DNA.

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Speaker 2: Engineering mosquitos,

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so that they can spread really good genes through the environment that would make them resistant to a malaria parasite.

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Every little breakthrough in each of those two projects is remarkable.

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Speaker 1: Yeah, and what do you think about the criticism that you also hear of course that it's not secure.

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And that you can create also the other side with it. What do you think of that? How do you see that?

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Speaker 2: I'm one of the biggest critics of it.

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I try to raise consciousness and make people concerned,

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because if you're not concerned things can be unintended consequences.

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If you are concerned it helps you plan for alternatives.

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But in particular, I suggested over the last 11 years, that 12 years,

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that we should have a surveillance mechanism in place where anybody that participates in these powerful technologies

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and all the ordering that they do of supplies should be monitored by the companies

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and ideally by the governments as well.

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Speaker 1: Why?

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Speaker 2: I mean, you wouldn't want surveillance on your everyday activities,

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but if you're dealing with synthetic DNA, that's not everyday activity.

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And nobody forcing you to work on synthetic DNA, but if you choose to work on synthetic DNA then,

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you need to be under surveillance because we're in a time where you don't know how powerful it is.

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And so, it's better to just have everything under surveillance.

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And a particular why I proposed, was looking for people synthesizing things that are extremely hazardous.

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Things like smallpox, and polio, and anthrax, toxin, and things like that. Cuz there's no reason.

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They should only be ordering that if they have permission from the government to order it and a very good reason.

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Speaker 1: Because that's all possible.

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Speaker 2: It's very easy.

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And so, you not only have to monitor how they order it as DNA, but you need to monitor the machines

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and the chemicals that they could use to do it themselves.

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But if you monitor everything, then it greatly reduces the probability they could do it themselves.

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Speaker 1: That's also the other side of CRISPR, you're able to on not a very simple way,

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but you can in a way you can do anything.

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Speaker 2: Yeah, CRISPR has a lot of power, but it's probably not the most dangerous, I mean,

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I'm not trying to reassure people.

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I'm just saying if you're going to worry,

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worry about the right thing which is worry about ordinary pathogens that you can find all over the world because those

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are much more powerful that anything you can do with CRISPR today.

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CRISPR and all of our amazing technology for reading and writing DNA, is now you can use for better surveillance.

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I mean, if its a million times cheaper, you can have it distributed work of surveillance.

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You can make faster and better vaccines, that are very responsive to emerging threats for the natural and unnatural

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and so forth.

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I think that revolution in reading and writing DNA is much more easily used for protection

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and prevention than it is for misuse.

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With misuse you just go out and get somebody who's got some serious disease and weaponize them with ordinary methods,

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not modern molecular biology.

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Speaker 1: And so, in the way by making it cheap, by making it possible-

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Speaker 2: Yeah.

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Speaker 1: Millions of people use, it's like the internet in a way. Is this correct?

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It's like you see that the date on the Internet is like it exploded. And then, it doesn't mean [CROSSTALK]

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Speaker 2: Well a slight difference between this and the Internet,

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I think is we have the opportunity of having a higher security, and safety.

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And I think in the Internet early days, it wasn't a top priority,

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and it ended up with kind of a culture that includes hackers, and computer viruses, and credit card,

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or just identity theft, and stalking, and so forth.

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I think if you had the equivalent thing in biology, it'd be much more serious.

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So if you have a computer virus, that might cause billions of dollars of damage.

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But a real virus could cause billions of dollars of damage and millions of lives.

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So I think we need to create a culture of surveillance and good deeds.

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Speaker 1: And that's happening now? What you're saying?

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Speaker 2: Yes it is. But we need to keep raising consciousness and keep that motivation going. Yeah.

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Speaker 1: It is good to stay critical also.

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Speaker 2: Yes, right.

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Speaker 1: And when you look at the future of, well,

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I actually once said that the universe is getting conscious by itself, which of itself, and the past and future,

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via the humans. What do you think of that idea?

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Speaker 2: That was definitely the case that one of the distinguishing features of human beings is our ability to think

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very deeply about the past and predict the future, and thereby avoid future existential risk to ourselves, our family,

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and to in fact the entire planet.

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So in particular, asteroids, and super volcanoes could destroy all of civilization, or, at least,

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throw it back into the dark ages by eliminating the social fabric and cooperation.

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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,

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we don't create global warming. If we do everything right, we could still die as a species.

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I think the antidote to that is to get us off the planet as a sort of a space genetics planetary species.

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And we have to start spreading outside of the planet.

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Speaker 1: Yeah there's also one of your goals I understand, is that correct?

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Speaker 2: Yeah, and I think we have a consortium for space genetics centered here at Harvard, but international.

