073001Don't Impede Medical Progress

By David Baltimore. Mr. Baltimore, president of the California Institute of Technology, received a Nobel Prize in Medicine for his work on cancer.

Once in a long while, medical science comes up with a wholly new way to attack disease. A few years ago, such an opportunity presented itself with the discovery that human embryonic stem cells can be grown in large amounts. This provided science with a tool whereby new cells, tissues and organs could be grown that could replace diseased ones. No other technology offers such an opportunity. But nonetheless the Bush administration is considering banning federal funding of this very promising area of investigation.

Critics of stem-cell research allege that the embryos (which could come from either abortions or in vitro fertilizations) should be accorded all the protections available to a fully formed person. To me, a tiny mass of cells that has never been in a uterus is hardly a human being -- even if it has the potential to become human. By treating the use of such stem cells as akin to murder, we would lose a great deal.

Only embryos harbor cells with the potential to become every part of the human body. Such stem cells could be used to make up for the deficits in brain and pancreas cells that cause Parkinson's disease or diabetes. It is the only present hope that those who suffer from these ailments have. But curing their diseases will require a great deal more research -- research that a federal funding ban would disrupt.

Persuading stem cells to become tissues involves the work of many types of scientists. Some of these scientists need to be involved in learning to direct stem cells to adopt particular fates. This research involves using the use of inducing molecules, few of which are yet known. Once we know how to induce particular cell types, we will need to integrate them into various organs. If we can direct stem cells to form the insulin-producing cells of the pancreas, they could then be implanted directly because there is an existing organ structure in diabetic patients. The brain is a particularly important target because of Alzheimer's and Parkinson's diseases.

But even if we can direct stem cells to form the different types of neurons lost in these diseases, we will still need to learn how to make them wire up correctly with the rest of the brain after they are transplanted. The regeneration of organs like the liver presents even more challenges because it would have to be built from scratch. This requires not only producing the multiple cell types that it contains, but also precisely organizing these cells into a three-dimensional tissue structure. Scientists in the developing field of tissue engineering are concerned with how to build such structures.

If the president bans federal funding of stem cell research, no building supported by federal funds could be used for such work. Thus, a scientist working in a university -- where indirect cost recovery permeates all structures -- could not simply get funds from a company or a private foundation, and do the work in his or her laboratory. The work would have to be done in space physically removed from other labs. But the need for integrating the highly specialized work of scientists with different skills suggests that the work will proceed most effectively in the existing buildings.

It has been suggested that adult tissues might provide an alternative source of stem cells. This is simply false. Adult tissues are not known to have cells with the potential to become all parts of the body. In adults, certain tissues (e.g., skin, blood and brain) do contain specialized types of stem cells, but they are not generic stem cells with the same properties as those derived from embryos.

Critics of embryonic research point to the remarkable capabilities of adult bone marrow stem cells. Not only can they reconstitute blood, but, a flurry of recent papers suggest, if transplanted into other organs, they may be able to generate neurons, muscle, liver and perhaps other cells, albeit inefficiently. It would be wonderful if these reports held up, but they are a long way from being definitive.

For adult stem cells to be a viable alternative to embryonic cells, at least three uncertainties would have to be resolved in their favor. First, when adult stem cells take on a new fate, they would have to provide the complete range of function. This has not been demonstrated. Second, the few types of adult cells that can be grown in laboratories would have to be able to make all of the many cell types in the body. No one has even claimed such an ability. Third, the process of changing fates, which is at best a very rare event, would have to be made efficient and controlled enough to regenerate whole organs. We are not close to achieving this. While research on adult stem cells should be pursued, we would be mad to trade their great uncertainty for the clear and exciting potential already evident in embryonic stem cells.

It has been suggested that, as a compromise, President Bush could allow work to go forward on existing cell lines but that federal support of work with new lines be banned. Unfortunately, we will probably need new lines because existing lines do not necessarily provide all of the capabilities needed for therapeutic stem-cell derivation. Also, more than 30% of all pregnancies spontaneously abort, making it hard to know if even the few existing lines come from nonaborted embryos. And to complicate matters further, the existing lines are largely tied up by commercial interests. This is a compromise that will anger many and satisfy few.

Embryonic stem cells hold remarkable promise for reversing the devastations of human disease. If the U.S. government does not fund this work, it will progress slowly in private laboratories and in foreign ones. The publicly funded American academic research effort is far and away the most effective research enterprise in the world. To refuse to allow it to participate in this exciting research would be an affront to the American people, especially those who suffer from diseases that could one day be reversed by these miraculous cells.