A review of the National Institute of Health's "Guidelines for Research Using Human Pluripotent Stem Cells".

The use of federal funds to support human embryonic stem cell research is illegal, unethical, and unnecessary. On behalf of Do No Harm: The Coalition of Americans for Research Ethics, the purpose of this letter is to advise the agencies reviewing NIH's "Guidelines for Research Using Human Pluripotent Stem Cells," 65 Fed. Reg. 51976 ("Guidelines"), of recent scientific developments that further demonstrate the immense potential of stem cell research that does not entail the destruction of human embryos, and of the concomitant absence of any medical need or justification for the federal funding of destructive human embryonic stem cell research.

Since February 22, 2000, the end of the comment period on the draft Guidelines, research using human stem cells not derived from human embryos has confirmed what prior evidence had long suggested: that adult stem cells (and other "post-natal" stem cells) have vast biomedical potential to cure diseases such as diabetes, Parkinson's, heart disease, and other degenerative diseases. This biomedical potential is as great as or greater than the potential offered by human embryonic stem cell research. Simply stated, adult stem cell research is a preferable alternative for progress in regenerative medicine and cell-based therapies for disease because it does not pose the medical, legal, and ethical problems associated with destructive human embryonic stem cell research.

Among the justifications stated in the Guidelines for pursuing human embryonic stem cell research was the allegedly limited potential of adult stem cells as compared to the purportedly enormous, yet speculative, potential of embryonic stem cells. In particular, NIH's response to comments urging the benefits of adult stem cell research highlighted four alleged shortcomings related to the biomedical potential of adult stem cells. 65 Fed. Reg. 51976. The agency stated that adult stem cells (1) had not been found in all cell types, (2) appear in limited numbers and can be difficult to harvest and grow in time for treatment, (3) are likely to pass on genetic defects, and (4) may not have the capacity to multiply as do "younger cells." Id. Recent scientific developments now support the contention, however, that these claims about the shortcomings of adult stem cells are not true, are not relevant to their therapeutic potential, and/or overstate the differences between adult stem cells and embryonic stem cells. Significantly, human adult stem cells can be pluripotent and have the ability to transform from one cell type into another, a fact largely unrecognized by the Guidelines. The scientific record now indicates that the supposed shortcomings NIH perceived in adult stem cell research either are illusory or can be overcome.

Moreover, an impressive volume of scientific literature attests to the fact that human adult stem cells--unlike human embryonic stem cells--are currently being used successfully in clinical trials to combat many of the very diseases that embryonic stem cells only prospectively promise to treat. Animal research strongly suggests that more therapeutic applications of adult stem cell research will follow.

Finally, the potential biomedical application of human embryonic stem cell research faces risks that are unique to embryonic stem cells, such as the tendency toward tumor formation. In addition, embryonic stem cells face the very real possibility of immune rejection, while use of a patient's own adult stem cells is free from this problem. Consequently, adult stem cells have several advantages as compared with embryonic stem cells in their practical therapeutic application for tissue regeneration.

Thus, contrary to the suggestions by supporters of destructive human embryonic stem cell research, federal funding of such research is not a necessary, or even a wise, use of limited federal research dollars. Other forms of stem cell research are more promising, are demonstrably more successful at producing beneficial treatments that are actually in use today, and do not present the significant problems and uncertainties (to say nothing of the ethical and legal problems) posed by destructive human embryonic stem cell research.

1. Adult Stem Cells Have Been Located in Numerous Cell and Tissue Types and Can Be Transformed Into Virtually All Cell and Tissue Types.

   Although it is true that human adult stem cells have not been found in every cell type, they have been found in many cell and tissue types including, but not limited to: brain (and other nervous system), (1) muscle, (2) retina, (3) pancreas, (4) bone marrow and peripheral blood, (5) cornea, (6) blood vessels (endothelial cells), (7) fat, (8) dental pulp, (9) spermatogonia, (10) and placenta. (11) In essence, where scientists have devoted time and resources to the identification of human adult (and other non-embryonic) stem cell types, they have generally found them.

