THE LAND OF OZ

“Men have become like gods. . . .
Science offers us total mastery over our environment.”

Sir Edmund Leach

In the famous 1939 movie The Wizard of Oz, Dorothy and her companions finally reach the Emerald City and promptly board a horse-drawn cab to go visit the great and powerful Oz.

“What kind of a horse is that?!” exclaims Dorothy, pointing at the carriage’s bright purple horse. “I’ve never seen a horse like that before!”

“No, and never will again, I fancy!” replies the cheerful cabby. “He’s the horse of a different color you’ve heard tell about.”849

As the scene plays out, the horse’s color changes from purple to red to yellow. There were no computer graphics back then, so to effectuate the dazzling special effect, filmmakers smeared grape-, cherry-, and lemon-flavored Jell-O pastes on three different horses.850

Remarkably, yesteryear’s movie magic is today’s scientific reality. No, to my knowledge, genetic engineers have not yet created a grape-, cherry-, or lemon-colored horse—or flying monkeys, for that matter, which are also in the movie. But, in principle, today’s biologists do have the wherewithal to create such things, if they wish.

Indeed, biologists have the technical ability to manipulate every part of the DNA of every living organism on the planet—plants, animals, bacteria, you name it. Therefore, engineering something as outrageous as a purple horse or winged monkey raises not the question, “Can we?” but “Should we?”

The question is especially important because genetic engineers tinkering with DNA are like children playing with a new toy—one whose complexity is well beyond their full comprehension. As Craig Venter, the pioneering American geneticist who contributed greatly to the Human Genome Project, confesses: “My view of biology is: ‘We don’t know sh-t.’”851

Some observers downplay the potential risks of our newfound power and lack of understanding. “I suspect any worries about genetic engineering may be unnecessary,” says British environmentalist James Lovelock. “Genetic mutations have always happened naturally, anyway.”852

Others see considerable risk, owing not to the technology, nor our relative ignorance, but to our grasping motives. “Genetic engineering has never been about saving the world,” warns Indian environmentalist Vandana Shiva, “it’s about controlling the world.”853

I agree with Shiva that our enemy is not science—which, at its best, is dedicated to opening our eyes to how the universe works—but our often willful, reckless use of it. Most of the time we mean well, but as we’re about to see, even our noblest intentions reveal our audacious and risky power struggle with nature.

LIFE FROM OZ

There are many laudable reasons genetic engineers wish to hack the DNA of animals. Doing so, they honestly believe, will enable them to find cures for deadly diseases, mass-produce medicines, and protect public health.

Case in point: Genetic engineers have transformed marmosets and cats into Oz-like creatures—animals of a different color, if you will—by supplementing their DNA with a green fluorescent protein gene from jelly fish. These transgenic animals glow with an eerie greenish color under ultraviolet light, so scientists can more clearly see how infectious diseases such as AIDS and Parkinson’s spread throughout the body.854

But is exerting such an unprecedented degree of control over the animal kingdom a good thing? Do the ends truly justify the means?

Here are some other examples of what’s happening in genetic engineering’s land of Oz. Judge for yourself.

Mental Health

“Globally,” reports the World Health Organization, “more than 300 million people suffer from depression, the leading cause of disability.” Moreover, it discloses, “depression and anxiety disorders cost the global economy $1 trillion US each year in lost productivity.”855

In order for scientists to successfully tackle this scourge of depression and other mental afflictions, they must first learn how mammalian brains work. Many of them—like eager youngsters poking around the insides of a clock to see what makes it tick—are doing so with the help of genetic engineering.

To that end, neurobiologist Ivan de Araujo and colleagues at Yale University recently published the results of their landmark study of rat brains. Its primary goal was to learn precisely which neurons control the two prongs of a rat’s all-important, predatory behavior: the hunt and the kill.

