Adult Stem Cells: Promise or Pipe Dream?

By on February 28, 2007

Do adult stem cells have enough promise to make the debate over embryonic stem cells moot? Two experts on opposite sides of the issue weigh in.

j-c-willkeJ. C. Willke, M.D.
Life Issues Institute

J. C. Willke, M.D., is president of the Life Issues Institute and the National Right to Life Committee. He is also founder and president of the International Right to Life Federation.
 

shane-smithShane G. Smith
CNS Foundation

Shane G. Smith is an independent consultant and science director of the CNS Foundation.

Part 1: J. C. Willke, M.D.: The Promise of Adult Stem Cells

Adult stem cells have actually been used since 1968, when the first bone marrow transplants were done to help cure leukemia. At the time, those doing these transfusions had not isolated the active cells. It took two more decades before a scientist in Wisconsin isolated the active cells from bone marrow and called them adult stem cells. Since that time, there has been an amazing cascade of continuing new developments in this field.[1]

There are three types of stem cells: embryonic, adult, and those obtained from umbilical cord, placenta, and Wharton’s jelly, which surrounds the three umbilical cord blood vessels connecting the fetus to the mother.[2] Stem cells are the basic primitive beginnings of all the different cell types in the organs of our body. This ability to develop into different cell types is characterized as omnipotent and pleuripotent.

Before we get into their function and uses, we must first review the known physiological facts. It is a simple scientific fact that each of you reading these words once was a single cell, a fertilized egg, a zygote, and that all you have done since that time is to grow up. As a single cell, you were already human (not a rabbit). You were already sexed (X and Y chromosomes), you were already alive (not dead—you were growing), and you were complete, for nothing has been added to the single cell each of you once were but nutrition and oxygen. Therefore, from a biological, scientific standpoint, it is impossible to draw a line in time from that first cell until the old man dies and say that before this “it,” the entity was not human life, but after “it” he was. Even so, in the face of this obvious fact, many people do disagree and decry the “five-day-old ball of a hundred cells,” stating that these do not look human. But of course, this is exactly what a five-day-old human, which you once were, looks like.

Where did these cells come from? In order to get embryonic stem cells, one must take a five-day-old living human embryo, cut him or her open, and remove embryonic stem cells from the inside. This of course kills this living human and is the basis for the ethical objection to this procedure.

Stem Cells and Conventional Wisdom

Adult stem cells are present in every organ of our body. It is these cells that produce the new growth that repairs injury and replaces dying cells. Umbilical cord cells are usually grouped with adult stem cells, as are stem cells taken from the placenta. The difference from embryonic ones is that adult stem cells are taken from the patient, cultured, and returned to the same individual. Umbilical cord stem cells come from another individual, the newborn infant, but are so primitive that they can often successfully be used in another human.

Just a few years ago, conventional wisdom held that adult stem cells are not as “plastic” as embryonic stem cells—that is, they cannot turn into as many different cell types and organs—and that adult stem cells are much more difficult to obtain and grow, whereas embryonic stem cells can be obtained in some quantities from “spare” frozen embryos. But this conventional wisdom has been completely replaced by recent advances. Adult stem cells are being discovered in one new organ after another. They are very plentiful in fat, skin, and multiple other organs.

Adult stem cells culture just as easily as embryonic ones, so this original objection no longer holds. Adult stem cells, perhaps to the surprise of most researchers, are being shown to be just as “plastic” and just as versatile as embryonic stem cells. New information and research in the last few years has been consistently showing that in one cell type after another, adult stem cells are capable of turning into (probably) all types of human cells, including those in the central nervous system.

Over the last two or three years, hardly a week has gone by but that I do not receive another report of a research advance using adult and umbilical cord stem cells.

There are currently over 1,100 clinical trials approved by the Food and Drug Administration going on in the United States alone using adult stem cells. These are being used to treat over seventy different human diseases and injuries. To date, embryonic stem cells are being used in animal experimentations, but nothing yet has been done with embryonic stem cells in humans.

Adult Stem Cell Breakthroughs

Let us itemize very briefly these breakthroughs.

