Thank you Senator Brownback and Senator McCain and distinguished senators of the subcommittee for the invitation to present to you today. Stem cells are a major medical breakthrough with tremendous potential but we are now at a 'Y in the road' as far as the future of medicine. In deciding our course, the way is clouded by opposing ethical views, vested interests of certain scientists, the biotech community, political allegiances and celebrities. I would like the members of the subcommittee and the audience to set aside all those factors for just a few minutes.

I ask you now to think about a very basic question: If your loved one was suffering from a terrible injury or disease, what type of stem cell treatment do you think would work the best: 1) their own cells, or 2) cells derived from embryos, fetuses or cloned embryonic cells?

I don't think you need to be a scientist to answer that question. It also turns out that if you look at the scientific evidence, not speculation about the future by prominent scientists on either side of the issues, but just the facts of where we are today based on clinical and preclinical trials, the logical choice in medical treatment is also the best medical treatment.

Stem Cells

Disease transmission - Slower rate of growth - Uncontrolled growth - More restricted development - Ethical objections - Less funding opportunities - Possible rejection More difficult commercialization

Embryonic or Fetal Stem Cells - Cloning - Cloned Stem Cells - Person's Own Stem Cells - Treatments for Wide Variety of Diseases and Injuries

I would now like to review the scientific data that prove that an intuitively obvious concept is also supported by the results of recent clinical trials and preclinical trials (experimental animal studies). First, I would like to review the clinical trials using stem cells and their derivatives in spinal cord injury and Parkinson's disease. Two clinical trials using fetal tissue have been done in the US and one on-going clinical trial in Portugal using a person's own tissue. All of these spinal cord injury trials are important to the question of stem cell research because the cells that survive after the tissue transplant are the stem cells and their early derivatives. The mature cells in the tissue except for some support cells would die off. The first study using fetal tissue was done at the University of Florida, beginning in 1997, in the treatment of syringomelia - a condition in which a large cavity forms in the spinal cord. Minced spinal cords (SC) from 4-8 different human fetuses taken from elective abortions were grafted into the cavity in the spinal cord. At 18-month follow-up of the first 2 patients, the condition of the patients was not very different. Another study was performed more recently using pig fetal tissue at Washington University and SUNY/Albany. There have been no further announcements regarding this study although the first patient was done in April 2001 . The study in Portugal has had impressive results using a person's own olfactory mucosa . The olfactory mucosa lines the upper nasal cavity and contains stem cells and cells that encourage growth of nerve cell processes called olfactory ensheathing cells. Patients with severe (complete) spinal cord injuries were operated at 6 months following the injury. Other patients in this study (not reported below) were up to 7 years post-injury with similar or better results. On the next page are the charts comparing the results from the first 2 patients from each of the 2 different trials.

In comparing the results of using embryonic tissues or using one's own tissue: 1) There was little change in the condition of the patients using the embryonic tissue. There appeared to be no massive rejection even though 4-8 different embryos were used for each patient in the University of Florida trial and no reports of rejection in the trial using pig cells used in Washington University and SUNY/Albany.                         2) In the Portuguese study, there were increases in motor and/or sensory scores by 1 month in almost all the patients receiving their own olfactory mucosa suggesting that a person's own tissue is more effective. The first patient done regained bladder control at 16 months after the treatment and no longer uses catheters. The second patient that had less improvement was the patient that had the largest lesion (6 cm) of all of the patients done so far. The changes observed might have been greater for the patients treated in Portugal if rehabilitative therapy was available there.

The clinical trials in Parkinson's disease had dramatic differences in their findings depending on the original source of the cells: fetuses or the person's own cells. In both cases, the cells were matured in culture before being transplanted into the patient. A clinical trial was done by Dr. Freed and colleagues in which 19 patients received cells derived from 4 different fetuses with abortions at 7-8 weeks after conception. The patients that were under 60 years showed about a 28% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS). About 15% of these patients showed severe decline in function at 1 year after treatment. In another Parkinson's study done by Dr. Michel Levesque, the patient who was 57 years old at the time of treatment, received cells derived from his own brain stem cells. This patient showed an 83% improvement in the UPDRS. Below is a chart that summarizes the percentage improvement in the 2 clinical trials.

The greater improvement and lack of harmful late effects using a person's own cells is primarily due to the fact that the cells were derived from an adult as opposed to fetuses. Of lesser contribution to the overall improvement probably was that the cells were genetically identical and not rejected. There was no evidence of massive rejection in any of the studies using fetal cells/tissues, even when pig cells were used without long-term immune-suppressing drugs to prevent rejection. However, better results were obtained using a person's own adult cells. The study by Freed and colleagues also suggests that the primary problem with the fetal cells is not rejection. Using cells derived from fetuses, the severe functional deterioration seen in several patients was due to overgrowth of the cells derived from fetuses, not a lack of cell survival. It is rather ironical that the qualities cited for the superiority of embryonic or fetal stem cells are actually responsible for causing problems. Rapid growth is not always a desirable quality as clearly seen with weeds in a garden or cancer in the body. In the Parkinson's study, cells derived from the embryo and the adult were both allowed to mature in culture, but the end result was quite different.