“Superior predatory skills led to the evolutionary triumph of jawed vertebrates,” the researchers explain. “However, the mechanisms by which the vertebrate brain controls predation remain largely unknown.”856

The Yale scientists discovered the hunt–kill neurons deep within the brain’s emotional center—the amygdala. To confirm this, they infused the neurons with light-sensitive DNA from common algae, transforming them into Oz-like brain tissue. By hitting these neurons of a different color with blue laser light, the scientists were able to trigger the rats’ hunt–kill behavior at will.

On command, the rats pounced on anything within sight, including bottle caps, wooden sticks, and live insects. “We’d turn the laser on and they’d jump on an object, hold it with their paws and intensively bite it as if they were trying to capture and kill it,” reports de Araujo.857

The technique of using light to trigger certain behaviors is called optogenetics. In other labs, it’s being used to force rats to run frantically in perfect circles or chug down milkshakes, and to force monkeys to abruptly swivel their gaze toward a designated target.858

Of course, this kind of basic research could one day result in effective treatments for depression and other severe mental afflictions, such as Parkinson’s, Alzheimer’s, and drug addiction. And that clearly is a great possibility.

But the research is already leading to mind-control technology that could one day be inflicted not just on defenseless rats and monkeys but on humans. Such a very real and present possibility is decidedly grim.

“This kind of direct mind control once belonged in science fiction,” exults Ada Poon, an electrical engineer at Stanford University.859 But, clearly, not anymore.

Physical Health

Motivated by wishes to “improve” nature—a conceit that presumes we humans know best—genetic engineers are meddling with the DNA of animals to make meats healthier and cheaper to produce. They also seek to turn animals into living factories to produce human medicines and human spare parts.860

Already approved by the FDA are:

Transgenic goats—goats with human DNA—whose milk produces antithrombin. It’s a blood-thinning protein used to treat people prone to lethal blood clotting in their legs and lungs.861

Transgenic chickens—chickens with human DNA— whose eggs contain sebelipase alfa. It’s a human enzyme that is the active ingredient in the drug Kanuma, marketed by Alexion, used to treat people who have trouble metabolizing fats. The malady leads to liver enlargement, fibrosis, cirrhosis, and cardiovascular disease.862

Transgenic salmon—Atlantic salmon with genes from a Pacific salmon and an ocean pout—now being marketed with the brand name AquaAdvantage. The Oz-like fish grow with abnormal speed, reaching market weight twice as fast as normal salmon. AquaAdvantage debuted in Canadian grocery stores in 2017 but has yet to be sold in the United States, although it’s expected they will be soon.863

Currently awaiting US government approval is a menagerie of other creatures from the land of Oz. They include: GM pigs with fleshier backsides and leaner pork chops; GM goats whose milk resists spoiling in warm weather; GM cows whose milk contains interferons, immunologic proteins that combat a wide range of human cancers and infections; and GM pigs to grow human-friendly hearts—a potential boon for thousands of Americans currently awaiting heart transplants.864

Muhammad Mohiuddin, a University of Maryland heart surgeon, for one, is elated about genetic engineering’s power to refashion the animal kingdom in our own image. He sees animals with human DNA as wonderful vehicles for harvesting human-like, rejection-resistant spare parts, “eliminating the shortage of donor organs including hearts, livers, kidneys, intestine, as well as insulin-producing cells for treatment of diabetes.”865

But some in the land of Oz are not content to stop there.

In 2016 the MIT Technology Review pulled back the curtain on renegade genetic engineers who are creating pig–human and sheep– human chimeras. Please note: whereas transgenic animals often have their DNA supplemented with human genes, these chimeras have actual human cells. Their vital organs aren’t just human-friendly but actually human.

As I write this, the far-out creatures are quietly being created by at least three teams in California and Minnesota against the wishes of and without any funding from the National Institutes of Health (NIH). The scientists see themselves laboring for a noble cause (not to mention a Nobel Prize), namely, creating a limitless source of body parts for people in need of them.866

But others are concerned about the possible dangers.