  • Spinal cord: Dr. Carlos Lima in Lisbon, Portugal, recently published his treatment of a number of patients who are paraplegic or tetraplegic following spinal cord injury. He took stem cells from the patient’s own olfactory (nasal) mucosal lining, cultured them, and then grafted them onto the site of the injury.[3] MRI scans later showed that the grafts had taken. All of the patients within a year and a half have shown definite improvement of motor function.
  • Parkinson’s disease: Using the patient’s own stem cells, University of Kentucky scientists successfully treated ten Parkinson’s patients.[4] Two earlier studies in 2002 in England reported improvement in five patients.[5]
  • Heart tissue regeneration: Adult stem cells have been shown to be capable of repairing cardiac tissue after heart attacks, even some length of time later. These studies involved obtaining adult stem cells from that patient’s body, culturing them, and then transplanting them into the coronary artery feeding the location of the heart attack or being injected into the heart muscle. Results of three recent studies all show heart function substantially improved.[6] Using the amniotic fluid that cushions a baby in the womb, fetal stem cells have been isolated, cultured, and then placed on a mold of biodegradable plastic. In one month, valves have been created.[7] Adult human cells from bone marrow were able to regenerate and self-repair damaged heart muscle.[8] Baxter International is using adult stem cells to treat 150 patients to create new blood vessels in their cardiovascular system. Small earlier studies showed substantial improvement of function.
  • Bone repair: Adult stem cells derived from the fat cells of a seven-year-old girl were used to successfully regrow a skull bone defect. Skull bones normally do not regenerate; therefore metal plates are used to cover defects. This girl had a defect totaling nineteen square inches. Bits of her own bone mixed with her own fat-derived stem cells were applied to the surface of the brain, resulting in the regeneration of a bony skullcap.[9] In addition, a number of studies have used the patient’s own adult stem cells to successfully stimulate repair of non-healing fractures.[10]
  • Eyes: Limbal adult stem cells, transplanted onto corneas damaged from disease or chemical accidents, showed recovery of sight in the majority of patients.[11]
  • Urinary tract: Female patients suffering from stress urinary incontinence were successfully treated with their own muscle-derived adult stem cells.[12] Doctors at Children’s Hospital in Harvard Medical School have succeeded in using a patient’s own adult stem cells to grow a fully functioning bladder.[13]
  • Diabetes: Adult stem cells have successfully increased insulin production in mice with type II diabetes.[14] Human trials will begin shortly. Researchers in the United Kingdom have created insulin-producing cells for diabetic patients from adult stem cells in umbilical cord blood.[15] In Argentina, stem cells from a diabetic patient’s own bone marrow was fed into his pancreas through an artery. Glucose levels returned to normal without medication.[16]
  • Lupus Erythematosus: Autologous non-myeloablative hematopoietic stem cell transplantation was done using the affected patient’s own adult stem cells. This life-threatening autoimmune disease was essentially cured in 50 percent of the patients who received such adult stem cells transplants.[17]
  • Sickle cell anemia: Patients suffering from sickle cell anemia are being successfully treated with cord blood transplants. This was first done in 1998. The adult stem cells from the donated cord blood successfully replenished the patient’s blood with healthy cells.[18]
  • Crohn’s disease: Patients with Crohn’s disease have apparently been cured after treatment with stem cells from their own blood.[19]
  • Muscular dystrophy: Out of Milan, Italy, at the San Raffaele Institute, has come research in dogs on muscular dystrophy. Published in the journal Nature, the study used adult stem cells in the treatment with substantial alleviation of weakness and other symptoms.[20]
  • ALS (Lou Gehrig’s disease): Amyotrophic lateral sclerosis (ALS) has been treated in rats at Johns Hopkins by transplanting adult stem cells into their spinal cords.[21]
  • Cystic fibrosis: Adult stem cells from umbilical cord blood have just been used at the Clinical Cell Therapy Lab at the University of Minnesota Medical Center. These have been differentiated into type 2 alveolar cells, which line the lung air pockets. This is a first step in developing the use of these cells for treating cystic fibrosis.[22]
  • Cartilage: Researchers at Children’s Hospital in Pittsburgh have successfully coaxed adult muscle stem cells to change into cartilage. Although it was done in rats, the next step will be human trials, again using adult muscle stem cells.[23]
  • Multiple sclerosis: In one study, injection of adult stem cells into patients with malignant multiple sclerosis gave significant improvement.[24]
  • Rheumatoid arthritis: A fifty-two-year-old woman with rheumatoid arthritis in twenty-eight joints was treated with adult stem cells. Within a year, her morning stiffness ceased. The study concluded, “This may be performed safely without the development of graft vs. host disease or serious infection.”[25]
  • Stroke: Very small embryonic-like stem cells mobilize into the blood stream to help repair damaged tissue from a stroke.[26]
  • Skin therapy: Adult stem cells hold a promise to treating baldness in humans. A study at the University of Pennsylvania reports using them to grow hair on bald mice.[27]
  • Reconstructive surgery: Chicago researchers are looking at a new adult stem cell technique that will replace implants for reconstructive surgery and body augmentation. This could have profound commercial implications for cosmetic surgery.[28]
  • Autoimmune disorders: Ninety percent of nineteen patients with various autoimmune disorders are in remission or have improved after treatment with their own blood stem cells.[29]
  • Teeth: New York scientists are exploring the possibility of using adult stem cells to regenerate teeth that have been removed.[30] The pulp of baby teeth contains up to two dozen adult stem cells that appear to be more versatile and longer-lived than many other adult stem cells.[31]

Summary

Only a few years ago, embryonic stem cells were thought to be far superior to adult stem cells. The only major problem voiced was the fact that they could be obtained only by “harvesting” (direct killing) five-day-old human embryos to obtain these cells. For those unconcerned about such destruction of human life, this offered a social problem, not a medical one.

As is obvious from the above litany, in the last few years, there has been an explosion of research on adult stem cells. We now know that there is no problem obtaining large numbers of these cells and that it can be done in a totally ethical fashion. We now know that adult stem cells have been obtained from most major body organs, and if progress continues, we may someday find them in every cell type. Furthermore, we are becoming more skilled at isolating these cells. The use of adult stem cells, as has been shown, offers no problem with host immunity as the cells come from a particular human being and are returned to that same individual. The use in this fashion of adult stem cells also obviates the risk of transmitting infection from host to recipient, as one cannot give oneself an infection.

