History of Stem Cell Research

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What is the history of stem cell research?

The history of stem cell research had a benign, embryonic beginning in the mid 1800's with the discovery that some cells could generate other cells. Now stem cell research is embroiled in a controversy over the use of human embryonic stem cells for research. In the early 1900's the first real stem cells were discovered when it was found that some cells generate blood cells.

The history of stem cell research includes work with both animal and human stem cells. Stem cells can be classified into three broad categories, based on their ability to differentiate. Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (e.g., identical twins). Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst and can form any of the over 200 different cell types found in the body. Multipotent stem cells are derived from fetal tissue, cord blood, and adult stem cells. Although their ability to differentiate is more limited than pluripotent stem cells, they already have a track record of success in cell-based therapies.

A prominent application of stem cell research has been bone marrow transplants using adult stem cells. In the early 1900's physicians administered bone marrow by mouth to patients with anemia and leukemia. Although such therapy was unsuccessful, laboratory experiments eventually demonstrated that mice with defective marrow could be restored to health with infusions into the blood stream of marrow taken from other mice. This caused physicians to speculate whether it was feasible to transplant bone marrow from one human to another (allogeneic transplant). Among early attempts to do this were several transplants carried out in France following a radiation accident in the late 1950's. Performing marrow transplants in humans was not attempted on a larger scale until a French medical researcher made a critical medical discovery about the human immune system. In 1958 Jean Dausset identified the first of many human histocompatibility antigens. These proteins, found on the surface of most cells in the body, are called human leukocyte antigens, or HLA antigens. These HLA antigens give the body's immune system the ability to determine what belongs in the body and what does not belong. Whenever the body does not recognize the series of antigens on the cell walls, it creates antibodies and other substances to destroy the cell.

A bone marrow transplant between identical twins guarantees complete HLA compatibility between donor and recipient. These were the first kinds of transplants in humans. It was not until the 1960's that physicians knew enough about HLA compatibility to perform transplants between siblings who were not identical twins. In 1973 a team of physicians performed the first unrelated bone marrow transplant. It required 7 transplants to be successful. In 1984 Congress passed the National Organ Transplant Act, which among other things, included language to evaluate unrelated marrow transplantation and the feasibility of establishing a national donor registry. This led ultimately to National Marrow Donor Program (NDWP) a separate non-profit organization that took over the administration of the database needed for donors in 1990. The 1990's saw rapid expansion and success of the bone marrow program with more than 16,000 transplants to date for the treatment of immunodeficiencies and leukemia. Adult stem cells also have shown great promise in other areas. These cells have shown the potential to form many different kinds of cell types and tissues, including functional hepatocyte-like (liver) cells. Such cells might be useful in repairing organs ravaged by diseases.

In 1998, James Thompson (University of Wisconsin - Madison) isolated cells from the inner cell mass of early embryos, and developed the first embryonic stem cell lines. In the same year, John Gearhart (Johns Hopkins University) derived germ cells from cells in fetal gonadal tissue (primordial germ cells). Pluripotent stem cell "lines" were developed from both sources. The blastocysts used for human stem cell research typically come from in vitro fertilization (IVF) procedures. The ethical concerns over this type of embryonic stem cell research has been expressed in the following US legal regulations:

In 1973 a moratorium was placed on government funding for human embryo research. In 1988 a NIH panel voted 19 to 2 in favor of government funding. In 1990, Congress voted to override the moratorium on government funding of embryonic stem cell research, which was vetoed by President George Bush. President Clinton lifted the ban, but changed his mind the following year after public outcry. Congress banned federal funding in 1995. In 1998 DHHS Secretary Sullivan extended the moratorium. In 2000, President Bill Clinton allowed funding of research on cells derived from aborted human fetuses, but not from embryonic cells. On August 9, 2001, President George W. Bush announced his decision to allow Federal funding of research only on existing human embryonic stem cell lines created prior to his announcement. His concern was to not foster the continued destruction of living human embryos. In 2004, both houses of Congress have asked President George W. Bush to review his policy on embryonic stem cell research. President George W. Bush released a statement reiterating his moral qualms about creating human embryos to destroy them, and refused to reverse the federal policy banning government funding of ESC research (other than for ESC lines established before the funding ban).

In the November 2004 election, California had a Stem Cell Research Funding authorization initiative on the ballot that won by a 60% to 40% margin. It established the "California Institute for Regenerative Medicine" to regulate stem cell research and research facilities. It authorizes issuance of general obligation bonds to finance institute activities up to $3 billion dollars subject to an annual limit of $350 million.



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