June 8, 2007
SCIENCE LETTERS: Adult Versus Embryonic Stem Cells: Treatments
D. A. Prentice and G. Tarne used their letter "Treating diseases with adult stem cells" (19 Jan., p. 328) to try to defend Prentice's previous claim that "over 65 human diseases" have been "effectively treated through adult stem cells" (1). Now Prentice and Tarne say that what he really meant was that adult stem cell treatments for 65 diseases are being tested for possible efficacy.

Clearly, enrollment of an experimental therapy in a clinical trial does not mean that it is an effective therapy. The purpose of clinical trials is, first, to establish safety and, second, to document efficacy. Many promising experimental therapies fail when they reach larger Phase II or III trials. Such is the case with adult stem cell therapy for heart attacks and breast cancer--two conditions for which Prentice and Tarne improperly claimed that adult stem cells provide effective therapy [see the Supporting Online Material of our Letter "Adult stem cell treatments for diseases?", 28 July 2006, p. 439 (2)]. Prentice and Tarne's Letter perpetuates some of the same false representations of research with which we took issue in our original Letter. The GDNF infusion trials they referenced do not document any contribution of stem cells to the apparent improvements in Parkinson's patients. A careful reading of the cited papers shows that stem cells were not even studied (3, 4). Further, they cite a case report of a single patient as evidence that bone marrow transplantation can be used to correct hair loss--a condition that remains on their posted list of adult stem cell treatments (5).

In an interview published in the Chicago Tribune shortly after our Letter was published online, Prentice admitted that some of his citations were unwarranted. "We've cleaned up that list now," he said. Asked how the errors occurred, Prentice said, "I think things just got stuck in" (6). In their Letter, Prentice and Tarne further disregard scientific accuracy by stating, "There are currently 1238 FDA-approved clinical trials related to adult stem cells.…" They cite search results returned by the NIH Web site clinicaltrials.gov to support their assertion. However, many of the clinical trials retrieved by searching for "stem+cell" in the therapy category have nothing to do with stem cell therapy and thus overstate the number of adult stem cell trials posted to that database (7). A repeat of Prentice's search found "system," "systemic," "brain stem," and the verb "stem" (as in "which stem from") in the last 10 listings of trials recruiting patients (647-656), but no mention of stem cells. The first 10 all relate to the use of stem cell transplants to replace blood-forming cells destroyed when chemotherapy or radiation is used as the primary treatment of the patient's disease (8). There are three trials for stem cell therapy in multiple sclerosis, but none for Parkinson's disease or spinal cord injury.

Prentice's erroneous claims are widely used and further embellished by opponents of embryonic stem cell research. For example, Focus on the Family set up a Web site last year opposing what they called "unproven, unsafe, and unethical experiments" with embryonic stem cells. The Web site referenced Prentice's claims and falsely asserted that patients "have access to adult stem cell therapy which currently provides safe and successful treatments for more than 70 diseases and injuries.… These are tangible therapies that are available today" (9). We stand by our statement that Prentice and those who repeat his claims mislead laypeople and cruelly deceive patients.     - Shane Smith, William Neaves, & Steven Teitelbaum

Response
Smith et al. criticized an earlier compilation of peer-reviewed studies with results showing benefits for patients with 65 conditions from nonembryonic stem cells. In our Letter "Treating diseases with adult stem cells" (19 Jan., p. 328), we thanked them for detecting a few technical errors in this list, but added that these do not affect our central claim--in fact, such health improvements have now been documented in patients with over 70 conditions [see the Supporting Online Material that accompanied our Letter (1)].
In none of these studies do the authors state merely that they are about to "test" whether adult stem cells may benefit patients or that they have begun "enrollment" in clinical trials. Rather, all these studies (including those on breast cancer and heart damage) are reports of completed trials in which patients with these conditions benefited.
They question our reference to the use of GDNF for Parkinson's patients. The focus of this therapeutic approach was improvement in patient health, which was achieved in these studies (2-4), rather than basic investigation of GDNF's mode of action. However, the finding that trophic factors such as GDNF act by stimulating endogenous stem cells has existed for years, has been demonstrated in animal models, and has been proposed by several authors for treating neurodegenerative diseases in humans [e.g., (5-9)]. Regarding the patient case report they criticize, this was hardly mere "hair loss," but rather complete remission of alopecia universalis (10).

We thank them for pointing out the vagaries of the NIH search engine, although we note that they only looked at trials currently recruiting patients, and not the complete list of trials. We had chosen a search term similar to that used by Dr. Battey, Chief of the NIH Stem Cell Task Force, who reported 563 adult stem cell clinical trials in 2004 (11). Closer analysis shows that currently there are only 1229 trials listed at clinicaltrials.gov that are related to the use of adult stem cells (12). Will all these trials automatically translate into safe, reliable, and widely available treatments? We do not know. That does not mean we should deny or belittle the tangible benefits that published approaches have already provided to some patients--benefits that remain lacking from any approach using embryonic stem cells. To suppress the evidence would be a disservice to patients.

In this context, we note that Neaves and Teitelbaum were very prominent in the wellfunded political coalition designed to amend the Missouri constitution in 2006 to authorize human embryo cloning and embryonic stem cell research. The Web site of this coalition, Missouri Coalition for Life-Saving Cures (13), continues to list "more than 70 diseases and injuries that could benefit from stem cell research," despite the lack of evidence regarding embryonic stem cells for such a claim and the widespread consensus that some of these conditions, such as Alzheimer's disease, are extremely unlikely candidates for a stem cell treatment in the future. On one point we agree with Smith et al.--It is gravely wrong to mislead laypeople and cruelly deceive patients.      -David A. Prentice & Gene Tarne
Article: Science 8 June 2007:_Vol. 316. no. 5830, pp. 1422 - 1423_DOI: 10.1126/science.316.5830.1422b