Bedtime Stories, Gastric-brooding Frogs, and Jurassic Park

by Arthee E. Jahangir

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“Gone” by Isabella Kirkland (painting)

Several weeks ago, I had an impromptu slumber party with two of my younger cousins, girls ages 7 and 9. I showed up to their home in Washington, DC well past midnight after a full day of museum visits and monument sightseeing. When I arrived, I expected them to be asleep or at least dwindling away into dreamland. I was mistaken—they were hyper as ever and wouldn’t let me out of their sight until I was between them, snuggled under the covers with the lights out. Even then, the chitchatting wouldn’t cease, which I guess is normal at a girl’s sleepover. While we were making big plans for the next day (morning run, tennis, and Just Dance for Wii), the eldest of the two sisters randomly asks, “So, can you make a human from HeLa cells?” Yes, she is only nine years old.

The girls had previously visited my home in New Jersey and found my dad’s copy of “The Immortal Life of Henrietta Lacks.” The idea of immortalizing human cells and growing them in a Petri dish both fascinated them and freaked them out. “No, you can’t make a human from HeLa cells, but a sheep has been made from cells,” I replied. Questions and exclamations from the both of them ensued for a period of time. I realized that I wasn’t going to sleep anytime soon, so as their awesome, older cousin/female scientist from the Big Apple, I told them a bedtime story—the story of Dolly the Sheep.

The next morning, my precocious cousins googled “Dolly the sheep” and instantly expressed their warm sentiments, “Aw! She’s so cute! OMG, she had TWINS AND TRIPLETS!” Finding myself in a perfect teaching moment, I explained to them how Dolly technically had three moms via somatic cell nuclear transfer (SCNT) (the process of taking the nucleus from a somatic cell and introducing it into an egg cell that had its nucleus removed) and the idea that scientists can use this and other technologies to rescue endangered species and perhaps even bring back extinct species. I had officially hit my “Science is so cool!” quota of the week. My cousins were so excited about the possibilities and reawakened my own enthusiasm for conservation genetics and cloning technology. Science and Just Dance: not a bad Sunday morning.

Little did I know that my geeky bedtime story was foreshadowing current news in the science realm. The following week, I repeatedly stumbled upon this picture of Rheobatrachus silus, the Southern Gastric-brooding Frog with a tiny froglet in its mouth. During reproduction, the female swallows her fertilized eggs and broods them in her stomach, in which acid production is suspended allowing for a temporary womb.  After several weeks, the time during which hatched tadpoles develop further, the mother regurgitates her fully formed froglets. This weird species has been extinct for over a quarter of a century and recently has been brought back to life, kind of.

A team of Australian scientists working on the Lazarus Project, led by University of New South Wales paleontologist Mike Archer, used SCNT, the same laboratory technique used to clone Dolly, to revive R. silus. For over five years, they injected cell nuclei from R. silus’ frozen tissue preserved since the 70s, into egg cells of the distantly related Great Barred Frog, Mixophyes fasciolatus. Recently they were finally able to get some of the egg cells to spontaneously divide and grow into a tiny ball of cells, representing an early stage of embryonic development. Although these embryos did not last more than a few days, genetic test results confirmed that the DNA from these cells was successfully transferred from the extinct frog.

The team remains optimistic that the obstacles are just technical and not biological, showing great promise as a conservation tool when hundreds of amphibian species are facing a catastrophic decline. This is also one of the first examples demonstrating at least an inch of possibility for success towards revival of an extinct species.

The Pyrenean ibex, commonly known as the bucardo, is another Lazarus Project candidate species that has shown promising results.  The wild goat went extinct in 2000 and in 2009 was successfully cloned and born alive, but died a few minutes after birth due to lung defects. The Lazarus Project’s results are yet to be published but Dr. Archer spoke publicly for the first time on March 15th at the TEDx DeExtinction event in Washington, DC, hosted by Revive & Restore and National Geographic.

The TEDx DeExtinction event was a daylong public discussion regarding the idea of bringing extinct species back to life, exploring the pros, cons, and broader implications. I was in town only a week before this marveling at the reconstructed fossils of DiplodocusTriceratops, and of course, Tyrannosaurus rex in the Hall of Dinosaurs at the National Museum of Natural History. Thoughts of a real life Jurassic Park swirled around in my mind. Now, a group of leading experts gathered to discuss the possibility of making science fiction into reality.

