Science Friday - Fish Eye Secrets, Human Genome Project, Science Diction 'Mesmerize.' Feb 12, 2021, Part 2

Episode Date: February 12, 2021

Seeing The World Through Salmon Eyes The saying goes, “The eyes are the window to the soul.” But for fish, the eyes are the window to the stomach.  As one California biologist recently learned, the eyes of Chinook salmon are like a tiny diet journal of everything it ate. But to read that journal, you have to peel back the layers of the eye, like it’s the world’s tiniest onion.  Miranda Tilcock, assistant research specialist at the Center for Watershed Science at the University of California, Davis talks to Ira about why she goes to such gooey lengths to understand what these salmon eat.  Two Decades Beyond The First Full Map Of Human DNA In February 2001, the international group of scientists striving to sequence the human genome in its entirety hit a milestone: a draft of the complete sequence was published in the journals Nature and Science. The project took 13 years to complete: In that time, genome sequencing became faster and cheaper, and computational biology ascended as a discipline. It laid the groundwork for the greater cooperation and open data practices that have made rapid vaccine development possible during the pandemic. In the decades since, researchers have been trying to better understand how genetics impact health. We’re still working toward the dream of personalized treatments based on a person’s specific genetic risks. Ira looks back at the successes and challenges of the Human Genome Project with Shirley Tilghman, a molecular biologist who helped plan the project, and served on its advisory committee. Then, with bioinformatician Dana Zielinski and Indigenous geneticist-bioethicist Krystal Tsosie, he looks to the contemporary hurdles for genetic research, including privacy, commercialization, and the sovereignty of Indigenous peoples over their own genetic data. Meet The Man Behind The Word ‘Mesmerize’ In the 18th century, a man named Franz Anton Mesmer came to Paris with a plan: to practice a controversial form of medicine involving magnets and gravity. Mesmer claimed his treatments cured everything from toothaches to deafness. His critics, however, weren’t so sure about that. Mesmer made enemies in high places, labeling him a con, and calling his type of practice “mesmerism.”  The story behind the word “mesmerize,” and other words about mind control are the focus of season three of Science Diction, a podcast about words and the science behind them from Science Friday.  Joining Ira to talk about the story behind “mesmerize,” and what else is coming this season is Science Diction host, Johanna Mayer. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Ira Flato. If you're the squeamish type, you might want to prepare yourself for this next conversation because we're going to talk about peeling eyeballs, fish eyeballs, that is. Because you know how they say the eyes are the window to the soul? Well, for fish, the eyes are the window to the stomach. Turns out that fish eyes are like a little tiny diet journal of everything that creature ate. But to read that journal, you have to peel back. the layers of the eye like it's the world's tiniest onion. But why would someone go to these lengths to understand what a fish ate? Well, I'll have to ask my next guest. Maranda Tilcock, Assistant Research Specialist at the Center for Watershed Science University of California at Davis. Welcome to Science Friday. Thank you for having me. That was a great introduction. So you can really do this. You can really peel a fish's eye to find out what it ate. Exactly. So just like you said, they as this amazing little diet journal, and they're composed of each of these individual layers.

And each of these layers represent a different period in this fish's life history. And what you can do is you can then put these pieces together to reconstruct their life, to see what they were eating. And if you know what they're eating, and if you understand the isotopes, these chemical fingerprints that are in our environment, then you can then make meaningful interpretations for these individual layers in a fish and better understand. what they ate, and importantly, where were they eating that food? Well, I understand that you study the Shaduk salmon in the California River system.

Tell us about why you want to study what the salmon are eating there. Salmon, Shinnik salmon in California are extremely important to us here in the Pacific Northwest. They're important culturally to the indigenous populations here. They're important economically. There is both a commercial and recreational fishery for you salmon because people like to eat them. They're more commonly known as king salmon in the stores when you go to buy salmon. They're also really important ecologically. They bring a lot of marine derived nutrients really far inland. But also, Chinook salmon play a role in our water supply here in California, which is

always a really hot topic. If you have low population of salmon, that means that they can limit the amount of water that can be pulled from the river for agriculture and urban use. And so if you have a healthy population, this can lead to more sustainable water use for our ag and urban uses. Do you share what the fish ate? Do you share this data with other organizations or people who need to know? Absolutely. We work with many different organizations to better manage for salmon. And using the lens to study what a fish is eating and ultimately what habitat they're using. This is really important for management and conservation. And this is something that the agencies here would like to know about. And so if we can have this tool, in our toolbox to help better understand what a fish is doing individually, we can make better management actions and decisions for on a population level to help increase these numbers of our salmon