As for plasticity, the above demonstrates very clearly that adult and cord blood stem cells are now being teased into creating a broad array of various cell types. If such progress continues, it holds promise of being able to use adult stem cells to possibly create all of the cell types in the human body.

It should be obvious to any observer that significant research advances in this field are being reported literally every few weeks. This is a frontier that is only now being opened up, and it is fair to assume that far greater progress will be made in the next few years.

In the face of the success of adult stem cells and the fact that embryonic stem cells have not made any breakthroughs, it is interesting that increasingly large amounts of government money are being funneled into embryonic stem cell research with very little going into adult stem cell research. In contrast, almost all of the above adult research has been done with private funding. Does private venture capital know something that our elected officials do not?

Notes

[1] National Marrow Donor Program “History of Marrow and Blood Cell Transplants.”

[2] The Toronto Star reported that University of Toronto scientists found a “jackpot” of stem cells in Wharton’s jelly (Joseph Hall, “U of T team discovers stem cell jackpot,” Toronto Star, Feb. 9, 2005, A01).

[3] Laurance Johnston and Sara Sa, “Olfactory Tissue Transplantation for SCI: Portugal Clinical Trials”; C. Lima et al., “Olfactory Mucosa Autografts in Human Spinal Cord Injury: A Pilot Clinical Study,” Journal of Spinal Cord Medicine 29 (2006): 191–203.

[4] John T.Slevin et al., “Improvement of bilateral motor functions on patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor,” Journal of Neurosurgery 102 (Feb. 2005): 216–222.

[5] Steven S. Gill et al., “Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease,” Nature Medicine 9 (May 2003): 589–595.

[6] Amit N. Patel et al., “Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study,” Journal of Thoracic and Cardiovascular Surgery 130 (Dec. 2005): 1631–1638; J. Joseph et al, “Safety and effectiveness of granulocyte-colony stimulating factor in mobilizing stem cells and improving cytokine profile in advanced chronic heart failure,” American Journal of Cardiology 97 (Mar. 1, 2006): 681–684; Bodo E. Strauer et al, “Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study,”Journal of the American College of Cardiology 46, no. 9 (Nov. 1, 2005): 1651–1658.

[7] This was reported at the American Heart Association Conference in Chicago on November 11, 2006.

[8] Young-sup Yoon et al, “Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction,” Journal of Clinical Investigation 115, no. 2 (Feb. 1, 2005): 326–338.

[9] “Stem cells from fat used to repair girl’s skull,” Associated Press, Dec. 20, 2004.

[10] Celia Hall, “Stem Cells Help Broken Bones Heal,” London Daily Telegraph, July 29, 2006; P. H. Warnke et al., “Growth and Transplantation of a Custom Vascularised Bone Graft in a Man,” Lancet 364 (Aug. 28, 2004): 766–770.

[11] T. Inatomi et al., “Midterm Results on Ocular Surface Reconstruction Using Cultivated Autologous Oral Mucosal Epithelial Transplantation,” American Journal of Ophthalmology 141, no. 2 (Feb. 2006): 267–275; E. J. Holland et al., “Management of Aniridic Keratopathy With Keratolimbal Allograft: a Limbal Stem Cell Transplantation Technique,” Ophthalmology 110, no. 1 (Jan. 2003): 125–130.

[12] Carr, L., et al., “Muscle Derived Cell Injection Technique to Optimize the Treatment of Stress Urinary Incontinence,” American Urological Association annual meeting, Abstract #1185, May 23, 2006.

[13] Hilary White, “Complete Bladders Grown from Patients’ Own Cells,” Lifesite.net, Apr. 4, 2006.

[14] “Stem cell cure hope for diabetes,” BBC, Nov. 12, 2006.

[15] Steven Ertelt, “Adult Stem Cell Research Breakthrough Produces Insulin for Diabetics,” LifeNews.com, July 10, 2006.

[16] “Stem cells implanted into pancreas of diabetic patient through an artery, Argentina,” Stem Cell Research Medical and Health News, Feb. 9, 2005.

[17] Richard K. Burt “Nonmyeloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus,” Journal of the American Medical Association 295, no. 5 (Feb. 1, 2006): 559–560.

[18] Christiane Vermylen, “Hematopoietic Stem Cell Transplantation in Sickle Cell Disease,” Blood 17, no. 3 (Sept. 17, 2003): 163–166; “60 Minutes II: Holy Grail,” CBS News, June 5, 2002.

[19] “Crohn’s Disease: Hematopoietic Stem Cell Transplantation is Option for Patients with Severe CD,” Blood Weekly, 23, Nov. 31, 2003.

[20] Maurilio Sampaolesi et al., “Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs,” Nature 444, no. 7117 (Nov. 16, 2006): 574–579.

[21] Leyan Xu et al., “Human Neural Stem Cell Grafts Ameliorate Motor Neuron Disease in SOD-1 Transgenic Rats,” Transplantation 82, no. 7 (Oct. 15, 2006): 865–875.

[22] “U of M Researchers Turn Cord Blood Into Lung Cells,” University of Minnesota, Nov. 1, 2006; Byron Spice, “Stem Cell Therapy for Cystic Fibrosis?Pittsburgh Post-Gazette, Dec. 21, 2004.