What if, for example, the human cells in these illicit chimeras proliferate beyond their vital organs—to their brains, for instance? The resulting creatures, possibly capable of human thought, could no longer be considered just pigs.867

“We are not near the island of Dr. Moreau, but science moves fast,” warns David Resnik, an ethicist at the NIH. “The specter of an intelligent mouse stuck in a laboratory somewhere screaming ‘I want to get out’ would be very troubling to people.”868

Hiromitsu Nakauchi—a Stanford University biologist who is trying to make human–sheep chimeras—concedes such a thing could happen. “If the extent of human cells is 0.5 percent, it’s very unlikely to get thinking pigs or standing sheep,” he says. “But if it’s large, like 40 percent, then we’d have to do something about that.”869

Public Health

I don’t know of anyone who would plead for the life of a mosquito, given 750,000 people die annually of mosquito-borne diseases, such as malaria, dengue fever, yellow fever, Zika, and encephalitis. For us humans, the mosquito is by far the deadliest animal on the planet.870

There are roughly 2,500 species of the dreaded insect buzzing around every continent on Earth, except Antarctica. Over the years, science has invented increasingly clever and deadly methods for controlling the size and lethality of mosquito populations. Chemical sprays are among our oldest weapons of choice, but mosquitoes are developing a resistance to many of them.871

We’ve also tried sterilizing male mosquitos—for instance, by zapping them with radiation or infecting them with a disease. When the eunuchs are released en masse into the wild and mate with females, nothing comes of the unions. Thus, the overall mosquito population is knocked down.872

More recently, Oxitec—a company in Abington, England has focused on ridding the world of Aedes aegypti mosquitoes, responsible for spreading Zika, dengue fever, chikungunya, and yellow fever. Oxitec has figured out a way to infuse the DNA of male mosquitos with genes that cause its offspring to self-destruct before reaching adulthood. The lethal genes come from the Escherichia coli bacterium and herpes simplex 1 virus.873

The GM mosquitoes—code-named OX513A—also have supplemental genes that make them glow under certain light. Thus, scientists are better able to see the Oz-like insects’ dispersal out in the field.874

The company has already released millions of OX513A in parts of Panama, Brazil, and the Cayman Islands—reportedly reducing wild Aedes aegypti populations by more than 90%, seemingly without any harmful effects to humans or the environment.875 Despite the successes, however, Oxitec has been having a hard time persuading residents of the Florida Keys to allow trials in their backyards.

“I am going to ask you, beg you, plead with you, not to move forward with this,” entreated resident Megan Hall at a 2016 board meeting of the Florida Keys Mosquito Control District (FKMCD).876 And it’s not just locals who are voicing concern. “DO NOT PERMIT!” writes a person from Lizuka, Japan. “Future ramifications are unknown and could be dangerous to the entire world.”877

These critics point out, and Oxitec confirms, about 0.03% of the GM mosquitoes end up being females, which creates a risk—albeit tiny—of someone being bitten and infected with the OX513A’s E. coli/ herpes simplex 1 genes. Also, Oxitec’s own lab research shows that about 4% of the mutant mosquitos’ offspring do not self-destruct and actually live on to bite another day.878

Other skeptics point out that even if Oxitec’s OX513As were ever to completely vanquish Aedes aegypti, other, equally dangerous mosquito species would inevitably flourish and fill the environmental vacuum— most notably, the Asian tiger mosquito, Aedes albopictus. “We’ve seen elsewhere . . . that when there’s a vacant niche, Aedes albopictus will move in,” notes University of Florida entomologist Phil Lounibos, “and it’s a competent vector [i.e., effective transmitter] of the same viruses.”879

All these concerns notwithstanding, a majority of Florida Keys residents and officials recently voted to allow the OX513A release. They point out that other possible remedies—such as spraying their neighborhoods with toxic pesticides—are hardly more desirable alternatives.

“I’m convinced that this technology is really needed in this industry,” says Phil Goodman, the FKMCD’s board chairman. “Because we are going to be dealing with these diseases for years to come, and coming out of the chemical industry, I can tell you there’s nothing on the chemical side that’s being developed for this.”880

As of this writing, proposals to release millions of the OX513A mosquitos in the Florida Keys is stalled. The test has been approved by local officials and the EPA, but no actual release site has been identified and approved by residents themselves.

