On the Development of a Genetic Noah’s Ark—Oliver Ryder, PhD—Kleberg Endowed Director of Conservation Genetics, San Diego Zoo Global

Richard Jacobs: Hello, this is Richard Jacobs with the Finding Genius podcast. My guest today is Oliver Ryder, Ph.D. He is the Kleberg Endowed Director of Conservation Genetics at the San Diego zoo and we’re going to be talking about plans to build a genetic Noah’s Ark that would have a 66,000 plus species. So Oliver thanks for coming. How are you doing?

Oliver Ryder: I’m doing fine. Thanks, Richard.

Richard Jacobs: Tell me a little bit about your work. How did this idea come about for this genetic arc?

Oliver Ryder: Well, the impetus for it was really to use advancing technologies to aid in the conservation of endangered species. And it’s only been about 60 or more years around 60 years that it’s been possible to grow cells from an animal outside of the body to grow them in the lab and freeze them and revive them so that they can carry out their function. And this provided immediately some advances, significant advances in scientific studies, and an understanding of the evolution of life, being able to study chromosomes and identify in humans and other species that errors in the transmission of chromosomes, errors that take place across generations cause diseases and cause problems for individuals. So in that background of this technology, half a century ago when the San Diego zoo started, its research effort focused on helping to conserve endangered species. The founder of that effort, a physician named Kurt Banushka brought with him from the medical school at the University of California, this technology, and started what he called the frozen zoo. And so over the years, this collection has grown to be probably the largest, most diverse, best characterized and most utilized collection of its kind. And although it has all of those attributes and accolades and it contains the cells of 10,000 individual vertebrates, animals with backbones so fishes, reptiles, amphibians, birds, and mammals. There are approximately 1200 species, but there are over 60,000 species of vertebrates. Now we realize that there’s never going to be a time when we could collect more samples, more biodiversity than now because we’re seeing an increase in the loss of species and the declines in their numbers. And also technology has arisen that so having access to these kinds of living materials from animals can contribute substantively to studies that benefit their conservation.

Richard Jacobs: What about the study of their attendant, microbiomes, their viromes, fungi, all those things. I mean, just that are associated with those species a lot that you’ve had a logging and all the omics, you’ve got maybe genetic material. But I mean, I know it was a monstrous undertaking, but are there any thoughts you have on that info afterwards?

Oliver Ryder: Sure. We think about that and you’re right, it is a monstrous undertaking. And we hope that these efforts can expand, but certainly, it would be a priority to expand the number of species for which we have viable cell cultures frozen. And so priority is to expand efforts so that other facilities like the ones that we have at San Diego zoo global exist in other countries and in other regions of the world so that there would be a broader catalog of a species that could be saved and be studied. The microbiome, of course, is very important. We understand how that influences animals and there’s a call and there’s an effort to have a global microbiome. But that’s another complicated undertaking. And we’re going to be happy to contribute to that, but probably our biggest contribution is going to be this bank of living cells that includes also reproductive tissues and cells.

Richard Jacobs: Okay. So you’re not just taking the DNA, but you’re taking the entire cell and you’re taking some of their gametes there at the somatic cells. But they’re the cells that produce egg and sperm.

Oliver Ryder: Yes, we have the living cells that we can replicate. The gametes you need to be used for fertilization. They don’t divide until they produce an animal or a zygote. And so this is a unified kind of effort and we feel confident that this will benefit the future and that as war is being learned in greater uses can be made of these cells to save species. It makes very good sense to collect more samples and bank more samples now.

Richard Jacobs: Are there going to be a few anchor species that you didn’t get a lot more data on than others?

Oliver Ryder: Yes, for now. Because we can historically, we’ve collected samples from San Diego zoo and the San Diego zoo Safari park and other so zoological institutions. Hundreds of facilities have sent samples to us for us to the bank but we’ve focused on cells that are high priority species conservation. So some of these are species that were extinct in the wild and were saved from extinction by zoos. So a species like the Shavano skis horse or the Arabian orcs or the black-footed ferret or the California condor or the Hawaiian Crow or Alala, all of these are our special targets, but now increasingly we see the need to integrate efforts to save species in natural habitats with those t00 that are preserving wildlife in human care. Like what we’re like, what zoos are doing and integrating these efforts because as species become more endangered, gene pools are shrinking to gene puddles and that threatens the future prospects of a population, which for us underscores the need to really be doing more banking now.

Richard Jacobs: So how far along is the project? How many samples do you have and how many more to go and what time period?

Oliver Ryder: Well, we have samples from 10,000 individual animals and it’s about 1200 species and subspecies. It’s richest in mammals and among the mammals, it’s richest in hoofed mammals and in primates and in carnivores. But it’s got a broad genetic diversity. So the future is that you know, we want to continue to collect this kind of material, but probably our greatest impact can be to help foster the development of facilities around the world, to share our techniques and to encourage others and to establish a global database about what samples have been saved from what species. So that we can keep track of this.