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And if one is to raise consciousness about the needs, the special needs that you have,

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that have to do with genetics in getting off the planet.

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Speaker 1: Yeah, that's really the beauty of the human genome.

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Speaker 2: The beauty of the human genome?

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Speaker 1: Can you explain it?

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Speaker 2: Well it's beautiful awe inspiring because it is in a certain sense very simple and very complicated.

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There's parts of it we don't understand. There's parts of it amazingly predictive and we understand well enough.

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It's beautiful, and it's a simple set of four letters, G, A, T, and C.

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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.

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Everybody talks about how complicated it is

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but really once you have a little bit of training it's amazing how much you can get out of human and other genomes.

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It's a beautiful structure. It's very elegant in the two strands and the way it replicates by separating.

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They're many things about DNA that's beautiful. You can build machines out of it. You can-

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Speaker 1: Print books?

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Speaker 2: And you can print books.

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Speaker 1: But you and your team somehow are astronauts because you say it's very simple

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but you are getting into the universe of the genome.

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Speaker 2: Right, yeah.

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Speaker 1: Everything that comes with it.

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Speaker 2: Right.

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Speaker 1: As an astronaut traveling through it, you discovering it-

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Speaker 2: Right.

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Speaker 1: More and more and more. So we are, it must be, how is that to be-

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Speaker 2: Right.

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Speaker 1: That far ahead?

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Speaker 2: Right, yeah, so when I say it's simple, I'm doing it from an unusual standpoint.

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It would be like an astronaut saying, it's simple to walk on the moon. Well maybe for you it is.

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And what happens is once you get a certain number of technologies working with nobody else in the world can use not

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because we've kept it a secret. I mean, we shared it openly it's a we're very interested and open asset.

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It's just that nobody, even though it's open they can't necessarily practice it that easily or they don't trust it

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or to be as easy as it looks.

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And so then we have the opportunity of using it for a couple of years

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and putting together another layer of invention and another on top of that.

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And recombining them in various ways to get hybrid inventions.

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And it just keeps in this positive feedback loop keeps going. And it's a very funny experience..

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It's like diving off a cliff [LAUGH] You get faster and faster as you hit the water. Yeah.

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Speaker 1: But you're not in the water yet..

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Speaker 2: Yeah, there may not be any water [LAUGH] It may just be free fall, yeah.

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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,

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still.

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Speaker 2: Yeah, there's a large research community, but within that, as a smaller set that do technology,

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and there's a even smaller set that does radical, basic enabling technology.

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So some of the technology developers might develop a particular drug for a particular disease,

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but then there's a tiny set that develop technology which can be applied to almost anything.

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So, reading and writing DNA can be applied to any organism, and can be applied even to things that are not biological.

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And those tools can be applied to themselves which is what creates this exponential of just grow, growing faster

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and faster.

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Is it the tools that you use to engineer DNA can be use to engineer the tools that you used to engineer DNA.

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It is very cyclic and the, it's just that's playful.

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Speaker 1: Yeah, and then exponentially growing means that, well, it grows very fast.

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Speaker 2: And what, yeah, what will it bring us in few years?

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Well, hopefully, what it'll bring us is higher safety, rather than less safety.

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And that requires that we talk about it a lot and be very thoughtful about it

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and encourage the new generation to be focused on safety security and modeling and extensive testing.

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But other than that I mean it will bring us whatever we want. It's unlimited.

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The question is not so much what it will do, it's what are the few things that it won't do.

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For example, even computers, which currently now, are not biological. Those could easily be biological in the future.

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The most amazing computer in the world, is the human mind.

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And if the human mind starts modifying itself, then it becomes even more amazing.

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Than a human trying to make a computer that can't yet think the way a human can.

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Speaker 1: So we think everything can be created. It's like a parallel universe that can be made.

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Speaker 2: Yeah, it could be revolutionary in terms of how unrecognizable it is a few years from now.

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Speaker 1: Yeah, so organized to inspire ten-year-old kids.

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That it's quite difficult to put to show what it will bring us.

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Speaker 2: Right, yeah, I mean, it's much easier to illustrate the revolutions in mechanical and electrical engineering.

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You can build like in the days of Edison, you could build a crude prototype for a motion picture camera and projector.

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And you can touch that, you can feel that, you can understand how it works.

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If you were to create a futuristic [INAUDIBLE] vision today, most of the mechanisms would be invisible.

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They'd be so small that there's no real way of observing them directly.

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And even if you could observe them it's hard to understand what they're doing.

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Because we're not used to thinking the way that a molecule thinks.

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A crisper molecule in order to cut it might jump around to 6 billion different places.

