- Welcome, everyone, to Wednesday Nite @ the Lab.  I'm Tom Zinnen.  I work here at the UW Madison Biotechnology Center.  I also work for UW Extension Cooperative Extension, and on behalf of those folks and our other co-organizers, Wisconsin Public Television, the Wisconsin Alumni Association, and the UW Madison Science Alliance, thanks again for coming to Wednesday Nite @ the Lab.  We do this every Wednesday night, 50 times a year.  Tonight it's my pleasure to introduce to you Professor Stan Temple.  He was born in Houston, Texas, grew up in Cleveland, Ohio, and then got his bachelor's, his master's, and his PhD and his post doc at Cornell University in New York.  He studied ecology and ornithology there.  Then he went to work for the World Wildlife Foundation for several years doing some work in the Indian Ocean.  There are worser places to work than the Indian Ocean, I'm guessing. 

 And then in 1976, he came to UW Madison, and he's been here every since.  Tonight, he's going to talk to us about de-extinction, a rather interesting idea.  If there was ever a one-word oxymoron, that's pretty close to it.  I'm looking forward to hearing how you go about doing this and what some of the implications are if we're able to do that.  Please join me in welcoming Professor Stan Temple back to Wednesday Nite @ the Lab.  [applause]  - Thank you, Tom.  Well, SpaceX may have pulled off something that he thought only a few years couldn't possibly happen, but we haven't pulled this off yet.  But it's coming.  It will happen.  You might wonder, I've spent my entire career trying to save species from extinction, how in the world did I get involved in something that seems rather futuristic but that perhaps offers a new tool to try to preserve species on the planet: de-extinction. 

 We have, unfortunately, lots of candidates to work with.  As you probably all know, extinction rates have risen dramatically.  It has given us a huge pool of species that have gone extinct in recent times because of human activities.  So it would be rather remarkable if we could sort of reverse that ominous trend that is ongoing.   De-extinction is one of those remarkable technologies that seems to have emerged largely as a part of the anthropocene.  The era that geologists tell us we've now entered in which human beings are basically taking hold of most of the Earth's processes and manipulating them to their own ends.  Looking around the room, I see that there are probably quite a few of you who remember the Whole Earth Catalog.  [laughter] And you may remember the opening paragraph, the opening sentence of the Whole Earth Catalog by Stewart Brand.  "We are as gods and might as well get good at it." [laughter] Well, I think those who accept that we've entered the anthropocene would probably say that we've already been playing God with nature, but we've not been very good at it.  Basically, most of our interventions in nature have had rather negatives consequences. 

 But maybe we're on the cusp of seeing a very novel intervention in nature that could actually offer what I've described here as a wicked solution to some of the wicked problems of the anthropocene.  And I think we all know what those wicked problems are.  Whether you look at the atmosphere, whether you look at the waters of the world, whether you look at the land, or whether you look at the living things on the planet, the trends are ominous.  These are wicked problems.  Problems that we just don't seem to be able to get a handle on and reverse.  And especially with regard to tonight's topic.  The global extinction crisis is rapidly advancing to the point where double digit percentages of most of the major taxonomic groups of organisms on the planet are now considered to be threatened with extinction.  So, we've made a mess of things.  And the question is: what are we going to do about it? Could we, in fact, help preserve, perhaps, the biodiversity of the planet and ensure a future that is as biodiverse as the one that we inherited? Well, to date, our attempts to secure a future for biodiversity have basically rested on three approaches.  For species that we have deliberately harmed, and very directly harmed, we can protect them. 

 We can basically say hands off, and sort of remove the human threats that directly harm them.  For species that we use, we can choose to either use them in a non-sustainable way or to use them in a sustainable way.  Conservation means using them in a way that doesn't inexorably drive them to extinction.  And finally, at least in recent years, we've been able to restore some of the damaged things on the planet.  Some species, some communities and ecosystems that have been badly damaged, we've been able to bring them back to health.  And now perhaps we're on the cusp of adding a fourth tool: biotechnology.  Biotechnology has not normally been used in the same breadth as biodiversity conservation.  In fact, for a long time biotechnology was often viewed with some skepticism, as perhaps a new threat to biodiversity on the planet.  But we all got an introduction of sorts to the possibility of something interesting happening out of biotechnology that might have some consequences for biodiversity when the book and the movie came out.  And for the first time people were presented with the idea that, wow, maybe extinction isn't forever. 

