Written Testimony to the Senate Commerce, Science and Transportation Subcommittee on Science, Technology and Space by James Kelly

Date: 01/29/2003

Mr. Chairman: I respectfully request that this written submission be accepted as testimony for today’s hearing on human cloning.

Due to a 1997 cervical spinal cord injury, I am among millions of Americans whose hope for living a healthy, normal life lies in the effective, successful use of medical research resources. For the past five years I’ve devoted my life entirely to understanding my medical condition, learning key issues that neuroscience believes stand in the way of its improvement, and identifying clinicians and researchers whose work safely, efficiently, and effectively addresses these concerns. I then contact and encourage these researchers to communicate, cooperate, and collaborate towards bringing promising medical research from the bench to the bedside.

Based on solid, peer-reviewed animal studies, the results of human clinical trials, and factual comments by leading scientists, my actions and viewpoints are formed purely with the practical development of medical research for the sake of cures in mind. I do not promote research for the sake of scientific, commercial, religious, or political interests.

Quite literally, the cloning issue stands to mean the difference between life or death for tens of millions of Americans, while millions more face life-long impairment should valuable resources be inefficiently squandered to possibly overcome the colossal safety and technical hurdles inherent in cloning. Therefore, in choosing its course on cloning, I respectfully ask the U.S. Senate to consider the following perspectives as though every American whose fate lies with medical science is a beloved friend or family member.

Promises made…

Cloning is being promoted primarily for two applications: 1) to produce genetically matched embryonic stem cells (or their derivatives) for transplantation purposes; 2) to study cells derived from cloning to better understand the genetic defects involved in inherited disease.

Regarding direct “therapeutic” applications, cloning is hoped to create genetically matched cells able to avoid immune rejection. However, in a recent study, an adult mouse twice rejected its own cloned embryonic stem cells.1 In reporting this finding, M.I.T. researcher Rudolf Jaenisch says:

“Our results raise the provocative possibility that even genetically matched cells derived by therapeutic cloning may still face barriers to effective transplantation for some disorders.”

Comments made by leading pro-cloning scientists reveal that these results weren’t wholly unexpected. In speaking to the President’s Council on Bioethics, Dr. John Gearhart of John Hopkins University said there was “no question” in his mind that embryonic stem cells derived from cloning “could be rejected. Absolutely.”

Dr. Irving Weissman of Stanford University went a step further by telling the council:

“I should say that when you put the nucleus in from a somatic cell, the mitochondria still come from the host (the egg).” He concluded, “And in mouse studies it is clear that those genetic differences can lead to a mild but certainly effective transplant rejection and so immunosuppression, mild though it is, will be required for that.”

It is important to note that fetal cells have been used in human clinical trials without rejection and without immune suppression. (The central nervous system is considered “immune privileged.”) It’s also true these studies have led to inconclusive and even negative results.2

Yet their failure had nothing to do with rejection. Therefore, despite Drs. Gearhart and Weissman’s admission that cells derived from cloning do not perfectly match the donor, the fact is that cells derived from cloning may indeed not be rejected for certain applications (as the Chinese and A.C.T.’s Dr. Lanza have recently claimed). However, from a pro-cures perspective, the key question is not what cells derived from cloning may or may not be able to do, but rather what are they undeniably, inescapably known to do.

Also, if the goal of therapeutic cloning for transplantation purposes is to provide genetically matched embryonic stem cells, which apparently it is not reliably able to do, and the goal of embryonic stem cell therapeutic research is to mature ESCs to fetal stages compatible with adult organs – but such fetal tissue has already produced failures that had nothing to do with rejection – then someone seeking a cure can’t help asking, “What’s the point?”

The technical issue that lies at the heart of cloning involves its inherent genetic “imprinting errors.”3

Simply put, creating embryos without both male and female genetic contributions leads to widespread, unpredictable genetic flaws in the permanent genetic code of every resulting cell, be it embryonic, fetal, or adult. In cloned animals these defects lead to high rates of fetal death, birth defects, stunted development, premature aging, disease, deformity, and early death. Comments by leading scientists in the cloning field bring home the sobering import of this crucial point:

MIT’s Rudolf Jaenisch says, “I have argued before, in Congress and other occasions, this is unsafe and will remain so for the foreseeable future. I believe there are actually principal biological barriers to make it ever really safe.”4

“All of the data on animal cloning demonstrate exceptionally high rates of fetal loss, abortion (and) neonatal deaths, and many cloned animals have devastating birth defects,” says Gerald Schatten, vice chairman of obstetrics, gynecology and reproductive science at the University of Pittsburgh School of Medicine.

Of particular concern are embryos that appear healthy but at the genetic level are a “gallery of horrors,” says Tanja Dominko, who conducted primate-cloning research at the Oregon Regional Primate Research Center in Beaverton.

Many of the birth defects observed in cloned animals are similar to the gross physical deformities and mental retardation found in rare genetic disorders caused by a phenomenon known as genetic imprinting, says Arthur Beaudet, professor of genetics at Baylor College of Medicine in Houston.

