"Filling the World with Monsters"

Bioengineering and the future of life.

Now do you say, that you are going to make Right your master and do away with Wrong, or make Order your master and do away with Disorder? If you do, then you have not understood the principle of heaven and earth or the nature of the ten thousand things. This is like saying that you are going to make Heaven your master and do away with Earth, or make Yin your master and do away with Yang. Obviously it is impossible.
― Zhuangzi, The Complete Works of Chuang Tzu

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A Presence and Absence of San Francisco

Godofredo Stutzin (1917-2010) was a cherished friend. One day, on the patio of his home on the outskirts of Santiago, Chile, we talked about Dolly, the sheep that was cloned from an adult sheep’s somatic cell. Our conversation turned to genetic engineering. I asked him what he thought of it, given his lifelong experience observing human treatment of animals. He grimaced, and opined that the practice would ultimately end up “filling the world with monsters.”

Godofredo was a Chilean lawyer, environmentalist, and outspoken animal advocate. His love and compassion for animals was legendary. At his parcela, he housed dozens of homeless dogs and cats, as well as injured wildlife. I sensed that over the years he became despondent seeing how people routinely disrespected and abused animals. He was certain that genetic engineering would not be a good thing.

I will be forever thankful for Godofredo’s hospitality, his inspiration, and especially his encouragement and support of my studies on Chile’s endangered huemul deer.

Godofredo Stutzin’s Presence and Absence of Saint Francis, his collection of animal and nature essays that reflect the duality of human behavior toward animals (Photo by T. Povilitis, off my book shelf).

Godofredo Stutzin at home in 1982, greeting one of his many rescue animals (photo by T. Povilitis).

Resurrecting the Dire Wolf

You've certainly heard about this! Colossal Biosciences, an upstart biotech company in Dallas, Texas, claims to have brought back the dire wolf, a large predator that lived about 250,000 to 10,000 years ago in the Americas.

Dire wolves were fierce animals that preyed on horses, camels, ground sloths, bison, and mastodons that existed during the Pleistocene. They had a bite force greater than that of the grey wolf, a species that they almost certainly dominated (much like, perhaps, grey wolves dominate coyotes today).

Here’s how Time magazine describes Colossal’s making of a dire wolf:

Relying on deft genetic engineering and ancient, preserved DNA, Colossal scientists deciphered the dire wolf genome, rewrote the genetic code of the common gray wolf to match it, and, using domestic dogs as surrogate mothers, brought Romulus, Remus, and their sister, 2-month-old Khaleesi, into the world…the first time de-extincting a line of beasts whose live gene pool long ago vanished. (The technique used somatic cell nuclear transfer, the same process used in the creation of Dolly the Sheep).

Yet Colossal didn’t literally resurrect the dire wolf. According to its chief science officer, it created a “functional equivalent” of the animal by changing a small but significant portion of grey wolf DNA, focused on physical features such as size, skull shape, musculature, and hair (20 edits across 14 genes out of about 19,000).

The resulting animals are not truly dire wolves since they are not genetically identical to the extinct species. There’s no way of knowing what important gene-related and epigenetic characteristics of dire wolves failed to be captured in the “de-extinction” process.

Did Colossal engineer a “monster” wolf of sorts, an animal that, if it were to roam freely, could create havoc in existing natural and human-dominated landscapes. How would declining mule deer populations respond to their presence? And just imagine how ranchers would react to powerful genetically-engineered predators pursuing their livestock on the open range. To say the least, this wouldn’t be a good public relations look for wildlife conservation!

Colossal assures us that its “dire wolves” will remain in captivity. At the same time it floats the idea of releasing them, given that some Indigenous communities have expressed interest in having them on their lands.

All this begs the question, "Toward what end?" There’s no wild habitat for dire wolves on Earth today that resembles that which existed during the Pleistocene. For Colossal Biosciences, the project’s not really about the dire wolf. It intends to advance gene-editing for other wildlife projects. But why the dire wolf? The experiment, some believe, is a flashy publicity gimmick to attract public attention and investors hoping to profit from exciting cutting-edge bioengineering.

I suspect that if Godofredo were alive today he would be among the first to question the ethics of Colossal’s dire wolf project. That’s because the “functionally equivalent” dire wolves have no wolf parents, will have minimal contact with humans, never be treated as pets, never be allowed to breed, and never be able to live out their lives as large wild predators would.

For the Good of Life?

