Read Present at the Future Online
Authors: Ira Flatow
STEM CELLS, CLONING, AND THE QUEST FOR IMMORTALITY
From my perspective as a physician, the need for this work is now greater than ever. Stem cell research can make a difference in people’s lives, and our efforts can serve as a paradigm for how we might ultimately be able to use many new developments in biology.
—DAVID T. SCADDEN, MD, HARVARD UNIVERSITY
In the movie comedy classic Monty Python and the Holy Grail, a cart rolls through the streets of a plague-stricken medieval village, while the cart driver calls out, “Bring out yer dead! Bring out yer dead!” Bodies of plague victims are piled high on the cart. But one body keeps sitting up and announcing, “Not dead yet, y’know!” If you go to Spamalot, the Broadway musical based on the Python movie, you can buy a T-shirt on sale in the lobby that says, “I’m Not Dead Yet….”
If I were you, I’d snap one up. In the future, mortality could be just another disorder that can be cured. There are two ways that could happen. You could clone your pet or perhaps your loved one or yourself. Or you could replace yourself, organ by organ, with stem cells that grow new body parts.
CLONING TO KEEP YOUR CAT FOREVER
In late 2004, a Texas woman paid $50,000 to a California company named Genetic Savings & Clone to have her late beloved cat, Nickey, cloned. Sometime later, she brought home “Little Nickey,” a nearly identical, nine-week-old kitten that she swore was her old kitty reincarnated. It was the first time an American pet had been cloned. The very first animal to be cloned was a tadpole, in the 1970s. The first cloned mammal was Dolly, a sheep born in Scotland in 1996. Since then other animals have been successfully cloned: lab animals, including cats, mice, and rhesus monkeys; livestock, including mules, pigs, and calves; and even endangered species, such as a guar, large wild oxen from India and southeast Asia, and a mouflon, a wild sheep. Genetic Savings & Clone was forced to close up shop at the end of 2006, saying in a letter to customers it was “unable to develop the technology to the point that cloning pets is commercially viable.” There were just not enough customers willing to pay the cost of cloning Snuffy, even when the price was dropped to $32,000.
In some businesses, though, that price may be a bargain. Thoroughbred racehorses, with proven racing ability, are now being cloned with the hope that the clones will give their owners a run for the money. A champion horse, with winnings of over $380,000, was cloned by a Texas breeder for the bargain price of $150,000.
Cloning your aging dog still presents more of a challenge. In August 2005, a team of South Korean scientists unveiled Snuppy, an Afghan hound who is the world’s first cloned dog. But because female dogs ovulate only once or twice a year, and at unpredictable intervals, one Snuppy required the use of more than 1,000 embryos, plus 123 surrogate mother dogs. Only 3 became pregnant, and only 1 gave birth to a healthy puppy, Snuppy. That long string of failures means a very high price tag, until dog cloning becomes a lot more efficient.
But there are other reasons to clone besides replacing a pet or breeding a winner. The usual reason for cloning plants or animals is to mass-produce rare or desirable organisms. Cloning means making an exact copy of biological material. Farmers and vegetable gardeners know that many plants and vegetables, including grass, potatoes, and onions, clone themselves. These plants send out a kind of modified stem called a runner. Wherever the runner takes root, a new plant grows, doubling your crop.
If you have potted plants that you cultivate indoors, you’ve probably done some cloning yourself. You’re certainly familiar with taking a leaf cutting from one plant and growing a new one. If you’ve ever done that, you’ve just cloned your original plant. (I have a Christmas cactus that is now the grandchild of the original.) You can do this because the end of your cutting forms a mass of nonspecialized cells called a callus. With the right amounts of soil, light, water, and nutrients, the callus will divide and begin to form specialized root and stem cells—growing into a new plant.
Then there’s tissue culture propagation, which botanical scientists and orchid fanciers use to grow rare plants. You can take pieces of specialized roots from a plant, break those roots up into root cells, and grow them in special culture. In nutrient-rich culture, the specialized cells become unspecialized, or dedifferentiated, into calluses. With the help of plant hormones, the calluses can grow into new plants that are identical to the original plant from which you took root pieces.
