Controversy continues to build over a claim that biotechnology researchers produced stem cells without harming embryos, as outside scientists question whether a fundamental element of the reported experiment undercuts the central contention of the research.
Almost two weeks ago, Advanced Cell Technology Inc., of Alameda, Calif., announced that its scientists had produced stem cells "using an approach that does not harm embryos." The company and its advisers said the experimental technique, involving several cells plucked individually from early-stage embryos largely without harm, could sidestep the moral quandaries that have dogged stem-cell research for most of the past decade.
Current methods for deriving embryonic stem cells -- the biological building blocks that transform themselves into nerves, bone and other human tissue -- rely on clumps of cells and require the destruction of five-day-old embryos.
Advanced Cell's share price soared the day its research was published in the journal Nature, as media outlets around the world reported that the company's scientists had derived new stem-cell lines in an embryo-safe way. Nature itself erroneously hyped the report with an embargoed press release inaccurately describing the researchers as using single cells extracted from embryos that remained intact. The publication issued subsequent press releases correcting the first.
Last week, following concerns raised by critics, Advanced Cell confirmed that none of the 16 embryos used in the research had actually survived. The company hadn't made the embryos' failure to survive clear in many previous public statements.
Advanced Cell officials say they haven't misled investors or anyone else about their research. Even so, outside researchers are raising new questions about the method used in the Advanced Cell research as well as about the company's conclusions.
Responding to the first round of doubts, Robert Lanza, Advanced Cell's vice president for research and the lead author of the Nature paper, said the two embryos that produced new stem-cell lines each consisted of eight to 10 cells and had seven cells removed. He said he believes roughly half of the embryos in the experiment would have survived if researchers had allowed them to grow, instead of discarding them.
He continues to maintain that the results -- they successfully derived two new stem-cell lines from multiple individual cells extracted from early-stage embryos -- prove it is possible to produce stem cells without harming embryos.
The new round of doubts focuses on the experiment's method. The researchers reported that the multiple cells extracted from each embryo were initially cultured together in the same laboratory dish. While the cells were physically separate, they shared a common fluid medium, which could have allowed them to exchange growth factors and other proteins that helped them survive.
Some outside researchers say that method, requiring scientists to extract more than one cell from embryos that consist of so few cells to begin with, could undermine Advanced Cell's conclusions that embryos wouldn't be harmed and a single-cell extraction would suffice.
"One of the flaws in this paper is that it draws conclusions that they don't really have the data to prove," said Barry Behr, a Stanford University embryologist and director of the university's IVF laboratories. "The sort of leaps of faith here are a little too big to leap."
Dr. Lanza says co-culturing the extracted cells, known technically as blastomeres, does appear to be necessary for the blastomeres to survive. "When you remove a blastomere from an embryo, you have to understand, that's a shock," he says. "The key for this to work is that you have to give it a little rest time, as otherwise it won't survive." But he says it won't be necessary to extract several cells from the same embryo in the future. He says the company has successfully cultured a single blastomere together with the "parent" embryo for a day or so following extraction -- something the team didn't report in Nature. And he says he believes it should be possible to co-culture several blastomeres plucked singly from several different embryos.
"In those early stages," Dr. Lanza adds, "these cells are really social, and need to communicate. . . . When you pull one away, it doesn't know what to do." He says the company's research team co-cultured blastomeres from the same embryo in order to limit the number of embryos used.
Indeed, fertility clinics already frequently extract single cells from early-stage embryos during in-vitro fertilization in order to scan for genetic abnormalities. That process, Dr. Lanza argues, could now also be used to develop new stem-cell lines.
But many stem-cell scientists remain skeptical of Advanced Cell's claims. "The really unfortunate thing about that paper is that they really didn't do the experiment" that garnered all the media attention, says Jeanne Loring, a stem-cell researcher at the Burnham Institute in La Jolla, Calif. "There are going to be questions at every step of the process until they do the experiment or someone else does."
Arnold Kriegstein, director of the stem-cell program at the University of California at San Francisco, said that trying to extrapolate an embryo-friendly method for deriving stem cells from the Nature report would be "a stretch."
Advanced Cell has capitalized on the research. Two days after the research was published, the company announced that it had raised $13.5 million from its existing investors, with the first part of the transaction set to close Sept. 7. The company's share price has since fallen considerably since it reached the agreement, closing on Friday, Sept. 1, at 71 cents a share, down more than 70% from the post-announcement high although still above where it was before the announcement.
Dr. Lanza says scientific critics of the company's research still haven't caught up to the full ramifications of his team's work.
"It's not a surprise, if you take a person out of the cold, that they have not given the same amount of thought" to the subject, he says. "It means they haven't thought it totally through, or that they don't have the knowledge base we have about how these cells work."
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