 Maybe biotechnology would allow us to do something that seemed impossible.  It was just science fiction, of course.  But pretty amazing how close to reality that science fiction has become.  Not only the technologies that might be used to bring a species back from extinction, but I also like the fact that the movie, especially, ended with a cautionary tale about unintended consequences.  This is something that we should think very deeply about before we undertake it.  So, as I've said, we've got lots of possibilities out there for bringing back extinct species.  And it's useful, I think, to talk about two different challenges of de-extinction.  We could talk about shallow de-extinctions.  These would be resurrecting species that have very recently gone extinct.  So recently that we've actually deliberately preserved genetic material with the hope that that genetic material might actually be useful for conservation purposes. 

 That would be in contrast to deep de-extinctions.  The extreme of deep de-extinction being Jurassic Park.  No one's talking about bringing back dinosaurs, so we can sort of move that off the table.  But resurrecting long extinct species.  By long extinct, I mean species that have been gone for centuries or millennia for which we do not have carefully preserved genetic material, in which we would have to use badly degraded genetic material in order to have any hope at all of trying to resurrect the species.  As you will undoubtedly know, it is the deep de-extinctions that have captured most of the media attention.  The shallow de-extinctions have largely been glossed over.  Although, they are the most likely to be the things that happen first.  And it really is quite recent that there's been attention to de-extinction.  It all really surfaced in 2013. 

 And as is often the case, there is an individual behind this becoming a sort of a media darling.  And that person is none other than Stewart Brand.  Stewart Brand of "We are as gods." Stewart Brand has a foundation called Revive and Restore that he's now dedicating to, in his lifetime, seeing the resurrection of an extinct species.  It really went public in 2013 with two very visible events.   TED Talks on de-extinct-- series of TED Talks sponsored by National Geographic on de-extinction, and the cover story of the National Geographic magazine that goes out to millions of people and of course has widespread media attention.  So, 2013 suddenly became the dawning of de-extinction, that this really was something to take seriously beyond just an interesting science fiction tale.  And of course you know you've really arrived when you have your own Wikipedia page.  [laughter] And de-extinction has a fairly sizable one that presents many of the ideas that have surfaced over the last few years.  So, de-extinction, this idea of resurrecting a species that has gone extinct, after the last individual of the species has died,  really will be an epic event.  And when I say epic, I really mean epic in terms of the history of life on this planet. 

 If extinction isn't forever, if we could really resurrect something once it's gone extinct, it is basically unprecedented in 3.8 billion years of life on this planet.  No species has ever come back from extinction.  Extinction has been forever.  This is stuff that gets you nominated for Nobel Prizes.  It also reverses a tragic period of human history.  For the last 50,000 odd years, human beings have been nothing but a cause of extinction.  The prospect of reversing that and allowing us to perhaps undo some of the harm that we've been doing over that period of time is really rather intriguing.  And at least from my perspective as a conservation biologist, someone who's devoted his career to trying to preserve the world's biodiversity, this really shakes a fundamental basis of conservation biology.  Conservation biology achieved its urgency basically on the premise that you don't get second chances.  You better save species while they still exist because if we let them go over the brink, we're never going to get them back. 

 Well, de-extinction promises to perhaps crumble that foundation of conservation biology.  Maybe-- Maybe we could bring them back.  So, as the discussions about de-extinction have developed, the arguments for and against doing this have become very long.  A very brief synopsis of some of the more compelling reasons why we ought to do it and perhaps why we ought not do it, beyond the rather facile argument that, well, we should do it because we can do it.  The utterly cool nature of de-extinction I take from a  direct quote from the chairman of the National Academy of Sciences Committee on Science and Technology, who listened to an afternoon of presentations about this and said, "The only reason I can think for doing this is that it's utterly cool." [laughter] And there's no question.  It is utterly cool.  Who wouldn't want to see a mammoth? Other argue, perhaps a little more seriously, that perhaps it's a matter of justice.  In recent times, virtually all of the extinctions that have occurred on the planet have been caused by human beings.  So perhaps it's an obligation that we have, if the technology is available, to try to bring those species back.  Many of the species that we pushed over the brink were species that were actually quite valuable to us. 