[23] Ryosuke Kuroda et al., “Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells,” Journal of Arthritis and Rheumatism 54, no. 2 (Feb. 2006): 433–442.

[24] G. L. Mancardi et al., “Autologous Stem Cell Transplantation as Rescue Therapy in Malignant Forms of Multiple Sclerosis,” Multiple Sclerosis 11, no. 3 (June 2005): 367–371.

[25] Richard K. Burt et al., “Introduction of Remission of Severe and Refractory Rheumatoid Arthritis by Allogeneic Mixed Chimerism,” Journal of Arthritis and Rheumatism 50, no. 8 (Aug. 2004): 2466–2470.

[26] M. Z. Ratajczak et al., “New Directions in Stem Cell Research,” Leukemia 20 (2006): 18–28; Woei-Cherng Shyu et al., “Granulocyte Colony-stimulating Factor for Acute Ischemic Stroke: A Randomized Controlled Trial,” Canadian Medical Association Journal 174, no. 7 (Mar. 28, 2006): 927-933; C. S. Stilley et al., “Changes in Cognitive Function after Neuronal Cell Transplantation for Basal Ganglia Stroke,” Neurology 63, no. 7 (Oct. 2004): 1320–1322; M. Y. Gordon et al., “Characterization and Clinical Application of Human CD34+ Stem/Progenitor Cell Populations Mobilized into the Blood by G-CSF,” Stem Cells 24, no. 7 (July 2006): 1822–1830.

[27] Rebecca Morris et al., “Capturing and Profiling Adult Hair Follicle Stem Cells,” Nature Biotechnology 22, no. 4 (Apr. 2004): 411–417.

[28] Steven Reinberg, “Stem Cells Promise Better Plastic Surgery,” Forbes.com, Feb. 17, 2005.

[29] Oliver Rosen et al., “Autologous Stem-Cell Transplantation in Refractory Autoimmune Diseases After in Vivo Immunoablation and Ex Vivo Depletion of Mononuclear Cells,” Arthritis Research 2, no. 4 (Feb. 2000): 327–336.

[30] M. T. Duailibi et al., “Bioengineered Teeth from Cultured Rat Tooth Bud Cells,” Journal of Dental Research 83, no. 7 (2004): 523–528.

[31] Brian Vastag, “Baby Teeth Pulp Stem Cells,” Journal of the American Medical Association 289, no. 19 (May 21, 2003): 2491; Masako Miura et al., “SHED: Stem Cells From Human Exfoliated Deciduous Teeth,” Proceeding of the National Academy of Sciences 100, no. 10 (May 13, 2003): 5807–5812.

Part 2: Shane G. Smith: Capturing Stem Cells’ Promise

Dr. J. C. Willke used his article “The Promise of Adult Stem Cells” to try to advance the notion that embryonic stem cell research need not be pursued because some adult stem cell treatments have already reached clinical application. Willke is certainly entitled to his opinions, but his selective emphasis of adult stem cell research perpetuates an argument that has already been exposed as relying on misrepresentations of published scientific papers.[1]

His opinion also does not reflect the consensus view among mainstream medical researchers who agree that both adult and embryonic stem cell research must move forward.

The apparent origin of Willke’s false claim is a reference list generated by David Prentice, senior fellow for life sciences at the Family Research Council who advises opponents of embryonic stem cell research.[2]

A review of those references revealed that Prentice’s list includes several unverified reports, including a newspaper article and anecdotal testimony given before a congressional committee. Where his list incorporated peer-reviewed scientific papers it frequently distorted the nature of the treatment under study.

For example, the drug infusion trials cited by Prentice (and by Willke) as evidence for a working adult stem cell therapy for Parkinson’s disease do not actually demonstrate any contribution of stem cell activity to the apparent improvements in Parkinson’s patients. A careful reading of the cited papers indicates that stem cell activity was not even studied.[3]

Many other references show that the therapeutic potential of adult stem cell treatments is inconclusive (e.g., heart disease), non-existent (e.g., breast cancer), or absurd (e.g., bone marrow transplantation as a treatment for hair loss).

Unfortunately, the claims put forward by Prentice—and now Willke—are often embellished to give the impression that adult stem cell treatments are currently in general use to treat a wide range of human illnesses.

On May 4, 2006, U.S. Senator Sam Brownback (R-Kansas) asserted: “I ask unanimous consent to have printed in the record the listing of sixty-nine different human illnesses being treated by adult and cord blood stem cells.” And on July 6, 2006, Missouri State Representative Jim Lembke (R-St. Louis County), who opposed Missouri’s recent stem cell initiative, wrote in the St. Louis Business Journal: “Science is showing us that adult stem cell and cord blood research is where we should be investing our efforts. Thousands are being treated and cured.”[4]

In truth, adult stem cell treatments are an important component of the medical arsenal against many illnesses, particularly blood-borne diseases like leukemia and many anemias. But adult and embryonic stem cells have their own distinct characteristics and their own distinct potential to advance science closer to new treatments. Adult stem cell research has flourished since its inception in 1968; it stands to reason that embryonic stem cell research, begun only in 1998, deserves that same kind of time to exhibit its promise.

