Despite Objections, Hopes Rise For Material That Could Repair Human Ailments Some Readers May Find Objectionable

By Faye Flam, The Philadelphia Inquirer

Biologist John Gearhart is happy to open the incubator in his Johns Hopkins laboratory and bring out a tray of plastic dishes holding the colonies of human cells that have catapulted him to scientific fame, fueled raging ethical debates in the federal government, and angered the Catholic Church.

The cells in question -- human embryonic stem cells -- have been hailed as a potential universal repair material for the human body.

Some believe that stem cells could allow doctors to grow cells that:

-- make the dopamine that's lacking in the brains of patients with Parkinson's disease;

-- grow insulin for diabetics;

-- and repair damage from heart attacks.

Some speculate that stem cells could be used to create both nerves to repair spinal cord injuries and skin to treat severe burns. They dream of using the cells to construct new organs.

Right now, there isn't much to see -- just a yellow fluid filling the teacup-sized petri dishes in Gearhart's lab. But suspended there are the same type of cells that make up a 3-day-old embryo, with the almost magical power to grow into all the hundreds of types of tissues that make up a human body.

Gearhart shows some photographs that capture the way stem cells can spontaneously metamorphose into tangles of nerves or clumps of muscle. Sometimes, he said, they form heart tissue that starts rhythmically beating in the dishes.

The goal now, Gearhart said, is to learn to control this process so that one day there might be large banks of stem cells, engineered to avoid rejection. In the future, ''any hospital anywhere can say, 'Give me some donor cells - liver cells, or heart cells,''' he said.

The study of stem cells is opening up an area of medical research comparable to genetics, said Ronald McKay, a stem-cell researcher at the National Institutes of Health. ''This is not just a sub-area of medicine,'' he said. ''I think this is the new biology.''

On the down side, these human embryonic stem cells have touched ethical and religious hot buttons. Gearhart offended the Catholic Church because he used tissue taken from aborted fetuses.

Biologist James Thomson of the University of Wisconsin, who tied Gearhart last November in the race to isolate human stem cells, also ran into rough ethical terrain for using leftover embryos created in fertility clinics.

As if there wasn't enough controversy, within days after those two achievements were announced, a Massachusetts biotechnology company claimed to have made stem cells using cloning.

Embryonic stem cells are not the only kind of stem cell known, but they are considered the most flexible, or ''pluripotent'' in the jargon. Any cell that can give rise to more than one kind of cell is considered a stem cell. Best known are bone marrow cells that can manufacture all the different types of blood cells.

Some animals, such as salamanders, seem to retain stem cells that allow them to regrow a lost limb or tail.

Some scientists think that stem cells exist in all human organs. Evan Snyder of Harvard University and NIH's McKay have used fetal tissue to collect and grow so-called neural stem cells, which they say can become different types of human brain tissue, and might work better than embryonic stem cells for treating brain disorders.

The ultimate stem cell, though, is the fertilized egg, which is considered not just pluripotent but ''totipotent'' because it gives rise to everything. Even after the first few divisions, the cells of early embryos retain that power. Separate them, as happens with identical twins, and they each form separate babies.

Eager to capture the potential of these cells, scientists such as Peter Donovan, now at Thomas Jefferson University, worked earlier in the decade to isolate them in mice.

Since then, scientists have tried to use stem cells to treat various diseases in mice. Earlier this month, Snyder announced a mouse experiment that showed stem cells might help fight Alzheimer's disease.

And at Philadelphia's Hahnemann University Hospital, Darwin Prockop has combined gene therapy with stem cells to test a possible approach to Parkinson's disease. He started with mouse stem cells that normally produced blood and genetically altered them to make dopamine, which is needed for Parkinson's disease

It was Gearhart's desire to solve the mystery of how an extra chromosome causes Down syndrome that got him interested in stem cells.

''We still don't know how that extra chromosome leads to the physical and neurological problems you see in Down syndrome,'' he said.