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Randomly knocking on the same wrong door until it finally finds the right place and then it will act.

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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?

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Speaker 1: Yeah.

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Speaker 2: So, I think people are not used to thinking molecularly

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but I try to encourage my lab to think like a molecule.

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Speaker 1: And how does a molecule think?

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Speaker 2: Well, they don't. They're very random and they're fast.

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And so you might try 400 times a second to do something

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and only get it right about once in 20 like making proteins in ribosomes.

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Speaker 1: Random is important.

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Speaker 2: Random, yeah, but also the randomness at the atomic molecular scale.

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But then all of the evolved machinery of life that overcomes that randomness and makes it very non random.

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So for example when your chromosomes separate, when your daughter cells replicate.

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It's almost perfect, it's not random.

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And so what you're doing is you're using the random noise of the energy of the cell.

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To make nearly perfect decisions that should be random.

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Speaker 1: Yeah, and then going back to the idea of the different techniques that we have now.

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The possibilities that it gives, is you really can create all kinds of, at the start, the sperm and the egg.

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So there, you can already change things, or prepare, for [CROSSTALK]

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Speaker 2: Well you can change it even before the sperm and the egg get together,

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you can change it in the sperm itself.

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Speaker 1: Yeah, but that's gonna create a human 2.0. You can create new-

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Speaker 2: Right, I mean, you can alter, well, we are already altering adult humans with gene therapy.

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Not just in ways that correct something that's wrong, that correct an inborn, inherited mutation.

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There are even some where we augment them as adults. For example, making them resistant to HIV.

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I mean, it's still medicine, because they might be at risk or already have AIDS.

379
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But the way you do it is not by a chemical that kills the AIDS virus.

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It's changing the human body so it no longer has the receptor for the HIV virus particles.

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Speaker 1: Incredible.

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Speaker 2: Yeah.

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Speaker 1: It's like being [INAUDIBLE]

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because we are now in the phase that you are in the middle of this scientific revolution.

385
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Speaker 2: Yep.

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Speaker 1: It must be incredible. Wow. I mean it's like-

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Speaker 2: It's not hard to stay motivated when you have a lot of people in the lab that are enjoying themselves.

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And making revolutionary breakthroughs on a regular basis. Very easy to get everybody motivated..

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Speaker 1: Yeah, yeah because [INAUDIBLE]

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Speaker 2: Right so the bleeding cutting edge of science and technology.

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Speaker 1: Yeah so could you explain to me how your work?

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Could you explain to me a working day in your [INAUDIBLE] cuz that's a very busy day.

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Speaker 2: Right yeah.

394
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Speaker 1: How do you work?

395
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Speaker 2: It wasn't that different from regular days.

396
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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.

397
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Together, we work on the same department in the same floor. It's just a short walk.

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And so from about four in the morning till about nine, I get to do, I get to think

399
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and work on without any interruptions.

400
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And then my day is packed with talking some science with my students and post doctoral fellows.

401
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And looking at their experiments designing and interpreting.

402
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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.

403
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And sometimes I get to visit with my daughter and granddaughter who live next door. And that's it.

404
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Speaker 1: I understood that you need sleep?

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Speaker 2: Yes.

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Speaker 1: But that you dream your experiments or you dream your experience and can you elaborate on that?

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Speaker 2: Well I'm narcoleptic, I have some kind of genetic problem that makes me fall asleep all the time.

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And, during the day, even though I get a totally normal night's sleep, it's dark, it's quiet,

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I fall asleep quickly at night. And I don't wake up in the middle of the night.

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But nevertheless, during the day I fall asleep. And what happens is I superimpose the dream state on the reality.

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And I can't always tell the difference, and I'll talk in my sleep. But sometimes it's very helpful.

412
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Usually it's a nuisance, but sometimes it helps me solve problems,

413
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and makes me look at things differently But you've seen it already? I've seen alternative ways of looking at it.

414
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The dream state is very unusual and creative, and it allows you to get out of a rut,

415
00:40:07,71 --> 00:40:11,49
what thinking about things the same way you've thought about them before.

416
00:40:11,84 --> 00:40:15,5
Almost always look at them differently in dreams.

417
00:40:15,5 --> 00:40:17,72
Speaker 1: Do you write them then afterwards? Are you writing them [CROSSTALK]

418
00:40:17,72 --> 00:40:26,36
Speaker 2: No, no, no, it's just sometimes if I have a really difficult problem, I'll just shut down.

419
00:40:26,62 --> 00:40:34,29
And then when I wake up, I have the answer. I don't have to write it down. I now know the answer.

420
00:40:34,84 --> 00:40:40,92
In other cases, something strange will happen, I might write the few notes, but I'll just forget about it.