populations. I found it really wild that you studied the lens of the fish to understand what it's eating. How did you arrive at that? So we originally saw this amazing poster in Florida from the lab that was lurking on large marine species. And when we first saw that, my first thought, thought for that is that this sounds too good to be true because at the time I was trying to understand the isotopic values between these different food webs of the floodplain and the river, the two pathways that salmon are likely to take here in California before going to the ocean. And the fish that I was working on was significantly smaller than these marine fish. I mean, we're talking like three to four inches max for these juvenile salmon. And not only did we

want to see if we can use this to reconstruct the life history for these juvenile fish, but also be able to use it for three isotopes instead of two, carbon, nitrogen, and sulfur. And so it was quite the long process of actually teaching myself this method and understanding how it actually works and adapting it for this much smaller fish here in California and seeing if we can actually apply this on a much larger scale. Yeah, because I watched the video of a fish eye being peeled and that looks like it took a while to learn. Yes. It was a long month with a very steep learning curve where I smashed a lot of eyeballs in that time trying to figure out how this actually works. And it became this kind of balance between, you know, you don't want the lens to be too wet because if it's too wet, you're going to smash it and the layers are going to smush together. And it's not going to work.

But on the other side, if it gets too dry, one of two things end up happening. It becomes really brittle. It'll actually shatter like glass. and your lens are going to be in like hundreds of little pieces. Or you can actually shoot it off your tray, like a tiny game of pool. And then the lens gets lost into oblivion somewhere in Lab, never to be seen again. Yeah, I hate it when that happens. Yeah.

I found it fascinating that the actually that the eye has layers to it. Is that unique to fish that they have layers, that they're like tree rings that grow another layer? Yeah. So so far, I found it to only be. unique to more of the aquatic species. It has been done in various cephalopods successfully. I've tried doing it in birds and frogs and was extremely unsuccessful. Their eyes are not the same. I have yet to try a mammal eye, but I hope to try someday once we can get back into lab. Speaking of eyes, then, where do you get your eyeballs from? I don't mean you personally. I mean for the work.

we actually get our eyeballs from carcass survey. So luckily for us, when we study Chinook salmon, they spawn and they die. And we have agencies that go around and actually do population counts and estimates based on the number of carcasses in the river. And then they're very kind and they pull tissues for scientists like me who might call them up and ask them, hey, can you also pull eyeballs from these fish so that I can look at their diets? And, you know, they take all that in stride and they pull the eyeballs for me and put them in little film canisters, actually. And that's how we store them in our freezer. And so they will send me hundreds of eyes every fall.

Did you ever think when you started out in your career, you'd be pulling fish eyeballs? Absolutely not. I think the scientist that was starting out five or six years ago would be absolutely shocked at what I'm doing now and wondering why would I do that myself. They're very smelling. When you get home from work to people say, oh, you've been pulling fish eyeballs again. I can smell it. Yeah, my husband doesn't like it if I have samples stored in the freezer at all before I take them to lab. And I do notice that a lot of the dogs at my work, suddenly started liking me a little bit more once I started doing fish eyes. Yeah, tell me a bit more about how the eye records what the salmon ate. Yeah, so the way the lens is

grind, it starts off as this very small core that's this little clear ball. And the layers are going to start to form around this ball. And this layer is forming. It's actually going to be integrating the food that that fish is consuming at that period in their life. So like when they're first developing and they have that yolk sack, you can actually see in their lens that they have this really high ocean value in their eye, even though they're living in freshwater. But it's because they have all that marine nutrients that their mom brought back for them. And so that actually integrates into that layer. And then the layer will then compress and it's no longer undergoing what's called protein synthesis, meaning that it's effectively locking in that isotopic value from that food web at that time in their life. And it's not going to

change and it's going to stay there permanently. And then that process just keeps happening as they move through their lives down the river or into the ocean, recording the food web that they're eating at that time. I also learned from watching you, I guess it was you in that video, peeling the lens, that, you know, we normally think of a lens being lens shaped, sort of, you know, oval, but the lenses here look like they're kind of round. Yeah, they're like a little pearl right there in the eye. And so the process is not as gruesome as it sounds. It starts off gruesome, I will say that, where you have the eye and you do have to cut open the eye to find the lens. But hidden within that eye, It's this beautiful little pearl-like orb in there that you pull out, and then that's the gruesome bits over. And you're left now with just this little tiny pearl onion that you can then start the peeling the peeling at that point either, which is also really nice. Does this tell you about whether any of the California salmon populations are endangered?