 We over exploited them.  Think of the passenger pigeon that I spoke about two years ago.  Once the most abundant bird in the world that fed eastern North America for generations was over killed to extinction.  Bringing back some of those very valuable resources that already had known value to human beings actually reestablishes lost value.  You could create new value.  You could be sure that if somebody pulls this off, there's going to be a theme park that's going to charge you to come and see the mammoth or the passenger pigeon or whatever.  And finally, at least from the perspective of conservation biology, we used to think of captive breeding as the tool of last resort.  The thing that you resorted to when all else seemed to be hopeless.  Perhaps now that's no longer the case.  Maybe biotechnology gives us a new tool of last resort. 

 The arguments for why not to do it are perhaps equally compelling.  It's obviously unnatural.  It's artificial.  Many people would argue for a wide variety of reasons that it's possibly even unethical.  Although, that argument can go either way.  Certainly I don't think there is any question that this would remove some of the urgency for conserving species, for preventing them from going extinct.  Having spent a career trying to prevent extinctions, I know that this will inevitably happen.  Some of the techniques that are involved would almost certainly cause animal suffering.  There would be individuals that would be created that would horribly abnormal.  And you could argue that there is an animal, welfare animal rights issue there. 

 It could be ecologically problematic Bringing back a species, especially one that's been gone for a long time, could almost amount to bringing a new invasive species into an ecosystem.  It could have a very disruptive effect on the ecosystem in which it was introduced.  And, finally, there's the arrogance factor.  That this is just plain hubristic.  It's people again thinking that there's a techno fix for all of the problems that we've created during the anthropocene.  So, as the arguments about whether we should or shouldn't do it have raged, the question really, I suppose very fundamentally is, okay, we can argue about whether it's a good thing or a bad thing, but could we even do it? Is it possible to actually bring back a species from extinction? And there are several ways, several technologies, that we know seem to hold the promise, some much more likely than others.   For very shallow de-extinctions, in many cases you could preserve gametes from a species before it goes extinct, and after that last individual dies, you could use those preserved gametes for in vitro fertilization and produce a new individual, accomplishing, essential, a de-extinction.  Cloning, of course, is a possibility.  Again, if you've carefully preserved non-reproductive cells, cloning is a technology that's now proven and has a fairly high probability of working.  And certainly if you have the forethought to carefully preserve those cells before that last individual died, you could resurrect the species. 

 Both of these techniques, whether you used in vitro fertilization of gametes that were preserved or cloning, have a distinct advantage in that they are producing a perfect replica of the extinct species.  The third technology, using genome editing in which you would attempt to modify the genome of an extant species by recovering ancient DNA from a long ago extinct species and using that ancient DNA to genetically engineer the DNA of the extant species.  This would not produce a perfect copy of the extinct species.  It might approximate it in a number of ways, but it would not be the extinct species.  It would indeed be something that may fall in the realm of synthetic biology in that it would not be a genetically modified organism that had just a few genes messed with.  This would be a completely novel organism that had a large suite of its genome modified, and a new form of life would be produced.  So, looking at these sort of in order of probability of success, in vitro fertilization with gametes seems to be the thing that could actually happen almost any time because we have the capacity to do this.  We have preserved gametes of a number of species that have gone extinct.  Quite often the last few individuals were in captivity, so it was relatively easy to preserve eggs and sperm in what have popularly been known as frozen zoos.  And even more recently, rather than just cryopreserving these gametes, the possibility that you might be able to take cells from an extinct-- Non-reproductive cells from an extinct species, you might be able to recreate gametes from stem cells so that you would be sort of artificially producing the gametes rather than just preserving them. 

 But in any event, this obviously requires some careful planning.  It requires careful preservation of the material.  And, obviously, it requires a living organism to be a surrogate for whatever embryo you end up producing this way.  We know we can do this.  We've not done it with an extinct species, but it's been done with threatened species.  An example here of an inter-specific embryo transfer  that resulted after in vitro fertilization.  In this case, the in vitro fertilization was the bongo, the cute little guy on your right.  The embryo that was produced was implanted in a surrogate mother, an eland, a closely related antelope, and the embryo was carried to term and a perfectly beautiful baby bongo was born.  So we know that the sequence, the technology, actually works.  We've done it. 