421
00:40:41,03 --> 00:40:45,56
And then, a month later, I'll realize, yeah, that was actually something that was useful.

422
00:40:45,56 --> 00:40:55,17
Speaker 1: Good, and when you look in the scientific field, what do you expect how your work

423
00:40:55,17 --> 00:40:57,17
or field will develop itself,

424
00:40:57,17 --> 00:40:59,17
Speaker 1: Or your scientific world?

425
00:40:59,17 --> 00:41:04,04
Speaker 2: Yeah, our scientific world, I mean, it doesn't really develop itself.

426
00:41:04,33 --> 00:41:16,5
It needs funding, it needs educated population to support it, and to add to join as the next generation.

427
00:41:17,09 --> 00:41:19,56
So, it's very far from self-renewing.

428
00:41:24,13 --> 00:41:29,58
But there is a component of it where we might inspire some of the other things that we need.

429
00:41:29,74 --> 00:41:34,16
We might inspire people to fund this and we might inspire youth to join.

430
00:41:36,57 --> 00:41:44,47
But a lot of it is a very unusual set of motivations and skills that not everybody has,

431
00:41:44,68 --> 00:41:50,5
not everybody reacts to a statement as I'm gonna look that up.

432
00:41:51,04 --> 00:41:57,93
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.

433
00:41:58,7 --> 00:42:05,45
I'm gonna research it. Prove or disprove it, yeah. But that's almost, that's the natural response that we have.

434
00:42:06,1 --> 00:42:13,13
And even if you look it up and you see evidence for it, online or in the literature, you say no,

435
00:42:13,33 --> 00:42:14,99
I still need to check it.

436
00:42:15,11 --> 00:42:19,3
I need to do a controlled double blind study to make sure that it's really,

437
00:42:19,78 --> 00:42:26,3
there wasn't any research are bias that sort of thing. So science is a very unusual breed in that sense.

438
00:42:26,3 --> 00:42:36,37
It really, some of them they don't need reminders that this is how they, this is really deep in their body

439
00:42:36,37 --> 00:42:47,11
and their soul. It's how they think about the world with deep curiosity, playfulness, but this rigor of inquiry.

440
00:42:47,11 --> 00:42:55,42
Speaker 1: Were you surprised that the techniques in a way are easy as you said? [INAUDIBLE] Research and understanding-

441
00:42:55,42 --> 00:42:56,41
Speaker 2: Right.

442
00:42:56,41 --> 00:42:59,4
Speaker 1: That it wasn't broadly picked up then.

443
00:43:00,06 --> 00:43:08,11
That everybody was using it because in a way it was successful for everyone to use, other scientists,

444
00:43:08,11 --> 00:43:09,72
were you surprised by that?

445
00:43:09,72 --> 00:43:16,59
Speaker 2: Well, most of the technologies are not useable until a technologist makes them useable.

446
00:43:17,62 --> 00:43:19,13
They may be derived from nature.

447
00:43:19,4 --> 00:43:25,34
I mean in fact they may be very sophisticated machines so, for example, DNA polymerase, CRISPR.

448
00:43:25,97 --> 00:43:32,06
These are all very, very complicated machines. It would be very hard to make from scratch.

449
00:43:32,31 --> 00:43:39,12
From first principles on a drawing board and then manufacturing it. Once you see them you can make variations on them.

450
00:43:39,18 --> 00:43:42,78
But making the first one without a hint would be very hard.

451
00:43:45,29 --> 00:43:50,22
But then the technologist is needed to change that from a natural form into something that's useful.

452
00:43:51,06 --> 00:43:54,96
And then to improve it and improve it until finally, it's usable by non-technologists.

453
00:43:57,18 --> 00:44:02,58
And the usual reason they don't pick it up is because the technologist either hasn't really made it work.

454
00:44:02,79 --> 00:44:07,63
I mean that sort of kind of works, works fall enough to polish but not enough for you to or someone else to use.

455
00:44:08,31 --> 00:44:12,96
Or it works but it's not very well documented, not very user friendly.

456
00:44:15,14 --> 00:44:19,15
So it's kind of a like you got to have a computer that works but it doesn't have any graphics,

457
00:44:19,15 --> 00:44:26,93
it doesn't have any real way that on ordinary person could interface with it.

458
00:44:27,96 --> 00:44:30,98
So it's not totally surprising when people don't pick up a technology.

459
00:44:31,3 --> 00:44:35,2
What's more surprising is when you don't even have to give it a nudge.

460
00:44:35,68 --> 00:44:41,05
It's like CRISPR, you just basically publish a paper and put some plasmids in Addgene

461
00:44:41,76 --> 00:44:44,81
and suddenly everybody gets it to work.