This doesn't tell us if they are endangered or not, but it does help us understand of whether or not how we're managing a population, if we're doing a good job or not, or if there is something that we need to change. And that's something that we are currently working on with a project that we call the Eyes and Ears project, because we're using both the islands and we're using the fish, Ooleth, or the Earbone to better understand what habitats these fish are using. And so the Ooliffe can tell us what river a fish came from. And then the Lens can tell us more about the habitats they're using along that river. and so we're ultimately hoping to better understand what we need to be doing in order to improve our management decisions and actions. Now you say that the ear can do it too?

Yeah. So the odolith or the earbone has been used for decades looking at the water chemistry and being able to detail which river a fish has been in and which river they took on their way out to the ocean. And this is found in just in the water chemistry and it gets into the odolith and you can actually like retrain. their migration route and map it out. And here in California, we're fortunate enough to have really geologically different rivers. And so this gives us a really strong different chemical fingerprints in each of the river that we can actually be like, okay, this salmon came from the American River, this one came from the Sacramento River, or this fish came from the feather river. And then we know what habitats exist along those rivers. And we can

then start beginning to relate the lens data to that with the food webs. So what do we know about the salmon runs from looking at these eyes? Well, the paper that has been recently published, this was more of a proof of concept for all the different applications that we're hoping to use it for. So we're hoping to eventually better understand those habitat needs that these fish have as juveniles and what freshwater habitats that they're using. And we want to know which fish that came back, these successful spawners, ultimately what led to their success, what kind of environment did they experience in the freshwater, what kind of environment did they experience in the ocean and what kind of food webs they were experiencing throughout their lives? And did that eventually lead to these long-term

successful spawning migrations? So you can't go fish shopping anymore and look at a fish in the eye lying in the ice and think about it the same way other people do? I absolutely not. I can't. I've watched different food network shows and I'll see them cooking an entire fish and all I can see is the lens in the eye popping out. And all I can think of is that that's cooking data. And those are missed opportunities. Thank you very much for taking time to be with us today. And good luck to you.

Thank you. Thank you for having me. This has been wonderful. Miranda Tilcock, assistant research specialist at the Center for Watershed Science at the University of California at Davis. We're going to take a break. And when we return, the Human Genome Project published its first draft of our genetics sequence 20 years ago this month. Wow, it seems like yesterday. Well, we're going to look back

on a monumental effort in science and the challenges for modern genomics, all coming up after this break. So stay with us. This is Science Friday. I am Irafledo. When you consider the history of science, the modern field of genetics is quite young. Genetic engineering, which we take for granted, dates back just to the early 1970s. Then in the late 1980s, when an international team of scientists decided to press forward to create a full sequence of the human genome, it morphed into a monumental moonshot-like effort that would cost $300 million and take 13 years from start to finish. This month marks 20 years since the first draft of that genome was published simultaneously in the journal's Nature and Science. In 2005, we were still discussing the Human Genome Project on this program in terms of its potential.

Here's geneticist Huntington Willard talking about how genomic sequencing could change medicine. If we can evaluate a given individual's entire genome at the cost of a thousand or maybe a few thousand dollars, that fundamentally changes the way we address disease, where you would bring people into the health care system, scan their genome, and look for the variants that might predispose to different types of disease. If we could do that genome-wide for thousands and thousands of diseases for literally everyone in the country that was entering the health care system, that would fundamentally change the way we provide health care in this country and around the world into a much more personalized form of health care. So now in 2021, what can we say about what we've actually gained and at what price? First here to look back with us is Dr. Shirley Tillman, a molecular biologist at Princeton University, former president of Princeton, She served on the advisory council that oversaw the project from start to finish.