The prevalence of genetic disorders in cloned animals and the lack of knowledge about reprogramming are the primary reasons the scientists who work on cloning and issues of reprogramming say they are skeptical that anyone can clone a human without genetic errors, Beaudet and others say.5

Says University of Pennsylvania Researcher Hans Schöler: “Our embryos can look very nice. But they are ticking time bombs.”6

Regarding genetic imprinting problems inherent in cloning, the creator of Dolly the sheep, Ian Wilmut, said in the peer-reviewed journal Nature: “It should keep a lot of us in business for a long time.”7

Which leads to two questions regarding the actual “promise” of therapeutic cloning:

How can cells known to contain widespread, unpredictable genetic flaws possibly be medically used with any degree of certainty regarding short- and long-term safety and performance?

How can such cells provide reliable material for research into patients’ genetic conditions?

For transplantation purposes, cells derived from cloning will have to incorporate into or “patch” the patient’s body. Cells introduced in immature stages (stem cells) will multiply and spread. Indeed, for some applications, such as Type 1 diabetes, multiple sclerosis, sickle cell anemia, and others, therapies designed to correct the condition’s cause will need to completely replace defective bodily systems with cells derived from cloning (assuming the genetic defect causing the condition can be fixed in cloning-derived stem cells).8

In reproductive cloning, genetically defective embryonic stem cells multiply and mature into genetically defective organs, as evidenced by the above-cited rates of deformity, retardation, and premature death in cloned animals. Yet cloning advocates would have us believe that the cells they freely acknowledge are unsafe for development into babies (reproductive cloning) will be somehow safe for repairing diseased or damaged organs (“therapeutic” cloning).

Regarding the testing of cloned cells for inherited conditions: University of Pennsylvania researcher Hans Schöler reports a key gene to early embryonic development (called Oct4) is missing or misexpressed in over 90% of embryos derived from cloning.9 According to New Scientist, Dr. Schöler sees proper Oct4 expression as only one of the first barriers most cloned embryos must cross. In a commentary on Scholer’s work,10 Davor Solter of the Max-Planck Institute of Immunobiology in Freiburg explains: “Misreprogrammed genes are like cockroaches. Where you see one there are likely to be many more under the surface.” Yet, as in its purported therapeutic “promise,” cells derived from cloning subject to random genetic defects and abnormal development are being presented as a reliable means for studying inherited genetic disease. In studying such cells, how would researchers be able to tell which developmental problems come from the patient’s original condition and which come from the cloning process?

Promises broken and misplaced trust…

Senators Hatch, Specter, Feinstein, and others tell us they support therapeutic cloning in the interests of America’s sick and disabled. Similar claims by pro-cloning scientists and commercial concerns induce desperate Americans to misplace their hope and trust. In fact, others afflicted by my condition (spinal cord injury) have come before you to ask that therapeutic cloning be permitted in the U.S. or, as Senate witness Christopher Reeve testified last March, “I’m out of luck.”

The sad truth is that Mr. Reeve is already out of luck, for according to his testimony (which he repeated at a recent cloning debate at the New York Academy of Sciences) he is basing his support of cloning on misinformation allegedly provided by embryonic stem cell researcher John McDonald of the University of Washington at St. Louis.11 In fact, Reeve’s testimony last March contained numerous false or misleading statements.12

To illustrate the inappropriateness of those with spinal cord injury using their condition to justify cloning, please consider:

According to leading SCI researchers, such as Drs. Jerry Silver, Martin Schwab, and Wise Young, the primary cause of paralysis resulting from spinal cord injury is not due to neuron loss or axon demyelination, which animal research indicates might be effectively addressed by embryonic- or adult stem cell-based therapies. Rather, most paralysis (eighty percent and more, according to Wise Young) is due to broken axons at the injury site.13 Therefore, avenues that offer real hope for addressing this issue in the foreseeable future — there are several, none of which involve cloning — are truly the brightest “promise” of curing SCI.14

Where stem cell use is indicated for injured spinal cord conditions (in cases of excessive demyelination or neuron loss), adult bone marrow stem cells and adult neural stem cells have shown themselves able in animal models (and in human clinical usage for Parkinson’s disease) to meet these needs.15 When taken from the patient, such cells (including olfactory ensheathing glial cells, which are known to remyelinate demyelinated axons and usher growing axons across the injury site) totally avoid rejection as well as the ethical, and safety concerns inherent in embryonic stem cell usage, cloned or uncloned.

Yet those paralyzed by SCI, including Christopher Reeve, are encouraged to believe their brightest and possibly only hope for regaining lost lives lies in cloning, when in fact their medical condition and the facts of cloning suggest they should demand that cloning be banned, restricting resources allotted for cures to avenues that offer more than futile hope.

In therapeutic cloning, the Biotech, pharmaceutical, and basic research industries are exploiting the paralysis of three-hundred thousand Americans to serve institutional and commercial ends under the guise of looking for cures. Millions afflicted by heart disease, diabetes, cancer, stroke, and other catastrophic, life-threatening conditions are likewise encouraged to pin their hopes on hype. I therefore respectfully ask the U.S. Senate to send the message loud and clear that it’s no longer acceptable for researchers and politicians linked to Biotech to simply claim that speculative, highly problematic research is supposedly conducted for the sake of cures, when in fact political, commercial, professional, or institutional motives may lie at the root of their plans. I respectfully ask the U.S. Senate to support Senator Sam Brownback in totally banning all forms of human cloning in America and slamming the door on a colossal, needless waste.