He wanted to watch how stem cells with the extra chromosome grow into different tissues. His first step was to get fetal tissue. Though President Clinton lifted a Reagan-era ban on such research, ''it took years to get the appropriate protocols prepared,'' Gearhart said.

And he couldn't use just any fetal cell. Unlike an early embryo, a fetus is not made of stem cells. Gearhart needed to separate the cells that later become sperm and eggs, which remain true embryonic stem cells.

Gearhart's challenge was to find such cells, isolate them and coax them to start growing.

Once he accomplished that, Gearhart said that keeping them in their original, embryonic state has been difficult because the cells tend to clump into ''embryoid bodies.''

The clumps look something like tumors called teratomas, which grow in the ovaries or testes. Jumbles of all sorts of human tissues, even hair and teeth, teratomas are thought to spring from stem cells that lose their way, said Gearhart.

Since November, when he and Thompson announced their success in growing human stem cells, Gearhart's been on a never-ending circuit of lectures and interviews. He plans to continue his investigation into Down syndrome, but with all the hopes for curing diseases, ''that doesn't mean you don't get swept up in some of the delusions of grandeur.''

Gearhart said that the American Conference of Catholic Bishops has objected that his work could encourage women to seek abortions. Gearhart argues that he has no connection to the women having abortions who agree to donate their fetal tissue to research.

Of the ethical questions surrounding stem cells, Gearhart says, ''Absolutely none of this is new.'' More than a decade ago scientists found that fetal tissue implanted in the brain could alleviate the symptoms of Parkinson's disease.

Gearhart said he is frustrated that in all those years the government hasn't developed a clear position on fetal tissue research.

Nor is there a clear guideline for working with the extra embryos created in the process of in-vitro fertilization.

Currently, any researcher getting federal funding is banned from using human embryos in research. Scientists could use fetal tissue, said Gearhart, until late last year, when the NIH temporarily barred federally funded researchers from using fetuses to make stem cells.

But the NIH has also said that the ban on federal funding should not apply to the study of stem cells already growing in a lab.

Congress is expected to debate stem cell research legislation this fall.

Cloning figures into the issue, too. In recent months, two companies announced they will use cloning to make stem cells. One of them, Advanced Cell Technology (ACT) in Worcester, Mass., was the first to clone cattle by coaxing an adult cow cell into becoming an embryo.

Last fall, ACT scientists created stem cells using cloning, but with a cross-species twist. They started with the DNA-containing nucleus of a human cell taken from one of their employees, and inserted it into the egg cell of a cow.

Cloned stem cells would have a distinct advantage, said ACT biologist Robert Lanza. They could be made from a patient's own DNA, thus eliminating the risk that the body will reject them -- a major problem with organ transplants.

Cow eggs are much easier to get than human eggs, which must be extracted through a complex and painful procedure, he said. And while some critics suggested the company was creating a bizarre cow/human hybrid, Lanza says that the stem cells in question are not capable of growing into a viable creature.

The other company, Geron of Menlo Park, Calif., provided funding for both Thomson's and Gearhart's human stem cell breakthroughs. Geron recently bought the Scottish Roslin Institute, where a sheep named Dolly was cloned, in order to acquire the technology for cloning animals and making stem cells.

Some of the concerns over cloning go back to the embryo debates. When scientists cloned Dolly, they created a blob of cells with the potential to become a lamb -- and proved it by implanting them into Dolly's surrogate mother.

If scientists used the same technique to make human stem cells, they would have to create a group of cells that, if implanted into a woman's uterus, could become a baby. That might, under some definitions, qualify cloned human stem cells as a human embryos.

To Gearhart, cloning fears have been exaggerated, but perhaps so have the hopes for stem cells. In his travels, he's run up against the mistaken perception that he can spin his stem cells into any organ, like spare parts of a car. In France, he got several requests from men who wanted him to use stem cells to build them a bigger penis.

At the same time, he said, he is worried that when he addresses patient groups, he finds they've pinned all their hopes on him and his stem cells, which are still far from finding their way into any therapy. ''To those people, you're a God,'' he said. ''I wasn't prepared for that.''