Welcome, Dr. Tillman. Thank you. Glad to be here. Nice to have you. Please take us back to a time when this monumental project was first kicking off. Did you think it would succeed the way it has? Well, I thought it would succeed. I never questioned that if we put our mind to it,

we would be able to organize a project to determine the order of the 3,000 bases in the human genome. Biology, unlike physics, for example, had been a very cottage industry kind of science. It had never embarked on something very grand, very large. And so could I have anticipated back in the late 1980s the impact it has had? Probably not. Let's start with some of the numbers. Can you put a number for us on how many scientists were involved in this project from start to finish? From start to finish, I would have to say that we are talking about hundreds, if not thousands, of scientists who were involved. The project did not begin in 1988 with the sequencing of the human genome. It began by sequencing organisms as simple as bacteria in yeast.

And it was during that time when so many scientists who never, for a minute, thought they were interested in the human genome, began becoming interested in how to do large-scale organismal sequencing. Was that the story of your involvement, too, first getting involved in the simple sequences of the small organisms, and then thinking, oh, maybe we can expand to the human? It was actually my interest. And I think as I participated in those early, early deliberations on even whether we should sequence the genome,

For one thing, the idea of sequencing three billion bases of human genome was just daunting at the time. So it made a great deal of sense for us to take a much simpler organism with a much smaller genome and say, well, let's learn how to do this properly by taking on a small project and expanding to larger and larger organisms, larger genomes, and thereby, by the time we really began in earnest sequencing the human genome, we had had at least a dozen years of learning how to do cost-effective and timely DNA sequencing. I'm trying to remember the figure that was thrown around back then the first time they talked about the sequencing. What it would cost to sequence the first genome? Something like it was in the millions, wasn't it? So probably the best way to think about what happened to the cost is that when I

joined the National Academy Committee in 1987, 88, I had been sequencing myself. And it was costing roughly $100 a base to do good sequencing at that time. And to sequence, let's say, a thousand bases would take you, you know, at least a week. We knew that if you extrapolated those, numbers and they didn't improve, there was no way we were sequencing the human genome. Today, we're at a place where an entire $3 billion base human genome can be sequenced for under $1,000 and in well less than a week. So that's the magnitude of the technology advances that have happened since those early days of the genome project. There were a lot of surprises that came out of the sequence. I mean, and I think the biggest one that I can recall at the moment as we speak is

specifically how small it was or is. And if by small you mean how many actual genes there are in the genome, absolutely. This came as an enormous surprise. And if I may say so, a humbling surprise to those of us who had always seen humans at the very top of a very large evolution. tree. And to discover that to be human did not require many more genes than it took to be a fruit fly or a soil worm was quite a shock, I think, to everybody involved in the community. And not only that, but this concept of junk DNA. Yeah. I remember in the early days when we talked about on Science Friday, 20 years ago, I said, we can't call it junk DNA. It's been preserved for how many thousands and thousands of years, it's got to be doing something.

Correct. And one of the most famous statements about junk DNA was made by the great molecular biologist Sidney Brenner, who said, you have to distinguish junk from garbage. Junk is what you put in your attic until its reuse becomes evident to you. And Sydney was absolutely right. The regions of the genome that did not appear to encode genes. themselves have turned out to be some of the most important regions of the genome to understand, because those are the regions that are controlling the activity of genes, whether a gene turns on or turns off in the right place and at the right time. That's what's being controlled by what we used to call junk. Let's talk about other surprises. I think one thing that surprised me

to learn is that there are still portions of the genome that we haven't fully sequenced. How can that still be? I know. It seems amazing 20 years later that there are still unknown parts of the genome. The parts of the genome that are most challenging to sequence are what are called repetitive regions of the genome. And these are regions where there's a simple sequence and it's repeated over and over and over and over again. And so when people break it. up the genome and go into sequence it, there's no way to know once you've broken it up, whether the repeat came from here or came from here or came from here. So there's still a little

bit of uncertainty in these very repeated regions about what the actual sequence is. And one other thing that we thought we would learn is we would find out there was a gene for this. There was a single gene for that. But it turns out there are very few diseases where one gene is actually going to change your outcome? And I think the even bigger surprise has come from an expectation going in that if you take very common diseases like heart disease or stroke or hypertension, the thought was, well, maybe they're going to be five or six or seven genes that are important in determining whether you have a high or a low risk for those diseases.

there are very, very few common diseases for which that is true. And that for these very common diseases, the genes that are affecting your likelihood are probably in the hundreds and maybe even in the thousands, which makes it very, very difficult to identify anyone that's really important. Interesting. Now, you were a biologist before we had a sequenced human genome. How did work like yours change in the aftermath of all of this? I think the genome has profoundly changed the way in which many, many biologists go about their work. For the vast majority of my career, I studied one gene at a time.

