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I remember standing in my kitchen cooking dinner for my son, and I just I suddenly just burst out laughing. You know it's just this. Suddenly this joyful thought of Is there a crazy that nature has come up with this incredible little machine? History of science is full of accidental discoveries, penicillin, perhaps most famously, but also gunpowder and nuclear fission. It makes them. Doesn't it because you don't know what you don't know you don't always what you're looking for her at. Sometimes you just gotta curious mine, so the research project that lead to Technology was really. You know. It was a curiosity driven project. Jennifer Downer is a professor of chemistry and biology at the University of California Berkeley And I've had a long time interest in understanding,
fundamental biology in particular aspects of a genetic control or in the way that evolution has come up with creative ways to regulate the. Suppression of information in cells. When you first heard literally heard the phrase, crisper just described that moment what your understanding of it was and what you kind of initially envisioned it facilitating. Well, when I first heard the acronym crisper, this was from a conversation with Jill Danfield. I had no idea tat was this was in two thousand six Danfield also Berkeley. Scientists have been studying bacteria that grow toxic environment, and so she was looking at bugs that grow in old mine shafts. And you know these pools of water that build up I'm in old mines that are often very acidic where they have various kinds of metallic contaminants to figure out what bugs are growing. There
How are they surviving? The key to their survival was called crisper clustered regularly. Interspaces short Palin, dramatic repeats say that five times Ass Danfield thought the bacteria had developed a sort of pattern based immune system to protect themselves. But exactly how it worked was a puzzle, help solve it. She recruited down and we ended up spending several afternoons where Jill was showing me her dna sequencing data from bacteria and in explaining what these sequences were. What began as a casual conversation about an obscure subject, grew to consumed out now, four years. Finally, she had a breakthrough as only
burst out laughing today on for economics, radio, the mine blowing discovery, that's already changing medicine and more a remarkable, Jean editing tool called crisper. That's right, I said Jean editing the implications of that boundless change. As I'm telling you, the story, I feel, is chill in my body and You think the genetic revolution is still years away. You should think again the technology for that is here now I'm happy from W and Y see studios. This is freakin comics radio, the explores the hidden side of everything. Here's your host, Stephen Gardner.
regulations on your future Nobel Prize Jennifer, Dowd hasn't won the Nobel Prize yet, but it's hard to imagine she won't we'll go back to when she started working with Jill Enfield doubt no learned that crisper were dna sequences stored in the cells of bacteria. You can think about it like a genetic vaccination card, its away that sells store information in the form of dna, from viruses to use in the future to protect cells. If that virus should show up again in the cell. But how does it work and what might mean if scientists could figure it out in two thousand and eleven having already stuff Crisper for a few years, Donna attended Microbiology Conference in Puerto Rico there. She- Emmanuelle shore plantier, then a researcher who MEL University in Sweden Carpentier was researching a mystery protein that she felt was the key.
Crisper. She endowed now began a long running collaboration. We were working together or to understand the molecular basis what are the molecules that allow bacteria to find and destroy? Earl DNA. That was the question that we set out to address and in the course of that research and in the course of that research, we figured out that a particular protein It has a name CAS. Nine is programmable by the cell, a protein that can be programmed to fight viruses. You can start to see where this is going there using thing that this casts nine protein does. Is it works like a pair of scissors, it literally grabs onto the dna and cuts it at that place at that precise place, bethought if nature could programme, this casts nine protein to precisely edit dna. Why couldn't make it turns out that when this is transplanted into animal or plant cells or human cells, it's possible.
