Where Stem Cells Stand

To politicians and activists, human embryonic stem cell research is a political flashpoint, with the federal government all but banning it and states battling to pick up the slack and fund their own homegrown stem cell research centers.

To scientists, it is a moral touch point whose potential to fight cancer, Alzheimer's and a host of other terrible afflictions is tempered by profound ethical questions.

And to patients, particularly very religious ones, the hope held out by stem cell research often clashes with spiritual beliefs.

But even as the sociocultural storm swirls over stem cells, research forges ahead. California is in the vanguard. And in that effort, UCLA is both a framer of the ethical debate and a primary player in the science.

"We now have a remarkable opportunity in biomedical research to utilize new technologies to come up with ways of treating human disease that we previously couldn't fathom," explains Owen Witte, director of UCLA's newly formed Institute for Stem Cell Biology and Medicine.

California laid the foundation in November 2004, when 59% of voters approved Proposition 71, providing $3 billion in bond funding to create the California Institute for Regenerative Medicine, a new state agency designed to regulate human embryonic stem cell research and provide funding through grants and loans for stem cell science at institutions across the state. That decision put California squarely at the forefront of national stem cell research efforts, but experts in adult human stem cells and in mouse embryonic stem cells have been active in Westwood for years.

At UCLA, bone marrow-derived stem cells have been used to reconstitute cancer patients' blood systems after high levels of chemotherapy or radiation since the 1960s, in the form of bone marrow transplants. More recently, researchers at UCLA have explored the idea that transplanted stem cells derived from the fat taken in liposuction procedures can help treat patients with narrowed, blocked arteries and weakened cardiac muscle.

Last March, the university established the Institute for Stem Cell Biology and Medicine, a campuswide effort bringing together geneticists, engineers, ethicists, chemists, policy experts, pathologists, immunologists, oncologists, hematologists and scientists from other disciplines.

Chancellor Albert Carnesale said at the time that the institute "will enable us to continue fostering such interdisciplinary collaborations and to build upon the existing body of knowledge for the benefit of people worldwide." And he announced that UCLA would provide $20 million over five years to launch the campuswide institute. The money will be used to pay for recruitment of a dozen new faculty positions, salaries and expansion of highly sophisticated laboratory space, infrastructure and supplies - the "critical mass" without which the university could not effectively compete with other centers for research funding.

"Every major advance in science that I'm aware of these days is coming from interdisciplinary work," says Witte, a renowned scientist whose laboratory research laid the groundwork for development of the targeted leukemia therapy Gleevec. "Stem cell research is a unifying science that requires different kinds of people to work together."

Case in point: On Friday, Feb. 3, UCLA will be host to "Stem Cells: Promise and Peril in Regenerative Medicine," a two-day academic conference followed on Sunday, Feb. 5, with a symposium, free and open to the public, in Covel Commons. Campus units involved in the event include the Center for Society and Genetics; the Institute for Stem Cell Biology and Medicine; Anderson School of Management; Mattel Children's Hospital; the College of Letters and Science; the School of Dentistry; the David Geffen School of Medicine; the School of Public Affairs; and the School of Public Health. "We want to be proactive rather than reactive," says Edward R.B. McCabe, chair of the Department of Pediatrics and director of the Center for Society and Genetics.

Grad Student Takes Spotlight

UCLA's high-profile position in stem cell science has not gone unnoticed in Sacramento. Top state politicians chose Westwood to hold a news conference last August to announce bipartisan opposition to a U.S. Senate bill that would place new limits on human embryonic stem cell research. California's Republican governor, Arnold Schwarzenegger, was there. Democratic luminaries included Sen. Dianne Feinstein and Los Angeles Mayor Antonio Villaraigosa '77. But it was a UCLA student who by all accounts stole the show.

Candace Coffee, a 26-year-old graduate student in the School of Public Health, spoke of her struggle with Devic's disease, a rare and potentially fatal autoimmune condition that left her temporarily paralyzed, permanently blind in one eye and dealing with constant pain and nausea from her regimen of 10 daily pills.

A self-described Christian from a conservative community, she did her own research before deciding to go public. "These are embryos that are already designated for destruction," Coffee says. "These are not fetuses; it's a matter of taking 5- to 8-day-old masses of cells that are going to be discarded and using them for something amazing - to take life that's already in existence and keep it there." Coffee believes Devic's could one day benefit from an emerging stem cell technology known as somatic cell nuclear transfer (SCNT).

Stem cells are the source of all we become - unspecialized cells that give rise to lungs, liver, brain, hair, heart - and the source of considerable excitement among scientists. Armed with ever more powerful tools, researchers are exploiting the power of stem cells to reveal vital information about human development. Such study could uncover new avenues for treating numerous conditions, from HIV, cancer and stroke to spinal cord injury and musculoskeletal disease; it could lead to a renewable source of replacement cells and tissue to treat metabolic disorders such as diabetes, or degenerative conditions as rare as Devic's or as common as Parkinson's, MS and heart disease.