I picked a gene that I thought was interesting and important. I studied it to death until I knew absolutely everything about it. And when I was done, I would then go on to another gene. What scientists do today is very different. You can now design an experiment in which you don't ask what one gene does in an organism. You can ask what all 22,000 genes are doing. And you can ask it all at once in one experiment. And that has radically changed the way in which we think about and do experiments in biology.

So it's really changed the landscape completely. Another big outcome of this project was the precedent it's set for data transparency. Can you talk about this? How this set the stage for a lot of how science works today? I think one of the proudest moments I had during my involvement was the decision to adopt what were indeed called Bermuda rules because they were actually voted upon by the community at a meeting in Bermuda. And that was the decision to make the DNA sequences that were flowing off sequencing machines available every 24 hours and to anybody, as I said earlier, who has a computer and can access the information. So that the sequences were there for everyone to see and to work on and to begin to understand, not just the people who were generating the sequence. We're looking back at 20 years of genomics advances right now. Has it accelerated to the point where if you want to predict what the next 20 years is like, it's just, it's almost impossible? Yes, I think you, that's exactly correct, Ira.

I think it's very hard to see where this field is going because things are moving so quickly. The field that has benefited the most from the genome project is certainly cancer. we now understand cancer so much more comprehensively than we did before the genome project. And the wonderful thing is that the knowledge is turning into therapies. And therapies that are far more exquisitely designed to stop the growth of the cancer than the old-fashioned ways in which we used to tackle cancer through radiation and chemotherapy. I think that the whole phase of cancer and cancer research cancer therapy has been changed by the genome project. It's had less of an impact on other branches of medicine, but I have no doubt that there are going to be

advances that come as the consequence of our understanding what exactly is in this blueprint of life called our genome. Well, I couldn't think of a better way to end our segment here with that kind of state. and I want to thank you very much, Dr. Tillman, for your work and for taking time to be with us today. It was a pleasure. Thank you for asking me. Dr. Shirley Tillman, Professor of Molecular Biology at Princeton, former advisor on the Human Genome Project. I'm Ira Flato, and this is Science Friday from WNYC Studios. We've been talking about the legacy of the Human Genome Project, which published its first draft of the

sequenced human genome 20 years ago this month. But what about the next 20 years of genomic research? Here to unpack some of the challenges they see as newer arrivals to the field. Let me introduce them. Dina Zelensky, a PhD candidate at the Sorbonne, a bioinformatician with the Paris Transplant Group, and a lead scientist at Sibilatac. Welcome, Dina. Thank you. Thanks for having me. And Crystal Sosie, a member of the Navajo Nation and a geneticist bioethicist. She's a PhD candidate at Vanderbilt University and co-founder of the Native Biodata Consortium. Welcome, Crystal. Thanks for having me. You're welcome.

Dina, let me start with you, since you wrote a piece specifically about the concern of privacy and genomic surveillance as we look to the future of genetic research, what are you most concerned about? So it's great to reflect back now on the Human Genome Project. It's hard to believe it's been 20 years, and I was actually taking high school biology at the time. And I think that one of the main advantages of the human genome project was that it really laid out data sharing principles. And this is really critical in order to advance in research. And I started working in the field of genomics 10 years ago.

And one of the first things I had to do was complete this human subjects research training. And so working with human data, I've always been. been very, very aware and very grateful, to be honest, to have access to that data. And so moving forward, I think we've done a pretty good job so far. But one thing that I think that is really changing is that individuals have access to their own genome. Before it was just these big consortiums that would collect data and anonymize the data. But now many of us have had, and myself included, we've had these direct-to-consumer tests like 23 and me, ancestry, My heritage. And so our DNA, one, is everywhere, but now we actually have the full sequence

sitting on our hard drives or in our emails or in these accounts. And so I think moving forward, we just have to continually adapt to the situation. I mean, privacy has always been a challenge, not just in genomics. And the thing is our DNA is probably our most valuable, our most private information in many ways. Well, you say our most private information, but now it's no longer private. Exactly. And I mean, it never really was. Your DNA is everywhere. But now it's very easy to sequence. It takes less than a day to sequence an entire genome on the order of hours now and less than a thousand dollars. You know, we saw one example of this ownership or non-ownership of DNA in the conviction of the Golden State Killer a few years ago on California, when data from one of his

