Frankenstein's Cat: Cuddling Up to Biotech's Brave New Beasts (8 page)

The public reaction to the Missyplicity Project revealed a large potential market for copied pets, and Hawthorne and Sperling launched a company to make it rain cloned cats and dogs. On February 16, 2000, Genetic Savings & Clone (GSC) was officially born. At first, the company funded research and offered tissue banking, allowing people to store their pets’ cells until cloning technology matured. (One page on the GSC website at the time suggested “a futuristic stocking stuffer: a gift certificate redeemable for the preservation of the animal’s DNA … It’s like a ticket to the future, today!”) The company was an instant sensation.

Only one small thing lay between a pet owner and his clone: getting the darn ditto machines up and running. Although the impetus for the entire endeavor was a well-loved mutt named Missy, with both cat and dog owners clamoring for cloning, the A&M team decided to try replicating both species. Much to the disappointment of dog lovers everywhere, success with cats came first.

The lucky feline was a calico cat named Rainbow, and the first step in copying her was swiping a sample of her cells. When it comes to cloning, nearly any cell that contains a complete set of genes will do. (Recall that Dolly came from a mammary cell, and skin cells are also commonly used.) The A&M team knew that other scientists had had good luck with cumulus cells—the specialized, mature cells that surround a developing egg—so that’s what they harvested from Rainbow.

But you can’t simply stick a random cat cell into a uterus and expect a new feline to grow. Researchers needed to get Rainbow’s biological code into the proper vehicle: an egg. To do so, the scientists employed a method known as somatic-cell nuclear transfer, the same approach the Scottish team had used to create Dolly. The technique involves extracting the DNA from an unfertilized egg and replacing it with instructions for making a clone. (The procedure is not unlike removing the custard from the middle of a Boston cream donut and refilling the donut with jelly.)

Westhusin and his team harvested ova from a clutter of lady housecats. They poked a tiny, turkey-baster-like tool called a pipette into each egg and sucked out its nucleus, leaving the rest of the cellular machinery untouched. The scientists took one of Rainbow’s cells and placed it inside the newly “enucleated” egg, between the inner and outer membranes. This cell-inside-a-cell was then shocked with an electric current that turned the membranes of both cells into Swiss cheese, creating holes that allowed the genetic contents of Rainbow’s cell to flow into the egg. The egg, thus “tricked” into believing it had just been fertilized by a sperm cell, began to grow and divide, just like a normal embryo.

The researchers ended up with three cloned embryos, each of which contained Rainbow’s DNA. They transferred these embryos into the uterus of a brown housecat named Allie. Although only one of these feline fetuses survived to term, that was enough, and on December 22, 2001, Allie delivered a little, mewing kitten. Testing confirmed that the kitten was indeed Rainbow’s clone, and she was given the name CC, short for “Carbon Copy.”
*

CC’s name aside, technically, clones produced through nuclear transfer are not
quite
perfect copies of their genetic donors. Though the overwhelming majority of genes reside in a cell’s nucleus, mitochondria—which produce energy for the cell and sit in the cytoplasm outside the nucleus—contain their own little genomes. Because nuclear transfer leaves the cytoplasm of an egg intact, CC had the mitochondria, and mitochondrial DNA, of her egg donor, rather than from her “twin,” Rainbow. Since the amount of DNA involved is so tiny, however, most discussion of clones ignores this small genetic discrepancy.

CC’s birth alone was a remarkable achievement, especially given cloning’s staggeringly high failure rate. Some of the embryos created by nuclear transfer don’t divide properly, some fail to nestle into the warm and welcoming uterine wall, some spontaneously abort themselves. In creating Dolly, for instance, the Roslin Institute researchers had made 277 attempts to make cloned embryos and ended up with just 29 viable ones. They were all transferred to surrogate mothers, and as time passed, the numbers dwindled further, until only one cloned fetus was left—the lamb that would be Dolly.

The challenges associated with cloning go beyond low success rates. Dolly died at age six, well short of a sheep’s normal life expectancy. The lamb’s creators maintain that her demise had nothing to do with cloning, pointing out that four other sheep in the barn also came down with the same contagious lung disease that took Dolly’s life, but scientists are still plagued by questions about the health of cloned animals.

