There is a new brewing controversy about the NIH “approved” human embryonic stem cell (hESC) lines (more a tempest in a teapot). These are the cell lines approved for federal funding with President Bush’s speech August 9, 2001, eligible based on their derivation occurring before the speech and also meeting specific criteria as published by NIH. Of the 78 hESC lines eventually identified as eligible, 21 lines are currently available for shipping, while the remainder of the lines are not available for research (some failed to grow, some were withdrawn by their owners, but the majority have not been thawed and tested.)

One criterion was that “Informed consent must have been obtained for the donation of the embryo.” Now Josh Keller of the Chronicle of Higher Education reports that adequacy of the informed consent obtained for some of the approved lines is being challenged (subscription required) and several top hESC research institutions are considering a ban on the use of some approved hESC lines. In an article in the May-June 2008 issue of the Hastings Center Report, Robert Streiffer of the University of Wisconsin claims that many of the consent forms, used for parents to donate their embryos for experiments, were inadequate and did not meet ethical norms. In particular, the forms used by BresaGen of Atlanta, GA (now owned by Novocell) and Cellartis AB of Sweden were singled out for their deficiencies. The two companies account for only 5 of the 21 approved lines. According to Rick Weiss (formerly of the Washington Post, now with the liberal Center for American Progress that opposes President Bush’s policy on hESC research), Stanford has now determined that those 5 lines will no longer be available to their researchers. Johns Hopkins will consider lines individually as researchers express an interest in using them. According to Nature news, Story Landis, head of NIH’s Stem Cell Task Force, says the NIH will not be taking any lines off its registry. And it’s unlikely that stopping use of the 5 lines will have any impact. The BresaGen and Cellartis lines are the least-requested lines in the whole collection, accounting for only 90 out of almost 1500 cell shipments, according to NIH’s website. The favorites by far remain the five original lines developed by Thomson in 1998.

The report appears targeted more for its political utility, potential ammo for another push to open funding for more embryo destruction. The study’s subtitle notes it provides “ethical as well as scientific reasons to overturn the Bush administration’s restrictions on federal funding for stem cell research”, Weiss notes “the Bush stem cell policy is untenable and in need of a major overhaul”, and both Streiffer and Weiss spend time on the same old litany of supposed problems with the approved lines, e.g., they “had been cultivated with mouse cells and were potentially contaminated with mouse viruses, seriously diminishing their value as therapeutic tools.” Then again, hESC are nowhere close to any therapeutic use because of their many practical problems in application.

The contamination canard is worth a brief sidebar here. Critics usually cite a 2005 Nature Medicine paper that shows contamination of hESC with animal sugars (in particular an animal sugar type abbreviated as Neu5Gc) due to the co-culture with mouse cells and use of bovine serum in the culture medium. But curiously, they only cite the first half of the paper, showing there is contamination, and not the second half (esp. Fig 3), which shows that the contamination can be removed. Likewise Thomson also showed in 2006 that the contamination could be removed even from existing lines, and “no detectable Neu5Gc was found on cells grown in fully humanized conditions.” Other research has shown similar results at reversing contamination. In a June 2005 article in Science (subscription required), there was some admission that contamination was not a real problem: “But Keirstead, Okarma, and others now say that those concerns, widely reported, may have been overstated. Gage and his colleagues noted that the sugar gradually disappears once cells are removed from the feeder layers.” Okarma of Geron was more direct in this interview in 2006: “So the stuff you hear published that all of those lines are irrevocably contaminated with mouse materials and could never be used in people — hogwash. If you know how to grow them, they’re fine.” Geron of course has plans to use the original approved lines for a clinical trial. But we’ll save more on Geron and some of the other myths about the approved lines for another time.

Back to the ethics, it’s ironic that proponents of hESC research are just now examining the consent forms, years later. Maybe it was the rush to get at the cells and the funding that made them overlook such niceties before now. Of course the original lines were derived in an unethical way—after all, the derivation involved destruction of a young human life. Stanford’s decision seems irrelevant given their location in California, where $3 billion of state taxpayer funds is mandated to be prioritized for research that is NOT eligible for federal funding. And given the controversial nature of destructive embryo research, the lapses in ethics at numerous levels make one wonder what confidence this might offer to current and future donors about being made aware of all pertinent issues.

(thanks to R.D. & N.C. for additional thoughts)