Richard Jacobs: How will scientists get access to the database? Will they make a special request and pay a fee. And then, you know, some of the cells are cloned and then given to scientists or how will this be utilized?

Oliver Ryder: Well, you know, we do the cells and expand them. It’s a renewable resource so it can be greatly expanded. It can’t be expanded infinitely because cells in tissue culture undergo aging or senescence, but by carefully by freezing cells when we have millions of them at early stages and then managing the way that we expand those cell cultures, we can provide a great deal of material. And now it’s possible for some species to make induced Clery potent STEM cells from these kinds of cells so that these are cells that can make any kind of cell in the body and they are immortal. So we are working on developing that technology as well. We have a process that reviews applications. So scientists contact us and ask for access and we are happy to receive those applications and review them and try to fill as many as we can.

Richard Jacobs: But what have you learned in the gathering of the samples? Things that you didn’t know or were unexpected?

Oliver Ryder: Well, the collection of samples in the frozen zoo has helped really inform several big projects. One is the tree of life, the relationships between animals using whole-genome sequencing and cells such as we have banked and in the frozen zoo and tissues that we can bank from animals as part as the time we’re getting some of the samples the frozen zoo can be used for producing very high quality genome sequences. And by comparing the genome sequences great insights have been gained into evolutionary relationships. For example, understanding the whales are derived from a common ancestor with cattle and our hippopotamuses and that the elephant is related to the Manatee and to creatures to which it has very little similarity now, but we can trace their ancestry through DNA. So that really informs the knowledge of the tree of life. In other cases the being able to produce these genomes allows us to understand something about the extinction risk of animals. And this is a very active area of research right now, how the small population effects have produced accumulation of deleterious mutations and also to identify the genetic heritable diseases, genetic diseases and endangered species so that these can be better understood and managed and used to provide better health care and prevent extinctions.

Richard Jacobs: How many of these species have not been sequenced before? Are most of them novel?

Oliver Ryder: Yes. I think that I mean, right from the very beginning after the human genome was sequenced the genomics community realized that to really reap the benefits of having produced a human genome that had to be placed in the context of the species with which humans are related to which humans are related. So originally there were 29 other mammals besides humans that were sequenced and the frozen zoo help contributes samples to those. And then there was a project called the genome 10K to sequence a genome of 10,000 vertebrate animals. And there have been now about 300 or 400. The count keeps going up, mammals that are sequenced and you might think that that’s a long way from 10,000, but we see how rapidly the technology is developing and its utility. And so the idea now is to sequence all of the 60 to 70,000 vertebrate species in a project that’s a genome 10K is morphed into a vertebrate genome project

Richard Jacobs: And you can see correlations. You could further elucidate, you know, lineage. I mean you can look for the appearance of endogenize viruses and track them. I mean, you’d be able to see a lot once you get a whole bunch of these sequences and analyze it.

Oliver Ryder: Right. And there’s a work that’s going on that’s about to be shared through scientific publications that have to do with taking several hundred or 247, I think it is, mammal species whose genomes have been elucidated and lining them up to see what features are in common and what features are different across the tree of life of the placental mammals. And that’s providing very interesting insights into diseases, human disease risk or human disease assessment, but also to conservation activities to learn more about populations of endangered species. Once you have a reference genome, then to be able to do studies of more individuals and get a kind of an understanding of this genetic structure of populations and interaction, the migration and between isolated population fragments and whether, which some populations harbor more genetic diversity.

Richard Jacobs: Well as because you’re helping to run the project. When a lab wants to use the data, are they agreeing also to share the results with you? Like, will you be privy to see all the research that comes to this?

Oliver Ryder: We are participating in the broad call of many scientists to make this data immediately available to the larger community. So we are part of a consortium that is committed to sharing this kind of information rapidly because there’s much more information there than any one team can analyze and it’s going to benefit broad segments of society. So it needs to be out there and shared. That’s one of our commitments.

Richard Jacobs: But what, if you did a series of regular publications, almost like a meta-analysis of everything that’s come out of your data, you know, this year, this is what’s come out this year, this is what’s come out, or every six months or so, it might be nice work if you guys would do a publication based on what’s being used and how, and what’s being looked into.

Oliver Ryder: Well, we’d love to track that. But it turns out that it’s not very easy because people may publish the data and not say where they got the sample from and they may publish the data and we don’t know about it. But there’s no doubt that we can track through. For example, gen bank there’s thousands of hits for San Diego zoo as a source of samples. And there are hundreds of species that the DNA that provided for a study came from us. So I think it’s sort of remarkable that a nonprofit zoo has contributed so fundamentally to this explosion of knowledge in the field of genomics.