As the graph demonstrates, the patient's own cells markedly improved and no debilitating side effects were observed. A possible explanation for these findings is that adult stem cells are the natural components of the adult body and endogenous mechanisms exist to control their growth and maturation to replace damaged neurons. The cells from the adult may have certain molecules on their surface (ligands or receptors) that keeps the cells from uncontrolled growth. Both studies allowed the stem cell to mature before implantation. If maturation of stem cell is a necessary safety step, then the fact that embryonic cells are so immature is a disadvantage.

It would be possible and simpler to have large-scale commercialization of cells derived from embryos or fetuses but the end product would be grossly inferior for the recipients.

There are many types of adult human stem cells that are readily available that lack the problems of overgrowth, rejection, and disease transmission. Most people do not need a total body replacement. Even if costly and complicated procedures of cloning are done to produce the human stem cells (not technically possible yet), the cells will not be genetically identical because of the mitochondrial DNA and improper imprinting. There is evidence that the debate is raging in the scientific community. A recent scientific article describing a clinical trial included an opinion that the authors, although using a patient's own blood stem cells, in no way support a ban on using human embryonic stem cells.

Preclinical Trials

Preclinical trials (experimental animal studies) not only provide the basis for future clinical trials described above, but also support the same conclusion that is reached in reviewing the clinical trials. There is abundant evidence that adult stem cells can be used as a therapy and are readily available in people. The conclusion from the preclinical studies is that adult stem cells work just as well, if not better, than embryonic stem cells and are probably safer. There is no need for embryonic stem cells especially cloned ones. Ten years ago, it was discovered that stem cells exist in the adult brain and spinal cord and can be readily isolated. Many initial ideas about adult stem cells in the brain were wrong. For example, the cells were first thought to only be present in rodents, but later found in people. It was once thought that only embryonic stem cells have the capacity to become many different cell types. More recently, it has been found that neural stem cells from adults have this potential. Stem cells and their cellular derivatives may be useful in many ways. In the nervous system, they can be replacement neurons, source of growth factors, or a substrate of growth. Another misconception was that adult stem cells might not be functional in their ability to transmit a signal to another neuron. There is recent evidence that adult stem cells can mature and form functional connections with other neurons in culture. A surprising finding was that many cells in the adult (not just the cells in the brain and spinal cord) have the potential to be neurons. Sources of adult human stem cells that are capable of forming neurons include the brain, olfactory mucosa in the upper nose, cornea, choroid and sclera of the eye, teeth, bone marrow, and skin. Further evidence that bone marrow can be a source of neurons for the brain is supported by findings in the patients' brains who have received bone marrow transplants. There is no reason to use embryonic/fetal tissue or to clone people to obtain genetically similar embryonic stem cells when there is a ready supply of stem cells in adult humans.

There are several studies that support the usefulness of adult stem cells. Stem cells obtained from adult spinal cord have been shown to survive and mature into neurons when transplanted into the brain. Transplantation of stem cells from adult human brain causes myelination to occur in a focally demyelinated spinal cord of the rat. Demyelination is common in spinal cord injury and disease states such as Multiple Sclerosis, and interferes with signal conduction between the neurons. Human cells from adult have been used to treat animal models of disease states. For example, human cells led to functional improvement in animal models of Parkinson's disease using human bone cells or using neural stem cells.
Human brain adult stem cells can even be obtained after death.  So if a person's own stem cells are not used there are other less objectionable alternatives.

Another alternative to the use of embryonic stem cells is human umbilical cord blood. Human umbilical cord blood has the potential to form neurons, as well as other cell types. Human umbilical cord blood injected IV caused a functional improvement when injected into experimental animals with traumatic brain injury or stroke. In the case of genetic defects, there are several other alternatives to cloning. One is gene therapy that has been successfully used in mice and humans. More recently stem cells have been used as vehicle to deliver genes to the brain.

Bone marrow stromal cells from adult rats promote functional recovery after spinal cord injury in rats when given 1 week after injury, even when the cells are injected intravenously. Bone marrow stromal cells also will migrate to site of a head injury when given IV and cause a functional improvement. Below is a brief summary (in italics) of recent findings using other treatments besides stem cell for injuries and diseases of the nervous system.

This summary is meant to make 2 major points: 1) Other treatments used alone or in combination with adult stem cells may hold the greatest promise in treating spinal cord injury and other damage to the nervous system, 2) While there is no ban on animal cloning, a review of recent literature revealed more than 40 articles of promising treatments other than stem cells for spinal cord injury but only 1 or just a few articles showing any therapeutic benefit of therapeutic cloning. The one article that received significant press coverage attempted to show a benefit of cloning in an animal study also revealed some of the difficulties with this procedure.


(ed. note:  the following requires extraordinary effort by most readers to understand)


Other cell types

Other cell types that do not form neurons also help in recovery. After selective demyelination in rat spinal cord, olfactory ensheathing cells myelinated axons and led to greater motor and somatosensory evoked potentials and a better functional outcome. Olfactory ensheathing cells promote locomotor recovery in the transected cord after delayed transplantation. These cells were also found to stimulate growth of motor axons. Olfactory ensheathing cells when used with methylprednisolone promoted functional recovery and axonal regeneration after lesioning of the corticospinal tract.