"I've seen a picture of one that was removed from somebody's ovary, and you can see where they got their name," he says, padding around the lab in blue booties slipped over his sneakers to guard against contaminating the room's vats, vials, and flasks. "It was a white, ghostly thing with teeth and hair. It was the ugliest thing I've ever seen in my life, like something from a Hollywood movie. And then you think, "That was cut out of somebody.'" Cullen slides a plastic container of red liquid under the microscope and peers at a clump of cells his lab has grown from one such monster. He grins. "When I tell my buddies these stories over dinner, it's a winner."
There are other stories about teratocarcinomas, the strangest tumor in the human body. Because they grow from sperm or eggs in the testicles or ovaries, these tumors bloom quickly, like diabolical embryos, sometimes swelling as large as grapefruits. Grotesquely mimicking the development of a normal embryo, teratocarcinomas can chaotically sprout all sorts of different tissue: blood vessels, teeth, hair; perverse approximations of eyes, arms, livers, kidneys. Some scientists say they've seen teratocarcinoma cells beat like miniature hearts, that the little monsters respond to a poke with a nervous shudder.
But for all their monstrous qualities, teratocarcinomas have one unique, very valuable characteristic: They contain stem cells, not unlike those found in an embryo or fetus, capable of developing into any number of types of tissue. And for Cullen and his colleagues at Layton BioScience Inc. in Sunnyvale, one particular teratocarcinoma -- removed in the 1970s from a dying 22-year-old man in New York -- is more than just a freak of nature. In the words of the company's CEO, it's a gift from God.
While the national debate over stem cells raged this summer, doctors at Stanford and the University of Pittsburgh quietly entered the second phase of a clinical trial to determine whether it's safe and effective to implant what seem to be neurons, derived from teratocarcinoma cells in the Layton lab, into the brains of stroke patients. If the therapy works, manufactured neurons will replace and repair damaged brain tissue, helping patients regain the motor functions they lost to stroke. The hope is that the cells could eventually be used to treat a variety of neurological disorders, including Parkinson's disease, Alzheimer's, and Huntington's.
But no one knows whether these cells actually repair the brains of stroke patients. Indeed, several researchers outside the study question the sanity of putting once-cancerous cells into human brains. Some suggest that Layton's trial, the only clinical study using such cells to treat stroke, has moved way too fast, without proving that the cells -- not physical therapy, the placebo effect, or brain surgery itself -- are responsible for the changes that patients are perceiving as improvement. They accuse Layton, a 10-year-old private company that has banked its future on these cells, of whipping up hype to attract investors. The hype, after all, is working: Red Herring named Layton one of its 100 companies to watch in 2001, and the still-unprofitable biotech firm has collected $30 million from friends, family, and venture capitalists, with an eye toward raising about $40 million more.
But the proof will be in the patients, many of whom report significant progress -- dead arms rising, fingers unfurling -- since receiving the cells. Whereas the controversial research on embryonic and fetal stem cells lingers at the promising stage, Layton's patients have literally opened their minds to the hope and hype.
Cullen, tossing his used booties into a trash bin and snapping off his latex gloves, puts it this way: "Stem cells are in the realm of the theoretical. What we're doing is in the realm of reality."
On Aug. 9, with the blue sky and flat ranchland of Crawford, Texas, as a serene backdrop, President Bush took to prime-time television to address a controversy he called one of the most profound of our time. At issue was whether the federal government should fund research on stem cells culled from discarded embryos and fetuses. After months of listening to scientists, abortion foes, politicians, talking heads, and dying patients, Bush finally made up his mind. He announced that the government would pay for research on existing stem cell lines, prohibiting subsidies for studies that created or destroyed more embryos, effectively alienating both the scientific and anti-abortion communities, satisfying no one.
In the wake of all the national soul-searching about the use of incipient or possible humans to produce stem cells for research, scientists involved in Layton's study coyly describe their work as "stem cell-like." Embryonic stem cells develop soon after a sperm cell fertilizes an ovum; as they divide, these stem cells can change form, or differentiate, into hundreds of types of tissue-specific fetal cells, which then become the mature cells that make up the body's tissues and organs. When transplanted into damaged sections of the body, scientists believe, such stem cells could become chameleons and interpreters, forming the tissue and molecular connections needed for repair and renewal. The ethical catch is obvious: These early-development cells can only be obtained from a spare embryo or fetus -- that is, from living tissue with at least the theoretical possibility of developing into a human being.
But the United States Conference of Catholic Bishops, a leading critic of stem cell research, says it has no moral objections to the science practiced by Layton, since it obtains stem cells from a tumor that merely behaves like (but is not) a human embryo.
Researchers first began studying this particular tumor in the late 1970s precisely because it behaved so much like an embryo; they were trying to determine how and why embryonic cells, which are all the same, differentiate to become skin, or heart, or kidney, or brain cells. They found, almost by accident, that this tumor's quasi-embryonic stem cells showed an astonishing determination to become part of the central nervous system. The finding surprised researchers: Teratocarcinomas usually don't display devotion to one part of the body.