Besides plants, some animals—including humans—clone naturally. Identical twins are clones. Under certain environmental conditions, the unfertilized eggs of some animals—small invertebrates, worms, some species of fish, lizards, and frogs—can develop into full-grown adults. This process is called parthenogenesis, and the offspring are clones of the females that laid the eggs.
DIFFERENT TYPES OF CLONING
Although cloning is often used as a blanket term, there are three separate and very different types of cloning. The first is recombinant DNA technology, or DNA cloning, which is used all the time in molecular biology labs. To make more of the same DNA fragment for study, a scientist transfers it from one organism into a self-replicating genetic element, such as a bacterium, yeast, or virus. The DNA then can be replicated in a foreign host cell.
DNA cloning would be very useful in gene therapy. The 1992 movie Lorenzo’s Oil, based on a real case of a boy born with a rare genetic illness that wasn’t discovered until the 1980s, is an excellent primer on molecular biology and the promise it offers to cure inherited illnesses. Gene therapy sounds simple: You could remove defective genes from a sick person, clone healthy genes, and use a harmless virus to convey them to the patient’s cells, where they would replicate themselves and take the places of the defective genes.
Unfortunately, right now, gene therapy is far from being therapy. In 1999, 18-year-old Jesse Gelsinger, who suffered from a rare metabolic genetic disorder, died in the course of a gene-therapy experiment for which he’d volunteered. Since then, gene therapy has been going very slowly. The main problem for researchers has been finding the right gene carrier, or vector, that will convey healthy genes into a patient’s cells, and allow them to begin replicating themselves. Viruses are often suitable, but of course many viruses are harmful. In Gelsinger’s case, scientists used the rhinovirus, which causes the common cold. It’s also big enough to carry genes. Since Gelsinger died, scientists have been working to come up with a viable substitute.
Then there’s reproductive cloning, the approach used to create Dolly and other animals with the same nuclear material as an existing animal—or a deceased pet. Scientists transfer genetic material from the nucleus of a donor animal’s adult cell—obtained from the samples you sent in from your pet cat—to an egg whose nucleus,
along with it its genetic material—has been removed. To stimulate cell division and growth, the reconstructed egg has to be treated with chemicals or electric current. Once the cloned embryo has developed far enough, it is transferred to the uterus of a female host, where it continues to grow and eventually is born as your new kitten.
But that means your kitten—and Dolly and other animals created with reproductive cloning—aren’t completely identical copies of the original donor animal. Only the clone’s nuclear DNA is the same as the donor’s. Some of the clone’s genetic material comes from the mitochondria, powerful cells in the egg. Mitochondria contain their own short segments of DNA, and acquired mutations in mitochondrial DNA may play an important part in aging.
So cloned animals often have unexpected kinks, including much poorer health than their donors. They tend to have compromised immune systems and can be prone to tumors, infections, and other complications. Many cloned animals simply haven’t lived long enough to tell us how clones age. Finn Dorset sheep like Dolly normally live to the age of 11 or 12. Poor Dolly had to be put down by lethal injection in 2003, when she was only 6. She had had lung disease and arthritis, which was crippling her. People with cloned pets often wonder why they lack some of the qualities that made the originals so endearing. Texas A&M researchers once had a sweet-natured bull named Chance. They liked him so much that they cloned him and dubbed the clone Second Chance. Unfortunately, Second Chance turned out to have a dangerous temper; he was much more of a raging bull.
Reproductive cloning also is hard to do. More than 90 percent of cloning attempts fail to produce healthy offspring, and more than 100 nuclear transfer procedures may be needed to make one successful clone. Dolly, for example, was a single success out of 276 attempts. Scientists hope to use this method to reproduce animals that have been genetically engineered to produce useful drugs, or to serve as
models for studying human disease. Researchers also would like to repopulate endangered animal species or those that are difficult to breed, such as pandas. But that remains a major challenge. (Cloning extinct animals would be even more difficult, because the egg and the surrogate mother would have to belong to different species from the clone.) So far, certain animal species, such as chickens, have resisted attempts to clone them. Cloning has been limited to only a few animal species, and some species may turn out to be more resistant to reproductive cloning than others.