To introduce changes to the dna very precisely and that's how the technology fundamentally works. Then came the night at home, cooking dinner for son when she burst out and joyful laughter at the sheer wonder and the massive Civilities is crazy. That nature has come up with this incredible little machine. So so there was that for moment and then- and I think that sort of morphed into a growing recognition that you know this technology was going to be very impact, fall in many different areas of science, Donna, together with your panties and several other colleagues, rode up their research and on June eighth, two thousand twelve formally submitted it to the journal science, whose public Twenty days later. Suddenly the world knew that the crisper cast nine system could be harnessed as a new, Jean editing tool, a new kind of genetic and
Nearing is revolutionizing scientific research. Scientists think crisper could launch a new era in biology and medicine. Crisper could help rid us of diseases like cystic fibrosis, muscular dystrophy and even HIV and cancer. Jennifer Dowd Anna had spent her career, largely cloistered in laboratories. She didn't have a high profile background. I grew up in a small town in Hawaii. Suddenly she was a scientific superhero. We explore those questions with Jennifer down that enough, a doubt not Jennifer, doubt no Jennifer dogma. For harnessing in ancient bacterial immune system. As a powerful, Jean editing technology read through prize was awarded to manual shall Plantier and Jennifer doubt no doubt and spent the past few years, reaching forward well trying to slow things down she wrestles with all this. In a book she CO wrote with another crisper researcher, Samuel Sternberg, it's called occur
in creation. Why the table it refers to what well at its core is the crisp virgin editing technology is, is now giving human beings the opportunity to change the course of evolution and Human beings have been affecting evolution for a long time right, but I think, now. There's a technology that allows a very specific changes to be made to dna. That gives us a new level of of control, and so you know it serve opening a crack and I sort of sea it is like analogous to opening a door the future. That is really you know, a change in the way that we think about our world as opposed to like a crack. In the dimension that we will fall through end all disappear, and not that kind of crack. We
the former, not the latter. So as you right in the book, we uncovered the workings of an increase, Or molecular machine that could slice apart viral dna with exquisite precision, so when you call it an incredible molecular machine. Your breakthrough of you and your colleagues is essentially an external human guided replica of what already exists, or are you kind of taking over the controls of what inherently exists? This is important were really taking over the controls of what already exists, and we're doing it by using this bacterial system, the cast nine protein to I end and make a cut in DNA in, let's say, human cells at a particular place, where the cells now repair machinery can then take over and do the actual editing. Wits amazing to me is the now
true repair. Machinery obviously exists, and maybe it works really well a lot of the time it just in the most drastic circumstances, like a cancer or a debilitating diseases I mean the healing mechanism from reading what you ve written is sounds as oats white stochastic. It's random unpredictable, something the catches something's it doesn't. Sometimes it works, sometimes it doesnt. So can you talk about the big picture of this repair? mechanism in and how well or poorly it does sure so. Dna repair happens all the time and cells and, as you alluded to it, has to work right most of the time, or we would probably not be here or we would all have a lot more cancer than we have in so we know that that sells, experienced double strand breaks to their dna were routinely and that they have ways of fixing those breaks, and so I would say that what this crisper technology does. Is it really taps into that natural?
or pathway. Since the announcement of the crisper cast nine technology, scientists around the world have been exploring its possibilities in many different arenas. Let's start with plants. I think it's important for people to appreciate that you know for certain that humans have been modified plants furled on time, genetically and good. Literally thousands of years exactly thank goodness rating and you realize, while I'm glad there's I'm glad, there's plant reading, but the other way that's been done traditionally is to use chemicals. Or even radiation to introduce a genetic changes into seeds, and then plant readers will select furs for plants that have traits that they want and, of course, You can imagine when you do something like that. You drag along a lot of traits that you probably don't want, and you know chain to the dna that you you don't even control for it right, so you don't even know where they are or what they might be doing, and so I think the opportunity here
Jeanne, editing and plants is to be able to make changes precisely so not to drag along traits that you don't want, but to be make changes that will be beneficial to plant sir, but to do that very precisely in Then we have the opportunity to do things like you know, give plants the ability to grow with much less water or to defend themselves against various kinds of infections and pests removing in due to climate change. I think, from the perspective of the world food supply, that's going to be extremely important going forward and will potentially allow us to have access to plants that are going to be much better, adapt for particular environments and to grow. We hope, without chemical interventions of different types, no good and how nervous some portion of the population is about the phrase genetically Mount, I'd organisms, even though, as you pointed out almost
The organism on earth has been genetically modified, for you know hundreds, if not thousands of years, this feels like a next level step that will raise all kinds of questions even in the plant world forget about humans or animals, yet of you know, governance and autonomy and so on. What are you what's on that in the in the plant flesh agricultural world. I think that you know it's really gonna come down to people having just two to information about. Where is our food coming from, so that people in different countries, evaluate these plants in the technologies used to create them and make their own decisions about what they want to do and having a precision tool that allows us to generate plants that are better, let's say adapted to partition, environments are middle, maybe have even better nutritional value and I I really believe that going forward that we can't afford to reject this. We really have to understand it.