To be sure, no discussion of human embryonic stem cell research is complete without acknowledging that there are many, most prominently President Bush, who hold moral and ethical concerns about what they view as a potential loss of human life. Proponents of the research counter that saving and extending human life is precisely the reason for supporting the science. In vitro fertilization clinics typically prepare many cells that are not used for impregnation. The unused or surplus cells are kept frozen as human tissue in case they are needed. When the tissue is no longer needed for pregnancy, proponents argue, it should be available for potentially life-saving stem cell research. But those on the other side of the issue contend that it is morally unacceptable to destroy embryos, a consequence of harvesting stem cells, even to save the lives of others.

State Funding on Hold

The battle over stem cells isn't restricted to Congress; it's being fought in the courts as well. UCLA's fledgling stem cell institute received a three-year, $3.75-million grant from the state to train 16 predoctoral, postdoctoral and clinical research scholars in stem cell science - the largest grant of the first wave of allocations to spring from the 2004 initiative. But that check isn't yet in the mail. Prop. 71 remains the subject of legal challenges filed by anti-tax and anti-abortion groups. Until the legal hurdles are cleared, funding from the state initiative is only theoretical.

"I cannot comment on when the legal challenges might end, but it is clear that if these challenges do not end soon we risk a loss of momentum that will diminish the chances of success for the California Institute for Regenerative Medicine," warns Gerald Levey, vice chancellor, medical sciences and dean of the David Geffen School of Medicine, and a member of the Prop. 71 board.

Supporters of the research also acknowledge that there are many ethical issues that must be carefully considered, a "difficult task that has taken up volumes," says Steven Peckman, an ethics expert and the UCLA institute's associate director for administration and planning. He notes, "There are some people who believe that any stage of human embryonic development, including stored embryos from in vitro fertilization, represent nascent human life and, as such, are inviolable or entitled to the same respect and protection as living people, and therefore should not be destroyed for research purposes." Peckman also explains that SCNT, the process by which human embryonic stem cells are derived, troubles some because the process was used to create Dolly, the cloned sheep: SCNT "could possibly be used to clone human beings through reproductive cloning. Reproductive cloning is against the law in California and many other states."

Those in favor of stem cell research, Peckman concludes, "acknowledge the significance of human embryos and underscore the importance of the ethical obligation to address human suffering. They also highlight the importance of protecting the rights and welfare of donors and possible future recipients of therapies created from stem cell science."

The leadership of the Institute for Stem Cell Biology and Medicine, in fact, is taking great pains to ensure that there is adequate informed consent and a protocol in place when residual tissues that would otherwise be destroyed are donated to create new stem cell lines for research. "We want to make sure that donors are well aware of how this material will be used," says Peckman.

Adult Stem Cells Differ

It is material that hasn't been readily available until now. Past UCLA studies employed adult stem cells. Although researchers at the institute will continue to work with adult cells, the expectation that there will soon be greater access to human embryonic stem cell lines changes the equation. "Most scientists don't believe that the stem cells found in the adult will have the repertoire of developmental capabilities that we see in an embryonic stem cell," says Judith Gasson, director of the Jonsson Cancer Center and one of the institute's co-directors.

Under Prop. 71, priority for grants will be given to stem cell research that meets the state institute's criteria and is unlikely to receive federal funding. That means that in addition to studies with adult stem cells and so-called presidential stem cell lines - the embryonic lines created before April 9, 2001, which have been the only ones available for federally funded investigations - researchers eventually hope to be able to work with previously inaccessible embryonic lines.

UCLA stem cell researchers are quick to caution that the revolutionary new treatments they hope will eventually evolve for diseases such as cancer, HIV and neurological, musculoskeletal and metabolic disorders are likely to be years, or even decades, away. "This is not an easy task and it will take time," says Hanna Mikkola, a former Harvard stem cell scientist who was the first faculty member hired by UCLA's new institute. "But this does open up the possibility for completely new approaches to treating diseases on which we have made very little progress for several decades."

Most of the 20 or so presidential lines are thought to be contaminated by materials that would prevent them from being used clinically and renders them more difficult to analyze. Adult stem cells, which help the body replace tissues that must be renewed continually throughout life, are descended from embryonic stem cells - the "mother" cells that have the ability to develop, or in scientific terms "differentiate," into every cell type in the body. Embryonic stem cells can also make identical copies of themselves, an action known as self-renewal. It is these two capabilities that make scientists so optimistic.

A Window on Health and Disease

Among the many promises of human embryonic stem cell research is that it will open a window into the complex events that occur during human development. Another area of UCLA in which stem cell boundaries are being pushed is the Department of Molecular, Cell, and Developmental Biology, where researchers are using model systems in an attempt to determine the genetic signals needed for cells to go into differentiated states. Finding answers to this fundamental problem could have profound implications on treatment for a disease such as cancer.

"More and more evidence suggests that cancer is a stem cell disease," says Gasson. "Many of our current therapies are not effective because they don't target the cancer stem cells. We need to understand the biology of the cancer stem cell so we can develop the next new wave of molecularly targeted therapies that go after those important cells."

Published Jan 1, 2006 12:00 AM