Stem Cell Debate Focuses on Morality and Money

Times Staff Writer

The iridescent ball sits motionless under the microscope, a bundle of tight-packed cells lying on a bed of gray, spindly fibers.

The ball contracts tightly. It releases. Then it contracts and releases again, all in the span of several seconds.

For the record:

12:00 a.m. Oct. 18, 2004 For The Record
Los Angeles Times Monday October 18, 2004 Home Edition Main News Part A Page 2 National Desk 2 inches; 68 words Type of Material: Correction
Stem-cell debate -- The word “embryo” was omitted from a sentence in an article in Sunday’s Section A about California’s Proposition 71, which would commit state money to research using stem cells. The sentence should have read: “The pulsating mass is filled with bona fide heart cells, created from cells of an embryo in a dish of orange-pink Kool-Aid-colored broth in an incubator at a Stanford University laboratory.”

The pulsating mass is filled with bone fide heart cells, created from cells of an in a dish of orange-pink Kool-Aid-colored broth in an incubator at a Stanford University laboratory.They came from stem cells and, if chance had treated them differently, they could have become skin cells, lung cells, pieces of brain or spleen -- any body tissue at all.


Embryonic stem cells -- the promise they hold and the ethical dilemmas they raise -- have become a high-profile topic in this campaign year, nowhere more than in California.

In a little more than two weeks, Californians will vote on Proposition 71, which would commit $3 billion in state money over the next 10 years to research using stem cells, most of them extracted from 5-day-old 150-celled human embryos.

Such research divides Americans in part because of an inescapable ethical issue: In time, the research may cure terrible maladies, but to get to that point, scientists must destroy human embryos.

President Bush, who has sharply limited the use of federal money to finance stem cell research, voiced one side of that argument during his second debate with his Democratic challenger, Sen. John F. Kerry: “Embryonic stem cell research requires the destruction of life.”

Kerry, in return, stated the opposing view: “I think it is respecting life to reach for that cure.”

Beyond that moral debate lies a pragmatic one. Is research into embryonic stem cells promising enough to justify $3 billion in taxpayer money? Just how advanced is the research? What are the risks? Can cures be found without using embryo cells?


Potential Effects

A taste of the potential can be seen at Hans Keirstead’s laboratory at UC Irvine’s Reeve-Irvine Research Center.

One day last month, Keirstead, an assistant professor of anatomy and neurobiology, showed a visiting reporter a movie.

On the screen, a rat with a splotch on its back staggered, its hind legs and tail dragging pathetically on the ground.

Then a second rat appeared on the screen, and this one looked a whole lot better: It was supporting its weight on its back legs, its tail smartly up and its hind feet alternating -- albeit clumsily -- left with right.

Both rats had spinal cord injuries. But rat No. 2 had received an injection of human embryonic stem cells that had first been coaxed to become oligodendrocytes, cells that wrap around nerve fibers, insulating them. Such insulation -- which many nerves lose when the spinal cord is damaged -- permits the transmission of electric signals.

Keirstead knows that nerves in the spinal cords of rats in his study are indeed being rewrapped by the treatment. He believes, but cannot yet prove, that this is the reason the animals improved.

“It’s tremendous,” he said. “It’s wonderful to run a lab where everybody comes into work smiling.... The animals are getting better, and you can see it.”

The hope is clear: If it can be proved that stem cell injections are helping relieve paralysis in rats, perhaps they could help wheelchair-bound humans.

Indeed, Geron Corp., a biopharmaceutical company based in Menlo Park, plans to seek permission next year from the Food and Drug Administration to conduct small trials in patients with spinal cord injuries. It would be the first clinical test of any embryonic stem cell therapy in humans.

But researchers caution against getting too excited. Keirstead’s work is preliminary. A rat is not a human being. And biology has offered seemingly bright hope before.

Gene therapy was touted in the 1980s as a fix for myriad ills. Two decades later, it has successfully treated one lethal immune disease in a few children, two of whom developed leukemia as a side effect.

As did genetic engineering, stem cell science may have profound effects on biological and medical research long before anyone is cured of diabetes or fitted with a lab-grown kidney.

Fred Gage, professor of genetics at the Salk Institute for Biological Studies in La Jolla, sees a time soon when scientists will use stem cells to understand diseases and screen for new drugs with an efficiency they’ve never enjoyed before.

“This is the next great transition in biology,” Gage said.

Researchers tentatively predict that stem cell therapies are most likely for such ailments as Parkinson’s disease that involve only one type of cell that merely would have to survive to confer a benefit. (In Parkinson’s, the disease destroys cells that normally secrete the brain chemical dopamine.)

Disorders such as Alzheimer’s disease, in which much brain death occurs and cells would have to perform the more complicated task of correctly linking up with other nerves, are far more challenging.