James Kelly
Granbury, Texas

  1. William M. Rideout III, Konrad Hochedlinger, Michael Kyba, George Q. Daley, and Rudolf Jaenisch, Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy. Cell, vol. 109 no. 1, pp. 17-27.
  2. Paul E. Greene, M.D., Stanley Fahn, M.D., Status of Fetal Tissue Transplantation for the Treatment of Advanced Parkinson Disease Neurosurgical Focus 1/7/2003.
  3. Rideout WM; Eggan K; Jaenisch R. Nuclear cloning and epigenetic reprogramming of the genome. Science 2001 Aug 10, 293; Humpherys D; Eggan K; Akutsu H; Hochedlinger K; Rideout WM; Biniszkiewicz D; Yanagimachi R; Jaenisch R. Epigenetic instability in ES cells and cloned mice. Science, Jul 2001; Humpherys D; Eggan K; Akutsu H; Friedman A; Hochedlinger K; Yanagimachi R; Lander ES; Golub TR; Jaenisch R. Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci U S A 2002 Oct 1.
  4. Rudolf Jaenish, Cloning: the Debate, New York Acadmeny of Sciences, May 20, 2002.
  5. Seeing double: Hype over cloning obscures its dangers, by Tim Friend, Seattle Times, 2003.
  6. Hans Schöler. Single gene failure explains cloning deaths. New Scientist, 14 May 2002, reference to Boiani, Eckardt, Schöler, and McLaughlin, Oct4 level and distribution in mouse clones: consequences for pluripotency. Genes and Development, May 15th 2002.
  7. Ian Wilmut, Cause of Sick Clones Contested, Nature, 11 January 2002.
  8. Ouyang J, Ni X, Chen B. (A preliminary result of treatment of progressive multiple sclerosis with autologous peripheral blood stem cell transplantation in China) Zhonghua Nei Ke Za Zhi 2001 Aug;40(8):550-2; By William J. Cromie, Adult Stem Cells Effect a Cure (Diabetes) Harvard University Gazette August 16th, 2001; Kevan C. Herold, M.D., et al, Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus NEJM — Abstracts, 346 (22): 1692-98; G. Kraft et al., “Clinical Application of Autologous Stem Cell Transplantation in Severe Multiple Sclerosis Treated with High-Dose Immunosuppressive Therapy,” Presentation at the 54th Annual Meeting of the American Academy of Neurology, April 16, 2002; Bernaudin, F., et al. Results of myeloablative allogenic stem cell transplant (SCT) for severe sickle cell disease (SCD) in France. American Society of Hematology meeting. Dec. 8. 2002.
  9. Hans Schöler. Single gene failure explains cloning deaths. New Scientist, 14 May 2002, reference to Boiani, Eckardt, Schöler, and McLaughlin, Oct4 level and distribution in mouse clones: consequences for pluripotency. Genes and Development, May 15th 2002.
  10.  Solter D. Cloning v. clowning. Genes Dev 2002 May 15;16(10):1163-6.
  11. March 5th U.S. Senate Testimony by Christopher Reeve; Christopher Reeve, Cloning: The Debate, New York Academy of Sciences, May 20, 2002.
  12. March 5th U.S. Senate Testimony by Christopher Reeve
  13. Davies SJ; Goucher DR; Doller C; Silver J; Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci, Jul 15 1999, 19(14) p5810-22.
  14. Dr. Carlos Lima; Human olfactory mucosa grafts in traumatic spinal cord injuries: a way to cure paralysis? Hospital Egas Moniz- Lisbon- Portugal, March 13th, 2002 online publication, BrainLand.com; Imaizumi T, Lankford KL and Kocsis JD (2000). Transplantation of olfactory ensheathing cells or Schwann cells restores rapid and secure conduction across the transected spinal cord. Brain Res. 854 (1-2): 70-8; Chopp M; Zhang XH; Li Y; Wang L; Chen J; Lu D; Lu M; Rosenblum M. Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 2000 Sep 11;11(13):3001-5; Geller HM, Fawcett JW. Building a bridge: engineering spinal cord repair. Exp Neurol (United States), Apr 2002, 174(2) p125-36.
  15. Lehmann M; Fournier A; Selles-Navarro I; Dergham P; Sebok A; Leclerc N; Tigyi G; McKerracher L; Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci, Sep 1 1999, 19(17) p7537-47; Billinghurst LL; Taylor RM; Snyder EY. Remyelination: cellular and gene therapy. Semin Pediatr Neurol 1998 Sep;5(3):211-28; Barnett SC, Alexander CL, Iwashita Y, Gilson JM, Crowther J, Clark L, Dunn LT, Papanastassiou V, Kennedy PG and Franklin RJ (2000). Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain. 123; Zhao LR; Duan WM; Reyes M; Keene CD; Verfaillie CM; Low WC ; Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 2002 Mar;174(1):11-20.
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