Regulated appropriately, but we do have to. I think we have to have this tool in our toolbox. Crisper Jean editing is also being put to use on animals. Scientists ensure engaged in controversial research, genetically modified beagles to be more musket ease. Miskities have been genetically modified to plead with and eliminate the species in an urgent attempt to wipe out carriers of dengue fever researches believe that they can recreate up. Will we mammoth by combined, dna with that of a modern elephant, theirs just one and made more than one company now that are using the Gina, in technology and animals like pigs to create pigs. Would be better organ donors for humans. I, like the micro pig to chinese genomics, institute BT. I began breeding micro pigs to study diseases, but now Oh they're gonna sell them as patents for sixteen hundred dollars and give in to the micro pay graze. Miley Cyrus
this has one? Yes, Patsy right, the idea of you no sort of offence for use in a way of gene, editing, innovate, making our animals that we think are cute. The animal, with the largest implications, of course, is the human coming up on Reaganomics radio. How long until essential employers or mates are scouring our genetic profiles to see. If we're worthy, I mean if you knew that you're potential made was high likelihood. Of developing early dementia, you might think twice. Before getting married and what keeps Jennifer down and I realized with this horror I realise that it was Adolf Hitler.
The gene editing revolution prompted by the work of scientists like Jennifer Downer, isn't the We Jean related revolution. These days they dont, let Stephen Dublin has going high Sierra hurry, there's also Social genomics with Social, Germans. Revolutions really just getting started, I would say: don't calmly, teaches geology and population studies at Princeton and I'm the co author of the genome. Baxter. You may remember calmly, from an old for economics. Radio episode called how much does your name matter. He has two kids, a daughter, I d, like the letter into son, I'm yo like the slaying, but those are just their first names, full names. Hard buried, Nora Jeremy Genco calmly, oh shit, Haynau, Augustus, Eisner, Alexander, wiser, knuckles, german Genco, Connollys or YO. Ok, where's, your first name, YO comes
where I think, you're Carson the Y chromosome, so dont calmly, the sociologist dad he's always had a crafty way of thinking about genetic, identity, so Dalton subtitled. Your book is what the Social genomics revolution reveals about ourselves. Our history in the future. Just begin by telling you What do you mean by the Social genomics revolution? What's revolutionary about it and describe kind of the arc of revolution and where we are in that ok, well, social, Germans, revolutions really just getting started. I would say: win Bill Clinton stood up in the EU the two thousand and announced at the book of life, had been decoded. We're here to celebrate the complete the first survey of the entire human genome without a doubt, this is the most important most wondrous map ever produced by human. Everyone thought everything was a shame. Suddenly we're gonna have personalized medicine. We were gonna, I don't know what
revolutionise the diagnosis, prevention and treatment of most, if not all human diseases, but actually not much happened for the first decade or so. The great scientific hope was defined, single, easily identifiable genes that controlled cancer or depression or intelligence or even just height, so that turned out be an exception, rather than the rule. Its Jason Fletcher he's an economist at the University of Wisconsin and Madison and he's colonies author on the genome factor, most of what we care about most of life's important outcomes, Are not one gene in one disease there more, like hundreds or thousands of genes, all with really tiny effects? If you can even find them having a map of the genome was one thing, but in the bill Clinton era there was a lack of good data that has changed, and now we have this, what I call The revolution is this: surfeit of cheap data, cheap genetic data just two decades ago. It costs a billion dollars to sequencing.