That’s why the overwhelming majority of scientists and medical organizations—including the American Medical Association, Association of American Medical Colleges, and the National Academies of Science—believe that both adult and embryonic stem cell research should be pursued. These organizations are joined by more than one hundred patient groups like the Juvenile Diabetes Research Foundation, the Christopher Reeve Foundation, Parkinson’s Action Network, and the CNS Foundation. The reason for this scientific consensus is that a balanced approach to adult and embryonic stem cell research will likely provide the greatest number of new treatments for the greatest number of people.

Finally, in describing his personal beliefs about embryonic stem cell derivation and its moral significance, Willke ignores a few important points.

First, he advances the premise that scientific facts tell us what something “means” in addition to what something “is.” I disagree. Scientific inquiry can provide information only about how something operates; it is up to each of us to decide for ourselves how that information factors into our beliefs about that thing’s morality. The same is true for each individual’s perspective of embryonic stem cell research.

Second, an embryo requires the nurturing environment of the womb to continue development beyond being a “ball of a hundred cells.” The pre-embryo produced in a dish prior to fertility treatment will remain just that if not transferred to a womb.[5]

Third, embryonic stem cells are derived from cells that remain after a couple completes fertility treatment. These surplus cells may be stored frozen indefinitely, donated to other infertile couples for the purposes of family creation, donated for research, or discarded as medical waste.[6] Strict ethical standards apply to the donation procedure when couples choose to donate their remaining cells for research, including the requirement that couples give their informed written consent. Many of these standards are promulgated in federal law.[7]

It is clear to me, after years of social dialogue, that there is strong bipartisan support for embryonic stem cell research that spans religious boundaries. There is also widespread agreement that adult and embryonic stem cell research should move forward with federal funding.[8]

Inaccurate arguments like those made by Willke only mislead laypeople and patients and give pseudo-intellectual cover to those who foist political obstacles upon embryonic stem cell researchers.

It is time that we removed politics from the research lab so that our scientists can advance toward treatments across the full spectrum of stem cell biology. That is the only way to truly and honestly capture the promise of stem cell research.

Notes

[1] Shane Smith, William Neaves, and Steven Teitelbaum, “Adult Stem Cell Treatments for Diseases?Science 313 (2006):438.

[2] See “Benefits of Stem Cells to Human Patients”; David Prentice, “Live patients and dead mice: The little-known story of the stem cells that actually work,” Christianity Today, Sep. 30, 2005.

[3] Steven S. Gill et al., “Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease,” Nature Medicine 9 (May 2003): 589–595; Seth Love et al., “Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain,” Nature Medicine 11, no. 7 (July 2005):703–704.

[4] Rep. Jim Lembke, “Stem Cell Ethics,” St. Louis Business Journal, July 7, 2006.

[5] Richard Schulz, “Preimplantation Embryo Development,” in Molecular Biology in Reproductive Medicine (London: Parthenon Publishing, 1999), 313–50.

[6] Andrea Gurmankin, Dominic Sisti, Arthur Caplan, “Embryo disposal practices in IVF clinics in the United States,” Politics and the Life Sciences 22, no. 2 (Aug. 2004): 2–6.

[7] Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council, Guidelines for Human Embryonic Stem Cell Research (Washington, D.C.: National Academies Press, 2005). A relevant page (p.83) can be viewed online here.

[8] Coalition for the Advancement of Medical Research public opinion survey released 5/16/2006; “Most Americans back research using stem cells, poll shows,” Wall Street Journal Online, June 7, 2005.

Part 3: J. C. Willke, M.D.: The “Stem” of the Controversy

I write in response to the rebuttal by Shane Smith to my article describing the situation today with adult stem cells. First, I would like to thank him for his concern. As I review his rebuttal, I find some things that I agree with, some things I do not agree with, and other things that are irrelevant to this issue.

My paper was primarily a positive one detailing the current uses and research using adult stem cells. In order to balance this, we must first look more critically at embryonic stem cells. To begin let us consider (1) infection, (2) rejection, and (3) tumor formation.

Infection

If and when embryonic stem cells are used to treat humans, we will find the medical establishment putting cells from one living human into another living human. The cell that is inserted into the patient treated can carry with it infection. An example of this occurred in early 2006. A woman had died and generously willed her organs to be used for transplantation. Four different people received her organs. Unbeknownst to the transplant surgeons, and undetected at the time, was a lethal but latent viral infection that was present in her cells. This infection lit up in all four of the recipient patients and was fatal in three of them. We could then think of the woman who donated the ovum who could have AIDS. That infection exists in the cytoplasm (the shell of her egg) and would be transmitted to the recipient, and the recipient patient will have contracted AIDS.

In contrast, when adult stem cells are used, they are obtained from the body of the patient, cultured, and returned to that same patient’s body; there is no possibility of such a catastrophe.

Rejection

Our readers are all aware of the fact that if a patient receives a transplanted kidney, that recipient’s body, left to its own natural functions, can attack and destroy that kidney, which is foreign tissue to the recipient’s body. An entire medical specialty revolves around the use of transplanted organs and anti-rejection drugs. These drugs are reasonably successful in preventing that rejection phenomenon, but they must be used for the balance of the recipient’s life and must be constantly monitored. Even so, in too many cases, a transplanted organ is eventually rejected anyway.