   Moreover, experiments using animals have recently isolated many additional adult stem cell and tissue types, including, but not limited to: skin, (12) liver, (13) and mammary gland. (14) Given the impressive pace of adult stem cell identification in the past few years--which invariably followed the pattern of (1) identification and isolation of the stem cell in animals, followed by (2) identification and isolation of the stem cell in humans--the imminent identification and isolation of the human adult stem cells of these cell and tissue types is highly likely.

   Even more important than the identification of human adult stem cells in most cell types is the fact that adult stem cells can regenerate healthy tissue and many can transform from one cell type into another. Thus, many types of human adult stem cells--including stem cells from fat--exhibit the ability to transform from one tissue type into many others. For example, plentiful adult stem cells from fat have been transformed into cartilage, muscle, and bone. (15) Readily accessible human adult bone marrow stem cells have been transformed into smooth muscle, (16) cardiac tissues, (17) neural cells, (18) liver, (19) bone, (20) cartilage, (21) and fat (22) Human adult neural stem cells have been reprogrammed to form skeletal muscle, (23) and have the ability to form all neural types. (24) Human adult stem cells from skeletal muscles can be coaxed into forming skeletal myotubes, smooth muscle, bone, cartilage, and fat. (25) Human adult stem cells from human dental pulp can be induced to differentiate into tooth structures. (26) And stem cells from placenta are reported to have been induced to form bone, nerve, cartilage, bone marrow, muscle, tendon, and blood vessels. (27)

   In fact, animal research indicates that adult neural and bone marrow stem cells may be able to generate virtually all adult tissues, including heart, lung, intestine, kidney, liver, nervous system, muscle, and the gastrointestinal tract (including esophagus, stomach, intestine, and colon). (28) Clarke suggests that "stem cells in different adult tissues may ... have a developmental repertoire close to that of [embryonic stem] cells." (29) The recent rapid pace of discovery of adult stem cells for a variety of tissue types, combined with their ability to form many, if not all, adult tissues, suggests that adult stem cells will ultimately be found in or be capable of transforming into every significant tissue type.

   In particular, the Guidelines evince concern that no pancreatic or cardiac adult stem cells had been identified. 65 Fed. Reg. 51976. In fact, however, human pancreatic and cardiac stem cells have been identified. Indeed, scientists have actually reversed diabetes in mice using the animal's own adult pancreatic stem cells. (30) This animal research has led to evidence of adult human pancreatic stem cells, which have been grown in culture and induced to differentiate into insulin-producing cells. (31) In fact, in 1999, well before the NIH published the Guidelines, the NIH was funding research involving insulin-producing adult human pancreatic stem cells. (32) These cells are available for use in potential technologies to reverse diabetes in humans.

   Recent evidence also indicates the ability of stem cells to transform into heart cells. Added to the numerous studies done in animals since 1995, these reports indicate that adult stem cells from skeletal muscle, bone marrow, liver, and the heart itself have the capacity to regenerate cardiac tissue and repair heart damage. (33) More recently, new evidence has emerged suggesting the existence of a human heart stem cell. (34) This research promises potential biomedical application to treat heart disease. In fact, myoblast transplantation has already been used in the first successful clinical application of human adult stem cells for treatment of cardiac damage. (35)

   Contrary to the impression created by advocates of destructive human embryonic stem cell research, these results for adult stem cell research are far more promising than any results obtained thus far through embryonic stem cell research. Indeed, researchers have yet to publish any evidence that human pancreatic cells can be generated from human embryonic stem cells, and have yet to show any evidence that human cardiac cells generated from embryonic stem cells in culture can form functional tissue in the body. The case for diverting scarce research dollars away from promising avenues of research and instead into human embryonic stem cell research in order to "cure" diabetes or heart disease is weak indeed.

2. Adult Stem Cells Can Be Reproduced To Create a "Virtually Limitless" Supply.

   Contrary to the assumptions expressed in the Guidelines, recent scientific evidence indicates the ability of adult stem cells to rapidly expand and implies that adult stem cells can be produced in ample quantities for biomedical applications. To be sure, adult stem cells are present in finite amounts throughout...