In the race to save species, genetic engineering is coming to nature

August 24, 2015 — The regal American chestnut once reached across the deciduous forests of the Appalachians and Eastern Seaboard. Its abundance was astonishing: Up to one in four of every large tree in eastern forests was a chestnut.

Birds nested in its branches. Squirrels and other small mammals clambered over its limbs. Bears, deer, turkeys, blue jays and squirrels ate its massive and consistent nut crop. Rural people gathered the nuts and logged the trees for their straight-grained, rot-resistant timber. The American chestnut was king of the eastern forest, a keystone species for humans and nature alike.

Then, probably in 1876, the fungus Cryphonectria parasitica escaped from a shipment of chestnut seeds from Japan. The fungus spread to American chestnuts, which — unlike their Asian counterparts that had co-evolved with the fungus — had no resistance. Within 50 years, the blight killed more than 3 billion American chestnuts. Except for saplings that periodically sprouted from diseased stumps and then died back, the chestnut had effectively disappeared from North American forests.

Beginning in the 1920s, government researchers tried crossing survivors with Asian chestnuts to produce disease-resistant trees that in all other ways resembled American chestnuts. Their efforts failed to yield a tree that both resisted disease and thrived in American forests. Later, the American Chestnut Foundation labored for decades to produce such a hybrid.

But in the 1990s, biologist William Powell tried a different approach. Powell used a bacterium to insert the genes for disease resistance into the American chestnut genome. In other words, Powell created a genetically modified organism that resembled an American chestnut in every way except that it resisted the chestnut blight as well as any Asian tree.

Scientists — still a minority — are beginning to wonder if genetic engineering can be used to help organisms adapt to change and actually increase the biodiversity of the planet.“I think if we can’t get this tree deregulated and out in a restoration program, you’re not going to get any genetically engineered tree out,” says Powell, co-director with forest geneticist Charles Maynard of the American Chestnut Research and Restoration Program at the SUNY College of Environmental Science and Forestry. “You can’t argue a better tree.”

Antithesis of Green?

To some, GMOs are the antithesis of green. Greenpeace calls them “genetic pollution,” warning on its website that “GMOs should not be released into the environment since there is not an adequate scientific understanding of their impact on the environment and human health.”

But scientists — still a minority — are beginning to wonder if genetic engineering can be used to help organisms adapt to change and actually increase the biodiversity of the planet.

“I think it really isn’t on the radar screen of the conservation community at all,” says Kent Redford, former lead scientist at the Wildlife Conservation Society and now head of Archipelago Consulting. Redford organized one of the first conferences, in Cambridge, England, in 2013, to consider the gnarly intersection of genetic engineering, nature and conservation.

“The conservation community has the potential to be tremendously affected by the activities of synthetic biology.” – Kent Redford “I saw a need for this meeting because this field is offering enormous potential in a whole different set of human endeavors,” says Redford. “And the conservation community has the potential to be tremendously affected by the activities of synthetic biology. And yet we as a field are very often the last ones to learn about new innovations in society. I got tired of always being in the group that never knew about the latest thing.”

Later that year in the scientific journal Nature, a half dozen scientists from several universities suggested that “facilitated adaptation” might be used in “rescuing a target population or species by endowing it with adaptive alleles, or gene variants, using genetic engineering.”

C. Josh Donlan, one of the authors of the Nature paper and executive director of the nonprofit foundation Advanced Conservation Strategies, compares the strategy with proposals to help species survive climate change by moving them to a new location. “Obviously that’s controversial. … If you’re going to put a novel species in a new environment, what are the unexpected ecological consequences that could have?” Perhaps, he says, it’s safer to use genetic engineering to help the organism adapt in place. “Instead of move the animal, move the genes to the species.”

“Our techniques and our abilities to modify genomes is just becoming more precise,” he says. “Instead of back-breeding or other, clunkier techniques, now we have the ability to modify genomes in a very precise way.”

Think about it: Producing a white pine immune to blister rust or North American ash trees impervious to emerald ash borer. Engineering corals to thrive in more acidic waters. Inoculating frogs with a gene to protect against chytrid fungus. Creating a genetic based pesticide that kills only a single invasive species.

This ability to look to unrelated species for solutions is one of the advantages of genetic engineering over traditional crossbreeding.Or restoring the American chestnut, which once cast tall shadows across the eastern United States.