In the event that cloning has occurred and is the source of embryonic stem cells, typically the nucleus of the new fertilized ovum is now the nucleus of the recipient patient. So far, no problems. However, the shell of the ovum into which the nucleus is planted is tissue from a different human. It has different DNA and contains other biological substances—mitochondria, for instance. This is foreign tissue to the recipient. In short, embryonic stem cells are foreign tissue to the person being treated with them and can be rejected by the recipient.

In contrast, if adult stem cells are used, there is no possibility of rejection, because the stem cells are taken from the patient’s own body.

Tumors

This is the big one. There is always the possibility that with future research this problem might be partially solved, but at the moment there seems to be no evidence of this on the horizon. Embryonic stem cells are extremely primitive. They can and do turn into a wide variety of different cell types when implanted in an animal. For example, such cells planted in the brain of a mouse have been found to produce tumors with different cell types involved, such as skin, bone, and cartilage. Such a tumor is usually fatal. Because of the proclivity to form multi-cellular tumors, and because at this stage of knowledge there is no way to control this wild cancerous growth, there are no plans known to this author at this time to use embryonic stem cells in treating human ailments.

In contrast to the above, adult stem cells are not quite as primitive as embryonic ones and consistently produce only the cell type into which they are introduced—e.g., if injected into cardiac muscle, they form heart cells but no other types.

Accordingly, there are three major obstacles to using embryonic stem cells that effectively bar their use in humans today and show no sign of a solution being found to these in the foreseeable future.

Sed Contra

Now a few observations regarding Smith’s commentary: He apparently has no objection to the use of adult stem cells; however, he certainly also favors the use of embryonic ones. My thoughts on the embryonic ones are listed above, but I note that President Bush has made available a considerable number of embryonic cell lines from frozen human embryos who had already been killed to obtain these cells. Those lines are available today to researchers and are being used. I note also that there is no law in the U.S. against the use of embryonic stem cells, nor is there any proposal in Congress to pass such a law. The argument is entirely about the use of your tax money for embryonic stem cell research.

He mentions David Prentice. I have met this gentleman, and he is a well-recognized authority on this issue. However, I have not seen him in almost two years. I have had no contact with him regarding the paper I have written and while I assume he would agree with my viewpoint, I certainly haven’t consulted with him in any way.

Smith decries several of my listed studies. I listed twenty-eight such studies, and all but a few reported on adult stem cell advances in prestigious medical journals. Almost all of them are animal studies, as is proper in the early stages of such investigations. Many of them, however, have also been used in limited studies on adults. Some of them involved increasing knowledge as to techniques, culturing, etc. He states that the studies I have listed on treating Parkinson’s were not legitimate. This is simply incorrect. In my paper, I list three legitimate studies reported in medical journals.

He mentions that adult stem cells are not useful in treating breast cancer. To my knowledge, he is correct; I didn’t list any such studies nor do I know of any.

He says that I give the impression that the adult stem cells are in general use. I am sorry if I did; that is simply not so. Almost all of these studies are very preliminary. Many are in animals, as is proper. Some have now moved to humans.

He mentions something about sweeping claims. I don’t believe these were reported by my pen. I am aware that there have been some reports by journalists that could be called sweeping, but all I can say is that they said that. I didn’t.

He notes a list of prestigious scientific and professional groups who favor embryonic stem cells starting with the American Medical Association. This is true. I could mention, however, that every one of these groups has a strong pro-abortion public policy. Each one flatly denies any association between abortion and later breast cancer, a position that is simply, professionally untenable. I hope that such groups can get past their deep pro-abortion bias and denial of the rights to live of newly conceived humans. At the moment, the signs are not encouraging.

He notes, “Scientific inquiry can provide information only about how something operates.” I certainly agree with this. Science gives us facts and how-to, but ethics judges whether these actions are right, proper, and acceptable in a civilized society.

He notes that an embryo “requires the nurturing environment of the womb to continue development beyond being a ball of a hundred cells. The pre-embryo produced in a dish prior to fertility treatment will remain just that if not transferred to a womb.” The above is true, but it completely misses the fact that this is total human life whether a single cell, hundreds of cells, whether pre-implantation, post-implantation, intrauterine, or ultimately extra-uterine. This is all the same living human. I might comment about his use of the word pre-embryo. The word is new terminology, used only in the last decade or so, and is a political rather than a biological term. My definition of a pre-embryo is several hundred million eager sperm swimming after one ovum. When one connects and penetrates it is no longer a pre-embryo but an embryo.

Terminology, of course, leads to opinions. He notes that unused frozen embryos are “cells.” This, along with the term “pre-embryo,” dehumanizes this growing being and is not scientifically accurate. This new embryo is already a living human being.

I would like to thank Smith for his criticism and hope that my response has been a respectful and professional one.

Part 4: Shane G. Smith: Stem Cells and Society

In his initial opinion piece and in his rebuttal to my response, J. C. Willke, M.D., thoughtfully presents the arguments of those who, like him, value the promise of adult stem cell research but oppose research using embryonic stem cells. I will do my best to respond just as thoughtfully but from the perspective of someone who respectfully disagrees with him.