Genome and now you and I could spit in a cup and send it to one of the popular sequencing outfits. Four hundred dollars or four hundred fifty dollars. We can get millions of answers. The question: what is our dna? Look like anyone who sends there's saliva into twenty three and me we're just a small saliva sample you'll, learn about your ancestry through your twenty three pairs of chromosomes and make you who you are to get their ancestry. Their supposed health risks has now basically agreed to the part of their database. That will be studied in this as well over a million samples of mostly, U S, citizens and all that data is being pulled. Together in both genetic analysis and social science analysis to try to understand the vast array of outcomes were interested in that's anything from all Emerson dimension on the hillside to measures of area? national attainment and socio economic position on the social science side. So we finally have big data sets with lots of generic mark
across the entire set of chromosomes and were now actually making robustness every centre, withstanding replication and seem pretty solid, and I think that's the start of the revolution, but warning it still early days. That's It's so humans are very complicated and the amount of data we're talking about, as in the millions or tens of millions of locations on our genome? So what does this mean for attack Ology Lake crisper Jean editing, I think that's gonna, be very exciting for a limited number of single Jean diseases, diseases like cystic fibrosis and sickle cell disease and Huntington's disease, but most things we care about in today's world heart disease. Alzheimer's I Q height Body Mass index, diet, these risk and all of those things our highly Polly Jeddak. That means that there is total of many little affects all across the chromosomes and
that and probably means we're not going to be doing Jean editing and in a thousand different locations in the genome. Who is now a time soon, but with all the genomics, data that are being accumulated, scientists have been devising a system to make sense. We have a tool that emerge, call the Polly genetic score to take all the small effects eyes. Your finding across many many many genes, and you add them all up, and then you ve created a sum The scale of your predicted likelihood of doing acts were extremely smoking or getting dementia we're going to college, but those scores aren't predicting very well right now so before. Or anything drastic happened. Socially. I would think that those scores were needed. Lot better. Wednesday is really start explaining a lot of the variation in society. Then I would start worrying worrying, because why the use by external authorities in company of this information. That's definitely scary and I think the other
Dimension is going to being in the marriage market where people just take it upon them I too want to no genetic information about their potential. Mates I mean if you knew that you're potential made was hi likelihood of developing. Dementia, you might think tat this before getting married. I mean you know phenotypes or for hookups, but China type is forever so the technology for that is here now it could using infertility clinics, it could be used dating apps, where people could put their genetic profile linked from twenty three in me to Okcupid selection, of course, is something we all do every
Ain't that we choose our friends, our allies and enemy is our political leaders. Some traits are observable, others less, so some are heritable others not if the selection potential afforded by these new technologies is frightening to you keep in mind the thing that's knew about this. Is the technology? Remember the eugenics movement that was certified by a preference for a preference for people of certain european ancestry and not all european ancestry, but certain just a favoured groups: to have more children and to be given resources. The exclusion of all other people and, of course, it led pretty directly to nazi fascism and the extermination of millions of people and also was used as the pseudo science behind at least decades of racial injustice. In the
the states and many other countries. That is the nightmare that has given Jennifer Downer actual nightmare, that really was one of the defining moment for me in terms of thinking about getting involved in the ethical conversation. So I had a dream in I was king away. I think I was in my office actually and a colleague of mine and came in and said I'd like to introduce you to someone And I d like you to explain the crisper technology to him and he led me. To a room and there was a light in the room, and there was someone sitting incentive silhouette in a chair with his back to me, and he turned around, and I realized with this horror, and I can feel it right now- I'm telling you the story, I feel is chill a body that that I realise that it was Adolf Hitler and he
we're? Looking at me with very, very intent, look on his face and in eager kind of look, you know, and he wanted to know about this technology, and I felt this incredible sense of fear, both sort of personal fear, but also a profound kind existential fear that you know if someone like that were to get a hold of a powerful technology like this, how would they deploy it? course it you know when I woke up from that dream and out. You know, thinking about it subsequently, and it was really scary to think of and I thought you know this- we have to proceed responsibly here. We cannot just your eye For me myself. I can't just carry on with my next experiment. In my lab Irene, you have to get involved in in a broader discussion about this. It's just too important a subject. I hear