While we await the outcome, I can’t help but remember what my friend and former Harvard colleague E. O. Wilson drummed into my head concerning the myriad, tiny, seemingly insignificant creatures that comprise the animal kingdom. “Remember, Michael,” he cautioned me, “it’s the little things that run the world.”

Mosquitoes are thoroughly unpleasant, and it’s hard to see what actual positive contribution they make to Earth’s web of life. But any reasonable person must stop and wonder what damage we inflict on the exquisitely designed web every time we pull on even the most seemingly insignificant thread of it.

LIFE FROM DEATH

Our age-old desire to control nature is especially evident in our current attempts to use genetic engineering to defy death. Here are two examples of what I mean.

Cloning Animals

On Monday, February 24, 1997, I became the first TV correspondent to interview Ian Wilmut, the Scottish embryologist who caused a worldwide sensation by cloning a sheep. She was named Dolly after the amplebreasted country singer Dolly Parton, because Wilmut cloned her from an udder cell belonging to a six-year-old ewe.881

Wilmut achieved this seeming miracle by using a technique called somatic cell nuclear transfer.882 SCNT was quite well known in science, but no one had ever used it to clone a mammal before—hence the screaming headlines and Dolly’s picture on the cover of Time magazine.883

The name of the technique is admittedly a mouthful, but SCNT is actually easy to understand. Just bear in mind somatic cells are simply body cells, each of which houses an organism’s DNA—the complete genetic recipe for making it from scratch.

Using SCNT, Wilmut extracted the DNA from the ewe’s udder cell and inserted it into an egg whose own DNA had been removed. The egg—now thinking it was fertilized, because it had a full complement of DNA—was placed inside the womb of a surrogate mother. After a normal gestation period of 148 days, the mother gave birth to Dolly, an exact baby duplicate of the six-year-old ewe.884

In the months after Wilmut’s bombshell achievement, a public debate raged about the ethics of cloning—especially when various shady groups came to light that vowed to use SCNT to clone humans. As ABC News’s science correspondent, I was in the thick of covering the emotional back-and-forth. At one point—after infiltrating one particularly bizarre underground group—I even found myself at the center of the media circus.

In the years since, the commotion has died down considerably. But there’s a chance it will ramp up again, because in January 2018, scientists from the Chinese Academy of Sciences, in Shanghai, announced they successfully used Wilmut’s SCNT technique to clone two long-tailed macaque monkeys.885

Monkeys, like us, are primates—so the achievement hits close to home. Robert Lanza, who used the SCNT procedure to clone a gaur, calls the announcement “an impressive breakthrough, which overcomes the last major hurdle in the field.”886

The Shanghai researchers insist they have no interest in cloning humans—but do concede their work could be used to further the controversial effort. “Monkeys are nonhuman primates that are evolutionarily close to humans,” admits Muming Poo, a neuroscientist and cloning team member. But there “is no intention for us to apply this method to humans.”887

While we wait to see where things go with primates, cloning mammals in general—including cows, horses, deer, mules, oxen, rabbits, and rats—has become a routine, money-making business.

One prominent cloning company—ViaGen Pets in Cedar Park, Texas—now offers ordinary people the opportunity to clone their favorite dog or cat. “People have a hard time wrapping their brain around that it is a real technology,” says Melain Rodriguez, a client services manager for ViaGen.

But it is.

For $50,000, ViaGen technicians will remove some body cells from your favorite pooch, freeze them, if necessary, and then use SCNT to create a genetic copy of him. Cloning a cat costs half as much.888

Mike Hutchinson, a veterinarian at Animal General in Cranberry Township, Pennsylvania, had his toy poodle cloned.889 He explains “even if you take a 16-year-old dog and you decide, ‘Now I want to do it,’ . . . [the cloning process] resets the clock. They [the dog’s aged somatic cells] go back to young again, which is pretty unique.”890

“It’s not a reincarnation of their pet,” Rodriguez is quick to clarify. “It’s not that same pet born over again, but it’s those same genetics and this . . . pet that they loved so much is somehow back in their life again.”891

