SECTION: CAPITOL HILL HEARING TESTIMONY

LENGTH: 1355 words

COMMITTEE: SENATE APPROPRIATIONS

SUBCOMMITTEE: LABOR, HEALTH AND HUMAN SERVICES, EDUCATION

HEADLINE: CLONING

TESTIMONY-BY: MARIA MICHEJDA, M.D., FOUNDER OF THE

AFFILIATION: JOURNAL OF FETAL DIAGNOSIS AND THERAPY

BODY:
Testimony Concerning the "Human Cloning Prohibition Act of 2001

" Maria Michejda, M.D. founder of the Journal of Fetal Diagnosis and Therapy

January 24, 2002

Honorable Senators, Ladies and Gentlemen:

It is an honor and a privilege to present my views on an aspect of the incredibly important issue that you are considering. My name is Maria Michejda. I am a physician and I have been and continue to be very active in research in the general area of fetal medicine. I am the founder of the Journal of Fetal Diagnosis and Therapy, the principal journal in the rapidly growing field of fetal medicine, and a co-founder of the International Fetal Medicine and Surgery Society. I served as an advisor on fetal issues in a number of academic and non-academic institutions, including the German and Dutch parliaments. Currently, I am an Associate Professor of Radiology and Nuclear Medicine at NYU and a Senior Staff Associate at the Immunology Center of Georgetown University. For over 20 years my main research focus was on fetal tissue transplantation and subsequently on the biology of stem cells derived from various sources, including fetal bone marrow obtained from spontaneous miscarriages, adult bone marrow, cord blood and peripheral blood. We have, in fact, initiated the first studies on fetal tissues from 2nd trimester spontaneous abortions over 10 years ago. As a consequence, we have developed considerable expertise in the acquisition, processing and application of this underutilized and noncontroversial source of stem cells. My initial studies on fetal tissue transplantation for the in utero treatment of congenital malformations focused on allogeneic transplantation of bone, bone marrow and neural tissue. This work, which was initiated at NIH and subsequently carried out at Georgetown, utilized non-human primates as models resulted in novel techniques for the treatment of neural tube defects in babies before birth. These studies also led to the appreciation of the unique properties of fetal tissue, including cellular regeneration, selfrepair, a high rate of cellular proliferation and differentiation, followed by rapid vascularization of the new tissue. We have focused our attention over the last ten years on the exploitation of the remarkable properties of fetal tissues in general and fetal stem cells in particular.

We have recently conducted extensive comparative studies on properties of stem cells derived from various sources. We examined stem cells derived from adult bone marrow, umbilical cord blood, adult peripheral blood and fetal bone marrow. The fetal bone marrow was, as I said earlier, obtained from 2nd trimester spontaneous miscarriages. Without going into extensive detail, we found that the fetal stem cells were superior in terms of their biological properties for transplantation, long-term engraftment and cellular reconstitution. One of the most important and beneficial characteristics of fetal stem cells derived from the bone marrow is that they are pluripotent and can differentiate into many lineages. They are also highly immature and immuno-incompetent. This means that they are not rejected by the host, in contrast to adult stem cells, and do not induce graft versus host disease. Also, unlike the other sources of stem cells, the fetal stem cells do not require matching of the donor and the recipient.

Today, I would like to present some of the biological problems of stem cells in their various flavors to you and to suggest that some of these problems may have disastrous consequences in terms of therapy. I would like especially to focus on stem cells derived from both reproductive and therapeutic cloning. Therapeutic cloning is achieved by asexual reproduction methods, which involve the so-called somatic cell nuclear transfer. This is accomplished by microinjection of the nucleus from a human donor cell that carries a complete set of chromosomes into a human ovum from which the nucleus has been removed. If the transfer is successful the oocyte containing the implanted genomic material will undergo several divisions to produce a preimplantation embryo known as the blastocyst. After five days, this entity is composed of 100-150 embryonic cells. It is then destroyed in order to create new embryonic cell lines in culture. In reproductive cloning on the other hand, the blastocyst is placed in the uterus and may develop into a baby. This has not been accomplished in humans but many animal examples are known.

Both therapeutic and reproductive cloning have the very serious problem of gene imprinting since all the genetic material comes from one somatic cell. The consequences of gene imprinting are profound and affect the very process of cloning as well as the product of the cloning. Simply put, the product can be defective. It is now well appreciated that the nuclear transfer process is highly inefficient and would be prohibitively costly and impractical for therapeutic purposes. Moreover, most clones die before birth during animal reproductive cloning and many survivors display various abnormalities. These include placental and fetal overgrowth, immunologic impairments, expressed by autoimmune diseases (such as the early arthritis diagnosed in the famous Dolly), and accelerated aging. The consequences of gene imprinting in humans are potentially devastating. Animals may be more tolerant to epigenetic aberrations, which may initially result in only subtle abnormalities. Such abnormalities cannot be ignored in human materials, particularly in embryonic cells derived from therapeutic cloning and used for transplantation, which would result in the transfer of the genetic abnormalities to the recipient. Such aberrations may not be evident at early stages but would become expressed at a later age. Consequently, cloning techniques to acquire stem cells for transplantation are impractical, costly and may lead to serious medical problems.

Besides the major ethical and medical problems associated with cloning, one should also take into account the possible legal consequences of professional responsibility and malpractice when something goes wrong. Finally, there is a limited supply of oocytes suitable for nuclear transfer. This will result in moral and medical pressures on women of reproductive age. Harvesting of human eggs is not free of dangers of infection, hemorrhage, malignancy and infertility, which will particularly affect women in financial need.

The initial euphoria associated with the promise of therapeutic cloning has now been tempered by the realization of the multiple problems. This has become evident in the research community and is beginning to be expressed in the popular press. While I fully agree with the National Academy of Sciences panel that more research is needed in the area of stem cells, I would like to point out that the problems associated with human cloning are profound and cannot be ignored. In fact, this could retard progress in the development of cellular therapies, which are in large measure one of the most exciting developments in medicine. A prohibition of human cloning will not inhibit stem cell research, but will focus attention on proven sources of stem cells such as fetal, cord blood, and adult cells and expand their curative scope. Here, I would like to reemphasize that pluripotent fetal stem cells derived from 2nd trimester spontaneous abortions exhibit proven highly proliferative engraftment and curative potentials that were made evident in transplantations many years ago. Fetal stem cells have most of the properties of embryonic stem cells but do not exhibit the uncontrolled replication that is a characteristic of the embryonic cells, which leads to teratomas, malignancies and chromosomal mosaicism upon transplantation.

In conclusion, technologies for safe and efficient cloning do not exist. Our obligation on one hand is to protect human life and the safety of patients, and on the other to prevent the dissemination of erroneous information about curative potentials of unproven sources of stem cells for human therapies.



LOAD-DATE: January 24, 2002