 We just haven't done it in the context of resurrecting an extinct species.  So the people that are excited about bringing back an extinct species, of course, are chomping at the bit.  Why don't you do it? Why don't you do it? You've got the material already cryopreserved.  Why don't you just get on with it? And, fortunately, the people who are responsible for those cryopreserved gametes are a responsible lot, and they basically responded that the material is safe where it is now, why would we want to bring this organism back into a world in which the problems that caused it to go extinct are still operating? A very good argument for basically waiting until the right moment.  Cloning from preserved non-reproductive cells.  This is what most people immediately kind of seize on as being the biotechnology that might result in a de-extinction.  This, again, requires that you carefully preserve some non-reproductive cells.  And then, using the procedures that we now call cloning, you could, in fact, produce an embryo.  Again, it would require a surrogate to carry that embryo, and, again, this is a process that has now been done a number of times with non-extinct species.   And a few years ago, it almost produced the first de-extinction. 

 The story is an intriguing one.  It is an ibex subspecies that occurred in the Pyrenees, and eventually this ibex species boiled down to one individual.  One female.  And as you all know, when a species gets down to the last individual, whether it's Martha the passenger pigeon or George the lonesome tortoise, we give it a name.  She was Celia.  Celia had a radio collar on so they could keep track of her, but they decided since she was the last one there was really no point in doing anything except let her live out her life.  Fortunately, in one of the events when they had to change the battery on Celia's radio transmitter, they decided to take some mammary gland cells from her with the idea that maybe we might be able to use these in some way in the future.  Well, shortly thereafter, Celia and her subspecies went extinct in the most unusual of ways.  A tree fell on her.  What are the odds? But in any event, the French and Spanish researchers had those cells and they figured, what the heck, let's give it a try. 

 They used the more or less standard cloning procedure.  They did actually get a few embryos.  They implanted them in a domestic goat.  One of the embryos went full term and died moments after it was born.  It was deformed and died.  But at least for a few minutes we actually had pulled off a de-extinction.  And it certainly points out, I think, the difficulties of using cloning as a procedure for bringing back extinct species.  The odds are pretty heavily stacked against it working with a very high probability of success.  Which brings us to the real science fiction part of this, which is the genome editing and synthetic biology approach.  This has only really been made possible just in the last few years by the development of genome editing tools, like CRISPR, and gene drives that would allow some of the change that we deliberately place into a genome to be rapidly replicated within a population. 

 The idea here is that you would go to the badly degraded DNA from a long extinct species.  And when I say badly degraded, this is really a mess.  It's small fragments of DNA without any sort of real context to what the context in the living organism might be.  One geneticist, I think, described it as taking the New York City phone book and turning it into confetti, and then, just for good measure, doing the same thing with the Boston phone book and mixing all that confetti up and then giving you this pile of confetti and saying, here, read this.  Well, it sounds impossible, but we are able now to start putting the confetti, that degraded DNA, back together.  And although we may not be able to completely get the genome back together, we would be able to get some fairly significant segments of DNA reconstructed.  And if you were able to do that, you could take a living species, an extant species, a close relative, and you could identify the analogous segments of DNA to the ones that you've managed to reconstruct.  And genetically engineering the extant genome, you would replace the pieces from the extinct species.  It would be an extreme example of a genetically modified organism.  It would not be a replica of the extinct species. 

 The passenger pigeon was one of the species that has captured a lot of attention for the possibilities of using this approach.  For the passenger pigeon, we've got thousands of specimens in museums.  We don't have any good intact DNA preserved, but all those thousands of specimens could yield a lot of fragments of DNA that we might be able to put back together.  And if we were able to do that, the closet relative of the passenger pigeon is the band-tailed pigeon of the western US.  It's very closely related so that by doing the substitution of band-tailed pigeon DNA with passenger pigeon DNA, you might be able to produce something of a viable genome.  And if you were able to do that in a stem cell, you might be able to reprogram that stem cell to produce eggs and sperm.  And if you were able to do that, you might be able to do in vitro fertilization and you might be able to produce and embryo.  And if that worked, you might be able to actually produce an organism.  Each of those steps, of course, has an incredibly small probability of success.  And the likelihood that this would produce a squab, a young pigeon, is pretty remote. 