462
00:44:46,42 --> 00:44:53,00
That's the more unusual situation, out of maybe a couple of dozen of technologies I've developed,

463
00:44:53,00 --> 00:44:56,68
maybe five of them are that easy for people to adopt.

464
00:44:56,68 --> 00:45:00,47
Speaker 1: Why it come that CRISPR is that easy to be adopted?

465
00:45:00,47 --> 00:45:09,91
Speaker 2: Well, some things require a new instrument, and new instruments require software,

466
00:45:10,26 --> 00:45:15,27
and so you've got all the engineering, conventional, mechanical, electrical, and software engineering,

467
00:45:15,56 --> 00:45:21,89
that you need to get that. So that takes about five years from the concept to something that people can use.

468
00:45:23,1 --> 00:45:27,02
When you have something that's basically what you found in the wild,

469
00:45:28,26 --> 00:45:33,73
then things that you find in nature tend to be highly evolved. It's as if an engineer made them.

470
00:45:34,1 --> 00:45:41,03
But whether they were evolved or however they got that way, they're got a good user interface sometimes.

471
00:45:41,44 --> 00:45:43,03
They do what you expect them to do.

472
00:45:43,03 --> 00:45:52,57
Speaker 1: And so why was CRISPR then, so it was also the general public picked it up?

473
00:45:52,57 --> 00:45:57,89
Speaker 2: Yeah, the general public, I mean, we know scientists picked it up because it's easy to program.

474
00:45:58,13 --> 00:46:04,34
The GSATs and Cs I think the general public they're a little strange.

475
00:46:04,55 --> 00:46:13,04
It's like the name is very cute name which wasn't nobody really intentionally made it a cute name recently anyway.

476
00:46:14,35 --> 00:46:24,21
Part of it is because there was some odd patent issues having to do with it that got some people's attention.

477
00:46:26,12 --> 00:46:30,49
I think part of it is just there was like it's like there was a,

478
00:46:30,49 --> 00:46:40,00
Speaker 2: A pent-up, it's kind of an overdue slot machine. Or it's a tsunami that's coming off the shore.

479
00:46:40,28 --> 00:46:48,12
And just before it is a whole bunch of technologies, that just before they hit shore, you blame it on one of them,

480
00:46:48,26 --> 00:46:49,8
but it's really the whole collection.

481
00:46:49,8 --> 00:46:54,35
And so I think it's a combination of those things, the name, the patents,

482
00:46:57,02 --> 00:47:00,88
and a lot of other things that have been building up for decades.

483
00:47:00,88 --> 00:47:12,15
Speaker 1: And CRISPR will revolutionize, or is revolutionizing the way we can work with the DNA?

484
00:47:12,15 --> 00:47:19,63
Speaker 2: Well, what I think, yeah I think its ability to read and write DNA and some of it's editing

485
00:47:19,64 --> 00:47:21,88
and some of it's rewriting DNA from scratch.

486
00:47:21,88 --> 00:47:24,32
There is a whole collection of technologies,

487
00:47:24,32 --> 00:47:33,21
there is suddenly many factors of ten maybe a million times easier to use more accurate and less expensive.

488
00:47:34,15 --> 00:47:40,6
And CRISPR gets most of the credit but there's this whole other thing sometimes called next generation sequencing.

489
00:47:41,31 --> 00:47:43,8
There are ways of synthesizing DNA on chips,

490
00:47:44,31 --> 00:47:49,4
these things if you didn't have all these things CRISPR would be much less interested.

491
00:47:49,4 --> 00:47:50,4
Speaker 1: Yeah now

492
00:47:50,4 --> 00:47:55,73
when all these developments all coming together I still don't completely understand what it means now.

493
00:47:55,73 --> 00:47:56,73
Speaker 2: Yeah.

494
00:47:56,73 --> 00:48:04,17
Speaker 1: Cuz it's such a revolution that I can't.

495
00:48:04,17 --> 00:48:10,77
Can you share what it means that this is happening now, and what it will mean for me and my family, and my daughter?

496
00:48:10,77 --> 00:48:13,17
Speaker 2: Well, nobody really knows what it means.

497
00:48:13,37 --> 00:48:22,26
In the same sense that if you asked even the greatest visionary in computer science in the 1950s what the computer

498
00:48:22,27 --> 00:48:27,55
revolution meant, he or she would probably not guess right.

499
00:48:27,87 --> 00:48:36,42
They probably would not guess Facebook, or maybe not even Google or search engines, or Google Maps.

500
00:48:37,72 --> 00:48:45,86
They might have said, it will be used for calculating logarithms for rockets, so you can do warfare better.