Colossal Biosciences claims that the purpose of its work is wildlife conservation. That’s the banner under which it operates. Its top priority is to “resurrect” the extinct wooly mammoth in order to transform the Arctic ecosystem.

Colossal proposes…to modify Asian elephant embryos (the mammoth’s closest living relative) so their genomes resemble those of woolly mammoths. These embryos could then theoretically develop into elephant-mammoth hybrids (mammophants), with the appearance and behaviour of extinct mammoths…the ultimate aim is to release herds of these mammophants into the Arctic, where they will fill the ecological niche mammoths once occupied.

When mammoths disappeared from the Arctic some 4,000 years ago, shrubs overtook what was previously grassland. Mammoth-like creatures could help restore this ecosystem by trampling shrubs, knocking over trees, and fertilizing grasses with their feces.

Theoretically, this could help reduce climate change. If the current Siberian permafrost melts, it will release potent greenhouse gases. Compared to tundra, grassland might reflect more light and keep the ground cooler, which Colossal hopes will prevent the permafrost from melting.

As you can imagine, not everyone thinks this is a good idea. Let’s be clear. This is a colossal experiment, with a primary purpose to “advance genetic editing” and the “understanding and genetic basis of cold adaptation in animals.”

Here’s a list of concerns, based in part on statements by Colossal, independent scientists, and other commentators:

Effects on animals involved in creating elephant-mammoth hybrids — The risk of trauma, suffering, or death to animals when:

1) extracting skin tissue from elephants to collect nuclei for gene editing, corresponding to parts of the woolly mammoth genome, to create hybrid nuclei;

2) inserting the edited nuclei—which houses the engineered DNA—into elephant eggs, extracted from female elephant “donors”;

3) implanting the early lab embryos grown from incubated eggs into the wombs of Asian or African female elephants;

4) managing the mother elephants during the long gestation period (22 months!) and afterward;

5) birthing and raising the mammoth-elephants;

6) transporting the baby mammoth-elephants to enclosures near where they will be released;

7) managing the health of the baby animals in the new environment;

8) getting the young animals to safely interact with one another (without a living adult mammoth to teach them);

9) releasing the elephant-mammoths into a wild environment they have never experienced; ensuring that they do not unduly suffer or die because of inadequate cold-resistant, disease, poor nutrition, behavioral problems, or other factors;

10) using animal “models” (usually mice) to test traits for bioengineered elephants, such as long hair and cold resistance.

At some point, if they survive, the mammoth-elephant hybrids would be considered wild animals, and likely treated like other wildlife (which raises a host of other humane and ethical questions).

Effects on wildlife and ecosystems where elephant-mammoths are introduced — The target area covers the vast Arctic biome called taiga, dominated by conifer trees, lichens, and mosses, with mosaics of wetlands, bogs, birch and poplar trees, and with important natural disturbances such as fire, insect population booms, and shifts in climate. Living communities of taiga are diverse and include, depending on continent, moose, caribou, brown bear, wolf, tiger, lynx, snowshoe hare, foxes, beaver, sable, mink, flying squirrel, pine martin, waterfowl, shorebirds, and many song birds. These animals all have their own special habitat needs, many of which are poorly understood.

Enter elephant-mammoths into this complex biome, one that has developed over a period of many thousands of years.

It’s beyond brazen, in my view, to assume that a bioengineered redoing of Arctic ecology could be accomplished without major harm to many existing taiga animals and natural communities. As is typically the case with swift environmental change, there would likely be winners and losers. But the details of such, in this case, appear to be of little concern to scientists born and bred in a human supremacist society that’s enamored of its technological wizardry.

A climate solution? — When mammoths disappeared thousands of years ago, the mossy forests and wetlands of the Arctic began to replace grasslands. Colossal seeks to reverse the process by introducing large numbers of mammoth-like elephants. The theory is that large herds of these animals could significantly limit permafrost thaw and in other ways reduce climate change risks.

Grasslands in the Arctic might more efficiently absorb carbon from the air than forests (which, if true, would likely be a good thing for climate). However, that’s by no means certain, given that trees generally, but not always (e.g., in drought prone areas), store more carbon than grasses.

According to Colossal, its mammoth-elephants would uproot and knock down trees, trample mosses and shrubs, and thereby increase growth of grasses (barring the possibility that they would overgraze grasses that emerged). They would also pack down enough snow, the theory goes, thereby reducing its insulation and allowing the cold air to reach the soil. This would presumably limit permafrost thawing (notwithstanding more direct sunlight hitting the ground), thereby retarding the release of stored greenhouse gases.