 And even if you did, it would not be a passenger pigeon.  Those of us who are skeptics have called it a Frankendove. [laughter] The ecologist Paul Ehrlich said what you would probably get is a very long-tailed band-tailed pigeon.  Similarly, with the woolly mammoth, it has been sort of joked that what you would get would be a very hairy Asian elephant.  Which brings us to the mammoth.  That is the other holy grail of de-extinction.  We've been fascinated with mammoths for years, and now the race to try to pull off this miracle of modern technology with a mammoth is on.  And there are several, of course, approaches.  One might be, as we are, unfortunately with climate change, thawing out the Siberian tundra and woolly mammoth carcases that have been frozen in the permafrost for millennia are now sort of thawing out, perhaps if you were incredibly lucky, you might find gametes.  Basically, those who know about the condition of the material that comes from these frozen mammoth carcases says forget about it.  There are no viable gametes left after thousands of years. 

 So, maybe you would find an intact cell, non-reproductive cell, that would allow you to actually clone a woolly mammoth.  And, again, those who have closely examined the material that's coming out of these carcases of woolly mammoths say, you know, we all know what meat looks like after it's been in the freezer for too long.  Well, that's pretty much what woolly mammoth tissues look like.  It's soup.  It's a mess.  And, of course, it's contaminated with all kinds of bacteria and fungi and the saliva of animals that have fed on it.  It's a mess.  So most people say forget about it.  You are not going to be able to clone a woolly mammoth.  So that leaves, essentially, the genome editing approach. 

 Perhaps, since we do know quite a bit now about the mammoth genome, perhaps we could actually do the genome editing.  In this case, it would involve genetically engineering the genome of an Asian elephant, the closest living relative.  Asian elephants, as you probably know, aren't doing too well themselves.  They are considered to be a threatened species.  So the idea that you're suddenly going to divert a herd, and it would take a herd to do this because it would take many, many, many replications before you ever succeeded, but to divert a herd of Asian elephants toward being surrogates to woolly mammoth embryos seems highly unlikely and probably irresponsible.  So this one maybe but the odds are against it.  A couple of years ago, Beth Shapiro, one of the experts on ancient DNA, especially mammoths, wrote a book with the intriguing title "How to Clone a Mammoth." On the dust jacket of her book though, she acknowledges that that title was sort of forced on her by the publisher in order to sell books, and she had a perhaps much more realistic title for what she would have called the book.  So, in any event, we're left with the possibility that we could pull it off.  We haven't yet, but stay tuned.  Probably in the not too distant future a de-extinction of some type will occur. 

 What would this contribute to conservation of biodiversity? Well, obviously, when you think about restoring, resurrecting, an extinct species, you're restoring what might have been a very important member of the ecological community that has gone extinct, particularly if it's a recently extinct species.  So, conservationists are not only concerned about preserving species, they're also very concerned about preserving the integrity of ecological communities and ecosystems.  So bringing back strategically important species and getting them back into the community they were once part of could make a lot of sense.  And we know that there are species that have gone extinct fairly recently for which we have now overcome the problem that caused them to go extinct.  You'll all remember a few years ago how much excitement there was when there was the mistaken identity of an ivory-billed woodpecker down in Arkansas.  And the reason everyone was so hopeful over that mistaken identity was that ivory-billed woodpeckers went extinct because we destroyed their habitat.  And in the hundred years or so that they've, for the most part, been gone, the habitat has regrown.  The bottom land forests of the southern US are back and the place where that alleged ivory-billed woodpecker was seen looked like perfectly good ivory-billed habitat, which made everyone hopeful.  An ivory-billed woodpecker.  As an ornithologist, I'd vote for bringing back an ivory-billed woodpecker. 

 Seems like a good idea.  Over in Tasmania, the thylacine, the apex predator, terrestrial  predator, was exterminated deliberately because of the mistaken belief that it killed sheep.  It's a large marsupial predator.  Certainly looked ferocious enough, but there was truly no evidence that it ever killed sheep.  But we all know important apex predators are in ecological communities.  And, certainly, bringing back Tasmania's apex predator would probably-- And it only went extinct in the 1930s.  So bringing back an apex predator would probably have some of the same beneficial impacts on the Tasmanian community and ecosystems that the reintroduction of wolves had on the Yellowstone ecosystem.  The quagga, another species that went extinct just decades ago.  The quagga was deliberately exterminated from South Africa.  It's obviously a relative of the zebra. 