THERAPEUTIC CLONING
The third type of cloning is called therapeutic cloning, and it involves the use of cloning technology in medical research. One day, it may allow the production of whole organs from single cells and make waiting lists for donations of organs such as the liver, kidney, or heart a thing of the past. Or therapeutic cloning could produce healthy cells that could replace damaged cells in degenerative diseases such as diabetes, Alzheimer’s, and Parkinson’s.
In 2002, one biotech company reported that its researchers had successfully transplanted kidneylike organs into cows. The team created cloned cow embryos by removing the DNA from donor cow egg cells, and then injecting the DNA from skin cells of a donor cow. The scientists allowed these cow embryos to develop into fetuses. Then they harvested fetal tissue from the clones and transplanted it into the donor cow. After three months, the team reported that they had not observed any organ rejection in the donor cow.
XENOTRANSPLANTATION
Another way that scientists are trying to make therapeutic cloning work is to create genetically modified pigs and harvest from them organs for transplantation to humans, or xenotransplantation. Pigs are good candidates for therapeutic cloning and xenotransplantation because their tissues and organs are quite similar to humans’. To create
what British scientists call knock-out pigs, they have to inactivate the pig genes that trigger the human immune system to reject a transplanted pig organ. They knock those genes out of individual cells, which they then use to create clones from which they can harvest needed organs. In 2002, a British biotech firm reported that it had produced the first “double knock-out pigs,” genetically engineered to lack both copies of a gene involved in transplant rejection.
One potential hazard of using organs from animals such as pigs is the possibility that some viruses that live in the pigs might find their way into humans and kill the recipient. This possibility is making xenotransplants still very controversial and in need of further research.
EMBRYONIC STEM CELLS
Therapeutic cloning often is described as stem cell research because both involve growing stem cells. What scientists need to grow human replacement parts are human stem cells, “blank” cells that have not yet decided what they will become. They might become heart, or
lung, or brain cells; they are just awaiting genetic instructions. The easiest place to find and extract such stem cells in large quantities is the blastocyst, a ball of cells that forms in the first few days after a sperm and an egg join. These cells—about 32 to 200—are the foundation cells for every organ, tissue, and cell in a human body. These stem cells have not yet differentiated themselves into the more than 200 kinds of specialized cells that can become blood, neurons, skin, or organ tissue in a human body. In 1998, biologists at the University of Wisconsin reported that they had succeeded in using cloning technology—removing cells from human embryos—to establish the world’s first embryonic stem line, or population, in the lab. The Wisconsin stem cells—along with most embryonic stem cells used for research—were extracted from embryos created by in vitro fertilization and were left at fertility clinics, frozen in liquid nitrogen, as spares by couples who already had succeeded in conceiving healthy children. (A small percentage of couples donates the spares to research.)
A blastocyst is no bigger than the period at the end of this sentence. Its inner cell mass contains 8 to 40 stem cells. Once the stem cells have been transferred into culture, they begin to proliferate. If after several months the original cells have grown into millions of healthy cells, without starting to differentiate into specialized cells, then they are known as an embryonic stem cell line, or colony. A line can replicate indefinitely in a lab—although stem cells do deteriorate as they age and accumulate genetic mutations. So researchers are always looking for new supplies of stem cell lines.
Adults have a small number of stem cells in many of their organs and tissues, including their blood, heart, skin, bone marrow, and skin. Adult stem cells also can be found in liposuctioned fat, pulp under baby teeth, amniotic fluid, placentas, or a newborn’s umbilical cord. But adult stem cells are scarcer in the body and harder to grow in the lab than embryonic stem cells, and they don’t seem to be as versatile: They might be limited to becoming cell types within the
tissue where they are found. (Cord cells produce blood cells and may prove capable of generating bone and cartilage cells.)