Frankenstein's Cat: Cuddling Up to Biotech's Brave New Beasts (5 page)

Throughout the 1980s and ’90s, studies provided proof of principle, as scientists created transgenic mice, sheep, goats, pigs, cattle, and rabbits that did in fact make therapeutic compounds in their milk. At first, this work was merely gee-whiz, scientific geekery, lab-bound thought experiments come true. That all changed with ATryn, a drug produced by the Massachusetts firm GTC Biotherapeutics. ATryn is antithrombin, an anticoagulant that can be used to prevent life-threatening blood clots. The compound, made by our liver cells, plays a key role in keeping our bodies clot-free. It acts as a molecular bouncer, sidling up to clot-forming compounds and escorting them out of the bloodstream. But as many as 1 in 2,000 Americans are born with a genetic mutation that prevents them from making antithrombin. These patients are prone to clots, especially in their legs and lungs, and they are at elevated risk of suffering from fatal complications during surgery and childbirth. Supplemental antithrombin can reduce this risk, and GTC decided to try to manufacture the compound using genetically engineered goats.

To create its special herd of goats, GTC used microinjection, the same technique that produced GloFish and AquAdvantage salmon. The company’s scientists took the gene for human antithrombin and injected it directly into fertilized goat eggs. Then they implanted the eggs in the wombs of female goats. When the kids were born, some of them proved to be transgenic, the human gene nestled safely in their cells. The researchers paired the antithrombin gene with a promoter (which, as you’ll recall, is a sequence of DNA that controls gene activity) that is normally active in the goat’s mammary glands during milk production. When the transgenic females lactated, the promoter turned the transgene on and the goats’ udders filled with milk containing antithrombin. All that was left to do was to collect the milk, and extract and purify the protein.
Et voilà
—human medicine! And for GTC, liquid gold. ATryn hit the market in 2006, becoming the world’s first transgenic animal drug.
*
Over the course of a year, the “milking parlors” on GTC’s 300-acre farm in Massachusetts can collect more than a kilogram of medicine from a single animal. And so, the humble goat—tin-can eater and petting-zoo star—has added a new item to its résumé: pharmaceutical manufacturer. The universe of pharming is rapidly expanding; labs and companies around the world are working to stock their barns, fields, and coops with animals that pump out medicines for ailments ranging from hemophilia to cancer.
^†
ATryn has now been joined by Ruconest, a drug produced in the milk of genetically engineered rabbits. Sold by the Dutch company Pharming, Ruconest treats hereditary angioedema, a genetic disease that causes painful bodily swelling.

Pharm animals, which push the boundaries of medical research and could save human lives, make GloFish look like child’s play. There is nothing frivolous about them. But that’s a double-edged sword. Making animals more useful also makes them more likely to be
used
. Genetic engineering allows us to exploit other species for new reasons and in new ways, expanding our supply of creature commodities. Of course, using animals for our own purposes isn’t new. Should we object because the technology is?

*   *   *

Scientists are working to coax all sorts of curative compounds out of animal bodies. Many of these substances are remedies for rare genetic disorders. James Murray and Elizabeth Maga—biologists and animal scientists at the University of California, Davis—on the other hand, have decided to use the tools of pharming to alleviate a much more pervasive problem: diarrhea. The ailment’s global toll is enormous, with more than 2 million children dying of diarrheal disease every year. It’s a ghastly statistic, and if Murray and Maga can begin to make a dent in that number, their work will be the most far-reaching pharming project yet.

As it happens, human breast milk is a potent antidiarrhea elixir. The liquid is full of compounds that boost a child’s immune system and attack invading bacteria. The evidence now suggests that infants who are breast-fed have healthier digestive systems and are less likely to suffer from diarrheal diseases than those fed purely on formula. Some of these effects can last even after breast-feeding ends; infants who drink breast milk for the first thirteen weeks of life are less likely to come down with gastrointestinal problems during their entire first year.