 But today South Africa has some of the best protected areas in the world, some of the largest national parks where, if you could bring back a quagga, there's a place where they could exist in a protected state.  De-extinction could also help in restoring the integrity of an ecological community by bringing back a species that had a keystone function.  The thylacine was probably a good example of that.  But there are many other species that have gone extinct and in their wake other species have gone extinct because they depended, in some way, on the extinct species.  An example of this that I stumbled on too while I was over in the Indian Ocean, Tom, enjoying tropical islands on Mauritius where the dodo once lived, was that there is a tree on the island that is, was at the time, approaching extinction because its seeds would not germinate at an adequate rate to maintain the population.  We figured out that the reason its seeds don't germinate is that they needed to pass through the digestive tract of a dodo in order to achieve a high enough germination rate to keep the population going.  We were able to demonstrate this by force feeding seeds to a somewhat uncooperative turkey.  [laughter] But it proved that point that if-- And no one is imagining we could bring back the dodo because we don't have any good material.  There is only one dodo specimen that still exists.  A very sad story. 

 But there's no hope that we would be able to bring back a dodo, but it's a good example of how these cascading effects can follow in the wake of one specie's extinction.  Even here in North America we have a large number of plant species that botanists describe as having anachronistic seeds.  Seeds that were clearly designed to either be dispersed or in some way treated by an organism that no longer exists.  Some of these are fairly familiar trees.  The buckeye tree, for example.  Osage, orange.  These botanists tell us were basically designed to be eaten and have their seeds either treated like the dodo did with the tambalacoque tree or dispersed by extinct megafauna, by species that went extinct thousands of years ago when human beings wiped them out.  So, there are these examples of where you could really restore the integrity of an ecosystem by bringing back key species.  But conservation biologists-- guess you'd have to say we have  to be a hopeful lot or we'd not be in the business of trying to save biodiversity.  But, although we'd like to be hopeful about this, there are a lot of concerns about unintended consequences and conflicts with existing conservation efforts. 

  At the most basic, if you were able to pull of de-extinction and you were able to do it with any kind of reliability and replicability, it would certainly make the extinction crisis that we're facing today seem a lot less calamitous.  We're already struggling to get people to sort of face up to the fact that we really are facing a crisis with the loss of biodiversity.  If we can cavalierly say, eh, don't worry about extinction, we can always bring them back later, it creates a moral hazard.  It creates the idea that why should we worry about it if we've got some insurance, you might say, that we could always undo the damage.  So, de-extinction, if it was pulled off and became a technique that had any widespread applicability, it would certainly undermine current efforts to prevent extinctions.  And during my career, I can virtually assure you that it will happen.  Every time there has been an endangered species that came into conflict with some special interest that was inconvenienced by our efforts to try to preserve the species, immediately the offers were made, well can't we catch those animals and move them somewhere else so they get out of our way so we can cut the forest, so we can drill, so we can mine, whatever it is where they live? We'll pay to have them captured and brought into captivity so you can have a captive breeding program just so they get out of our way and are no longer an inconvenience.  This becomes the ultimate cop-out.  We'll pay to preserve some DNA, and we'll preserve, we'll have them brought back when they are no longer an inconvenience for us.  There's also the possibility of conflicts. 

 And the conflicts are ones that would occur, I would say, primarily if you succeeded to the point where you actually got to putting the organism back in nature.  Putting those organisms back into an ecosystem, into a community that they've long been absent from, becomes almost the ecological equivalent of an invasive species.  It would be very disruptive to the existing community.  It might even threaten species.  But it would certainly change the structure of the community.  We also imagine that if you were successful in bringing back an extinct species, it would capture so much attention that you would want to actually create a place where the resurrected species could live and thrive, essentially creating a nature reserve for it.  And lest you think that we're sort of dreaming about that, in Russia, in Siberia, the Russian government has renamed one of their nature preserves Pleistocene Park.  [laughter] In anticipation of having Pleistocene megafauna to one day put back there.  And, certainly, we are already heavily overburdened with commitments trying to save species from extinction.  If you bring back an extinct species, once the biotechnology crowd has finished with their work in the lab, they're going to hand it off to people like me and say, here, turn this into a viable population. 

 Do something with it.  And it becomes a conservation dependent organism that we would have to devote resources toward managing.  There is an upside, though.  An it's not basically de-extinction.  The upside that many conservation biologists have seized on is the possibility that these very technologies that seem to have been so narrowly focused on the task of resurrecting an extinct species could actually be harnessed to prevent extinctions.  So, how could these tools be used for preventing extinctions? One that has just, actually in the last month, been published in "Nature" has to do with the severely endangered northern white rhino.  One of the most endangered mammals in the world, down to literally a handful of individuals.  The idea here is that you might be able to take some of the preserved non-reproductive cells from animals that have, for the most part, lived in captivity, and you might be able to induce them to become pluripotent stem cells.  And if you were able to do that, you might be able to produce gametes, you might be able to produce a fertilized egg, and you might be able to implant the embryo on the closely related southern rhino, white rhino.  In this case, the process is already underway, as the diagram sort of says. 