Resurrecting Extinct Species

In the natural scheme of things, species come and go—sometimes explosively and in great numbers. Like the mass extinction 251 million years ago that wiped out more than 95% of all living species.892 And the one 66 million years ago that snuffed out 76% of all species and 80% of all animal species, including the dinosaurs.893

Please note all five known mass extinctions happened long before we humans entered the picture, so we didn’t cause them. The mass extinctions happened naturally, for reasons we honestly still do not understand.894

One certain take-away from the fossil record is this: nearly always, the extinction of one species creates opportunities for other species to rise and flourish. In that endless, unsentimental fashion, natural selection is always striving to maximize the planet’s overall health—the way wise pruning promotes healthy branching patterns.

In a brazen attempt to interfere with this age-old natural process, genetic engineers are now attempting to de-extinct species long gone. In one greatly hyped initiative, scientists are trying to resurrect wooly mammoths, those ultra-photogenic, shaggy, pachyderms that began disappearing 10,000 years ago, with the rapid thawing of the little ice age.895

The idea was first made plausible in 2008, when a team led by Pennsylvania State University scientists announced it had successfully mapped a large portion of the wooly mammoth genome. The scientists did it by collecting DNA fragments from the hair of two frozen animal specimens.896

“If you want to bring a species back to life, the mammoth would be almost as dramatic as a dinosaur,” says veteran science journalist Henry Nicholls. “It is a fair bet that a complete genome and closely related species would make it easier to pull a Crichton on a mammoth than on a dinosaur.”897 Michael Crichton wrote Jurassic Park, a novel wherein genetic engineers bring dinosaurs back to life—with disastrous consequences, I might add.898

Today, there are two prominent groups competing to make “Jurassic Park: Wooly Mammoth Edition” a reality. One of them is led by Harvard geneticist and media showman George Church.899 The other, by the controversial South Korean biologist Hwang Woo-suk at Sooam Biotech, in collaboration with Russia’s North-Eastern Federal University.900

Church’s team has already implanted forty-five mammoth genes into the DNA of an Asian elephant—the mammoth’s closest living relative— in hopes of one day creating a hairy, cold-resistant, mammoth-like elephant. One science writer suggests nicknaming the hypothetical, Oz-like creature a mammophant or elemoth.901

By contrast, Woo-suk’s team is going for the whole enchilada, hoping to recover a completely intact mammoth genome from the frozen mammoth carcasses buried throughout the Siberian tundra. If successful, they will follow the same SCNT cloning procedure Ian Wilmut used to create Dolly. They will insert the mammoth DNA into a denucleated Asian elephant egg and then let it gestate inside an Asian elephant mother’s womb for two years.902

Both teams face huge technical hurdles, but also questions about the wisdom of what they are doing. “The bigger question is: should we do it?” says cell biologist and science writer Helen Pilcher, author of Bring Back the King: The New Science of De-Extinction. “What would be the point?”903

Some argue we have a moral obligation to bring back species we unjustly killed off—for example, by our wanton destruction of their natural habitat. Others note that among all possible causes for the wooly mammoth’s demise, humans are not at the top of the list. Instead, it’s likely the hulking pachyderms—along with saber-toothed cats, ground sloths, Native American horses, camels, and much of the day’s cold-hardy vegetation—simply failed to adapt to the precipitous global warming that happened 10,000 years ago.904

Of course, there’s no denying we’ve caused or helped cause the extinction of countless other species. A 2014 study led by Duke University estimates that current annual rates of extinction are about 100 to 1,000 times higher than they were before we existed.905 The implication, right or wrong, is we, along with climate change, are largely to blame.

Even if it’s true, trying to de-extinct species is just further evidence of our stubborn desire to seize control of the natural world, without any real understanding of the possible consequences of doing so. I liken it to a well-meaning person without any carpentry skills offering to rebuild your house after tearing it down.

There are huge uncertainties associated with de-extinction. Could resurrected species survive in the modern world? Where exactly would we place them, given the original reasons for their disappearance might still exist, and might even be worse? And what about resurrected animals becoming pest species, foreign intruders that would disrupt today’s ecology?