One of the compounds responsible for these effects is an enzyme called lysozyme, a microbe destroyer that bursts bacterial cells like balloons, causing the cellular membranes to rupture and the disease-causing contents to spill out. Lysozyme is naturally present in the milk of all mammals, but it’s especially concentrated in human breast milk, which contains three thousand times as much of the enzyme as the milk of some other animals. (Infant formula, which is usually made from cow’s milk, has only trace amounts of lysozyme, at best.)

Murray and Maga want to extend the protective effects of breast milk to infants who don’t nurse or children who have grown too old to do so. Their plan is to harness the power of pharming, engineering dairy goats that make extra lysozyme in their milk. The pair hopes that this genetically modified milk can be used to both prevent and treat childhood diarrhea. Like the scientists at GTC, Murray and Maga set out to create their supergoats using microinjection.
*
They squirted the human lysozyme gene into fertilized goat eggs and implanted the resulting embryos in surrogate mothers. One of the embryos grew into a little kid named Artemis, a transgenic female with a penchant for mulberry leaves.
^†
She lives out at the university’s goat barn, and one day, Murray took me to see her.

The barn is home to 150 assorted goats—representing a variety of wonderfully named breeds, including Alpine, Nubian, Toggenberg, and LaMancha goats—but Artemis has pride of place, making her home in a private enclosure directly in front of the entrance. Artemis, now a fully grown adult doe, is mostly white, with some black markings around her eyes and the classic goat accessory: a long white beard. As soon as we reach her pen, Artemis sticks her head in Murray’s hands, waiting for him to stroke her ears. After Artemis matured, she became what’s known as the “founder female”—by breeding her, Murray and Maga generated a whole line of transgenic goats.

Today, Artemis’s heirs are all over this facility, living in a line of wire-enclosed pens stretching out behind the barn. It’s been raining all morning, and many of the goats are still huddled underneath their small wooden shelters. As we walk down the slick, hay-strewn path, the animals begin to “baa” and traipse over to us through the mud. I don’t think I’ve had a close personal encounter with goats since I was a child, and I’ve forgotten how endearing the animals can be, with their wide-set eyes, their oversized ears, and their eagerness for attention and affection. The goats jostle one another, poking their noses through the holes in the wire fence, angling for pets from Murray and me. We happily oblige.

As we dole out our goat rubs, Murray points out the genetically modified animals. I’m glad he does, because they look just like all the other goats, and I never would have recognized them on my own. Eight of the transgenic females are pregnant, due to deliver a batch of new kids in the next month or two. With newborns to care for, these does’ udders will fill with lysozyme-rich milk. They’ll make up to two liters a day of the stuff, for about three hundred days after they give birth.

Murray and Maga have carefully analyzed the milk from Artemis’s heirs and found that it does indeed contain elevated levels of lysozyme—1,000 percent more than normal. They’ve also demonstrated that the milk has protective effects in pigs, which have a digestive anatomy that is similar to our own. Compared with piglets that sucked down conventional goat milk, young pigs that got the special, transgenic stuff had lower baseline levels of coliform bacteria—including
E. coli
, a common cause of diarrheal disease—in their guts. They also had stronger immune systems and healthier small intestines. And when the researchers
tried
to make the pigs sick, by feeding them a delicious
E. coli–
laden soy broth, the piglets slurping down the lysozyme-rich milk fared better.

These results are giving Murray and Maga confidence that the modified milk will do a human body good. So in September 2011, they asked the FDA to review the milk from transgenic goats and officially rule whether it’s safe for human consumption. They are still awaiting a verdict. Though Murray acknowledges that nothing can be 100 percent risk-free, he thinks that lysozyme is pretty safe. The compound is well studied and naturally present not only in our milk, but also in our tears and saliva. As Murray points out, “You’ve been eating lysozyme since the day you first swallowed.”

Still, Murray and Maga aren’t sure whether—or when—the FDA will rule in their favor. As of now, GloFish are the only transgenic animals available to the American public, and the federal government doesn’t seem eager to give the neon swimmers any company. Ironically, it’s the makers of useful transgenic animals—the ones designed to be sources of food or medicine—that are struggling to get the official stamp of approval. GloFish sailed through because they were totally trivial, designed purely to be pets. It is, of course, appropriate for an animal intended for human consumption to be subjected to a higher level of scrutiny, but the end result is that these organisms can get stalled in a never-ending regulatory process. Even if the FDA approves their transgenic goat milk, there’s no guarantee that American doctors or patients will embrace it.