relatives in an ancestry database helped them track him down. I mean, is this the kind of thing that's going to keep happening over and over again? Honestly, I hope so. I say that with a bit of reservation. I think that genomics has been an incredible tool for forensics, but I hope that it rests with forensics and I am a bit concerned that it will be exploited for unnecessary surveillance. But in terms of using it for forensics to convict people who committed violent crimes, I share my DNA. I consent to have my DNA shared in these databases. If my DNA can help find someone who committed a violent crime, I'm all for sharing it. That being said, I think, and I understand people's concerns, when we share our DNA, we're not just sharing our own DNA.

I'm sharing that of my siblings, my mother, my family members. So it's really a tough call. I'm very much open to sharing data, but I am a bit wary, to be honest. We have to take a short break, and when we come back more on the challenges ahead for human genomics, with my guests, Dina Zelensky and Crystal Sosi. Stay with us. We'll be right back. This is Science Friday. I'm Ira Flato. In case you're just joining us, we're talking about challenges for genetic research.

Twenty years after the first draft of the human genome was published with my guests, Dina Zolinski, a bioinformatician with the Paris Transplant Group and a lead scientist for Sybiltec, and Crystal Sosie, an indigenous genocetian. geneticist bioethicist with Vanderbilt University and the Native Biodata Consortium. Crystal, I introduced you as a co-founder of the Native Biodata Consortium, which gets to an issue we've talked about in different ways on this program in the past. Indigenous sovereignty over genetic data. Please remind us how big an issue this is. Yeah. So when we talk about precision medicine and health, we're always promising that the next advantages in innovation,

will be conferred to those individuals that contribute the genomic information. The pandemic has shown that preventative health care and structural barriers to access to health care probably highlighted more about health disparities than this unpronounced supposed future advantages of health care. Indigenous peoples have, you know, willingly or unwillingly contributed their DNA for the supposed betterment of humankind. Need I remind everybody what happened after the completion of the human genome project. We had the completion of large-scale diversity projects, such as the human genome diversity project and 1,000 genomes project, which were denounced by over 600 plus indigenous nations worldwide

that went to the United Nations because they were concerned about privatization and commercialization and exploitation of indigenous genomes. And what has happened to those biomarkers collected from indigenous peoples from Central and South America, those biomarkers are now freely and openly accessible to companies such as Ancestry DNA and 23 and Me. Ancestry DNA has posted revenues over a billion dollars every holiday quarter since 2017. So we always have to ask ourselves, what exactly are the protection? related to data privacy and commercialization, the rate of technology outpaces our regulation of these new technologies.

And while we think that these protections are conferred by laws, such as the Genetic Information Non-Discrimination Act, laws change. Companies are bought and sold. So we have to ask ourselves, what's the commercial value of the data that we are being asked to freely give away? And how can we look to communities and empower communities to self-directed decisions? that are being made using their data. Dina, you contributed your data and you gave it away freely.

Do you not feel the same kind of threat here that exists? Not quite in the same way, no. Individuals of European ancestry make up the vast majority of genetic studies. And that's really problematic because they only make up 6% of the population. And I completely understand the threats to underrepresented populations. We should be sequencing these underrepresented. populations, but we should be sequencing them with the idea of making genomics research more equitable, of giving back to these communities, not just taking from them. That being said,

I can't even explain how useful data like that from the Thousand Genomes Project has been. I've used it in most of my projects. I have whole human genomes at the tip of my fingers. When I'm accessing this data, as well as other scientists, I think we generally have good intentions. So I currently use it in a study to better understand Parkinson's disease. That being said, I think in many cases a lot of this data has restricted or limited access for researchers versus commercial entities. I agree here that we really should limit what industry can or cannot do with our data. Crystal, you mentioned preventive care and the pandemic. The Human Genome Project, I remember, promised to tell us everything about her genome.