In my view, adult and embryonic stem cell research are both important areas of biology that can and should be responsibly conducted for the betterment of human health.

As I read Dr. Willke’s comments I have to wonder if he and I are reviewing the same scientific literature or observing the stem cell policy debate with the same information. Below I present my understanding of the issues he raised so that the readers of PublicSquare.net can make their own judgments about the relative value of adult and embryonic stem cell research.

Infection

Willke singles out embryonic stem cells as a possible source for viral transmission between donor and recipient. However, his reasoning ignores the fact that methods to ensure the safety of cultured cells from viral contaminants have been in use for years and are even commercially available.[1]

Moreover, healthy bone marrow (a source of blood-forming adult stem cells) is frequently obtained through cell registries such as the National Marrow Donor Program. Interestingly, the National Marrow Donor Program requires that their affiliates screen donated bone marrow for viruses like HIV, hepatitis B, and hepatitis C.[2] I am puzzled as to why Willke assumes that this same safeguard would not also be applied to supplies of transplantable embryonic stem cells.

I also do not understand how the tragic, extreme example related in his rebuttal demonstrates that an FDA-approved process of stem cell donation would not include appropriate quality assurance procedures.

Willke also mistakenly generalizes all adult stem cell transplants as being autologous. A transplant is “autologous” when transplantable cells are harvested from and then returned to a patient as a part of his/her own care. But there are many situations in which an autologous transplant is impossible or unsafe, including when (a) patients are too weak to undergo the stem cell extraction procedure preceding an autologous transplant (as cancer patients sometimes are), (b) laboratory methods have not yet been devised for the culture or expansion of the specific type of cell to be transplanted, and (c) the cells to be harvested from the patients irreversibly carry disease (as is the case with sickle cell anemia or even viral infection) so returning those cells to the patient accomplishes no therapeutic benefit.

In these cases, the best option is often an allogeneic stem cell transplant, where transplantable cells are obtained from a healthy genetically matched donor.

Rejection

It is true that autologous stem cell transplantation carries a much reduced risk of immune rejection. But again, Willke ignores allogeneic stem cell transplantation by implying that adult stem cell transplants are prepared only from an autologous source. Donor-derived adult stem cells are very much susceptible to rejection.[3]

I agree with Willke that donor-derived cytoplasm and mitochondria may confound attempts to generate patient-specific embryonic stem cells through somatic cell nuclear transfer. However, I strenuously disagree that the absence of scientific understanding here presents a reason to abandon the development of this technique. Rather, it argues for the involvement of cytoplasm and mitochondria experts early in the process.

Tumorigenicity

This is one of the great myths of the stem cell debate: that no treatment will ever be developed with embryonic stem cells because these cells spontaneously form cancers in animals.

In fact, while undifferentiated or “unspecialized” embryonic stem cells do show a potential for uncontrolled growth (like a cancer), these cells are not the same cells that medical researchers need to repair damaged or diseased tissue. What are needed are the specialized cells (like the specialized neurons that would be needed to treat Parkinson’s) derived from unspecialized embryonic stem cells.

Available scientific evidence suggests that once an unspecialized stem cell has been transformed into a specialized cell it loses this cancer-causing ability.[4] Researchers are now developing cell purification techniques to prevent unspecialized cells from being transferred into patients, thus guarding against the risk of spontaneous cancers.

For example, Dr. Hans Keirstead at the University of California, Irvine, has developed methods to prepare highly pure populations of oligodendrocyte progenitor cells (e.g., cells that will transform into those that re-insulate damaged nerve fibers) from unspecialized human embryonic stem cells.[5]

The Geron Corporation is now developing an early-stage clinical trial that will investigate the safety of transplanting these oligodendrocyte progenitor cells into patients who have suffered a severe spinal injury within months of their injury.[6]

It is important to note that scientists are aware of technical hurdles facing the development of embryonic stem cell therapies, but their identification of these hurdles should not be misconstrued as evidence that these therapies are not possible. Rather, adequate funding for stem cell research should be made available so that scientists can address these issues and generate safe and effective therapies as quickly as possible.

White House Policy

I hardly think there’s reason to celebrate the accident of timing that allowed the first federal dollars for embryonic stem cell research to be allocated on President Bush’s watch. The Bush Administration has repeatedly moved to diminish and destabilize this field by (a) restricting federal funding to a limited number of embryonic stem cell cultures in existence before the arbitrary date of August 9, 2001, (b) vetoing the Stem Cell Research Enhancement Act of 2005, a bill that passed both houses of Congress with strong bipartisan support and would have expanded funding for embryonic stem cell research, and (c) supporting failed congressional efforts to criminalize some scientific explorations of stem cell research subject to ten years imprisonment and not less than $1 million in fines.[7]

Not surprisingly, the National Institutes of Health managed to fund only $38 million in human embryonic stem cell research grants out of its $27.9 billion Fiscal Year 2006 budget.[8] By contrast, the California Institute for Regenerative Medicine has allocated $57 million to this field in the past twelve months and promises to contribute up to $3 billion in research grants over the next decade.[9]

Adult v. Embryonic Stem Cells

Willke advanced the notion that embryonic stem cell research need not be pursued because many adult stem cell treatments have reached clinical application. He also clarified that he authored this notion independently, and I appreciate his doing so.