And that’s not all.

A 2017 study led by Carleton University biologist Joseph Bennett and published in Ecology & Evolution found de-extinction efforts drain resources from much-needed conservation efforts racing to save today’s precious, endangered species. “Even using the optimistic assumptions that resurrection of species is externally [i.e., not taxpayer] sponsored,” the scientists report, the funding that inevitably would be needed to protect and preserve resurrected species “would lead to fewer extant species that could be conserved, suggesting net biodiversity loss.”906

In other words, de-extinction efforts could make things worse, not better. According to the study, if we took the resources being used on today’s flashy efforts to raise the dead and instead used them to rescue spectacular creatures currently teetering on the edge of the cliff—like black rhinos, mountain gorillas, and Sumatran tigers—we’d be able to save two to eight times more endangered species than we are doing right now.907

LIFE FROM SCRATCH

As Hollywood publicists are wont to say about movie sequels, “If you liked how genetic engineers mapped plant and animal genomes, you’re going to love how they’re committed to re-writing them, with all sorts of customized changes thrown in.”

Except this is not a movie pitch. It’s happening.

As I explained at the start of this section, all DNA is constructed from just four main molecules—A, T, G, and C—which always pair up as AT and GC. With just these two pairings, it is possible to write an infinite number of genomes, or recipes for life. It’s akin to being able to write an infinite number of books by using just the dots and dashes of Morse Code.

In 2010 a team led by geneticist Craig Venter successfully pieced together—DNA pair by DNA pair—the genome of a well-known bacterium. The scientists then implanted the freshly minted genome into the denucleated cell of a different bacterium. They named the resulting synthetized creature, appropriately enough, Synthia.908

That singular achievement not only made history, it inspired a bold, futuristic mindset. “Many scientists now believe that to truly understand our genetic blueprint, it is necessary to ‘write’ DNA . . . from scratch. Such an endeavor will require research and development on a grand scale.”909

That mission statement comes from GP-Write (Genome Project-Write), a congress of scientists who aim to construct the genomes of every living organism on Earth from scratch, the way Venter’s team did with Synthia. For these scientists, GP-Write is the logical sequel to GP-Read, the successful mapping of genomes, including the historic transcription of the human genome in 2003 [see FRANKENSTEIN: MEMORY LANE].

“We are going from reading our genetic code to the ability to write it,” says Venter. “That gives us the hypothetical ability to do things never contemplated before.”910

Besides replicating existing genomes, GP-Write scientists intend to redesign them and ultimately create entirely novel life forms, sprung entirely from the human imagination. As I said, the possibilities of writing genomes with just the AT and GC pairs are endless—including grand modifications to the natural, standard-issue human design.

“When people are thinking about the engineering or synthesis of the human genome, they immediately jump to a Brave New World of designer babies,” says Nancy J. Kelley, a co-founder of GP-Write. “That’s not where this project is going.”911

But, of course, that is precisely where efforts like GP-Write are taking us, notwithstanding Kelley’s astonishing naivete. As I explained in the last chapter, it is such self-inflicted blindness—scientists plunging ahead simply because they can, not necessarily because they should—that alarms me the most.

In Heraclitean Fire: Sketches from a Life Before Nature, Erwin Chargaff, the eminent Columbia University biochemist and DNA research pioneer, reflects on the two great discoveries he witnessed in his lifetime: nuclear energy and genetic engineering. Both resulted from hacking into once-sacred nuclei, he writes, “the nucleus of the atom, the nucleus of the cell. In both instances do I have the feeling that science has transgressed a barrier that should have remained inviolate.”912

Before passing away in 2002, Chargaff was especially concerned genetic engineering was taking us in a grim and dangerous direction. Once we create a new life form, he said, “it will survive you and your children and your children’s children.” Such “an irreversible attack on the biosphere,” he lamented, “is something so unheard of, so unthinkable to previous generations, that I could only wish that mine had not been guilty of it.”913