Doesn't this sort of tell people, hey, we know everything about you now, and ignore the nurture part of the nature-nurture debate? What I can tell you, as a geneticist, my first skepticism and what I always tell tribal leaders is that genetic data is just the easiest type of data to collect. But genetic data does not predict as much about disease risk than we eat. think. Other things, such as access to care, cultural factors, colonial factors relating to health, probably contribute more to the health differences in outcomes than actual genetics itself. Things like diet, environment, and lifestyle are things that we should be looking at and definitely socioeconomic status factors. But these are the hardest bits of data to collect. And so we really can't build truly robust models without looking at these other factors related to health. So looking at genetics

and biological factors is sometimes a little bit of a cop-out. We don't necessarily properly convey the limitations of genetics and biological research to the lay public. There's a lot of, unfortunately, disinformation related to how much biology actually contributes to health. And it creates these false relationships between, for instance, genetics and ancestry and genetics and identity, especially when we as geneticists use terms like genetic ancestry, not telling everyone, though, that these are statistical inferences made out of small bits of the genome. Dina, do you see these same limitations? It's very interesting, actually, to bring up ancestry.

Ancestry is pretty complicated, and I think, like Crystal said, our DNA is, is rarely deterministic. There are very few mutations that we know of that will lead 100% to a trait or disease. And ancestry is very complicated. We basically will match an individual's DNA to a database of people who are defined by geographic borders. And DNA doesn't necessarily respect these borders. What ancestry can tell you is simply where in the world you happen to share different percentages of your DNA. It does not define who you are. If the big scientific advance of 20 years ago was reading out the full sequence of the human genome, and the big advance of the last 20 years has been this large-scale analysis of how groups of genes relate to health,

and as we are talking about environmental factors. Dina, what do you think the next big advance is? One, I think equitable research and sequencing more than the 6% of the population that is of European ancestry is critical, and I think that is happening. I'm really happy to see that there are initiatives to sequence underrepresented populations. And I think they will be transformative at making genetics research and the results that we find available to all populations. And the other thing is I think that with all of the advances in computational tools

and Crystal mentioned this, we can't keep up with the technology in many ways. Even in the last 10 years, the technology has improved enormously. We have now sequencers that can sequence very long stretches of DNA. One of the main limitations of the technology was that DNA is often only read in these short sentences of about a hundred to a few hundred letters called nucleotides. I think the next step will be finally sorting out the link between genes and traits and diseases. It's going to happen at a much faster rate than it has happened in the past 20 years. But I think if we continue going in the way that we have been going, that we will get there eventually. And Crystal, do you agree with

that? That is the concerning part, is that what we're seeing are ethical, questions of the past that still have not been resolved, that are being born yet again today as if they are new questions. The next big discoveries to advance genoist technology will be likely founded small or yet untested populations as we move from looking at common variance contributing to disease to rare variants. These are the same populations that have been historically oppressed. And even for members of the majority population, shenomid privacy is threatened. And these concerns are compounded for small communities like us. And it's really unfortunate for me and really frustrating for me because we have seen all of the events that have occurred related

to discussions of racial justice and injustice last year. And now I'm seeing terms like diversity being conflated with equity and justice. Where in in genomics, where diversity is really only limited to just including more members of diverse and underrepresented peoples on a plate without giving them agency over what happens to their DNA and data. That's not justice. And what we really need to be doing is talking about what it means to partner with communities and individuals to give greater decision-making autonomy and authority to those people

that are contributing the information. If this means benefit sharing in terms of actually giving back to the people that contributed to the information, that would be a positive direction that I would like to see in the next 20 years. But the only way that we'll do that is if we have more people who are from those underrepresented communities actually doing their research and actually directing the research and actually provided a seat at the table in which our voices are actually listened to. Great points. I want to thank you for taking time to be with us and wish you all great luck in your research.

Thank you, Ira. I hear it, which means thank you. Dina Zelensky, a bioinformatician with the Paris Transplant Group, and Crystal Sozi, an indigenous geneticist bioethicist with Vanderbilt University and the Native Biodata Consortium. I'm Ira Flato, and this is Science Friday from WNYC Studios. I want to do a little exercise here. Close your eyes for a moment. But hey, not if you're driving or walking. Okay. What do you think of when you hear the word mesmerize, hypnosis, perhaps, or maybe something so beautiful you can't take your eyes off it? Well, the origin of this word is the subject of the first episode of the new season of Science Diction, our podcast about words and the science stories behind them. And joining us to tell us more is Johanna Mayer, producer and host of science fiction right here in Brooklyn, New York.

