Thursday, February 6, 2014

De-extinction: Extreme GMOs in conversationist's clothing

De-extinction is the name given to several approaches that Biotech Boosters promise will eventually be able to bring back extinct species.

It is offered as a plausible solution for healing what Steward Brand calls "the huge hole" that humans have made in nature over the past 10,000 years.

It is hard to deny we have created a "hole" in nature. Ever since the dawn of agriculture, we certainly have been messing things up, and we sure aren't slowing down. We have now converted most of the world's arable land into farms and fields. We are pushing the rest of the biosphere into fragmented "nature reserves" while we line the Earth with rows and rows of the few dozen species of plants and animals that we've come to depend on. This massive conversion of the world's diversity into human foodstuff created a food surplus that spurred the rapid growth of the human population. Further, it provided the opportunity to specialize human labour: in the past, everyone had to subsist through finding their daily bread. Now, we have food production systems that allow us to become soldiers, scientists, politicians, miners and bankers. Many of these professions devastate the land, air, and sea through feverish cycle of extraction, production, consumption, and waste. And the "hole" gets bigger.

Thousands of species have been driven to extinction, and with accelerating industrialization, hundreds of thousands more are either endangered or vulnerable (Barnosky et al., 2011). Environmentalists have been sounding the alarm for decades but their appeals to change course are hushed by the clamour of progress. Industries are digging their claws ever further into ecosystems that have been until now "off limits" --the steepest mountains, the thickest jungles of the Amazon and Congo basins, the deep ocean waters, the once permanently frozen Arctic-- and an increasing population expects and demands the very lifestyle responsible for ripping the hole Brand claims we've made ever more wide.

In light of this harrowing situation, de-extinction is being tossed around in newspaper articles and magazines, from the New York Times to National Geographic, as a radical and powerful way of healing the wounds we've cut and are cutting still every day. Indeed, Brand himself has claimed that because we have the technology to bring back lost species we may have "the moral obligation, to repair some of the damage." With his wife, he's co-founded a nonprofit organization to get the idea up and running.

Not all are so enthusiastic, however. Perhaps the hesitant tone of many feature articles indicates just how well Jurassic Park's dystopic lesson was burnt into our memory cells with a dire warning as to what could happen if we don't keep our hubris in check.

Of course, few people are intent on bringing back velociraptors or tyrannosaurus (let alone another opportunistic sequel with Goldblum repeating (again!) the lines: life will find a way!). Instead, on the table are what appear to be relatively benign discussions about resurrecting those beings we've personally had a hand wiping off the face of the Earth: the passenger pigeon, the wooly mammoth, the thylacine, to name a few. (Needless to say, however, we shouldn't rule out what they may try to do: scientists are stretching their genome sequencers into the remote depths of the past as best they can and have recently decoded a 700,000 year old horse ancestor's genome (Shapiro & Hofreiter, 2014)). In any case, perhaps the more mouth-watering prospect amongst such conservation-minded technophiles is that of resuscitating species now poised at the edge of the abyss, such as the Javan rhino, with its 40-60 kettled souls, or the Siberian tiger, whose numbers have slunk below 400. Some of these critically endangered species do not breed in captivity and producing these species in labs could protect them from what is otherwise certain annihilation. The World Wildlife Federation has called the possibility "exciting."

But, like every fairy tale, we should know that "happily ever after" is really just a literary device employed to make us feel good, not something that is actually conceivable in a complex, messy and everchanging world. This article's intent is to inject an ounce of sobriety into the discussion. Of course, you may now be thinking that I am making the typical "safe is better than sorry" claim that holds back great ideas. Perhaps you want to quote Goethe at me, reminding me that boldness has genius and power and magic in it. Perhaps you would like to bring to my attention that Jurassic Park's "worst case scenario" is highly unlikely (do we really expect the removable ceiling panels to collapse, only to leave our feet dangling for the vicious fangs of the velociraptor poised below?). Indeed, what do we really have to worry about? That passenger pigeons are going to take over our cities? We already have those spikes on every possible roosting spot to prevent our urban pigeons... surely they will also prevent passenger pigeons from causing similar sorts of mischief?

1. De-extinction may well be just a promissory note for laissez-faire economics
One of the biggest problems with de-extinction is that it keeps us complacent towards the environmental crisis. It helps prop up the attitude that the march of science will essentially guarantee that all of our ills are solved. We will not need to change our lifestyles and can continue existing under the spell of consumerism and infotainment. It is not our responsibility to take personal initiative in helping address issues like "extinction" because we have technical experts working on it.

And yet, one might wonder what would happen if we continue to plunder and destroy while leaving extinction to the experts. The experts may well bring back the Eastern Elk (that disappeared in 1896) or the Newfoundland Wolf (the last one was shot in 1911), and dozens of other species to boot. But in what meaningful way can we be healing the "huge hole" in nature if the habitats that these creatures would live in no longer exist? What is the value of de-extinction if the resurrected species end up in zoos or in the ├╝ber-affluent's bizarre collection of personal curios to show off with?

