Reprinted from Science Progress.
Last week’s publication of papers reporting the production of pluripotent stem cells from non-embryonic sources ranks as one of the most exciting achievements in modern biology. Yet the predictable triumphalist sounds emanating from the White House and certain opponents of embryonic stem cell research should not obscure the fact that—as Wisconsin’s James Thomson himself pointed out—the controversy actually delayed the production of induced pluripotent stem cells by years. During that period hundreds of embryos have been destroyed in order to make stem cells lines.
Also obscured in the past few days is that without human embryonic stem cell lines, the Wisconsin and Kyoto groups would not have known what the earmarks of pluripotency are and therefore could not have accomplished their breakthrough at just about the same time, barely edging out other labs working on the same problem.
But sour notes should not ruin the sweet smell of success of scientists who refused to be distracted by the political and ideological turmoil swirling about them. Prizes and recognitions are sure to come their way in the next months and years, as well they should. Their work will jump start the field of regenerative medicine, which many believe to be the most exciting approach to alleviating human maladies since the burst of accomplishments in pharmaceutical discovery after the Second World War.
What are some of the other implications?
- The development of iPS cells is not only a victory of stem cell biology, it also marks a success for the star-crossed field of gene transfer. The techniques used to reprogram skin cells came straight out of attempts to re-engineer genes by using retroviruses to carry new code into the cells’ DNA. Thus genetic research gets a boost as well.
- As various stem cell experts have noted, researchers will need embryonic stem cells will for some time, both as the gold standard for establishing and recognizing pluripotency and also for determining whether the induced pluripotent stem cells can indeed do all the same work as embryonic stem cells. Considering the multitude of possibilities presented by the concept of regenerating tissues and organs, it could be years before a comprehensive set of answers to the latter question is available.
- Thus rationality should dictate expanded support of embryonic stem cell research in order to advance the science of induced pluripotency. Unfortunately, with these successful experiments as an excuse we can anticipate a hardening of opposition to any expansion of public funding.
- It will take some time, perhaps a year or two, to find transcription factors that do not stimulate tumor formation, and perhaps more time to understand the mechanisms of genetic reprogramming. Safety issues thus now become an important next phase as work in this field becomes the norm.
- On the state level, jurisdictions that were apparently frozen out of the science by local politics but boast substantial assets in scientific research can now be part of the process. However, it will take them some time to scale up to the sophistication of research groups in states that have been friendlier to cutting edge stem cell biology, such as California and Massachusetts.
- Some below-the-radar related issues may now become apparent. For example, one of the common methods for understanding and addressing the genetics of disease and for drug testing is the creation of lab animal models. When the public learns more about these chimeric animals, they may not be comfortable with them. as some grow from cells derived from human sources including, say, cells from people with Alzheimer’s disease that have been stimulated to become, neurons. Sen. Sam Brownback has introduced a bill to prohibit some of these experiments and President Bush has raised objections to “human-animal hybrids.”
- Scientists may explore a variety of other technical possibilities. At some point many will realize that pluripotent cells can be programmed to become sperm and egg cells, perhaps from persons who are otherwise infertile. And although the induced pluripotent cells currently lack the ability to divide into embryos, it’s a sure bet that there will eventually be interest in rendering them totipotent. Genetic modification of embryos by the introduction of “designer” stem cells is also in prospect, though how soon no one can tell. Further debates are likely to rage about the propriety of such procedures.
From a long-term perspective, this episode is a reminder of the power over life represented in the new biology. Ironically, this discovery reinforces the larger concerns of those who have opposed human embryonic stem cell research: the production of induced pluripotent stem cells is a giant step in the growing human mastery of biological nature.
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Jonathan D. Moreno