Although the idea of bringing back dinosaurs is inarguably very cool, there doesn’t appear to be any genetic material from 65 million years ago, so at the most, we would be looking at a Pleistocene park. Some of the favorite extinct species discussed at the event were the Woolly mammoth, Saber-toothed cat, Passenger pigeon, Tasmanian tiger, and Chinese river dolphin, just to name a few. Although it was established that we live in a time when bringing back extinct species is no longer a fantasy, it is still far from being a reality.

There are currently at least three techniques that are being used for de-extinction. The first is cloning by SCNT (as described earlier) or similar techniques, and then implanting the embryos into a surrogate mother of a closely related species, effectively producing the extinct species (like the bucardo). The second is to create hybrid genomes of the extinct species with a related living species. By studying the differences of the genomes, scientists can replace the living species’ alleles with different alleles that belong to the extinct species. New genome-editing techniques, such as CRISPR RNA guided nuclease described by George Church, promises to be a powerful tool in allelic replacement. Subsequent breeding would result in the revival of the extinct species. This technique is promising for the revival of passenger pigeons because SCNT is not successful in birds.

The third technique is incremental back breeding, which is a way that some scientists want to bring back the auroch, the ancestor of the domestic cow. Regional primitive cattle breeds that have some auroch-like traits would be specifically mated, with human assistance (i.e. artificial insemination or embryo transplantation), to help gradually create a new lineage of auroch-like cattle. All these techniques have shown some success and therefore look promising, but there are many complicated challenges at each step of the way.

Even if and when scientists overcome the numerous obstacles of establishing an extinct genome into a viable cell and finding a surrogate mother that is able to bring the offspring into the world, a whole new series of philosophical, ethical, and moral questions will arise. Is the species of the revived animal really the same as the extinct one? Will it behave the same way? Who will raise it? Where will it live? Will it be able to survive in the wild? Should scientists breed a more resilient version of the extinct species? Will it be able to mate and breed a population? Should humans continue to “play God?” These questions are the tip of the iceberg and most of them have yet to be answered.

The DeExtinction talk was live-streamed online and after watching most of it (there were over twenty-five speakers, so give me some credit), it was clear that the scientists and science enthusiasts were pretty divided on the to-revive or not-to-revive question. The main reasons why people advocate de-extinction is that it would preserve biodiversity, restore “keystone” species in failing ecosystems, gain knowledge and advance technology to prevent more extinction, and to bring justice to the species that have been wiped out by humans.

Criticisms for de-extinction were mostly related to the vast uncertainty of sustaining a population of a revived species, how it would effect the environment, and its negative effect on the hard-working efforts of conservation. Many of the evolutionary biologists agreed that there should be a very well defined set of factors to determine which species are the ideal candidates for de-extinction. What they disagreed on though, was which species.

An ecology and evolution graduate student’s love affair with passenger pigeons obliged him to present a long list of reasons arguing that the pigeon is an ideal candidate (i.e. it recently went extinct, was eradicated by humans, its natural habitat is flourishing, needs minimal parental rearing, will not outstrip habitat resources). However, another speaker began her presentation by stating that the passenger pigeon is a poor candidate because of its huge population size and complex social behavior. She believes the ideal candidates are the ones that are evolutionary more historic, the species that are more distantly related, which by definition, will be more difficult to bring back without the aid of closely related living species.

More than a few conservation biologists felt that de-extinction would compete with conserving endangered species. The foundation of conservation is that extinction is forever. If de-extinction forfeits that maxim, how will it affect the efforts of saving endangered species? I particularly find it hard to believe that de-extinction will derail conservation. I think it would actually bring attention and increase the value of conservation. It is another reason to become excited about preserving biodiversity, especially when the rate of extinction is increasing exponentially. De-extinction will most likely remain as a very difficult feat to accomplish and will not be equally plausible for all species. It will be a last resort for a lucky few, so attention would not be stolen from conservation of living endangered species.

While I think that funding for science should be given to fields with higher global and humanitarian priorities in these tough financial times, I do not think de-extinction is one of those fields. I do hope at some point, de-extinction will receive more financial attention, but right now private funding seems to be the way. It is important to recognize though that there will be much new knowledge that will be discovered on the way to de-extinction. As Dr. Archer suggested with the Southern gastric-brooding frog, understanding how the frog’s hormones can stop the stomach from producing gastric juices could have useful applications for people who have digestive problems (like my brother and everyone else I know).  It may not be the most altruistic argument, but the greatest reason why I’d like to see the revival of an extinct species is to experience the wonder and awe of making something that once was a dream (or a bedtime story) become a reality.

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