Nor should we underestimate the impact that de-extinction technologies could have on pushing ahead the business-as-usual agenda. In a recent interview, Stanford University's Hank Greely warns that in a world where resurrection is a technical possibility, rare species may cease to be a political inconvenience suppressing the free pace of economic development. As he notes: "suppose developers want to build on a last bit of land where an endangered bird lives. And suppose they say, ‘We will be happy to pay for freezing [the DNA or eggs]. Now let us build our golf course’” (link). Like the worthless "fish ladders" and "wilderness corridors" used to squelch out concern over hydro-dams and mining projects, de-extinction could easily become a part of the repertoire of options that corporations have to sway public sentiment. In the simplest terms, we may be trained not fear extinction anymore because the marvels of biotechnology have made extinction itself go extinct!

In a broader sense, de-extinction could thereby functions like advertising for the biotech industry. Like "golden rice" engineered to "cure" vitamin A deficiency in children, de-extinction would be an idea with considerable moral force, useful to compel people that the biotech industry is a beacon of good in the world. This is a particularly important message to promote, considering the scrutinizing public continues to paint the industry as secretly hiding its trident and diabolical horns (Geez, I mean Monsanto has been voted the world's most unethical company for how many years now?). De-extinction can boost the dividends of these companies immeasurably if it is part of an integrated strategy to sway the Average Josephine from reluctantly accepting unlabeled foods (as they do now) to praising the industry for its ethics and responsibility.

2. Hodge-podge biology
Beyond economics, the biology itself turns out to be less promising that it seems. The term "de-extinction" is itself a lie. Scientists are not actually capable of bringing back anything. This is not hyperbole. There are solid genetic, epigenetic, and environmental reasons why current plans to de-extinct a lost species amount to nothing more than risky, transgenic chimera-making; extreme GMOs masquarading as restored species.

First off, it is unlikely that scientists will have access to a full genome of an extinct species. Without this access, they will have to either take the missing genes from a related species or synthesize them in the lab. In both cases, this means that the genetic code is not the genetic code of the extinct species. It is a trans-species hybrid, a genetically modified organism, modified to an extent far surpassing anything that has ever appeared on earth before. If you don't know anything about the risks of GMOs, browse this blog site and familiarize yourself with the subject. I will not repeat the arguments here.

Still, we can ask the question: Is it possible to imagine a scenario where patching together DNA from an extinct species with its closest known relative avoids these risks? Consider humans, chimpanzees and bonobos. We are said to share 99% of our DNA with chimps, and 98.7% with bonobos. And yet, we are widely different from either of them. In turn, chimps and bonobos apparently share over 99% of their DNA with each other, but again, there are significant differences in the physiology, form, and behavior of both these species. The take home message is that small differences in DNA can have huge impacts (especially when multiplied by the effects of epigenetic and environmental factors, see below). If rock pigeons and passenger pigeons differ in 1% of their DNA and we are only missing fragments of the passenger pigeon genome, then the likelihood that the missing DNA is different from a rock pigeon is certainly less than 1%. But it is also certainly more than 0%, and the only way to ascertain with absolute confidence that the difference is 0% is if we had an intact passenger pigeon genome to compare it to. But if we did, then this would make the whole enterprise of substituting rock pigeon DNA for passenger pigeon DNA superfluous. So we are left gambling.

Even if scientists have the entire genome of an extinct organism, they are not out of hot water just yet. In fact, this is where the real problems come in. It is vastly unlikely that the scientists would have the full genome of a sufficiently different number of organisms needed to create a viable population. A minimum amount of genetic diversity is necessary in a population in order for the species to propagate sustainably without entering into an ever-weakening cul-de-sac through interbreeding. To create such a viable population, scientists would have to insert random differences into the genes of the different organisms of the species. This would be to mimic the normal genetic diversity that makes up a healthy wild population of any species. In practice, this implies undertaking hundreds of separate transgenic modifications on hundreds of genomes, or zapping the genomes with doses of radiation to induce mutagenesis, in either case multiplying exponentially the opportunities for something to go wrong by way of disrupting genetic networks, pleiotropic factors, etc. (see my Genetics 101 for details on this).
Beyond the gene, we have epigenetic factors. Epigenetic factors can be thought of as all of the cellular elements that contribute to how a gene is expressed. Now because passenger pigeons died a long time ago, we no longer have access to viable eggs. We have passenger pigeon genome but we do not have a passenger pigeon egg. What we do have are eggs from related species, such as rock pigeons and band-tailed pigeons. We would need to somehow put the passenger pigeon's genome into one of these other pigeon's eggs so to initiate embryological development. The main de-extinction technique to accomplish this would be to take one of the other pigeon species' cells and modify the DNA within to match the cells of the passenger pigeon genome. We would end up with a rock or band-tailed pigeon egg interpreting and expressing a passenger's pigeon's DNA.

