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Two Takes on iPS cells in Nature

Posted by Jesse Reynolds on April 10th, 2008

Since the November announcement that scientists derived stem cells that appear to have the power of those from embryos (but without embryo destruction), much hay has been made about the stem cell debates’ future. As I describe in a new short essay published at the Hasting Center's Bioethics Forum, many advocates of embryonic stem cell research have been remarkably skeptical, if not outright dismissive, of the  new technique’s potential, called induced pluripotent stem (iPS) cells. Two articles – one in Nature and one in an offshoot journal - indicate the spectrum of response.

On the balanced end of the spectrum, journalist David Cyranoski assesses the prospects for iPS by examining “five things to know before jumping on the iPS bandwagon.”  His conclusions?

  • Anyone can do it: Fact (mostly)
  • Everyone can have their own custom-tailored cells: Fiction (unless you're rich)
  • The cures are on their way: Too soon to tell
  • Embryonic stem cells are the same as iPS cells: Fact (so far, anyway)
  • iPS cells have no ethical issues: Fiction (depends on what you want to do)

Notwithstanding the article’s snide title, Cyranoksi’s approach is critical yet balanced. In fact, I don't think anything this tough-but-fair, has ever been published in an outlet such as Nature or Science on cloning-based stem cell research, which is the primary rival to iPS.

Perhaps his most interesting point concerns iPS's  potential to derive patient-specific custom stem cell lines - the "personal biological repair kit" that's also the long-standing goal of cloning-based stem cell research. Cyranoski cites a neuroscientist who assert that patient-tailored iPS cell lines "would take a ridiculous amount of money" - at least several hundred thousand dollars. If that's that case, wouldn't such lines derived via cloning be at least as expensive? 

At the other end of the spectrum, Nature Reports: Stem Cells published a commentary by researcher Thomas P. Zwaka which goes so far as to imply that human stem cells have already been derived via cloning (here called somatic cell nuclear transfer). Discussing cell reprogramming (that is, iPS), he says that:

[I]n contrast to reprogramming by SCNT, the acquisition of pluripotency [by iPS] requires multiple days, and it is still unclear which sorts of cells can be reprogrammed. Not only does SCNT currently yield higher-quality pluripotent cells, it also possesses a significant advantage because it does not use genomic alteration to introduce reprogramming factors....

Suppose, though, that iPS cells can be generated without genetic manipulation. Many labs are pursuing this goal, and it could be achieved soon. Does this mean that SCNT can be discarded, that it should become a relic like mouth pipetting? Absolutely not! [emphasis mine]

Not only does the author fail to mention that human stem cells have yet to be derived from cloning, but he also skips over the two major risks posed by the technique: the need for numerous fresh human eggs, and the technical groundwork it would lay for human reproductive cloning.

Previously on Biopolitical Times:

Gene of the Week: the Ruthless Dictator Gene

Posted by Jesse Reynolds on April 9th, 2008

Nature opens a news article with this:

Could a gene be partly responsible for the behaviour of some of the worlds most infamous dictators?
Selfish dictators may owe their behaviour partly to their genes, according to a study that claims to have found a genetic link to ruthlessness. The study might help to explain the money-grabbing tendencies of those with a Machiavellian streak - from national dictators down to 'little Hitlers' found in workplaces the world over.

Reading the article a bit more deeply, one learns that the researchers based their conclusions on a well-known psychological game in which volunteers (in this case students) are given money, as well as the power to distribute it among other people. The researchers looked at a gene that had previously been linked to "pro-social" behaviors, and found a correlation. The students who kept the money for themselves instead of sharing it were more likely to have a shorter version of the gene.

Psychologists and economists have nicknamed this experimental situation the "Dictator Game." Although the researchers who used it in this study reference the name of the game in the title of their article, they phrase their observations in terms of the degree of "altruism" exhibited. But Nature's reporter casts the experiment as revealing a "ruthless dictator gene." In turn, that framing was adopted by various othernews outlets, using attention-grabbing titles like "Some are born despots" and "Dictatorship may lie in ones genes."

This case goes a step beyond the excessive simplification of much reporting of genetic associations, which too often touts the gene for happiness, aversion to foods, or propensity to vote. And it goes beyond typical misleading framings that, once established, dominate news coverage. In this case, a news article in one of the world's most respected scientific journal tells us that a genetic characteristic can lead to the worst of possible human behaviors. To the extent that this framing becomes adopted as truth, how will society react to the identification of the gene in individuals? Or in fetuses? Or during preimplantation genetic diagnosis?

Protecting research subjects from a broken system

Posted by Marcy Darnovsky on April 8th, 2008

Jesse Gelsinger

The current issue of The Hastings Center Report includes five articles about human research protection. One of them, "Eight Years after Jesse's Death, Are Human Research Subjects Any Safer?," asserts that

despite the press exposure and public outcry that followed [Jesse Gelsinger's 1999 death in a gene therapy clinical trial], no progress has been made in fixing the broken system of protections for human research subjects. These people…are still at serious risk of exploitation and harm.

Many things stand in the way of better protection, but perhaps the greatest obstacle is the lack of adequate federal oversight.

The article is especially significant because of its authors' expertise and experience. Adil E. Shamoo is a researcher in the University of Maryland's Department of Biochemistry & Molecular Biology and the founder and editor-in-chief of the journal Accountability in Research. Paul Gelsinger, the father of Jesse, has worked to improve human research protection since his son's death. Both have played lead roles with the human rights organization CIRCARE, Citizens for Responsible Care and Research.

The CIRCARE website includes a collection of documents about Jesse Gelsinger's death and the ensuing revelations about the researchers' egregious conflicts of interest, deliberate omissions in the consent form Jesse and his family signed, and scandalous lack of oversight by the FDA. In a 2001 essay titled "Jesse's Intent," Paul Gelsinger tells the story of his son's death and his own journey from complete trust in the researchers to sharp critic of a badly broken system.

One revealing episode takes place on the Gelsingers' back porch two months after Jesse's death. Paul Gelsinger asks head researcher Dr. James Wilson, who has come to Arizona with the results of Jesse's autopsy, whether he has any financial interests in the outcome of the study. Wilson replies that he is an unpaid consultant to Genovo, the biotech company that would profit from the research.

It was only later that Gelsinger learned that Wilson in fact owned a 30% share of Genovo. The following year, when it was sold to another biotech firm, Wilson received $13.5 million in stock.

The moral from my pov: Until these kinds of conflicts of interest are eliminated, research subjects will never be safe.

Previously on Biopolitical Times:

Burying the Lead

Posted by Osagie Obasogie on April 7th, 2008

A research article published in this week's Proceedings of the National Academies of Sciences has a finding on sex selection that has startled some in the media: American couples of Chinese, Korean, and Indian heritage are unusually likely to have a boy if they already have girls. This suggests that these families have a son-preference leading them to select the sex of their second or third child to ensure that it is male. While the American media have frequently reported on sex selection and shifting sex ratios abroad, this seems to be the first empirical evidence that the practice and its consequences do not simply happen "over there."

The authors do not speculate which sex selection techniques couples are using. But the article and its coverage play into a popular yet problematic framing: son-preference and sex selection are posed only as demographic problems where choosing too many boys means that there won't be enough girls to marry them when they grow up. This fixation with sex ratios obscures the human stories behind these selection technologies, where women are often treated brutally for not delivering boys and unwanted female children are sometimes cruelly neglected. For a more comprehensive perspective on the social conditions surrounding sex selection, check out this online journal written by Sunita Puri based upon her extensive research into the lives affected by sex selection.

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