Speedy Breeding

In trying to engineer blight resistance in chestnuts, Powell realized the fungus created fatal cankers by the production of oxalic acid. So he looked for a gene that detoxified the acid. It turns out the gene is widespread in nature. But he didn’t find it in an Asian breed of chestnut; he found it in wheat.

This ability to look to unrelated species for solutions is one of the advantages of genetic engineering over traditional crossbreeding. “We can actually go a little further afield looking for resistance genes,” says Powell. “In breeding you’re basically limited to species that you can either cross naturally or force to cross.”

Another advantage: speed. Other researchers spent decades crossing American and Asian chestnuts to acquire resistance, then had to backcross the hybrids with American chestnuts to re-acquire traits of the American chestnut that had been lost.

Forest geneticist Charles Maynard examines transgenic American chestnut trees at the tissue culture shoot stage. Photo by Hannah Walker, Cornell Alliance for Science.

Powell and colleagues, on the other hand, were able to insert the gene for resistance and leave the rest of the American chestnut genome alone. “We don’t have to carry a lot of baggage,” says Powell. “We’re being very precise with what we’re adding in.”

Powell has produced several candidate varieties with all of the genetics of American chestnut and even better resistance to chestnut blight than Asian species. Now all he needs is time — perhaps lots of it — to navigate the federal regulatory process. Powell and colleagues will have to work with the U.S. Environmental Protection Agency, the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service, and the Food and Drug Administration. APHIS, for example, treats genetically modified plants as potential pests and “regulates the import, handling, interstate movement, and release into the environment of regulated organisms that are products of biotechnology.”

“All three of those agencies will have some part of the regulatory puzzle before we can pass these trees out to the general public,” says Powell.

The regulatory gantlet affecting GMOs began shortly after the first laboratory genetic modifications more than 40 years ago. Genetic engineering had hardly been imagined, much less studied. “So they started setting up a lot of regulations so we didn’t make any mistakes,” says Powell. “But that was 40 years ago, and there’s been a lot of research since then.” Public apprehension has made it difficult to loosen regulation of GMOs, he says.

“I don’t think the people who made those rules were actually thinking of chestnut. I’ve got a feeling that this is going to force them to rethink this whole process,” says Powell. “I’m hoping we can get through it in about five years. I’ve got 10 years till my retirement.”

No Panacea

Meanwhile, other trees are waiting in the wings.

The emerald ash borer, an Asian beetle first detected in Michigan in 2002, has spread to 21 other states and Canada, threatening to vanquish native ash species in the wild. Paula Pijut, a plant physiologist with the U.S. Department of Agriculture Forest Service and Purdue University, has been developing a process to engineer ash tree species to express a protein from a strain of Bacillus thuringiensis, a natural insecticide commonly known as Bt.

Scientists are working to develop a genetically engineered ash tree that resists the invasive and deadly emerald ash borer. Photo by Leah Bauer, USDA FS Northern Research Station (Flickr/Creative Commons)

“I think we have made some great advances in a short amount of time,” Pijut says. “I would hope in the next four to five years we could say we have emerald ash borer–resistant material for planting purposes. We are getting really close.”

Even so, as Pijut writes in a recent paper, while genetic engineering holds huge promise against emerald ash borer, it’s “no panacea because of regulatory limitations.”

Regulations on genetic engineering combine with restrictions built into green forest certification programs to stymie rapid and innovative use of GMO trees to adapt to climate change and introduced pests, says Steven Strauss, professor of forest biotechnology at Oregon State University.

“No one can really use GMOs now because the regulations are very difficult and because we have these green certification systems,” Strauss says. “Pretty much everywhere in the world, if you’re green certified, they won’t let you plant them, even for research.”

The Forest Stewardship Council, one group that sets standards for forest certification, currently prohibits the use of GMOs in certified forests. “I think the precautionary principle underlies many of the concerns,” says Brad Kahn, communications director with FSC’s U.S. office. “In the absence of conclusive evidence that GMOs will not cause negative impacts on forests, the membership has decided they should not be used in the FSC system.”

A better regulatory approach, says Strauss, would be to give agencies the ability to fast-track approval in response to a forest pest or other evolving threat. He also suggests that forest certifiers rethink their GMO policies.