But what about the carbon released from taiga forests if they were degraded and destroyed by mammoth-elephants? Would the grasses that presumably replace the forests store enough carbon to compensate? With a shift toward grassland, would the frequency of wildfires increase, thereby accelerating further burning of forests and release of carbon dioxide? Ecological outcomes in the Arctic depend on the totality of natural events, direct human activities, and climate change, and on what areas of that vast region we’re talking about.

This gets pretty complicated, eh?

If the underlying assumptions of this “mammoth’ experiment turn out to be valid, could positive ecological change happen fast enough to alter the trajectory of climate change? One problem for jump starting the effort is that elephants have a very long gestation period of 22 months. So, how long would it take to build up large herds of the mammoth-like elephants to transform arctic vegetation? Go figure.

Well, could technology again come to the rescue? Colossal Biosciences is exploring the creation of artificial wombs for mass production of elephant-mammoths!

By the way, if changing the taiga is the goal, why not boost populations of existing large herbivores like reindeer, Yakutian horses, moose, musk ox, yaks, sheep, Kalmykian cows, and bison over wider areas, as is being done in Russia’s “Pleistocene Park”? Does the Arctic really need genetically-modified elephants to modify the existing ecosystem?

Finally, one has to ask what drove the wooly mammoth to extinction in the first place. It disappeared during a time of arctic warming. Yucheng Wang, a researcher at the University of Cambridge, concluded that the warming trends at that time were the main factor driving the mammoth’s extinction, with the added pressure of growing human numbers and mammoth hunting. Given climate warming and further human expansion in the Arctic, would we not see history repeat itself?

It seems to me that Colossal Biosciences has set out to test a grand theory at substantial risk to existing arctic life, as well as to genetically-modified experimental elephants. However, with colossal’s financial resources and visions of great profits for investors, who’s to question them?

Pardon me for doubting that the company has the best interests of the living world first and foremost on its mind. My opinion might change if Colossal came out in favor of addressing overconsumption of natural resources by affluence countries and overgrowth of the world’s human population. These fundamental drivers of the extinction crisis are apparently of no concern.

Some of Colossal’s other projects, geared toward helping existing endangered species, are more favorably received than restoring long-extinct wildlife. For example, take the red wolf, a species that once occupied the eastern and southern-central U.S.

About 50 years ago, the U.S. Fish and Wildlife Service began trapping animals from what remained of red wolves (in Texas and Louisiana) to establish a captive breeding program. Red wolves from that program were then released at the Alligator River National Wildlife Refuge in North Carolina. However, because of insufficient and continued loss of habitat, illegal hunting, and deaths from vehicle strikes, the wild population has struggled with only with about 20 wolves left.

Colossal wants to improve the genetic diversity of red wolves by creating a separate captive population of cloned animals that can ultimately be released into the wild. The idea is to enrich the red wolf’s limited gene pool.

However, here’s the catch: Colossal’s “genetic rescue” won’t address dismal habitat conditions. It’s hard to imagine that the protected habitat that red wolves need will be sufficiently expanded, roads removed, and poaching controlled within an already overcrowded, overdeveloped eastern North Carolina that has considerable hostility toward wolves. Unless a dramatic and unexpected change in human behavior and land use occurs, the red wolf will be condemned to permanent captivity.

I don’t mean to pick solely on Colossal Biosciences with my criticisms. There are very questionable genetic manipulations afloat for blatantly commercial purposes, like “glofish,” which are produced by inserting a gene from sea corals into fish.

Moreover, Colossal isn’t the only biotech company to employ genetic engineering in an attempt to revive an extinct animal. You may recall the creation of the first extinct animal to be cloned back in 2003, in an attempt to resuscitate the Pyrenean ibex.

The process involved inserting DNA from a frozen skin into domestic goat eggs that had been emptied of their original genetic material, and implanted into closely related wild goats. Of the 208 embryos the researchers implanted, only seven goats became pregnant, and just one embryo made it to term. The newborn died of respiratory failure minutes after birth, apparently from a lung defect.

Other efforts have proven more promising. California-based Revive & Restore extracted cells from frozen tissue of a long deceased black-footed ferret believed to have important genetic variants no longer occurring in the wild ferret population. The DNA from those cells was implanted into the egg of an adult domestic ferret. Three clones were produced, one of which bred and raised two offspring. These animals, if successfully released, are likely to improve the genetic health of the wild population.

