CRUCIAL CELLS OF HUMANS ISOLATED.

Byline: Nicholas Wade The New York Times

Pushing the frontiers of biology closer to the central mystery of life, scientists have for the first time picked out and cultivated the primordial human cells from which an entire individual is created.

The cells, derived from fertilized human eggs just before they would have implanted in the uterus, have the power to develop into many of the 210 different types of cells in the body - and probably all of them. Because they can divide indefinitely in culture without the signs of age that afflict other cells, biologists refer to them as immortal.

Eventually, researchers hope to use the cells to grow tissue for human transplants or to introduce new or improved genes into people.

But there is a thicket of ethical and legal issues, as well as technical problems, to be overcome. The cells are obtained from embryos created at in vitro fertilization clinics and so far do not seem definably different from the primordial cells from which an entire individual is created.

Though some of the scientists involved in the work see nothing unusual about working with these cells, other researchers say they must be treated differently, given their human potential. Once the work becomes widely known, it could draw criticism from those who say it is wrong to interfere with nature by doing any kind of research on cells like these.

Known as human embryonic stem cells, they have eluded capture until now because they exist in this state only fleetingly before turning into more specialized cells, and need special ingredients to be kept alive outside the body.

The new cells have many possible uses of which the most promising is to grow new tissue, of any kind, for transplant into a patient's body. The cells also might offer effective routes to human cloning, although both the researchers and their sponsor deny any interest in this application. Another likely use is in gene therapy, the insertion of new or modified genes into body tissue.

Two forms of human embryonic cells have been developed, one by a team under Dr. James A. Thomson of the University of Wisconsin in Madison, the other by Dr. John Gearhart and colleagues at the Johns Hopkins University School of Medicine in Baltimore, Md. Thomson's work is reported in this week's issue of Science, and Gearhart's in the Proceedings of the National Academy of Sciences.

Financing banned

Congress in 1995 banned federal financing of research on fetal cells, including those derived from embryos, and the university researchers whose work was announced Thursday were funded by the Geron Corp. of Menlo Park, Calif., a biotechnology company that specializes in anti-aging research.

``It has potential health benefits which I think are extremely promising, and I am sorry that the law prevented us from supporting it,'' said Harold Varmus, director of the National Institutes of Health.

After an egg is fertilized it divides several times and forms a blastocyst, a hollow sphere with a blob of 15 to 20 cells, known as the inner cell mass, piled up against one wall. It is from these cells that the embryo develops. Thomson grew his embryonic stem cells from the inner cell mass of blastocysts left over from a fertility treatment and due to be discarded. Patients who had undergone fertility treatment donated the blastocysts to be used in research.

As an embryo grows and develops its cells become irreversibly committed to their fates as specialized components of the body's organs. A pocket of cells, known as embryonic germ cells, is protected from the commitment process so as to create the next generation of eggs and sperm.

Gearhart's group has developed embryonic stem cells from the germ cells of aborted fetuses. The cells developed by the two groups may well be equivalent but this has yet to be proved.

If researchers are able to use the cells to grow new tissues, the work could alleviate the shortage of livers and other organs for transplant. Cultures of the cells in the laboratory could be nudged down different developmental pathways to become heart or bone marrow or pancreatic cells. Before reaching their final stages, the about-to-become heart cells, for example, could be injected into a patient's ailing heart. Guided then by the body's own internal regulatory signals, the cells would develop into new, young heart tissue, supplementing or replacing the heart cells already there.

The same approach should in principle work with any tissue of the body. Human embryonic stem cells would thus serve as a universal spare parts system. Because the cells grow and divide indefinitely in culture, very few blastocysts would be needed.

Ethics debate

The ethical status of the cells is also likely to be a matter of discussion. They cannot become a fetus, as their blastocyst no longer exists, yet are very similar, if not identical, to the 20 or so primordial cells from which the embryo develops.

Both research groups refer to their cells as ``pluripotent'' because, when injected into a mouse with no immune system the cells develop into many of the major tissues of the body. The tissues are disorganized and do not develop into a normal embryo.

The cells also could be ``totipotent,'' meaning they can form every one of the body's cell types, but the experiment to prove this point would be unethical. The test for totipotency, developed with mouse embryonic stem cells, would involve injecting stem cells into another blastocyst. A normal mouse usually will develop but is composed of a patchwork of cells, some from the blastocyst, some from the injected embryonic stem cells, proving the stem cells retain all their powers.

It would be unethical to perform such an experiment on people but if it could be done, it seems likely that the human embryonic cells cultured by the researchers also would prove to be totipotent. If so, they might be capable in principle of contributing to the generation of a new individual.

But ethicists say great care must be taken in work involving human embryonic cells. ``Any time you take a cell off a blastocyst, that cell could be used itself to create a human being, so some groups in our society believe that in making it transplantable you have derailed it into becoming a kidney or some other tissue,'' said Lori Andrews of the Chicago-Kent College of Law, an expert on the laws governing reproductive technology.