I don't mean to at all diminish year your argument, but I hear a lot of scientists make a similar agreement which, as we know, look what we're doing our best on our end, and we really want to have this conversation kind of in public, especially with people who have the leverage, mostly politicians. Let's say to make smart choices. My question is: does good mechanism or forum, for that kind of conversation really exist. Well, I think we're kind of building it- has we're going at some level. I've been in all in organizing a number of meetings other there right now there are fairly small in focus, but the idea is to really answer. We hope that question that you just posed is how do you do that? How do you bring people from these different walks of life together? So they can have a meaningful discussion. And I dont have the answer yet, but I do think that it has to involve formats that are accessible to people. It cannot just be a bunch of academics. You know
that may talking in the silo to each other and bright exactly it cannot be that it has to be used various ways. I think the media are going to be very important. I think people that right science fiction are gonna be important. I think that move makers are going to be important musicians and various kinds of visual artists are going to be important. You think all of those people are very skilful at communication. Communicating ideas and they can do it in some ways much more effectively than you know, a lot of technical jargon, whatever achieved so probably the most enticing, and certainly the most controversial aspect of crisper- is the power to reach human beings, whether an individual with an illness or a generation of a family or maybe an entire population. So obviously it's a gigantic area, then something that Probably nobody doesn't bring a lot of strong prior to the table. With already. But can you just talk about
this issue and you're thinking about the issue, in kind of where you landed, I've seen evolution and my own thinking quite frankly- and I think that I sort of have gone from feeling very uncomfortable with you no sort of the thy of making changes to human embryos, especially for anything that would be considered. You know not medically essential to to thinking that in oh, there may come a time, I dont think we're there now and it's. I don't think it's right around the corner, but I ain't there. A come a time when that sort of application is embraced and is going to be deployed, and- and I think that for me the important thing is not to reduce it's actually to understand it and and really think through the implications. Not let me ask you just to take a step back and talk about actual therapeutic. I guess treatment
and the difference between germ line and semantic editing. Ah, yes, this is very important to understand the difference. So most of the applications that we ve been talking about, especially in medicine. Right now involve what we call somatic cell editing, and that means making changes. To the dna in cells of a particular tissue in a person that's already fully developed, but those changes do not become heritable. They can't be passed on to the next generation, but the contrast. That is changes to the germ line and that means making changes to the dna of embryos or eggs or sperm changes inherited by future generations and become effectively permanent in the human genome, and so I think, there's a profound difference between those two use because if you are doing something that affects one person, you know it has to be regulated. Course. You have to make sure that its safe and effective, but it affects just that one person, whereas
if you make a change that affects somebody's all of their children and all of their children's children, etc. That is really profound and it really does affect ultimately, human evolution and pray. Emily. Let's say I cared enough about some strain of Herod ability enough to do. It would say on a fair, the wide scale then, Similarly, it would increase my incentive to maybe diminish the supply of non germline treated people re, so you you could imagine in Attica, territory are well, I mean it doesn't take long, even fair minded, as you know, a kind of flabby his mind to get together their pretty quickly right, I mean the patent so for this reminds me a bit of the potential for GEO Engineering. You know intentionally altering the planet's atmosphere to change a temperature in case global warming gets really Struck them so one of the key questions there is, you know, governance who gets to control the thermostat, and I know you ve been very outspoken in that you really flung yourself
