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Cloning, it's not

Feb. 16, 2004
Judy Siegel-Itzkovich
The Jerusalem Post

National leaders and legislators who are tempted to ban certain types of medical or scientific research should first take a look at the history books. George W. Bush, take note.

More than three-quarters of a century ago, Josef Stalin's science adviser, Trofim Denisovich Lysenko, persuaded the Russian dictator that Charles Darwin's evolutionary theories were nonsense. Instead, he promoted the work of Jean de Lamarck, the 18th-century French naturalist whose theory of heredity - that traits acquired during one's lifetime can be passed on to one's children - was eventually discredited. As a result of the ban on Darwinian research, American genetic research - which had been head-to-head with Russia - surged forward, and no decent geneticists were produced by the Soviet Union for 40 or 50 years.

Prof. Irving Weissman, a senior immunology researcher, cancer biologist and experimental pathologist at Stanford University in California - who has publicly railed against the Bush Administration's policies regarding research on embryonic stem cells - dug up this history during a recent interview in Jerusalem.

Weissman was here to receive the prestigious Rabbi Shai Shacknai Memorial Prize of the Lautenberg Center for General and Tumor Immunology at the Hebrew University-Hadassah Medical School. The prize was established by New Jersey Senator Frank Lautenberg in memory of his rabbi, who died of cancer at the age of 38. Every year, the center chooses an outstanding researcher in the field, who comes to Israel to receive the prize and lecture a number of professional audiences. Several recipients of the Israeli award have gone on to win Israel's Wolf Prize and even the Nobel Prize.

Weissman, who directs Stanford's Institute for Cancer/Stem Cell Biology and Medicine, is a physician, but after graduating from the university's medical school he decided he couldn't excel in both clinical medicine and research, so he chose the latter. He was born and raised in Great Falls, Montana, where there are few Jews ("most of them were my relatives," he recalls). His father was a businessman and his mother was a pianist who studied at Juilliard.

"My grandmother fled from Austro-Hungary and settled in Butte, Montana after World War II. She was reading a Hadassah newsletter that mentioned that her brother - Daniel Auster - had become mayor of Jerusalem." She had had no idea he was alive, let alone a prominent leader of the Yishuv. The two later had an emotional reunion.

Weissman was turned on by science at a very young age."Already at the age of 15, I was working in a lab, and by the end of high school, I had written three scientific papers on the same subject I do now."

BUT NOW he has over 500 papers under his belt, as well as numerous awards, including the J. Allyn Taylor International Prize in Medicine (2003), the California Scientist of the Year award (in 2002; 11 recipients have gone on to become Nobel laureates), and the Ellen Browning Scripps Society Medal (2001).

He spent much of the Seventies and Eighties studying how the thymus gland, a major player in the immune system, develops. But he is best noted for his groundbreaking research in hemapoietic (blood-producing) stem cells; Weissman was among the first to isolate these important cells in mice and humans. This work has paved the way for dozens of experiments that explore the cells' ability to fight disorders as varied as cancer and Parkinson's disease.

Weissman's interest in lymphocytes - white blood cells that gobble up invaders to fight disease - led him to find out how they malfunction to produce the cancer cells which cause lymphoma. He targeted two types of lymphocytes - B cells and T cells - and looked for a common ancestor.

Then, in 1988, he and his Stanford team made history by developing a "process of elimination" to isolate hemapoietic stem cells from a pool of bone marrow cells. He explained that he did this by accumulating as many blood-cell-binding antibodies as he could and using them to screen out non-stem cells; when an antibody was attached to a cell, that cell was eliminated. Finally, two antibodies known from previous research to bind to stem cells were added to the small group that remained. The few cells left in the pool were tested to see if they were really stem cells by injecting them into mice whose blood systems had been destroyed by radiation. The researchers found that as few as 30 of these cells saved half the mice, jumpstarting and replacing these survivors' blood supplies.

