To watch Irving Weissman draw pictures of red blood cells and T lymphocytes on his office whiteboard is to catch a glimpse of the investigative passions that fuel his research. After filling the board with dashed-off circles and lots of linking lines, the professor of cancer biology tap-tap-taps on the ultimate object of his diagram—a solitary, blood-forming stem cell. “It’s the only cell that self-renews, so it obviously must know which genes to turn on, to make more blood cells,” he says.
Stem cells’ self-renewing property is both good news and bad news for people with cancer. The good news: at least in the blood-forming system, adult stem cells can be used to regenerate cells destroyed by radiation and chemotherapy. In a patient with metastatic breast cancer, for instance, “in order to get to the dose that kills all the cancer cells, you’ve killed all the blood-forming cells,” explains Weissman, MD ’65. “In 40 percent of cases, the bone marrow has breast cancer cells in it, so [if you do a transplant using the patient’s own marrow], you’re going to redeliver the breast cancer to the patient.” In the mid-’90s, Weissman and colleagues demonstrated that giving breast- and blood-cancer patients only blood-forming stem cells regenerates marrow without the risk of reintroducing cancer.
The bad news: cancer has its own stem cells, according to breast-cancer studies at the University of Michigan and Weissman’s research on mice with leukemia. “The cell that’s really important for the cancer, the one that spreads the cancer from one part of the body to the other, is a cancer stem cell,” he says. But even bad news may lead to better treatment: Weissman hopes he and others can identify the genes that allow cancer stem cells to self-renew, then develop drugs that target those cells.
At Stanford’s new Institute for Cancer/ Stem Cell Biology and Medicine, Weissman wants to bring together researchers and clinicians who will investigate adult stem-cell therapies and methods to combat cancer stem cells for many types of malignancies. A leading figure in adult stem-cell research, Weissman will direct the $120 million institute, which received $12 million in seed money from an anonymous donor in December.
Eventually, Weissman also wants the institute to create new human pluripotent, or embryonic, stem-cell lines. While adult stem cells may only be able to create one type of tissue—blood stem cells form blood, muscle stem cells form muscle tissue and so on—pluripotent stem cells can generate any type. Weissman wants researchers at the institute to be able to study pluripotent stem cells that carry mutations found in cancer and in other genetic diseases, including Parkinson’s and Alzheimer’s.
In August 2001, President Bush restricted federal funding for embryonic stem-cell research to projects using existing cell lines, none of which carry such mutations. To create the mutation-carrying lines, researchers may use a lab technique called nuclear transplantation: removing an egg’s nucleus and replacing it with an adult nucleus, then, after the cell has divided and formed a ball of cells called a blastocyst, removing the stem cells.
This process is controversial. Removing the stem cells destroys the blastocyst, which some consider a human life. Others are concerned because nuclear transplantation employs the same steps as human reproductive cloning, except for the ultimate implantation in a woman’s uterus. Weissman sees a clear distinction between the two. “I was chair of the National Academies committee that called for a legally enforceable ban on human reproductive cloning because it was so dangerous,” he says.
Nuclear transplantation is the subject of competing U.S. Senate bills and White House criticism. Weissman hopes the federal government will follow California’s lead and allow it. “If the President is objective and serious about human diseases,” he says, “he’ll look at all of the new data before he makes his final decision.”