501
00:48:46,05 --> 00:48:55,34
Or you can do accounting better, so that you don't have to have human calculators. So I think the same thing.

502
00:48:55,34 --> 00:49:04,83
Well, for what society will do with its enhanced ability to read and write DNA is we will modify ourselves

503
00:49:04,83 --> 00:49:12,54
and our environment and the way we obtain food and [COUGH] all the materials that we use,

504
00:49:12,73 --> 00:49:14,75
including very smart materials like computers.

505
00:49:15,27 --> 00:49:21,93
All these things will be altered beyond recognition in a fairly short period of time.

506
00:49:21,93 --> 00:49:26,99
Speaker 1: We'll all live that time or is it?

507
00:49:26,99 --> 00:49:37,59
Speaker 2: Well, I was alive in the 1950s, so yeah, we might be in the equivalent time.

508
00:49:37,7 --> 00:49:43,02
But everything's moving faster now and one of the things that's moving faster is our ability to reverse aging.

509
00:49:43,45 --> 00:49:49,15
So if we can reverse aging, then yes, you will definitely be around to see all sorts of things,

510
00:49:49,35 --> 00:49:55,48
because there's no law of physics that we know of that requires vision.

511
00:49:56,84 --> 00:50:05,4
We know that there's a continuity of life that goes back 3 billion years, so there's no particular reason why,

512
00:50:05,4 --> 00:50:14,94
Speaker 2: Humans or animals in general have to senesce and get old and break,

513
00:50:15,83 --> 00:50:21,45
because some of the cells in the body keep on living in the next generation.

514
00:50:21,45 --> 00:50:25,4
Speaker 1: That's also where your lab is, also active [INAUDIBLE]

515
00:50:25,62 --> 00:50:33,59
Speaker 2: Yes, right, we have very active projects, plural, on aging reversal.

516
00:50:34,22 --> 00:50:41,14
Not so much on longevity, where you don't wanna prolong the end of life, which is unpleasant and expensive.

517
00:50:41,84 --> 00:50:48,1
And where you become a less productive member of society, less engaged.

518
00:50:48,78 --> 00:50:54,3
What you wanna do is reverse it back to a time where you were at your optimum performance,

519
00:50:55,2 --> 00:50:58,84
a young person like 65 years old. [LAUGH]

520
00:50:58,84 --> 00:51:01,5
Speaker 1: And do you think that's possible?

521
00:51:01,5 --> 00:51:07,39
Speaker 2: Well, it's not only possible, it's been done in animals.

522
00:51:08,23 --> 00:51:11,99
Now those animals may or may not be good models for human.

523
00:51:12,18 --> 00:51:19,6
But certainly the time is ripe for testing things that either cause longevity in animals or aging reversal in animals.

524
00:51:20,24 --> 00:51:25,74
And then test to see if they can cause aging reversal in larger animals and humans.

525
00:51:25,74 --> 00:51:27,88
Speaker 1: How can you do the aging-

526
00:51:27,88 --> 00:51:29,14
Speaker 2: Well,

527
00:51:29,48 --> 00:51:36,57
there are many things that have been shown to increase animal lifespan by a factor of two to a factor of ten.

528
00:51:37,35 --> 00:51:44,13
There are things that involve, I mean, not to get too technical, but mitochondria, the tips of chromosomes,

529
00:51:44,13 --> 00:51:53,26
the telomeres, the growth factors and muscle related proteins, like myostatin pathway.

530
00:51:53,9 --> 00:51:56,00
So there's all these pathways that are pretty well understood.

531
00:51:56,51 --> 00:52:02,65
And if you harness a little of each for gene therapy, then you could try them separately and in combinations.

532
00:52:02,65 --> 00:52:07,5
Gene therapy is particularly easy to go from an idea to a test of it.

533
00:52:08,04 --> 00:52:16,46
You don't have to take a side route where you randomly screen through millions of pharmaceutical compounds.

534
00:52:16,77 --> 00:52:23,39
And we talk about reverse aging, how does that affect the fact that you are able to, how far are we in that?

535
00:52:23,39 --> 00:52:25,16
Speaker 1: You have gene therapy for that?

536
00:52:25,16 --> 00:52:31,45
Speaker 2: Well, we have lots of demonstrations in animals, both in extreme extensional longevity,

537
00:52:31,99 --> 00:52:36,15
and reversal in some cases. Many different ways of doing that.

538
00:52:36,6 --> 00:52:42,3
And so we're collecting all those that are known for small animals and we're applying them to large animals

539
00:52:42,3 --> 00:52:50,67
and to humans. Coming off the gene therapy trials is much easier, but we're still just beginning on that.