Strauss himself experiments with GMO poplars, primarily for use in plantations. By engineering such trees to be more productive, he says, researchers can help conserve natural forests by reducing demand for wood products they produce. About 5 percent of the world’s forests are planted in plantations, which supply about one-third of all industrial wood. “By being efficient and productive in a limited area, you really can reduce the area you need to harvest industrial wood,” says Strauss. “This is one more technology for that.”

Genetic engineering would also allow the creation of a productive but sterile commercial tree that produces wood products but won’t jump into nearby natural forests because it can’t reproduce. Says Strauss, “I consider that a very valuable conservation tool, because again you can get the productivity and the stress tolerance you want without worrying about the spread into wild areas.”

“We should be able to use these powerful tools without these extraordinary delays. But we can’t. And it’s a travesty.” – Steven StraussStrauss is science advisor to the Forest Health Initiative, a collaborative biotechnology group that includes Powell’s chestnut research. The group hopes to smooth the regulatory pathway for approval of other GMO trees to resist pests such as Dutch elm disease and hemlock woolly adelgid.

“From a conservation point of view, it’s forest health that really matters — both industrial and natural,” Strauss says. “We should be able to use these powerful tools without these extraordinary delays. But we can’t. And it’s a travesty. The world has been so set against it now for about 15 years that you almost have to restart the conversation. You know, re-open our minds. It’s quite a challenge.”

Ousting Invasives

One of the most visible proponents of biotech solutions to conservation has been the Long Now Foundation, founded by Stewart Brand, the technologist and environmental forward-thinker who famously wrote in the opening pages of the 1968 Whole Earth Catalog, “We are as gods and might as well get good at it.”

This past spring, in a two-day workshop in Sausalito, California, Long Now (under the rubric of its Revive & Restore program) invited 52 molecular biologists, conservation biologists, veterinarians and other specialists to brainstorm biotech solutions to environmental problems.

To reduce the need for pesticides that can harm nontarget species as well as their intended target, researchers are investigating options for genetically modifying mosquitoes. Among the methods are RNA inhibitors — molecules that bind to and disable key worker molecules within cells — to eradicate invasive species that disrupt ecosystems and crowd out native species. “If you bind to the right ones you will stop a cellular process from happening and kill the cell,” says Ben Novak, a researcher at Revive & Restore. “The cool thing about this is you can design these RNAis to match specific codes.” So, for example, RNAi might be engineered to bond to the RNA of invasive Argentine ants — but only Argentine ants. The RNAi could then be sprayed like an insecticide that kills only a single invasive species. “If it works, it could be revolutionary, a game changer,” says Novak. Workshop participants suggested that a similar approach might be used to weaken the fungus responsible for the currently fatal white-nose syndrome in bats.

To reduce the need for pesticides that can harm nontarget species as well as their intended target, researchers are investigating options for genetically modifying mosquitoes to suppress populations that carry diseases such as dengue and chikungunya. Release into the wild of male mosquitoes with this modification (a procedure known as “release of insects carrying a dominant lethal,” or RIDL) would allow them to breed with unmodified females, producing nonviable offspring. By flooding an area with RIDL males (a twist on the decades-old sterile-male approach to pest management) authorities could ensure that nearly all attempts at reproduction produce … nothing. The FDA is considering giving approval to release RIDL mosquitoes in the Florida Keys. The method is also being discussed as a way to kill exotic mosquitoes in Hawaii that carry avian malaria, which is killing native forest birds, particularly honeycreepers.

The ability to engineer an end to an invasive species raises a question, however: Should we?But that could be only the beginning. A RIDL-type approach might also be used to confer a gene in mice so that all offspring are male. Swamping invasive mice, on an island for example, with hordes of modified mice would eventually extinguish the population. “When their life spans are done, the invasive rodents are gone,” says Novak.

The ability to engineer an end to an invasive species raises a question, however: Should we? A zebra mussel engineered to rid the pest in the U.S. might find its way back aboard ship to southern Russia where it would wipe out the species in its native range. Moreover, just because a species is nonnative and invasive, is that a good reason to eradicate it? Some have proven useful over time, both economically and environmentally, or have established themselves so thoroughly in an ecosystem that to remove them could release a cascade of unintended consequences for native species. Without an adequate regulatory framework for the use of genetic modification to rout invasive species, Australian environmental scientist Bruce Webber and colleagues wrote in a recent article in the Proceedings of the National Academy of Sciences, “this putative silver bullet technology could become a global conservation threat.”