There are about 300 wild black-footed ferrets in fragmented population units spread across a half dozen western U.S. states. Improving genetic variation within the species is one matter, but its survival and wellbeing ultimately depend on expanding and connecting black-footed ferret populations across what have become increasingly human-dominated landscapes.

Other scientists are using gene editing in an attempt to help corals adapt to warmer waters and survive climate change. Such efforts are admirable, but unless conservation efforts overcome human activities that are stressing coral reefs (pollution, overfishing, warming oceans, and sea water acidification), diverse coral communities will cease to exist.

In short, genetic engineering is not going to save life as we know and love it. I recall Dr. Hugh Iltis, a distinguished botanist and combative environmentalist, warning his audience at the University of North Carolina in 1972, that there is absolutely no substitute for on-the-ground protection and restoration of nature—that “without habitat there can be no preservation.”

At least Matt James, Colossal’s chief animal officer, seems to get that: “What we’re doing gives us the ability to help accelerate recovery, but recovery still is dependent on the conservation of wild habitats.”

Blowing the lid off Pandora’s Box

Colossal’s CEO and founder Ben Lamm envisions a future where scientists can biologically create almost anything, with ongoing advances in genetic engineering and artificial intelligence. He assures us that his company will use its technology only for good, yet admits that the sky’s the limit for others who may be less well-intended.

Lamm’s colleague, George Church, a co-founder and lead geneticist for Colossal, believes that creating new species through genetic engineering "could be done and could be a good idea if you want to have a species with a particular niche.” Like Lamm, Church is keen on directing evolution.

So, which is it? Do scientists know best, or does nature know best? Is Barry Commoner’s third law of ecology now defunct?

It takes great hubris to assume that humans can wisely manipulate four billion years of natural evolution, a process that’s responsible for today’s living world. Now, suddenly, we’re smart enough to undo mistakes we’ve made by changing the genetics of life for its own good. Are you skeptical?

I find both the exuberance of its proponents and the speed at which bioengineering is being ushered forth most troubling. Sixty years ago, Rachael Carson showed us in Silent Spring that going too far and fast with technology has dire consequences for life. For a short while, in the 1970s, I kind of believed we learned that lesson.

It may boil down to how much confidence people have in biotechnology to do more good than harm to the living world.

You might prefer that scientists take over the processes of organic evolution. Conversely, you might prefer letting nature heal itself by way of the beings and processes it currently has on hand. Or, you might favor a bit of both.

However, in our society, decisions will be made by those with the most economic and political clout. They will likely determine whether we focus on “resurrecting” or preventing the extinction of species.

Will genetic engineering spiral out of control? I’m fairly certain that if Godofredo Stutzin were somehow resurrected, he would insist that it won’t be contained. To that, I’d say, welcome back to the Anthro-piss-scene [sic]!

Our best shot at avoiding bad outcomes of bioengineering may be through international agreements enforced by site inspections, like those that have been done for weapons of mass destruction (albeit with varying degrees of success).

A good start would be a moratorium on de-extinction, such as the “mammophants” proposed by Colossal. There’s a serious shortage of ethical and scientific scrutiny of such research, and, from what I can tell, nothing in the current decision-making process that incorporates the views of people representing animals and plant species that stand to lose most from its applications.

A moratorium, of course, will be a hard sell to policy makers that, for the most part, are enthralled by technology, novelty, quick fixes, and profits. Of relevance is the struggle to get an international consensus on restricting germline editing in humans that causes heritable genetic changes. This despite calls by prominent researchers and bioethicists to do exactly that.

If, like Godofredo, you’re deeply pessimistic, cheer up—there’s still hope. Consider that our civilization hasn't yet blown itself up with nuclear weapons. It hasn’t yet destroyed itself with gain-of-function pathogens, or produced dreadful dragons through genetic manipulation. That’s because many people are talking about this stuff, and can influence society to be sane.

Maybe we can’t avoid worst outcomes. However, under the laws of probability, wise leaders could yet emerge across the globe to get genetic engineering under control. Nothing is impossible.

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I can imagine, a half century from now, a couple sitting near a nearly lifeless lake, in a post-apocalyptic world, reflecting on the fact that the monsters we released were actually ourselves. Perhaps we can prevent a grim future, maybe not. But we sure better try.

Not a chimera but rather a colony of Magnificent Bryozoan attached to a branch in a Florida lake. Why would anyone want to mess with natural evolution, the most creative phenomenon the world has ever known? (An unedited photo by T. Povilitis).