 The San Diego Zoo and other institutions that are the custodians of these carefully preserved cells are already on this pathway and may pull it off.  If they do, it's not going to resurrect an extinct species, but it would certainly help preserve an endangered species.  We don't have that many of these rhinos left.  Getting genetic material from each and every one of them to perhaps incorporate into a recovered population is incredibly important, and this is one way to do it.   It's also possible that we could use some reproductive cloning as a tool of last resort for some of these tragic cases where a species boils down to that one remaining individual.  Or a few individuals that are incapable of reproducing.  This is the very last Rabbs' fringe-limbed treefrog.  There is only one left in the world.  He is still alive.  He is named after George Rabb, who is the most prominent amphibian conservationist of our age. 

 I'm not sure it was an honor to name a nearly extinct frog after you when you've spent your life trying to preserve them, but perhaps those cells that have been retained from Rabb's fringe-limbed treefrog could be used to clone him.  A year ago, I gave a talk down in Chicago, and George Rabb was in the audience.  So to interject a little bit of humor into the talk, I said, you know, I think if I had my choice, I'd rather clone George Rabb than his treefrog.  It would probably have more benefit for amphibian conservation.  But there are lots of these species that end up often going extinct in captivity when we're down to the last few individuals, like the white rhino, that are incapable of reproducing or down to the very last individual.  Cloning might be able to pull it off.  There's also the possibility of undoing a very serious problem for endangered species that we have been able to recover.  Many of these species have passed through severe population bottlenecks.  And in the process of declining to such low numbers, they've lost most of their genetic diversity.  We've been able to bring these species back numerically, but the populations that resulted are genetically depauperate. 

 The Mauritius kestrel, a species that I cut my eye teeth on as a conservation biologist, was literally down to a handful of individuals when we started work on them in the early 1970s.  There are now almost 800 of them.  But they are virtual clones of one another.  They have virtually no genetic diversity.  We've been able to go back to museum specimens of Mauritius kestrels from the 19th century and early 20th century, before the population crashed, and it's not hard to find alleles that are no longer present in the recovered population.  In this case, if you could recover those alleles and put them back where they belong, you're not crossing species lines, you're not technically even doing genetic engineering, you're just putting the alleles right back where they belonged, you could make a huge difference in the long-term prospects.  We're actually doing this right now with the black-footed ferret.  It went through an extreme bottleneck.  Again, down to very small numbers.  We've been able to recover the black-footed ferret, but it's genetically depauperate. 

 And, again, going back to museum specimens, we've been able to find alleles that simply are gone, that were lost during the bottleneck.  And there is a project underway now to try to put those alleles back where they belong and improve the black-footed ferrets' long-term prospects.  Genetic engineering also might help us deal with some of the wickedest problems that conservation biologists face.  One of the most intractable of these are introduced exotic diseases that native species have no resistance to.  And we have a troubling accumulation of species that are going extinct or are in trouble because they've been unable to cope with a pathogen that we have introduced into their range.  Here in the US, perhaps the most dramatic example are the Hawaiian honeycreepers.  Incredibly vulnerable to avian malaria and avian pox, which are diseases of continental birds that make birds sick but don't necessarily kill them.  But in Hawaii, the Hawaiian honeycreepers, in their long isolation, no longer have any ability to cope with these common bird diseases.  Imagine that you could find the gene that confers resistance to avian malaria.  It's probably a very conservative gene because lots of birds seem to have this resistance, and that you could genetically modify Hawaiian honeycreepers. 

 Essentially applying gene therapy to them to help them deal the disease.  The American chestnut is now ecologically extinct.  We've been trying for almost a century now to find chestnut trees that are resistant to the chestnut blight and have been completely unsuccessful.  The American Chestnut Foundation has finally thrown in the towel and said a resistant American chestnut simply does not exist.  So, what do we do? Do we just say, well, okay, the chestnut is gone.  We're not going to be able to resurrect it.  Or, now that we've discovered the three genes that confer resistance to chestnut blight in Asian and European chestnuts, perhaps we could essentially genetically engineer American chestnuts very specifically by giving them the ability to cope with this otherwise deadly disease.  The project is already underway.  So, who knows? Maybe the most abundant tree in the eastern deciduous forest might one day be back.  And indeed, just to demonstrate to you that the things I'm talking about are timely... 