Biodiversity Boosters

Revive & Restore is also proposing genetic engineering to actually boost biodiversity.

A program known as Revive & Restore is proposing to use genetic material from museum specimens to boost genetic diversity in black-footed ferrets as they return from the brink of extinction. Photo by J. Michael Lockhart / USFWS (Flickr/Creative Commons)

Black-footed ferrets, once common in the Great Plains, were believed to be extinct due to attempts to eradicate prairie dogs and to sylvatic plague — until 1981, that is, when a Wyoming farm dog brought one home. A population of about 120 was discovered nearby. In 1987, two dozen were captured. Six died, but the remaining 18 entered a captive breeding program. Captive-bred ferrets eventually replenished the natural population.

There was one problem, however: The tiny number of participants in the captive breeding program meant low genetic diversity among the offspring — a condition that reduces resilience and could lead to future populations being threatened. So Revive & Restore is considering the use of genetic engineering to introduce traits using genetic material gleaned from museum specimens more than a century old. The organization is also exploring biotech creation of genetic resistance to the plague, which devastates both ferret populations and the colonies of prairie dogs on which they feed.

Other species that have been listed as possible candidates for genetic engineering as a way to boost foundering populations include the Hawaiian crow, Arabian oryx, Attwater’s prairie chicken, golden lion tamarin, crested ibis, cheetah, northern white rhino, Yangtze giant softshell turtle, wombat and Tasmanian devil.

One of Revive & Restore’s most extraordinary biodiversity-boosting projects is the use of genetic engineering to restore the long-extinct passenger pigeon — or something a lot like it. The foundation calls it “de-extinction.”

Samples of toe-pad tissues from museum specimens (the pigeon went extinct in 1914) have yielded about 85 to 90 percent of the bird’s genome. “That’s as good as we’re going to get,” says Novak, the lead researcher on the project. He and colleagues have matched the DNA fragments to the genome of the closely related band-tailed pigeon.

Trying to genetically engineer all the differences between the passenger pigeon and the band-tailed pigeon would require — at least for now — an impossible amount of work. So instead, Novak will look for the important genetically coded differences between the species. “It might come down to that there are only five or six major traits that matter,” says Novak. “There’s no point engineering things that do nothing.”

Objections to the enterprise include arguments that the engineered bird won’t be a real passenger pigeon, the world doesn’t need a pigeon that flocks by the hundred of millions, or Revive & Restore is messing with Mother Nature.Revive & Restore plans to inject engineered germ cells into band-tailed pigeon embryos. Offspring will contain both band-tailed and passenger pigeon genes. “You breed enough babies, and eventually one of them is going to be the cross between the engineered sperm and the engineered egg and you have your engineered bird,” Novak says.

Objections to the enterprise include arguments that the engineered bird won’t be a real passenger pigeon, the world doesn’t need a pigeon that flocks by the hundred of millions, or Revive & Restore is messing with Mother Nature.

“Why bring about a genetically modified band-tailed pigeon that looks somewhat like a passenger pigeon? I really can’t think of a good reason,” David Blockstein, senior scientist for the National Council for Science and the Environment, wrote in an essay for the Center for Citizens and Nature. “Certainly from the perspective of biodiversity and ecological integrity it is difficult to imagine why a pseudo–passenger pigeon is better than none. The ecological niche of the passenger pigeon is as gone as the bird.”

“There are people who feel that no matter what we do, this is going to be a horrible distraction, a horrible mistake, and they’re completely against it,” Novak says.

But, says Novak, the point is not to create a “still frame from the past.” It’s really about using genetic engineering to promote something more functional. Those “somethings” might include extinct aurochs, Tasmanian tigers and even woolly mammoths.

Re-creating replicas of departed species “is about trying to facilitate the management of whole ecosystems by recognizing the many different ecological roles that an ecosystem needs to function and trying to get those functions back,” says Novak. “That’s the motivation for bringing back a passenger pigeon or a mammoth or any other type of extinct animal. We’re not really after the animal itself. We’re after the role that it plays in the environment.”

For now, GMO approaches to boosting conservation remain in the laboratory. But someday soon, conservationists still fighting a rear-guard strategy against species loss will find it necessary to decide what to do about applying this technology — which juxtaposes perhaps their greatest hopes with perhaps their greatest fears — to solve some of their most challenging problems. It will be an interesting call.