| Testimony
of Michael D. West, Ph.D. President & CEO Advanced Cell Technology, Inc. Senate Appropriations Labor, Health and Human Services, and Education Subcommittee December 4, 2001 Mr. Chairman and members of the Subcommittee, my name is Michael D. West and I am the President and Chief Executive Officer of Advanced Cell Technology, Inc., a biotechnology company based in Worcester, Massachusetts. INTRODUCTION I am pleased to testify today regarding human embryonic stem cell and nuclear transfer technology and their applications in medicine. I would like to first speak to the potential benefits of this emerging science, and then speak to some of the questions and concerns that have been voiced. The Potential Benefits of ES and NT Technology Human Embryonic Stem (ES) cells are unique in the history of medical research for at least two reasons. First, they alone are totipotent stem cells. By stem cells, we mean cells that can branch out like the stems of a tree, becoming other cell types. By "totipotent" we mean to say that they stand near the base or "trunk" of the developmental tree and so are capable of forming any cell or tissue type needed in medicine. In addition to forming any cell type, they are unique in their ability to self-assemble into complex multicellular tissues such as intestine, full thickness skin, kidney tissue, and so on. They differ in this respect from adult stem cells that are "pluripotent" - that is, capable of forming several, but only a limited number, of cell types. One can think of adult stem cells as limbs further out on the branches of a tree. While able to branch out in several different directions, only the trunk of the tree branches out into every leaf and limb. An example of adult pluripotent adult stem cells are the bone marrow stem cells now widely used in the treatment of cancer and other life-threatening diseases. The second distinguishing feature of ES cells is the ease with which they can be purposefully modified in a precise manner. This precise genetic modification is designated "gene targeting". The enhanced ability of ES cells to be modified with precision likely opens the door to many hundreds of clinical applications making human cells of any kind, genetically modified in any way to "heal" mutations in genes, something never before possible in medicine. These two unique characteristics of human ES cells open the door to manifold novel therapeutic strategies. It may not be an exaggeration to state that the combination of the ability to precisely genetically modify these cells by targeted modifications and the ability to make any cell type may have as profound an application in medicine as the ability to arrange electrical components has made in the electronics industry. To attempt to name every disease that potentially could be treated using this technology would require a larger report. Here are just a few examples. Neurons could be manufactured to treat degenerative diseases such as Parkinson's and spinal cord injury. Gene targeting to find and "heal" mutations could be used to manufacture neuronal stem cells for childhood retardation from diseases like Rett syndrome. Heart and skeletal muscle cells could be used for heart failure and age-related skeletal muscle wasting, and targeted genetic modification could be useful in muscular dystrophy. Blood forming cells would be useful in bone marrow grafting after cancer treatments, and anemias. Precision genetic modification could lead to better therapies for inherited blood cell disorders such as sickle cell anemia and infectious diseases such as AIDS. I would argue that the debate over the number of human ES stem cell lines approved for federal funding largely misses the point. Human ES cells obtained from IVF preimplantation embryos are not identical to the patient, that is they are "allogeneic". We should expect that such cells derived from the 20-60 approved lines would be rejected by the patient's immune system. The primary purpose in funding human ES cell research is not just the pure pursuit of human knowledge, but rather to accelerate the delivery of novel therapeutics to afflicted people. We must address from the beginning how we are going to make these cells useful in transplantation. The Use of Nuclear Transfer in Medicine The recent success in the cloning of animals from body cells demonstrates that the transfer of a body cell into the environment of an egg cell can "reprogram" it back to an embryonic developmental state. We have recently demonstrated that such technology actually rebuilds the replicative lifespan as well, suggesting that "young" cells can be derived from "old" cells. This is a profound development and perhaps the ideal solution for making real the longstanding dream of transplantation medicine; namely, to be able to offer any patient, even an aged patient, young healthy embryonic stem cells of from which any kind of cell could be make all of which would be their own cells, not expected to be rejected by their immune system. Nuclear transfer offers an important solution to the problem of tissue rejection. Every year many thousands of people die because of the inability of liver, kidney, or other tissue with the right constellation of markers to allow it to accepted by the body as self. It is estimated that three thousand people a day die from degenerative disease potentially addressed by therapeutic cloning. This new procedure would begin with the patient donating living cells to a physician, who would then reprogram them back to a totipotent state using the cloning procedure. This is called therapeutic cloning, to distinguish it from reproductive cloning which is designed to clone an entire human being. Therapeutic cloning does not involve the cloning of a human being, it involves the medical use of cloning to make living cells. The cells and tissues made from these cloned stem cells would be expected to be grafted stably for the life of the patient without immunosuppression. Responses to Concerns and Objections: 1). The preimplantation embryo is a human life and to use therapeutic cloning is to "clone and kill". Answer: In the first few days following the fertilization of an egg cell by a sperm cell, there develops a microscopic ball of cells called a preimplatation embryo. This embryo is destined to die unless it implants in the uterus to form a pregnancy. Indeed, it is estimated that 50-80% of these preimplantation embryos naturally formed in a woman's body never implant and therefore die, naturally. Prior to day 14, the preimplantation embryo has no body cells of any kind, and, in fact, has no cells even committed to somatic cell lineages. Indeed, the embryo has not individualized. Once this ball of cells attaches to a uterus, one or even two or more individuals can form from it. It is therefore proper to say that it is not yet an individual. At ACT, we neither allow cell development beyond day 14, nor do we implant the cells in a uterus. 2). Therapeutic cloning is merely theoretical; there is no reason to suggest it will work. Answer: There are published reports of success of therapeutic cloning research in at least two mammalian species; namely mice (1-2). While never performed in a human, the animal data suggests that therapeutic cloning has great promise. The National Academy of Sciences has formally recommended in a report titled "Stem Cells and the Future of Regenerative Medicine" as follows: "Recommendation: In conjunction with research on stem cell biology and the development of potential stem cell therapies, research on approaches that prevent immune rejection of stem cells and stem cell-derived tissues should be actively pursued. These scientific efforts include the use of a number of techniques to manipulate the genetic makeup of stem cells, including somatic cell nuclear transfer.3" 3). Allowing therapeutic cloning would cause a "slippery slope" effect, whereby regulating human reproductive cloning would not be possible. Answer: In reality the procedures to clone a human being are well known in the scientific literature. The widespread use of therapeutic cloning would not significantly increase the likelihood of the success of an effort to clone a human being. In addition, laws can easily be written to allow one and prohibit the other as reproductive cloning requires the transfer of a cloned preimplantation embryo into a uterus. 4). Therapeutic Cloning will lead to "embryo farms". Answer: Therapeutic cloning guidelines could easily be constructed to limit development to less than 14 days as is the current practice with in vitro fertilization. Summary In conclusion, nuclear transfer and human embryonic stem cell technology offer novel pathways to develop lifesaving therapies that will impact the lives of millions suffering from such diseases as Parkinson's disease, diabetes, arthritis, heart disease, kidney failure, spinal cord injury, liver failure, skin burns, blood cell cancers, to name only a few. The gravity of this issue calls for a compassionate, reasoned, and dispassionate debate. History will judge us harshly if we as a society fail to recognize and deliberate carefully upon a medical technology that could so powerfully alleviate the suffering of our fellow human beings. |