Nature Speaks. Are We Listening?
Geron's rush to clinical trials using hESCs

E. Christian Brugger
(c) Culture of Life Foundation 2009
Reproduced with Permission
Culture of Life Foundation

Even those minimally familiar with the stem cell debate are aware of the vast disparity that presently exists between the clinical usefulness of human adult stem cells (hASCs) and embryonic stem cells (hESCs). Not only have hESCs, despite billions of dollars spent, not given rise to a single clinical success (none, zero); but until recently, there had not even been a single clinical trial using hESCs accepted by the Food and Drug Administration (FDA). This illustrates the concern of that regulatory body and the wider field for the serious problems associated with hESC therapies, the most serious of which is tumor formation.

That's changed. The first clinical trial in humans has recently been approved by the FDA. Geron, the big California biotech company, was given permission to conduct a stem cell trial "safety study" on patients with recent acute spinal cord injury1. The patients will receive injections of a type of undifferentiated nerve cell (oligodendrocytes) derived from hESCs that have been found in animal studies to stimulate nerve growth and produce healthy myelin (the nerve coating important for neurological conduction). Geron is confident that issues of safety, tolerability and efficacy have been worked out and that its experimental protocol is above criticism.

Not all share Geron's confidence. Neuroscientist and stem cell researcher Evan Snyder, for example, of the Burnham Institute in San Diego, warned: "There's a lot of debate among spinal cord researchers that the preclinical data itself doesn't justify the clinical trial;" and John Gearhart of the University of Pennsylvania, a leader in hESC research since 1998, warned that "we're still … a long way from really understanding a good deal about these cells and how to use them safely"2.

Another significant voice weighing into the conversation is James M. Wilson, researcher at the University of Pennsylvania School of Medicine. In a provocative piece in Science magazine entitled "A History Lesson for Stem Cells," Wilson says he fears history may be repeating itself in the wild enthusiasm for rapid results he sees in the field of hESC research3. Similar dynamics were seen in the 1990s in his own field of gene therapy. During that time gene therapy was touted confidently as the definitive answer to a wide range of diseases. Large numbers of sufferers harbored fervent hopes that the burgeoning field would find cures to their conditions. Theoretical models, which turned out to be simplistic, were developed and used to demonstrate that the new approach "ought to" work. The exaggerated claims of eager researchers were publicized by an uncritical media and stirred unwarranted enthusiasm at a popular level. And big biotech companies pushed to move from the research to the clinical phase as swiftly as possible in pursuit of commercial advantage. Are not each of these found today in relation to the field of hESC research? Wilson says he detects "haunting echoes" of the early days of his own troubled field. Haunting? You see, Wilson was the lead researcher on a premature clinical trial using gene therapy that killed an 18 year old boy, Jesse Gelsinger, in 1999. Geron's approval reminds him of the "hyperaccelerated translation to the clinical" that occurred in gene therapy just a decade ago.

Wilson is certainly no defender of human embryos. His cautions, he says, arise from his desire to help obviate avoidable setbacks in the field of hESC research. Yet his warnings are telling. They remind me of something my colleague Helen Alvare said to me recently: "Nature has its own way of speaking to us. It doesn't hit us over the head; but it speaks clearly enough." What's nature saying about the move to begin trials on humans using hESCs? Was nature speaking through the tragic case of the 13 year old Israeli boy reported last month, who received experimental hESC injections in Russia for a degenerative brain disease and as a result contracted multiple brain tumors4? Many were horrified by the outcome, but few were surprised. Stem cell scientists have warned repeatedly of the danger.

Contrast this with the avalanche of successes in the last couple years using adult stem cell therapies5. In the last two months alone, reports have noted that ASCs were successful in treating stroke patients6 and curing the formerly incurable Crohn's Disease7. New evidence suggests ASC's may help treat Multiple Sclerosis8. ASCs from bone marrow were recently used to grow new blood vessels to treat peripheral artery disease9 and to improve blood flow and ventricular function in patients with heart disease10. And most exciting, although presently only tested in mice, scientists recently demonstrated that genetically engineered adult stem cells are capable of zeroing in on cancer cells and destroying the cancer while sparing the normal cells11! Moreover, mice studies have also dramatically demonstrated that ASCs can be used to heal damage to the cornea of the eye12. What's nature saying?

Will Geron succeed in demonstrating the clinical safety of hESC therapies? I have serious reservations about the present trials. But if it doesn't succeed this time, scientists will eventually overcome problems such as tumor formation. But it will have been done on the backs of the corpses of thousands of human embryos. Does nature have an alternative?


1 See Geron's press release at [Back]

2 Quoted in Jennifer Couzin, "Celebration and Concern Over U.S. Trial of Embryonic Stem Cells," Science, vol. 323, no. 5914 (January 30, 2009), p. 568. [Back]

3 See Science, vol. 324 (May 8, 2009), pp. 727-728. [Back]

4 N. Amariglio, A. Hirshberg, et al., "Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient," PLoS Med., 6(2) (Feb 17, 2009):e1000029; abstract at,f1000m,isrctn [Back]

5 For a helpful summary of 2008 successes see [Back]

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