to the ethical and practical elements of this technology, but I'm various where you stand on the kind of biggest MRS scariest cause. I hate windward knee jerk scared of new technologies at her premier face a wonderful. But I do wonder you're thinking on that. Well, I think it's very important to you kind of alluded to this, but I think it's very important to emphasise that You know this technology, I think is going to overall, is going to have a very positive benefit to human beings in many ways: I'd really like to make sure that people get that message, because I think it's either, he, too, you know, try to make things sound exciting by making a sound, really scary shunned, and I think this is a technology that-
Billy were already seeing incredibly exciting advances. You know, opportunities to cure genetic diseases that have had no treatments in the past to advance the pace of clinical and other types of research, and they make it possible understand the genetic basis for disease and then be able to do something about now when you have that information, so I think what needs to happen is that scientists now into really engage with government regulators and, frankly, also with religious leaders and the kinds of thought leaders to make sure, first and foremost, that there is a very clear understanding of the science behind this as much as possible. Let's pretend that this technology within a couple generations works so beautifully that it extends lifespan by twenty percent or fifty percent or two hundred percent. Do you think about what happens in terms of obvious things like you know, global resources if people are living twice as long, but also
how we as animals would respond to that scenario in which scarcity diminishes so much of the scarcity being a short lifespan. It seems that humans are relatively slow to adapt to the the diminishment of scarcity over time like it seems we still eat, for instance in the town for a century as though the next meal may or may not appear on the horizon. Some curious. If the sudden they're, all these extra years in terms of everything, labour markets and retirement and the essential issues like what do I do now for those next eighty four hundred years that Dino Jennifer, Downer and her colleagues helped facilitate, do think about those things. Well, there's lots of interest in that task to create. Now, as you know, especially here in Silicon Valley, I think for me
it really would come down to are those extra years high quality years and are they years where people could be contributing importantly to society, and if the answer is yes, then I think that is something that is is interesting to think about. If the answer is no than I dont think, I certainly don't think that sound very appealing at all? I thought I'd rather take short and healthy than the long and miserable, but I think that the prospect of enhancing human health, if that goes hand in hand with a jetty. I certainly would like to see it be something was available to communities around the world, not just to a few people. Uncertainty as there is around the future of crisper cast nine and the genetic revolution generally, you probably won't be surprised
and there's also uncertainty about where the proceeds from these discoveries will flow. As you can imagine, they are potentially huge Jennifer doubts and his team filed patent rights early on the crisper system on virtually any living thing, but not long after a researcher funds young from the Broad Institute of MIT and Harvard filed crisper patents on an important subset of living things. The conflict went to the federal patent trial and appeal board, which ruled and junk favour. The final outcome is far from settled. Coming up on economics, radio, I would ask you to name a very famous early down to earth midwestern billionaire, it's easy right. So would you please give a very warm welcome to the Oracle warrant, but not that famous midwestern millionaire.
My name is Charles Coke in German and CEO of Coke industries he's also one half of the Coke brothers, who are not universally beloved, brothers are trying to buy America? How does he feel about having gotten involved in the political arena look, I know would be nasty and unpleasant. I did know it would be this dishonest, Charles Coke, isn't much of a media fixture, but he sat down with free economics. Radio to talk about the past the core issues of the day. I will let anybody and who will make the country better. Why do you care personally, so much about shaping Heidi at large. We felt revolution to get rid of royalty, and we don't need royalty here so persuade me of your. I guess the level of confidence that, if you could reform- as you see fit, that it would really work well
I mean I don't know and we get to what kind of person Charles Coke really is. I have to say- and I say this with the US respect your total nerd. Aren't you know a lot of fun a guy. I was a rugby player. You give me. Charles Cook speaks that's next time on for economics, radio for economics, radio is produced by w in my C studios and W productions. This episode was produced by Gregg resolve ski or staff also Shelly Louis Christopher Worth Merit Jacob Stephanie, Tam Eliza, Lambert, Alison huh. Very Emma Morgenstern Harry Huggins and Brian Gutierrez. You can subscribe to for economics, radio on Apple podcast or sticker reverie get your progress, also Fr Economics, dot com, you can find our entire archive you can stream or download every episode we ve ever made. You can read the transcripts you can find,
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Transcript generated on 2021-01-23.