Welcome back, Johanna. Hey, Ira. Okay, so where does the word mesmerize come from? Well, it actually comes from a person, namely a Dr. Franz Anton Mesmer. And so Mesmer was a doctor in the 1700s, and he practiced this very strange form of medicine called Animal Magnetism. Have you ever heard of that? Not in a bar maybe, but not in terms of practicing it. Yeah, it's because it's not really a real thing.

But the idea behind it, Mesmer believed, was that there was this invisible fluid that flowed in all people. And at the time Newton's law of gravitation was actually sort of a relatively recent thing. And Mesmer believed that gravity affected this supposed fluid in us also. So, you know, he thought that it would end. and flow, just like the tides. And he ran into trouble when this fluid would get locked inside a person. So the cure for that would be to figure out some way to unblock it. It was like a plumbing issue, kind of. But the term mesmerized actually came from this doctor's critics. They refused to validate

animal magnetism. They were like, that's not a real thing. We're not going to call it that. And so they called what he was doing mesmerism. So this doctor was said to have mesmerized his patients. Mesmerized his patients? What did he do to his patients? Well, Ira, he did all sorts of really weird stuff. So his first breakout treatment was with this woman named Franzl Osterlin. And poor Franzel had a whole host of afflictions that were plaguing her. Everything from a toothache to convulsions to occasional bout to paralysis and just nothing that they were trying was working to cure her. So Frantzel walks into Mesmer's office one day and he's like, great, perfect opportunity to test out this animal magnetism theory, see if there's anything to it. So first he asked Frantzl to drink this sort of

iron-rich concoction. And then he took magnets and he ran them all up and down her stomach and legs trying to unblock this fluid. And to be clear, this should not have caused any sort of sensation. But according to Franzel, she said that she first felt pain, and then that changed to burning heat. And then suddenly her afflictions just went away. So that was Mesmer's first sort of like breakout treatment. And from there, things really escalated. He would bring groups of patients into these like kind of dimly lit, eerily decorated rooms. He would pace around wearing this purple silk robe. He would wave his arms over their bodies. And he even had this magnetic iron wand that he would use to supposedly move around this fluid. And I mean, these treatments could be

really kind of disturbing to witness. Patients would go into fits. There would be convulsions. They would yell. But the thing was a ton of them claimed to emerge. these sessions healed. Wow. So did it actually work then? I mean, probably not. Although it depends on what you mean by work, though, right? Because, I mean, to be clear, Frantz Anton Mesmer was a crank, but something was working. I mean, many patients claimed that they were cured and felt better. And the thing is, these early practices from Mesmer are widely cited as kind of one of the first demonstrations of the placebo effect. Huh, really?

Yeah, and I mean, Mesmer's legacy is still present in a lot of modern medical treatments. Some say that he even laid the foundation for modern hypnosis treatments. A little-known psychoanalyst named Sigmund Freud was a big fan of Mesmer. And, I mean, some even go so far to credit him for sort of very early iterations of talk therapy treatments. But, you know, on the other side of the coin, some say that Mesmer's associations with these practices have kind of kept them from being fully accepted by mainstream medicine. But I mean, one thing that you definitely can say that Mesmer gave us is a demonstration of the power of suggestion on our minds. Cool. That's a great story. So what else can we expect from Science Diction's new season?

Well, our theme this time around is mind control. So we've got lots of stories about that. next week you can expect an episode on the word lunacy, which comes from the Latin for moon. And it's really a story of why we thought the moon controlled both our moods and our minds for a long time. And even further down the pike, we have the word robot, which is a word that has surprising literary origins. And it's really about what happens when you create a mind that can't be controlled. So all sorts of fun stuff coming down the pike. And fun stuff is what we like here on. Science Friday. Thank you. We'll be looking forward to that, Johanna. Thanks, Ira.

Johanna Mayor, host of science fiction, of course, living in Brooklyn. And that's about all the time we have for today. If you missed any part of this program, or you'd like to hear it again, subscribe to our podcasts, or ask your smart speaker to play Science Friday. Oh, one last thing before we go. We're teaming up with the organization 500 women scientists to bring you the Breakthrough Festival will be live streaming events that feature the the work of women scientists, talking about ancient birds, sneeze spread, and a whole lot more. It's happening, write this down, February 15th through 21st. Details are up on our website, ScienceFriday.com slash breakthrough festival.

Have a great weekend. We'll see you next week. I'm Ira Flato.