It’s impossible to draw definitive conclusions about Dolly—or any other single case—but since her death, biotech companies have cloned hundreds of farm animals, and we’ve amassed much more data on the health of clones. The evidence is troubling. Failures and defects are a normal part of reproduction—not every fertilized egg implants in the uterine wall, and stillbirths and birth defects can happen no matter how an animal comes into being—and assisted reproductive technologies, such as in vitro fertilization, increase the risk of certain abnormalities. But clones, at least in some species, are more likely to suffer from birth defects and health problems than animals made by other means.

That’s what the FDA concluded in a nearly thousand-page report, published in 2008, on the health of livestock clones. While the agency found no evidence of unusual health problems in cloned goats or pigs, it reported that cloned cattle and sheep do have an elevated risk of abnormalities. In particular, the animals are at risk for “large offspring syndrome,” which can cause respiratory and organ problems in the newborns and complications for their surrogate moms. Cloned cows and sheep are more likely to die in the womb or shortly after birth than their conventionally conceived counterparts. However, the data reviewed by the FDA also showed that if the youngsters can be safely shepherded through the first six months of life, they seemed to develop into perfectly healthy adults, and when these clones reproduce the old-fashioned way, their offspring appeared to be normal. That said, the FDA also noted that “it is not possible to draw any conclusions regarding the longevity of livestock clones or possible long-term health consequences associated with cloning due to the relatively short time that the technology has existed.”

Scientists believe that many of the poor outcomes seen in cloning can be traced back to a process known as genetic reprogramming. When a sperm cell fertilizes an egg, it initiates a cascade of changes. Some genes get turned on, while others are switched off, as the embryo grows and divides. Throughout the course of development, various genes are constantly being amplified or silenced, particularly as cells become specialized, or “differentiated.” The activation or expression of certain genes equips a cell to join the heart, for example; the expression of different genes turns a cell into part of the skin, or the blood, or the brain instead.

For years, scientists thought cellular differentiation was irreversible—once a skin cell, always a skin cell. Dolly’s birth smashed that assumption. Through the process of nuclear transfer, the scientists had managed to take the DNA from a differentiated mammary cell and turn it into something that a developing embryo could use. Cloning other adult mammals reinforced the discovery that nuclear transfer can reset genes contained in specialized cells back to their embryonic state. It was an astonishing accomplishment, turning back the genetic clock, but this process may not always go perfectly. As Westhusin explains, “An egg knows how to take a sperm cell, and the DNA that it has, and it knows how to reprogram it so that it turns some genes on and some genes off. A nucleus in a skin cell is not packaged like a nucleus in a sperm cell is. An egg knows how to reprogram a sperm to initiate life but it doesn’t know exactly how to reprogram a nucleus from a skin cell.”

Incomplete or flawed reprogramming can leave an egg with genes exhibiting an abnormal pattern of expression, which means that scientists might be creating a whole new cow with DNA that’s stuck on the wrong settings. Depending on what genes are expressed abnormally, the result can be everything from an egg that’s not even viable in the first place—and thus never develops into a fetus—to an array of birth defects. Though we don’t know much about the health of cloned cats and dogs (there simply haven’t been any large, long-term studies on the subject), errors in genetic reprogramming can affect any species.

Fortunately, CC was “vigorous at birth,” all her little feline toes intact. For about a year, CC, Rainbow, and Allie lived at the lab, where the scientists monitored their health and showed off the trio to visitors. When the cats’ scientific duties were complete, the researchers decided to place the felines in adoptive homes. Duane Kraemer, a veterinarian and physiologist who was part of the cat cloning team, claimed CC, and one December day, I went to meet her.

*   *   *

As I pull into a hotel parking lot in downtown College Station, I am nerdtastically excited. I’m about to meet my first clone! I pause to collect myself before heading inside to meet Kraemer; I want to play it cool. (Blurting out, “So let’s go see the Frankencat!” would be a tad unprofessional.)