HAVING "CONQUERED" the stem cell riddle in the mouse, he proceeded to identify the stem cell in man. But since he couldn't ethically or practically conduct such experiments on patients, he and his fellow researchers decided to make mice more like humans. They created a special mouse, known as Hu-SCID, that had all the components of the human immune system.

Twelve years ago, Weissman and his team reported in the Proceedings of the [US]National Academy of Sciences that they had found a candidate for the human blood-forming stem cell. He co-founded a company called StemCells to develop the research, and in 1996 Weissman carried out a number of clinical trials that used the newly discovered stem cells to treat cancer patients. He related that one trial involved women with terminal breast cancer that had spread throughout their bodies. The study dealt with the problem, found in many cancer patients who get autologous (from self) bone marrow transplants - cancer cells remained in the blood. In this trial, the researchers removed bone marrow, purified the stem cells and reinfused them back into the patients after they had been given chemotherapy. These patients were found to be free of residual cancer cells. Results of the study were published two years ago in Biology of Blood and Marrow Transplantation. With the results of subsequent trials just completed, Weissman said larger studies will soon be launched.

Publicity about his successful work on human stem cells "was the first time we hit politics."

The chairman of President Bush's bioethics council demanded a public apology from Stanford University, accusing the school of trying to conceal the nature of its stem cell research and mischaracterizing the bioethics council's views.

Stanford has said its new cancer institute will conduct stem cell research using nuclear transfer techniques that some consider to be a cloning of human cells. However, Stanford said characterizing its work as cloning is wrong because the institute won't create human embryos, just cells.

In December 2002, the US President's Council on Bioethics demanded a public apology from Stanford for "obfuscating" the nature of its research. The council's chairman, Dr. Leon Kass of the University of Chicago, charged that "Stanford has decided to proceed with cloning research without public scrutiny and deliberation."

Stanford Medical School dean Dr. Philip Pizzo countered: "Although I certainly respect the views Dr. Kass expresses as an honest scientific interpretation, I disagree with his characterization of what the institute proposes to do and the process by which we will do it."

Weissman, who had just been appointed head of the institute, said Stanford's research "shouldn't be considered cloning because its goal is to study disease, not create a baby or replacement organs."

The Stanford researcher said Americans are pitifully unaware of scientific issues.

"I have asked reporters to draw an embryo, which consists of a few cells, and almost invariably they draw a fully formed fetus." He has tried to educate legislators and journalists about the issues, but they are only able, he says, to "cope with sound bites" that are not long enough to explain complex subjects.

Although removing cells from embryos not used for IVF is regarded by Judaism and Islam as perfectly kosher and ethical if it is done to help treat disease, the Catholic Church, evangelical Protestants, anti-abortion groups and women's rights organizations call it murder.

WEISSMAN ADDS that last year he was invited by the Vatican to present his views on stem cells along with other researches.

"The Pope, who has Parkinson's disease, could himself possibly benefit from embryonic stem cell treatment," he stated. But the church did not take the research seriously, he continued. A press release was issued after the visit to say the Vatican opposes such scientific work.

Stem cells appear during the first few days of pregnancy, providing the raw materials to form the human body. Scientists like Weissman hope to coax stem cells into forming replacement organs and tissues to treat a large variety of chronic diseases, from diabetes and multiple sclerosis to Alzheimer's, Parkinson's and heart disease.

The Bush Administration cut federal funding for embryonic stem cell research conducted on any cells beyond a limited number of existing stem cell lines. Private money could be used to finance the research, he explains, but private interests, like pharmaceutical companies, will tell researchers what to do - things aimed at making profit and not necessarily at making discoveries.

Weissman and his colleagues believe nuclear transfer could provide an unlimited source of genetically identical stem cells. This method usually involves the replacement of the nucleus in a human ovum with genetic material from an adult cell, then giving it a jolt of electricity to start the cells replicating as stem cells. Stanford wants its researchers to harvest these cells and use them for research, without ever implanting them in a uterus. This has the potential to cure a slew of diseases, said Weissman, who stresses that this cannot be termed "cloning." It creates only human cells for repairing damaged organs or creating new ones.

Copyright © 2004, The Jerusalem Post