In the United States, the debate over genetic engineering has been dominated by loud antitechnology activists, and a stamp of government approval may not be enough to overcome pervasive fears about the safety—or ethics—of GM products. So Murray and Maga are hedging their bets and establishing a second herd of goats in Brazil, which is among a handful of countries—including Argentina, China, and India—poised to become major powers in the world of agricultural biotechnology. (The nation is already a leading grower of genetically modified crops.) The Brazilian government, which has been bullish on biotech, has given Murray and Maga’s colleagues at the Federal University of Ceará $3.1 million to create their own herd of lysozyme goats. Once the goats are up and bleating, the international research team will start human trials in Brazil, studying the milk’s effects in healthy adults and then healthy children. If all goes well, they’ll move on to trials with those who might really be able to benefit from the milk.

The Brazilian team is headquartered in Fortaleza, along the country’s northeastern coast. The region is home to some of Brazil’s poorest towns and villages, where as many as 10 percent of kids die before their fifth birthday. Transgenic goats’ milk may be a much-needed salve. Assuming the human trials are successful, Murray and Maga see the milk being used in several ways. Doctors could give it to infants who aren’t breast-fed, in order to help them develop healthy immune systems. Or they could prescribe it for toddlers who are no longer nursing, in order to keep their guts in tip-top shape. Or the milk could be used as a
treatment
itself—administered alongside rehydration therapy to infants, toddlers, and kids suffering from diarrheal disease. As an added bonus, the milk would also provide some much-needed nourishment, combating the malnutrition that often goes hand in hand with intestinal disease.
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The ultimate goal, Murray and Maga say, is to get their goats into towns and villages all over Brazil. Instead of keeping a herd of normal goats, families would raise transgenic ones, and anyone drinking the animals’ milk would benefit from the supercharged levels of lysozyme.

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Keeping children alive seems like such an unobjectionable endeavor, but doing so through genetic engineering makes many of us uncomfortable. The anxiety comes in many forms. There are legitimate concerns about health risks, but these are easy to address—that’s exactly what human trials are for. The other objections are more philosophical—and harder to answer with cold, hard data.

Take, for instance, the worries about animal exploitation. The development of our new genetic tools has coincided with a growing concern for the rights and welfare of animals. In 1975, just as scientists were learning to mix and match DNA, Peter Singer published his famous treatise
Animal Liberation
. In it he railed against “speciesism,” arguing that our mistreatment of animals, and our exploitation of their bodies for food or research, was akin to the subjugation of women or racial minorities. Animal suffering matters, he said, and we have an obligation to minimize the pain and distress we inflict upon other species. It was the birth of the modern animal rights movement, and in the years since, activists have launched a variety of diverse campaigns, lobbying governments to grant full legal rights to great apes and protesting companies that test cosmetics on rats or rabbits.

Those working to extend animal rights are motivated by a wide range of philosophies and goals, but one of the common themes is that animals have a basic
intrinsic
value—that is, that they are inherently valuable on their own, solely because they are living creatures with whom we share the Earth. On the other hand, when we use animals for food, or fiber, or drugs, we reduce them to their
instrumental
value, treating them as mere tools to be used or resources to be tapped.

Much to the chagrin of the animal rights crowd, biotechnology lets us turn animals into even better tools. With genetic engineering, we are giving animals the very traits we want to exploit. We are engineering lab rats guaranteed to suffer from the very medical afflictions we want to study and reprogramming dairy animals so they produce not only milk but also medicine.
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As Richard Twine, the Lancaster University sociologist, notes of pharming, “Animals that have previously been defined as agricultural commodities are becoming pharmaceutical commodities. Biotechnology might be inciting new forms of commodification within human and animal relations. It’s potentially multiplying the uses to which profits can be made from different forms of animal life.”