Kraemer is one of the university’s senior scientists. He grew up on a dairy farm in Wisconsin and had planned to spend his life there, milking his family’s cows. Then, as an undergraduate, he fell in love with research. He racked up five degrees—bachelor’s degrees in animal husbandry and veterinary science, a master’s in reproductive physiology, a PhD in reproductive physiology, and a degree in veterinary medicine—and joined A&M’s faculty. He founded the Reproductive Sciences Laboratory and mentored dozens of students, including Westhusin. Now in his late seventies, he says he still gets a thrill every time he sees an embryo. He has a big smile, oversized glasses, and protruding ears, with a soft voice that sounds like it could give out at any moment.

We hop into Kraemer’s car and my adventures in Cloneland begin. (Over the course of the day, I’ll spend some quality time with CC, as well as snag a few minutes with Bruce—a cloned bull who would rocket a blob of his very valuable snot onto my sneaker—and Dewey, the world’s first cloned white-tailed deer.) It’s a short ride to Kraemer’s ranch-style house. He ushers me around back, and as we push through the chain-link gate into the yard, his wife, Shirley, comes barreling out the door. I assume we’ll be following her back inside the house to meet CC, but the couple points me in the opposite direction, to what looks like a big wooden shed in the yard.

“CC has her own house,” Kraemer says. “For her and her kids and her husband.”

Kraemer built the structure himself, and when he takes me inside, I am duly impressed. It’s a bilevel, with a living room, a kitchen, and two small lofts. It has plumbing, heating, and air-conditioning. Should the cats ever get the urge to read, there’s a set of bookshelves packed with the dissertations that Kraemer’s students have written over the years. The back door opens into a screened-in patch of yard—cluttered with toys and branches—so the felines can get some sun and fresh air. It is, I have to admit, at least as nice as my own apartment. (What’s a girl got to do to be reincarnated as a cloned cat?)

We find CC luxuriating on the landing. Kraemer walks over to give her a kindly rub, but she wriggles away and goes to sit on the windowsill, where she gazes out upon her kingdom. Her back sports gray stripes, and her belly, paws, and cheeks are bright white. She has green eyes and a small brown beauty spot, Cindy Crawford–style, just above her mouth. I stare into the face of pet cloning, and it stares back, twitching its soft pink nose. Despite not being a cat person, I have to admit that CC is—from a purely objective, scientific point of view, of course—pretty cute.

The Kraemers have given CC a good life—not only a house, but also a family. “We figured we should probably breed her because people would want to know whether clones could reproduce,” Kraemer says. The matchmakers introduced CC to a gray tomcat named Smokey, and in 2006, CC gave birth to four kittens. One was stillborn, but the others were perfectly healthy.

As I wander around the cat house, I keep tripping over various members of the cat clan. One hangs out on a shelf in front of the AC, another claws furiously at a scratching post, while a third lounges languidly in a chair. CC keeps watch over the brood from her perch.

“I never thought I’d have a cloned cat,” Shirley confides.

No? I laugh. That wasn’t part of your life plan? “Is it strange?” I ask.

She pauses, then says, “Not as strange as when we had the lion.”
*

So far, CC shows no signs of health problems, cloning-related or otherwise, and a few months after I met her, she celebrated her tenth birthday. But there is something off about CC: She doesn’t look like her genetic twin. Rainbow was a calico, her white fur splotched with gray and orange. CC, on the other hand, doesn’t have a lick of orange in sight.

The most likely explanation for the discrepancy is a phenomenon known as “X inactivation.” Like female humans, female cats have two X chromosomes. In calicos, the gene that codes for black fur is on one of these X chromosomes, while the orange gene is on the other. In any given cat cell, only one X chromosome is active. Westhusin and Kraemer surmise that in the cumulus cell used to create CC, the X chromosome carrying the orange gene was turned off.

CC is a reminder that DNA sequence isn’t all that matters. An animal’s characteristics also depend on how a gene is expressed. All along the genome, little molecular tags act as dimmer switches, turning genes on and off, making them more or less powerful. Some of these genetic settings are inherited and others are modulated by the environment. The chemicals and nutrients that a fetus encounters in utero, for instance, can make certain genes more or less active. Clones, carried to term by surrogate mothers, develop in different prenatal environments than their genetic donors did. Even after birth, early life experiences can alter gene expression in a multitude of ways. These environmental differences could easily lead to discrepancies between Fido One and Two.
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