Does this matter?
It turns out it does. The cytoplasm, mitochondria, biochemistry, size, temperature, and a host of other factors are all different in the two species. But these factors all influence how the passenger pigeon's DNA will be read. In other words, the context of the genome influences how it is expressed. Genes do not have functions independent of context, their context defines their function. A temperature difference, for example, can turn off certain genes and turn on others, and alter the way that groups of genes interact together. Genetics without epigenetics is just a bunch of inert strings of DNA floating around in a soup. Epigenetics is what activates the genes and plays a strong role in directing what exactly it is that they do. In other words, we may have created some sort of pigeon but it is not a member of either of those two species. We would have created an entirely new species and called it de-extinction just to make ourselves feel better and perhaps to excite the big conservation organizations.

The problems don't end here either. At some point, presumably, the new organism (with its bricolage of a patched-up genome and its cellular structure lifted from another species) is born. What does it do? How does it live? People like to think that animals are unlike people in that the young of our species require an upbringing and initiation into culture by their caregivers, whereas animals can essentially make it on their own. This is increasingly recognized as an anthropocentric illusion. Countless species, from parrots to pumas, depend on interaction with their caregivers and peers to develop in such a way that they can make it in the world. Interestingly, some of this behaviour appears to be handed down, tweaking and adjusting itself generation upon generation, showing evidence of "cultures" or "traditions" in the animal kingdom (Avital and Jablonka, 2000). A human denied contact with other people during its critical early years ends up missing something essential. Its "humanity" is compromised. To some extent, this is true for other species as well. The relationship between organisms and what they pass on through their networks of relations, are all a part of their species just as much as their genes or their epigenetics.

And then there's the ecosystems. Stewart Brand hopes that we may able to produce an organism that is "functionally identical" to how the original organism behaved in its ecosystem, but this is obviously untestable and unverifiable and therefore something that scientists would merely have to take on faith. Nevertheless, his hope is itself shortsighted for the simple reason that ecosystems do not remain static. They evolve so it makes as little sense to try and match an extinct species' DNA to an extinct ecosystem as it does to try and match an extinct species' DNA to a contemporary ecosystem. If, say, 500 years ago we compromised an ecosystem by destroying some species in it, the ecosystem has had 500 years to mend this hole through evolving new interconnections and relations. Because the ecosystem has evolved since that species went extinct, it may not be fair to either the introduced species or the persisting species to mess things up in the name of "healing the wounds."

Stewart Brand: Ecosystems are self-healing if we let them.

Or, dare I say... "life will find a way"?

3. Summary

De-extinction is trying to pull a fast one on us: it is an extreme form of genetic engineering being pushed on the public for what are likely largely economic reasons (I am obviously not denying that there are some scientists that are pursuing this purely because they are interested and think it is "cool" or "ethical"). This does not mean that ethical and sustainable de-extinction is not possible. I could imagine a situation where large quantities of still living populations' DNA (and epigenetic structures) are conserved as a last resort in case their populations started plummeting. Such a bio-bank would provide some insurance in the case of a major catastrophe (human induced, or perhaps from an asteroid, etc.). If done correctly, it would need no transgenic (GMO) technology, no epigenetic cross-species shortcuts (it would be cloning instead of genetic engineering), and could even be part of a program introducing the new organisms into actual biological relationships ecologically established members of its species.

However, I have very little faith that this is how de-extinction is likely to proceed, especially considering its main proponents are also those promoting synthetic biology, geo-engineering, and other extreme forms of human-induced changes to the biosphere (such as Church (2013) and Brand (2013)). It is therefore up to us to foster the dialogue we need to in order to ensure that de-extinction (if done at all) is done safely, humanely, and ethically. If we don't then overzealousness, economic interest, and hubris will continue to run their course and into the tragedy of our age another scene will be written.

References

Avital, E., & Jablonka, E. (2000). Animal traditions: Behavioural inheritance in evolution. Cambridge, UK: Cambridge University Press.

Barnosky, A. D., et al. 2011. Has the Earth's sixth mass extinction already arrived? Nature 471:51– 57.

Brand, S. 2013. The dawn of de-extinction: are you ready? TED 2013. TED, Long Beach, CA. Available from http://www.ted.co/talk/stewart_brand_the_dawn_of_de_extinction_are_you_ready.html

Church, G. 2013. Hybridizing with extinct species. TEDx Deextinction/National Geographic, Washington, D.C. Available from http://longnow.org/revive/tedxdeextinction/

Greely, H. 2013, March 15. De-extinction: hubris or hope. TEDx DeExtinction/National Geographic, Washington, D.C. Available from http://longnow.org/revive/tedxdeextinction/

Shapiro, B., & Hofreiter, M. (2014). A paleogenomic perspective on evolution and gene function: New insights from ancient DNA. Science 343(6169),

Switek, B. 2013. The promise and pitfalls of resurrection ecology. National Geographic. Available from http://phenomena.nationalgeographic.com/2013/03/12/the-promise-and-pitfalls-of-resurrection-ecology/

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