Testimony before the Senate Appropriations Subcommittee on Labor, HHS and Education by Anton-Lewis Usala, MD

Date: 07/18/2001

July 18, 2001

Senators,

I appear before this subcommittee to discuss embryonic stem cell research, and alternative technologies that are currently under development in the company I founded. Our focus was to develop a method to regenerate and replace damaged patient tissues as a treatment for various human diseases. I developed a proprietary scaffolding, based on the structure of embryonic tissue scaffolding, to which adult cells can attach. The hypothesis that we first tested in multiple tissue culture, animal, and toxicology studies, was that upon binding to this embryonic-like structure, patient cells would be signaled to promote areas of the genome that are normally only promoted during embryogenesis and early fetogenesis. During this time, cells that are not committed to becoming a specific kind of cell, explosively differentiate into specialized tissues. As they do, they make connections and are modulated to integrate with all surrounding cells in a manner that is species specific.

The proprietary scaffolding that my company has developed apparently enables regeneration of a specific kind of tissue called mesenchymal tissue. One of the three embryonic germ layers, mesenchymal tissue gives rise to connective tissue, blood vessels, bone, cartilage and parts of skin. In pre-clinical animal studies, we have demonstrated regeneration of blood vessels and skin in animals suffering from chronic diabetic and surgical extremity lesions.

Years are required for an idea to be tested first in the petri dish, then in controlled animal efficacy studies, then in safety studies. Years are required to build the infrastructure to safely and reproducibly build a product for human clinical trials. Immense amounts of time and money are required to efficiently put the pieces into place that will give the Food and Drug Administration confidence that the risks for patients in experimental clinical trials are worth the potential benefit.

My company is currently nearing completion of its first human clinical trial, with what I believe are exciting results. We have not yet submitted the final report to the Food and Drug Administration, and the data have NOT yet been peer reviewed. However, photos of chronic diabetic foot ulcer wounds in some of the patients treated with a single injection of our scaffolding appear to show rapid, well vascularized tissue regeneration, and closure of the ulcers within 2 to 8 weeks. These ulcers were refractory to multiple forms of therapy and were unhealed for 2 to 12 years prior to our therapy.

Yesterday, on the Today show, a segment was aired showing a mother injecting insulin into her four year old diabetic child. The mother stated she was extremely supportive of embryonic stem cell research if it could cure her child. It is not honest to bring before this Committee people such as myself, who have chronic illnesses for which there is no cure, as a valid argument for funding human embryonic stem cell research. There are many alternative paths; and if there is a legal or ethical reason not to conduct this research, public resources can be all the more effectively focused on those alternative paths.

There are private companies in human clinical trials using porcine derived neurons as a treatment for Parkinson’s disease. The first project my company embarked upon also utilized porcine tissue sources as a treatment for diabetes. We showed remarkable pre-clinical success in transplanting porcine tissue into diabetic dogs, without immunosuppressive therapy, and maintaining the tissue without rejection . Others in Europe and New Zealand have conducted human clinical trials utilizing microencapsulated porcine tissue. Pre-clinical animal studies utilizing adult human stem cells have to date demonstrated at least as much efficacy as human embryonic stem cells, and the advantages of using embryonic stem cells is only theoretical at this point in time.

There is little data to support, or infer, that embryonic human stem cells have any advantages over adult human stem cells in medical research. As a scientist in the field of human tissue regeneration, it is clear to me that integrating functional new tissue, not simply healthy tissue, into a diseased area requires integration of hundreds if not thousands of signals. Several years ago, children and patients with diabetes came to the House and Senate to request lifting the ban on fetal tissue research. At the time, many at the NIH believed the less differentiated fetal pancreatic tissues would be a better source for human transplantation as they should be less immunogenic. This, too, was hailed as a medical miracle. Subsequent studies, both in the United States, and in Europe, demonstrated this not to be the case, and the successful transplantation studies in Canada, using adult cadaveric pancreatic cells, have removed fetal tissue sources from the limelight.

Having diabetes 42 of my 43 years, I can bear witness to the fallacy of consensus medical thinking. As a child, I remember my physician telling my mother that multiple NIH funded studies showed blood sugar control did not make any difference in whether or not I would develop vascular complications. Indeed, when I was in medical school in the early eighties, this same dogma was being taught.

At ten years of age, I reasoned that nature kept blood sugars within a normal range, and I surreptitiously injected myself with fast acting insulin at meals to prevent my blood sugar from rising (as occurs in patients without diabetes). People who thought like I did were labeled as extremists. It was not until the early 1990’s that multiple reasonably well designed studies demonstrated that in fact, blood sugar control is the single largest determinant as to whether a child will develop complications such as kidney failure and blindness. However, hundreds of thousands of children developed renal failure between 1960 and 1990 because of this medical consensus mistake.

We all agree that the diseases for which cures are sought through embryonic or adult stem research are responsible for a great deal of human suffering, as well as economic cost to the nation. According to the National Bioethics Advisory Commission, most of us also agree that human embryos are deserving of respect. It is for that last reason that these hearings are being held.

As I testified last September before this subcommittee, the mass of cells that begins the process of specific differentiation occurs very shortly after conception. The promotion of a specific and integrated genome pathway results in the beginning of that particular species of animal. The embryos that are fertilized in vitro differentiate and integrate their cellular signals in a specific way that are human. When they acquire rational thought or feeling is as yet debatable; when they are defined as human is not.

The real question before Congress is whether or not this research should be funded by the federal government. Whether it is scientifically valid is not an issue that Congress can resolve — for if there is no legal or ethical issue, it should be considered by the relevant regulatory bodies as any other approach is considered. However, the legal and ethical issues are paramount. As Dr. Frank Young, a former FDA Commissioner and physician scientist says:

I believe that the only defensible position is that life begins at conception whether in the petri dish or the uterus. To destroy embryos for only potential benefits that are promised to suffering people before the work is done in animals is misleading, inappropriate and in my opinion, utilitarian ethics. We do pre-clinical tests of medicines in animals rather than rush into humans to avoid mistakes as much as possible. Why rush into experiments or trials with ES before completing animal studies and exploring adult stem cells?

As I said before this subcommittee in September, all societies are ruled by law, even unjust societies. The difference between a just and an unjust society is the set of precedents the society chooses to use in establishing its law. In my view, the United States is a uniquely just society, being the first government in the history of humankind where the rights of the individual supersede the perceived right of the State. This is the foundation that was established by the first ten amendments to our Constitution. Should human embryonic stem cell research be funded, it will be the first time in U.S. history the Federal government has determined the best “use” for a human being. This would be a cataclysmic paradigm shift. The perceived right of the State will have superseded the right of the individual. Even during the horrific times of slavery, the Federal Government did not fund programs using human beings for State purposes (although clearly individuals did).

Enthusiastic medical consensus on a promising idea does not make any potential therapy a medical breakthrough, and a congressional subcommittee is probably not the ideal forum for discussing the scientific validity of one form of research compared to another. Existing regulatory bodies, such as Internal Review Boards and the Food and Drug Administration, are better equipped to assess the validity and safety of such research data. However, I am grateful that this subcommittee has taken such time and effort to hear both the scientific, as well as the societal, case regarding human embryonic research. It is one of only a few appropriate forums to link all of these arguments together to best serve the national interest on all levels.

In my view, the suffering caused by as yet incurable diseases, can more quickly and with more certainty, be alleviated by the multiple efforts that do not require a paradigm shift in our national character. Such a paradigm shift would necessarily result from Federal funding of human embryonic stem cell research.

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