Pioneers of Promise
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The Search That
By Dale Keiger
In the early 1980s, Curt Civin just wouldn't give up. The Hopkins director of Pediatric Oncology (and the King Fahd Professor of Oncology and Pediatrics) was a mere assistant professor in those days, trying to find a process that most everyone else in his field had concluded was too difficult, that some observers had dismissed as unneeded, and that no one wanted to pay for. Civin didn't care. He believed there had to be a way to isolate in bone marrow what are called stem cells, and that once he figured it out, great benefits would derive from the discovery.
He was right.
Marrow stem cells are not quite the beginning of the chain of human cellular life, but they're close. From them arise red and white corpuscles and platelets--the blood and immune system. Many researchers understood their promise. Consider the potential for treating patients with various forms of leukemia. Leukemia is susceptible to very high doses of chemotherapy. But those doses destroy the marrow. Doctors had been trying to regenerate marrow by means of transplanted marrow cells. Unfortunately, the new marrow sometimes contained cancer cells, which were then reintroduced to the patient's body and caused the cancer to recur.
If Civin could isolate purified stem cells only, the patient would gain all the benefits of a marrow transplant without the attendant risk of reintroduced cancer. And because isolated stem cells don't contain mature functional immune system cells (T lymphocytes), doctors could transplant them without worrying about graft-versus-host disease (GVHD), in which donor cells attack the patient's body. Furthermore, stem cells might be useful beyond cancer, to treat or cure genetic blood or immune disorders.
Civin couldn't find anyone to fund his research. So he relied on money provided by the Hopkins Oncology Center for the establishment of new laboratories. He and his research associates made the shrewd guess that stem cells have their own unique antigens. Antibodies target antigens, so if stem cells had antigens, then you could, the researchers reasoned, make antibodies directed at them, antibodies that could be used to isolate the stem cells like a magnet drawing away iron filings. Sure enough, the team discovered an antigen now designated CD34. The CD34 antibody binds to the CD34 antigen, providing the means to "pull" only the stem cells from a complex sample of bone marrow cells.
Civin's discovery paved the way for better cancer therapies for children and adults. Around the world, physicians now perform thousands of transplants of purified stem cells. Hopkins does about 125 per year to treat leukemias, lymphomas, myelomas, and other conditions such as sickle cell anemia, thalassemia, and aplastic anemia. Last year, the Intellectual Property Owners Association named Civin as its "Inventor of the Year." (He became eligible for the honor when discovery of the CD34 antibody and his stem-cell purification technology were awarded patents and, in 1996, FDA approval.)
He and his colleagues are now working on stem cell gene therapies. They want to use stem cells and the cells that develop from them as a way to immunize patients against their cancers. They're also trying to put specific genes in patients' stem cells so that, for example, those cells will now be "armed" to attack the cancer cells.
Notes Civin, "Stem cells are much more plastic than we thought they were. If you take preparations of purified muscle cells and put them in an environment ideal for formation of blood, they will produce blood cells. Similarly, there are brain cells, probably neural stem cells, that also will form blood."
He and his colleagues are now examining stem cell genes to determine what genes go wrong in stem cells that develop into leukemias, and what goes further wrong when the leukemia cells become drug resistant and cause the patient to relapse despite treatment. He says, "These will be the targets for drugs of the future."
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