Efforts to Resuscitate Extinct Species May Spawn a New Era of the Hybrid

FELLOW TRAVELER: Techniques from synthetic biology might allow scientists to recreate a living bird from the extinct passenger pigeon's DNA. Image: Louis Agassiz Fuertes

WASHINGTON, D.C.?A bird that once darkened the skies of the 19th-century U.S. no longer exists, except as well-preserved museum specimens bearing bits of DNA. An ambitious new effort aims to use the latest techniques of genetic manipulation to bring the passenger pigeon back, as North Dakotan Ben Novak, a would-be de-extinction scientist working on the Revive & Restore project at the Long Now Foundation, told the crowd at the TEDxDeExtinction event here on March 15.

"This [pigeon flock] was a biological storm that was rejuvenating resources and allowing other animals to thrive," Novak said of the storms of Ectopistes migratorius feces that used to fall like rain on the landscape of eastern North America. Plus, with the regrowth of forest on the east coast "there is more passenger pigeon habitat every year."

But if a bird looks like an extinct passenger pigeon, has some of the genetic code of the passenger pigeon, but does not act like a passenger pigeon because it is raised by other breeds and few in number: is it a true passenger pigeon? That is just one of the questions posed by the idea of de-extinction?deliberately resurrecting species killed off by human activity or inactivity. And that question may just challenge one of the fundamental concepts of biology: what determines a distinct species.

Welcome to the new era of the hybrid. Species have always been promiscuous and enjoyed porous boundaries, but synthetic biologists and other scientists seem set to blur those boundaries out of existence.

Tainted animals
The bison now repopulating the U.S. West?s plains bear the genetic traces of their cattle forebears, residue of an effort that began in the 19th century to breed an animal that could survive the brutal Great Plains winters and drink less water than European cows. Wolves racing through the western landscape with black coats instead of the traditional gray can thank ancestors that got frisky with dogs. And does a Florida panther that carries genes from the Texas cougar count as less of a panther, even if the effort is all that stands between the species and extinction?

"Purity is not found in species," argued Kent Redford, a conservation biologist and former chief scientist at the Wildlife Conservation Society at the DeExtinction event. "We ourselves are not pure," bearing traces of genetic intermixing with Neandertals, Denisovans and perhaps other extinct hominids.

So what counts as a species then? Per the dictionary, a species is "a class of individuals having common attributes or designated by a common name." But biologists more precisely count species as a group of organisms that can interbreed to produce fertile offspring. So the horse and donkey are species, although those aren't their species names, and the mule is?well, it's been a little unclear since Carl Linnaeus came up with the species designation in 1753. As a (usually) sterile hybrid, the mule doesn't count.

But mules certainly do live and cases of mule fertility have been reported from antiquity down to the present day. Mules have even been cloned?and now, with the development of techniques to cut and splice DNA almost at will, scientists might be able to remake the mule into a fertile hybrid. But first they would rather apply the technique to endangered or extinct animals, like the Pyrenean ibex known as the bucardo or the Asian wild cattle called the banteng.

Rise of the hybrid
When a new animal is born it bears a mixture of both parents? genetics. So what then is an animal that has parents from two different species? The term hybrid was first used to describe the offspring of a tame sow and a wild boar. Or, as Redford put it, "something humans wanted." But now hybrids often bear a linguistic taint, neither fish nor fowl?almost as bad as a genetically modified organism, which, of course, all commercial species now are to one extent or another.

But purity still exists in the wild. Or does it? Traffic fatalities have caused swallow wings to shorten to enable quicker takeoffs just as fishing pressure has caused many wild-caught fish species to shrink in size. Bacteria rapidly evolve resistance to our best antibiotics. Humanity directs evolution unconsciously?except when we do it consciously, introducing useful suites of genetic information like the ability to produce a toxin poisonous to insects inserted into crop plants that was originally made by a bacterium.

With crude technologies such as cloning, where an entire cell nucleus is swapped from one species to another, this has already been done to revive an endangered species. An ordinary cow gave birth to a banteng?Bos javanicus, a species of wild cattle from Asia?in 2003. Although the scientists involved were worried that the hybrid might look more like an ordinary cow, out popped a banteng that lived at the San Diego Zoo for seven years?a diminished life span but a life nonetheless. "It was surreal to see this exotic animal from the jungles of Southeast Asia born in an Iowa field that reeked of cow manure," recalled Robert Lanza of Advanced Cell Technology, the company that helped achieve the feat.

Now new technologies such as an enzyme that can precisely cut DNA, known as Cas9 (for clustered regularly interspaced short palindromic repeats-associated system 9) and also derived from a bacterium, may enable scientists to stitch strands of DNA in and out of the genetic code. Find the genes that make a mammoth different from an elephant?say, sebaceous glands, hair growth, extra hemoglobin in the blood to withstand cold temperatures, among other traits?insert those into a strand of elephant DNA, and begin to make mammoth sperm and eggs. Then impregnate the mammoth's closest living relative, the Asiatic elephant, and wait for a baby mammoth to be born.

Only it won't be a true mammoth, because its mother will have something to say about how those genes are expressed, from epigenetics to the micro biome. "A gene doesn't tell you how to read it and make an organism," noted biologist David Ehrenfeld of Rutgers University at the DeExtinction event. "The genetic code is more like a database than an instruction manual." In other words, even the best genetic transcript?something still out of reach for many extinct animals and plants?will not provide the detailed source code needed to build version 2.0 of the extinct organism. He added: "All the words of Hamlet are in the dictionary, but if I scan the dictionary, Hamlet does not fall out of it. A strand of DNA can be read in hundreds or even thousands of ways."

And then there's the danger of the favoritism of humans that could lead some artifact "species" to predominate. "Who would have dreamed that genetic engineering in agriculture would diminish the biodiversity of agriculture? We lost tens of thousands of genome diversity from plants," Ehrenfeld added. As he noted, it's hard to predict the ultimate impact of a given technology.

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