540
00:52:51,31 --> 00:52:54,86
It's looking very promising, but it's too early to say.

541
00:52:55,52 --> 00:52:59,04
And something that might even work for large animals may still not work for humans.

542
00:52:59,04 --> 00:53:08,74
Speaker 1: Yeah, what is in the line of work you're now which really thing, or in research project,

543
00:53:08,74 --> 00:53:17,49
or your project where you're working where you really feel like I hope this will develop as soon as possible?

544
00:53:17,49 --> 00:53:30,31
Speaker 2: Well, I mean, top priority, I guess, would be transplantation of organs, malaria for developing countries,

545
00:53:30,31 --> 00:53:38,32
and aging reversal for industrialized nations, and preventative medicine in general is the strategy.

546
00:53:39,6 --> 00:53:47,78
And then right behind all of those, once those are all working and we improve our basic human condition,

547
00:53:49,39 --> 00:53:51,34
then space genetics.

548
00:53:51,34 --> 00:53:53,00
Speaker 1: One second. [INAUDIBLE]

549
00:53:53,00 --> 00:54:04,52
Speaker 2: Sure, yeah.

550
00:54:04,52 --> 00:54:10,04
Speaker 1: So when you looked at the projects, what were you-

551
00:54:10,04 --> 00:54:13,98
Speaker 2: So the projects that I find most compelling and exciting, in terms of applications,

552
00:54:14,44 --> 00:54:21,17
are transplantation of organs. There's a gigantic need for that.

553
00:54:21,17 --> 00:54:28,19
Speaker 2: Gene drives to eliminate malaria, and then for developing nations.

554
00:54:28,45 --> 00:54:34,59
And then aging reversal for industrialized nations where most of the morbidity

555
00:54:34,6 --> 00:54:38,8
and mortality is due to diseases of aging.

556
00:54:38,8 --> 00:54:44,34
You want to get at the core of that, and then once you have all those things which are drains on our economy,

557
00:54:44,62 --> 00:54:47,25
if you can solve all those, then you can reduce.

558
00:54:47,38 --> 00:54:53,79
Then you have more money available for things like space where we really need to get off the planet to avoid super

559
00:54:53,8 --> 00:54:58,39
volcanoes and asteroids. And that has a genetic component as well.

560
00:54:58,39 --> 00:54:58,51
Speaker 1: Okay, in what way? What's the genetic component?

561
00:54:58,51 --> 00:55:11,24
Speaker 2: Well, we have radiation sensitivity, and our bones rot at low gravity.

562
00:55:11,99 --> 00:55:22,61
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.

563
00:55:23,07 --> 00:55:27,15
And so our body was designed for normal gravity.

564
00:55:27,58 --> 00:55:31,18
And as soon as you don't have normal gravity, you have muscle

565
00:55:31,19 --> 00:55:38,5
and bone wasting because the body thinks it's doing a physiological feedback loop to keep everything right.

566
00:55:39,02 --> 00:55:49,44
But you need to have muscles and bones even in low gravity because when you touch something with weak bones,

567
00:55:49,67 --> 00:55:54,56
you'll crush your bones and And you need muscles to move things around.

568
00:55:54,72 --> 00:56:01,18
So, anyway, those are some of the things that are problematic.

569
00:56:01,4 --> 00:56:06,56
And also, there's questions like what do we bring with us? Do we bring all the species of the Earth?

570
00:56:07,32 --> 00:56:16,44
Or do we leave out the giant sequoia, and the bowhead whale, and smallpox. Do we [COUGH].

571
00:56:13,76 --> 00:56:16,17
Speaker 1: We can create that again on Mars [INAUDIBLE]

572
00:56:16,44 --> 00:56:26,05
Speaker 2: We could, yeah, but we haven't done that yet. We have not really recreated.

573
00:56:27,46 --> 00:56:29,62
And so it's a big decision, is whether you take it with you.

574
00:56:29,69 --> 00:56:33,86
In fact, some of them, it could be that their ecosystem is fragile enough,

575
00:56:34,08 --> 00:56:36,7
that you can't really make it with our current knowledge.

576
00:56:37,11 --> 00:56:43,14
So having the complete DNA sequence of everything in the planet may not be enough to recreate some of the more complex

577
00:56:43,15 --> 00:56:43,95
ecosystems.

578
00:56:43,95 --> 00:56:46,86
Speaker 1: Yeah, but when you create it [INAUDIBLE]

579
00:56:46,86 --> 00:56:52,91
Speaker 2: Yes, that's correct. Yeah, yes, we're big on double two sides on,

580
00:56:52,91 --> 00:56:53,58
Speaker 1: [INAUDIBLE]

581
00:56:53,58 --> 00:56:55,58
Speaker 2: Yeah, the story?