Richard Jacobs: Hmm. Yeah. It’d be interesting if when you’re done or even now you create a virtual zoo. As I looked through the samples, let’s say, a video comes up with the animal itself and I could literally see, Oh wow, the sequences for a black fitted ferret look at it. And that might be another level of data that’s missing if you don’t have that.

Oliver Ryder: Well, we’re trying, I mean that’s what we’re thinking about and that’s sort of a backfilling kind of exercise. And there are other databases that keep track of animals and at the global scale, integrating all of these heterogeneous databases becomes one of the big data opportunities and challenges of our time.

Richard Jacobs: Yeah. I just think that’d be really cool to have, literally, cause you’re a zoo, you know, do also a virtual zoo like that, where we could look through things. So very cool.

Oliver Ryder: We and other people are working on things like that.

Richard Jacobs: Yeah. What’s your estimated time for it to get to the next 10,000 and then to get it to all 66,000?

Oliver Ryder: I think it’s going to take a while. If you look and find out for all of these named species, some of them, a significant number of them were collected very few times. And if you went out to try to find them it could take a long, long time. It’d be prohibitively expensive. So the idea is to sort of start on the things that are the easiest to get ahold of and encourage efforts. But all around the world today, there are wildlife scientists and forensic biologists and law enforcement officers people who have their hands on animals that could collect a sample. And if there was a network in place that was ready to receive samples from rare opportunities to tame a specimen from an animal then we could make a lot more progress. I think that the way that we’ve been building the frozen zoo is adding 300 to 400 new species a year. So that’s going to take a long time to get to 60,000. That’s why we all need to have more people involved. And it’ll be very tough for fishes because some of some fishes have been collected only, rarely and the ocean is a big place.

Richard Jacobs: How many of each creature or species or subspecies is enough to have? How many different examples?

Oliver Ryder: That’s a great question. And we would like to have more as better basically, but we have a limited capacity to process samples. So we look at something around, 20 to 50 individuals. It depends if they’re related. And it depends if it’s a species that we’re really focused on. For some species where we have basically the entire gene of a species. We want to be sure that we collect that for species where we have the opportunity to collect the entire gene pool. We should be able to do that for other species. We might want to have a representative example. But if we want to use these samples for genetic rescue, we want to be sure that we could reconstitute as much as possible of the genetic diversity of a species that’s on the brink of extinction.

Richard Jacobs: Yeah, this seems like a very important fundraising type thing. I mean, I don’t know if you’re doing this, but I would say like if you put out a call to action, we need funding and if you pay for sequence sending of a particular creature, then you get some kind of name recognition or bonus. And maybe people would like that if they could say, you know what, I really want to sequence dolphins. And so they fund you and you go after dolphins and someone else likes ferrets or you know, whales or whatever it is. That might be a nice way to fundraise and get people really into it for particular types.

Oliver Ryder: I think that’s a good suggestion. And I think that we want to try to have this become more a process of global ownership and broad recognition of the importance of undertaking this kind of work and having supporters for it. So we do have a wildlife Conservancy that people can donate to. And a portion of that money goes to efforts that we use to save particular species and that includes banking specimens from that. And when we look at our conservation projects, we look at the full spectrum of conservation, preserving habitat for the species, mitigating against the causes of its decline, but also trying to bank specimens so that we would have important resources for contributing to the recovery of species that are in decline.

Richard Jacobs: Are there any particular ones that I don’t know, it would be easy to get funding for and other ones maybe that aren’t cute or weird or scary that no one really cares about and would be difficult to get funding for it?

Oliver Ryder: Well, it’s really complicated, Richard. Many people love tigers and so we can get tigers from zoos. But there and many people love rhinos and we can get rhinos from zoos, but some, there’s one species of rhino, the Javan rhino that none of them are in zoos and nobody has ever collected a sample from them. There are no cell cultures from Javan rhinos and people are very attracted to the great apes. But like gorillas, but we don’t want to harm them or harass them. So how can we get the samples from gorillas in the wild that’s really precluded at this point? So the targets of opportunity have an interface between scientific interest, popular interest, ethical considerations which are a huge component of our work and then being able to export those samples to a laboratory. Numerous details.

Richard Jacobs: Very good. What’s the best way people can find out more and donate and see what’s left on the list to the sequence.

Oliver Ryder: Well thanks. We have a website that’s institute.sandiegozoo.org and there you can find out about our conservation effort and look to see about our frozen zoo and other projects that we have for conserving endangered species.

Richard Jacobs: Well, very good. Oliver, thank you for coming on the podcast and what you’re doing is really important so I hope that you guys get some real kick-ass marketing and get these sequences going as soon as possible. So I’m glad you’re doing what you’re doing.

Oliver Ryder: Thanks for your interest. Richard,