  Four hours ago.  Headline.   In this case, not genetically engineering Hawaiian birds but going in and using genetic engineering to basically wipe out the mosquito vectors.  There were no native mosquitoes in Hawaii until we introduced them along with the avian diseases.  But perhaps we can get rid of the mosquitoes and spare the Hawaiian birds from extinction.   It's possible too that genetic engineering might prevent extinctions in the face of climate change.  We know that many of the species that are being threatened by climate change have subpopulations that are able to cope with some of the extreme climate conditions that are predicted to be coming our way.  In this case, you could, in fact, find those genes in a population that can cope with extreme drought or heat for the species and do what has been termed facilitated adaptation.  So essentially speed up the process of adapting to the changing climate, since most species seem not to be able to adapt on a timely enough basis to keep up with the pace of climate change.  This would sort of be an alternative to what many people are proposing, which is assisted colonization, where you would simply move the population from the place where the climate is predicted to be inhospitable and move it somewhere else where you think the climate is going to be more suitable. 

 A much more challenging, perhaps, proposition.  Edith's checkerspot butterfly has sort of become the poster child for this, but many of you may have seen the headlines just in the last few months that they're now talking about perhaps using this approach with coral, where corals that are very sensitive to rapid climate change, they have found populations that seem to be able to cope, perhaps using biotechnology we can get the spread of those adaptive genes into wider populations.  So lots of possibilities here to help me with the types of things that I do, preventing extinctions and many of these we have tried very hard to get the de-extinction crowd excited about, and they just don't seem to get it.  It's always, "Oh, no, no, no, no, look over here, woolly mammoth, woolly mammoth." They say this is mundane.  This is, you know, this isn't exciting.  Nobody's going to get nominated for a Nobel Prize by doing this.  So, the technology is there, the opportunities to use it are obviously there in many cases, we'll see what happens in the coming years.  So, if we are going to use biotechnology in a way that contributes to preserving the biodiversity on the planet, thoughtful people, including the International Union for the Conservation of Nature that now has a special committee coming up with guidelines, if you will, for how to use biotechnology, they've come up with a few, I would say, no-brainers.  Use science, not sentiment and sensationalism, to pick the species that you're going to work on.  You want it to work. 

 You want it to work spectacularly, not just be a media sensation.  Consider the conflicts and unintended consequences.  Again, the Jurassic Park scenario.  Thank goodness that that was put into the movie, that it does have the possibility for having very bad consequences.  Make sure that you don't compete or distract from ongoing traditional conservation efforts.  Consider the ethical dimensions of this.  This is something that, sadly, in all of my many discussions, and I have been part of quite a few of the discussions over the last four years, I would have to say the lab crowd doesn't get the ethical dimensions of this.  They are still sort of hooked on if we can do it, we will do it, get out of our way, don't make life difficult for us.  But there are ethical dimensions that are very real that should be considered.  And obviously think really carefully before you released any of these products of biotechnology back into natural ecosystems. 

 So, in the end, conservation biologists, I think, have largely concluded that our priority has to be taking care of the 10 million or so species that are already with us.  Our hands are basically filled trying to prevent the extinction of those species.  In light of the huge number of species that are threatened and that are likely to go extinct in the very near future, bringing back a few favored species through modern technology seems like a dramatic sideshow.  It's not going to make a net positive contribution to biodiversity on the planet.  Nonetheless, I think it's very important that the folks who work in the lab with these biotechnologies and the people who work with biodiversity in the field should have an open dialog and make sure that what they're doing really has the greatest potential for having a very positive outcome.  But, still, one worries about the anthropocene problem.  The arrogance of human beings thinking that for every problem we've created there's a techno fix.  And this seems, at least for the biodiversity crisis, to be nothing more than a techno fix that we wouldn't need if we had just figured out how to restrain ourselves.  So I'm going to end here with a quote from one of my childhood mentors, who I think nailed it.  She didn't live long enough to hear talk about the anthropocene, but Rachel Carson had this to say. 

  So, thank you very much.  [applause]   I work here at the UW Madison Biotechnology Center.