582
00:56:55,58 --> 00:56:59,85
Speaker 1: Yeah what's the story [CROSSTALK]

583
00:56:59,85 --> 00:57:08,55
Speaker 2: So a nine year old girl sent us two copies of that poster and we put it on the wall.

584
00:57:10,02 --> 00:57:14,94
But it's based on our, she had read about our project in the news.

585
00:57:15,56 --> 00:57:16,66
It's small project

586
00:57:16,66 --> 00:57:23,47
and it mainly benefits from the technology that we've developed for other projects like human medical research.

587
00:57:24,13 --> 00:57:29,64
But these things, we bring the price down a million-fold, and then, you can use it for reading

588
00:57:29,65 --> 00:57:31,63
and writing DNA from ancient samples.

589
00:57:32,78 --> 00:57:39,47
And [INAUDIBLE] mammoth is that the Asian elephant is the closest relative to the mammoth.

590
00:57:39,69 --> 00:57:43,87
And it's so close in fact they're both closer to each other than they are to the African elephant.

591
00:57:44,27 --> 00:57:48,56
And the Asian elephant can breed and make offspring children with African elephants.

592
00:57:48,72 --> 00:57:53,9
So probably, the Asian elephant and the mammoth are basically very close to being interfertile.

593
00:57:55,2 --> 00:58:03,43
And so, one way of focusing on modern day species is to extend the range of the Asian Elephant.

594
00:58:03,73 --> 00:58:04,89
It will already play in the snow.

595
00:58:05,05 --> 00:58:13,58
But you could extend it all the way out to -40 degrees in the tundra of Canada, Russia, and Alaska.

596
00:58:14,22 --> 00:58:16,35
And furthermore, so you get a benefit to the elephant.

597
00:58:16,87 --> 00:58:21,28
But you also get a benefit to the tundra, because the tundra is melting.

598
00:58:21,75 --> 00:58:23,14
And there's experiments

599
00:58:23,14 --> 00:58:33,51
and field studies that indicate that a mammoth-like creature could keep the temperature colder by up to 20 degrees in

600
00:58:33,52 --> 00:58:34,38
temperature.

601
00:58:34,38 --> 00:58:35,05
Speaker 1: [INAUDIBLE]

602
00:58:35,05 --> 00:58:45,83
Speaker 2: So the experiments for the idea followed by experiments is that trees absorb about twice as much light

603
00:58:45,84 --> 00:58:57,02
and so that's a warming effect and the grasses have roots that protect from erosion and then punching down the snow.

604
00:58:57,35 --> 00:59:00,32
The big fluffy insulating layer of snow in the winter time,

605
00:59:00,49 --> 00:59:05,31
if you punch that down you can get penetration of the cold winter air.

606
00:59:06,21 --> 00:59:11,24
And these three things put the mammoths or sorry the elephants or mammoths will knock down trees

607
00:59:11,25 --> 00:59:16,25
and replace them with grass A, much richer ecosystem full of some small animals.

608
00:59:17,71 --> 00:59:25,04
Anyway, we did the experiment replacing mammoths with a combination of caribou, which is one of the biggest mammals,

609
00:59:26,02 --> 00:59:32,82
and tanks, Soviet tanks, that would knock down the trees cuz carabao can't knock down trees but elephants, [INAUDIBLE].

610
00:59:32,82 --> 00:59:40,28
Anyway, it was about 15 to 20 degrees, it's the difference between the experimental and the control site.

611
00:59:40,28 --> 00:59:43,58
Speaker 1: Well, there's a variety of projects we are talking about here.

612
00:59:43,58 --> 00:59:46,41
Speaker 2: Yes, right. Yes, yeah.

613
00:59:46,41 --> 00:59:46,43
Speaker 1: Or working.

614
00:59:46,43 --> 00:59:48,43
Speaker 2: Well, we haven't scratched the surface yet.

615
00:59:48,43 --> 00:59:49,43
Speaker 1: Can you-

616
00:59:49,43 --> 00:59:50,77
Speaker 2: Keep going?

617
00:59:50,77 --> 00:59:51,43
Speaker 1: [INAUDIBLE]

618
00:59:51,43 --> 01:00:00,83
Are there any particular things that you would like to share with the- I think we've covered a good sampling of it.

619
01:00:00,83 --> 01:00:09,28
Speaker 2: We covered the personal genome project, data incorporation in the DNA-

620
01:00:09,28 --> 01:00:11,27
Speaker 1: The future.

621
01:00:11,27 --> 01:00:13,31
Speaker 2: The future. Yeah, I think we covered it.