Cell Out

BOSTON -- President Bush's veto of the stem-cell legislation last week is likely to have little effect on the progress of science in this exciting and emerging field -- and that's the crux of the problem.

Currently, scientists seeking to study human embryonic stem cells have two options: Accept federal funds and focus only on a handful of cell lines created prior to Aug. 9, 2001, or decline federal dollars and gain access to the much larger, and constantly increasing, number of cell lines created since then -- assuming they can find an alternative funding source.

Many of the newer lines grow better in culture, and because they encompass a far broader range of genetic diversity, they provide a greater basis for comparison and mechanistic understanding. The legislation vetoed by the president would have made the new cell lines eligible for federal support.

The differences in the quality of approved and off-limits embryonic stem-cell lines will become especially pronounced over the next several years, as scientists learn how to make "custom" cell lines containing the genetic material from patients suffering from a range of important medical conditions, such as Type 1 diabetes and Parkinson's disease. (The technique involved is called somatic cell nuclear transfer, aka, therapeutic cloning; it is the method that South Korean researcher Woo Suk Hwang falsely claimed to have perfected.) The disease-based human embryonic stem-cell lines are expected to provide valuable clues into the mysterious origins of debilitating conditions.

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The study of human embryonic stem cells has been plagued by three basic problems, problems that the president's recent veto is certain to exacerbate. But first, a little background.

Because human embryonic stem cells can develop into any cell type, they have obvious potential for medical therapy. If researchers learned how to turn embryonic stem cells into insulin-producing cells, for example, these cells might be used to treat diabetic patients.

Adult blood stem cells have been used clinically to replace blood cells lost in the treatment of several types of cancer. But adult stem cells may not exist for every tissue type in the body, and thus do not offer the same range of clinical possibilities as embryonic stem cells.

Blood stem cells were identified decades before human embryonic stem cells were first isolated, allowing the technology years to develop. Clearly, this does not mean (as is often claimed) that adult stem cells are effective while embryonic stem cells have failed; nor does it mean that other types of adult stem cells will prove as useful as those from the blood.

The ability to develop cells with properties similar to embryonic stem cells but without the destruction of an embryo -- the premise of one of the two less controversial stem-cell bills the president did agree to sign -- may be a worthy goal; yet it does not seem likely to be realized in the near future, despite the credible efforts now underway.

Now, let us return to human embryonic stem cells, and challenges of studying them:

The Haves vs. the Have Nots. Scientists seeking to use the best human embryonic stem-cell lines rely on private funds and (less frequently) state money to back the research.

In effect, this has created a two-tiered system, where the relatively small number of scientists, institutions and regions able to attract this kind of support have been able to work with the best cell lines. This advantage will become especially pronounced once the disease-based cell lines come on board. Investigators dependent upon federal support will be stuck with the same old cell lines, and it's not difficult to anticipate the migration pattern of the best young scientists.

Given that conservatives frequently decry the accretion of research resources by academic enclaves in the Northeast or West Coast, it seems (depending on your perspective) either cruelly ironic or entirely appropriate that the president's veto -- embraced by many conservatives -- will almost certainly augment the scientific advantage of these so-called liberal elites.

Perpetual Fundraising. Most fundamental medical research in the U.S. is funded by the National Institutes of Health, with grants awarded on the basis of extensive peer review. While the process is far from perfect, it nevertheless is well defined, and driven by the quality of the underlying science.

Scientists seeking support for stem-cell research ineligible for federal funding must constantly shimmy and shake for donor after donor, hoping to land the big fish, or enough small fish so that the science can continue. This is an inefficient use of time and energy, and might result in funding decisions based on the charisma (or lack thereof) of the researcher, rather than on the quality of the proposed experiments.

Polarization. Arguably the most distasteful consequence of the president's veto will be an increasingly bitter dialogue between those who support embryonic stem-cell research and those who feel it crosses a moral line. As the battle for funding moves to the states, we are certain to see more of the exaggerated claims already advanced by both sides of this divide.

Supporters of embryonic stem-cell research frequently have suggested that cures are just around the corner; Woo Suk Hwang's oft-quoted promise to a paralyzed 10-year-old boy -- that "you will walk again" -- is, perhaps, the canonical example. Would that this were true. The science of embryonic stem cells is in its earliest days, and we are likely many years away from any sort of meaningful clinical application.

Conversely, opponents of embryonic stem-cell research have consistently misrepresented the achievements of adult stem-cell technology. The widely circulated list of adult stem-cell successes assembled by the Family Research Council, for example, has recently been discredited by a group of stem-cell researchers in the journal Science.

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If the president's veto ultimately doesn't change the course of existing research, then why should we care? Opponents of the science will take comfort in their belief that the veto has prevented our acceleration down a slippery slope, providing important new opportunities to stall existing experiments and perhaps develop less controversial alternative approaches.

Meanwhile, those of us who believe in the clinical promise of embryonic stem-cell research remain convinced that discovering how stem cells work represents a scientific challenge of the highest order. To solve this problem, we will need all the best minds that our country has to offer -- and we'll require their full attention, which should be focused on how to turn stem cells into cures, rather than how to turn promises into money.