The fact remains that Willke’s initial opinion piece was similar in structure to an argument originally advanced by David Prentice. Further, a Prentice-authored version of this claim appears on the website of the Life Issues Institute, a pro-life group for which Willke serves as president.[10]

Since the Prentice argument has been exposed as relying upon distortions of published scientific literature, I felt it appropriate to introduce that critique into our current discussion.[11]

What is truly important here is that each of us who are engaged in the national discourse on stem cell research—including Willke, Prentice, and myself—remember that lay people take our words very seriously. We have a responsibility on both sides to present claims that are based upon accurate, unbiased science.

I continue to disagree with Willke’s interpretation of the legitimate papers he cited as supposed evidence that glial-derived growth factor infusion comprises a stem cell therapy for Parkinson’s. I maintain that a careful reading of the cited papers indicates that stem cell activity was not even studied.[12] I have even communicated with a co-corresponding author on one of the cited papers (Gill et al.) who considers his study to be “growth factor research,” not stem cell research.[13]

In my role as science director for the CNS Foundation, I regularly hear from parents interested in taking their special-needs children to off-shore stem cell clinics. I worry that an unintended consequence of these false claims is that more patients or their loved ones will internalize these claims out-of-context. There is then the danger that they will enroll at rogue clinics offering so-called treatments that have not been rigorously reviewed by the medical community and may even cause harm.

Confusing the Issue

Willke invokes the abortion debate when addressing the support that respected medical groups like the American Medical Association have expressed for embryonic stem cell research. I do not understand how these two issues are related. If his position is that the practice of discarding unviable or excess embryos created for fertility treatment constitutes some technical form of abortion, then I would suggest that his quarrel is first and foremost with in vitro fertilization methods and not with embryonic stem cell research.

Terminology

Willke is correct: the term pre-embryo does not show up in medical textbooks. I could have used more accurate scientific terminology (such as “morula” and “primitive streak”) to describe embryonic development prior to the blastocyst stage at which embryonic stem cells are derived. Since the purpose of our discussion is to present scientific ideas to non-scientific people, I chose instead to describe that phenomenon using terms and concepts that lay people understand.

As to the definitive moment at which a human life like his and mine begins, that is something about which everyone will need to make their own judgment based upon their beliefs and experiences.

Summary

Good people have a right to disagree. I do not agree with Willke’s perspective on embryonic stem cell research but I do respect it. We seem to share a healthy sense of wonder about the promise of stem cell research in general, and I hope that many of the exciting adult stem cell studies he referenced in his first essay do indeed lead to new treatments and cures.

Where we part company is on the issue of what to do with those special cell clusters leftover from fertility treatment. I recognize and share the universal sentiment that the human embryo deserves respect. The obtainment of human embryos for research must be governed by strict ethical safeguards that protect the safety and privacy of donors and ensure that research involving human embryonic stem cells serves important research aims that cannot be reached by other means.

I am heartened by the fact that a strong majority of Americans across all faiths and political affiliations support responsible explorations of stem cell biology—including the use of human embryonic stem cells—for meritorious scientific research and therapy development.[14]

I sincerely thank Willke for participating in this discussion and hope that the readers of PublicSquare.net feel empowered to participate in our national dialogue on stem cell research.

Notes

[1] See, for example, BioReliance.com.

[2] National Marrow Donation Program, 19th Edition Standards, June 23, 24.

[3] National Cancer Institute, “Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers.”

[4] Hannes Hentze, Ralph Graichen, and Alan Colman, “Cell therapy and the safety of embryonic stem cell-derived grafts,” Trends in Biotechnology 25, no. 1 (Jan. 2007): 24–32.

[5] Gabriel Nistor et al., “Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation,” Glia 49, no. 3 (Nov. 2005): 385–396; Hans Keirstead et al., “Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury,” Journal of Neuroscience 25, no. 19 (May 11, 2005): 4694–4705.

[6] See “Patient Information” section of Geron website.

[7] See “Federal Policy” on National Institute of Health Stem Cell Information website; President Bush’s veto message regarding H.R. 810; “President Bush Calls on Senate to Back Human Cloning Ban,” Whitehouse.gov.

[8] “Estimates of NIH Funding for Various Diseases, Conditions and Research Areas,” National Institutes of Health.

[9] See California Institute for Regenerative Medicine.

[10] David Prentice, “Selected references documenting the scientific advances in ‘adult’ stem cell research – current treatments update,” Life Issues Institute.

[11] Shane Smith, William Neaves, and Steven Teitelbaum, “Adult Stem Cell Treatments for Diseases?Science 313 (2006):438.

[12] Steven S. Gill et al., “Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease,” Nature Medicine 9 (May 2003): 589–595; John T. Slevin et al., “Improvement of bilateral motor functions on patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor,” Journal of Neurosurgery 102, no. 2 (Feb. 2005): 216–222.

[13] Personal communication with Dr. Clive Svendsen via e-mail on 8/31/2006.

[14] Coalition for the Advancement of Medical Research public opinion survey released 5/16/2006; “Most Americans back research using stem cells, poll shows,” Wall Street Journal Online, June 7, 2005.