Scientists also warn that there is much still to be learned about the long-term risk of giving people tissues derived from stem cells.

How long would engrafted cells survive? Might some become cancerous? Could cells injected into spinal cords or brains connect inappropriately, causing troubles of their own?

With all those questions, the prospect of cures remains alluring but probably distant. Indeed, some researchers fear that political pressure, the desire for profit and the desperation of patients will push therapies to the clinic too soon -- with bad outcomes, even some deaths.

If that happens, “given the controversial nature of this field, that’s going to make for some very hard times,” said James Thomson, a professor of anatomy at the University of Wisconsin at Madison, the first to extract human embryonic stem cells.

A more optimistic view comes from a prominent advocate of embryonic stem cell research, Dr. Irving Weissman, director of the Institute for Cancer/Stem Cell Biology and Medicine at Stanford.

“Nobody should go into this thinking that tomorrow, three years from now or five years from now we should have cures,” he says, “but nobody should think that 20 years from now we won’t have many.”


A New Science

Many of the uncertainties exist because the field of embryonic stem cells is so new.

The science is rooted in a fascinating biological problem: How does a complicated body with many different tissues arise from a single fertilized egg?

The key lies with each cell’s experience during the growth of embryo and fetus. Where a cell resides in the developing body determines the chemical signals to which it is exposed. That, in turn, dictates which genes are turned on or off -- and whether a cell will end up as a fat, brush-fringed absorber of food in the gut or as a delicate, branched fiber sending electrical signals in the brain.

Early in the development of the embryo, when none or few of those decisions have been made, cells retain the ability to develop into any tissue.

At that point, days after fertilization, the embryo is a hollow ball called a blastocyst, with a small blob of cells jutting into the fluid-filled center.

In 1981, scientists using embryos from mice extracted cells from the blob and successfully grew them in a state of quasi-suspended animation: The cells would divide indefinitely without “deciding” what type of cell to be.

Researchers then found that if they changed the chemical broth in which the cells were grown, the cells would shed their indecision and turn into a jumbled-up mixture of tissues.

Not until 1998 was a similar feat achieved with human embryo cells, by Thomson’s team at the University of Wisconsin.

Researchers were quick to see the medical possibilities. If they could learn some basic biochemical rules, they could ply the cells with the right signals and turn them into just the type a patient needed.

But just as quickly, the discovery created a policy dilemma for the federal government, which funds most biological research in the nation.

The embryos used in research almost always come from fertility clinics. When couples who have trouble conceiving a child seek in vitro fertilization, fertility doctors often produce more embryos than they implant in the woman’s womb. The excess embryos are frozen in case the pregnancy fails and the couple wish to try again. As a result, an estimated 100,000 or more embryos now sit, frozen in liquid nitrogen, destined in most cases to be discarded.

Supporters of stem cell research argue that no harm is done by thawing some of those embryos and using them for research. Opponents disagree.

In 2001, Bush resolved the issue by saying federal money could be used only for research using embryonic stem cell lines already in existence. A stem cell line is a colony of living stem cells maintained in a lab culture. Not a single test tube funded with federal dollars can be used on any experiment involving cells taken from embryos after Aug. 9 of that year.

At the time, the administration estimated that 78 allowable cell lines existed around the world. Today the number of available and useful lines is 22; some were not usable, some were duplicates, some were not living and others, because of licensing or exporting restrictions, were not accessible.

Those cell lines have proven valuable. They were used to make the nerve-wrapping cells used in Keirstead’s rat experiments, for instance.

But many scientists say the restrictions are, or soon will be, a roadblock.

Some of the lines are hard to grow, and all of them were created when embryo cells had to be grown with mouse skin cells to keep them alive and dividing. Some researchers, although not all, think that possible contamination from animal viruses may limit the cells’ value.

Perhaps most important, the cell lines come from a small number of embryos and thus do not represent anything close to the genetic variability in people.

Some young researchers say the restrictions make them worry about pursuing human embryonic stem cell work.

“Right now it’s not inhibiting my work, but I can for sure see where it will if the policy stays the same,” said Scott Dylla, a postdoctoral researcher in Weissman’s lab.


State Funding Mulled

Faced with the federal restrictions, California advocates for embryonic stem cell research began to contemplate whether the state could take over the federal government’s traditional role as the funder of basic biological research.

Doing so, they argued, would hasten the possibility of cures and also potentially base a new advanced industry in California.

The idea found a financial backer in Bob Klein, a wealthy developer of affordable housing. Klein’s 84-year-old mother has Alzheimer’s disease, and his teenage son is diabetic. His son’s diagnosis two years ago drove Klein to search for a cure, leading him to believe that embryonic stem cell research offered the most hope.

Klein spent $1.4 million of his own money to get Proposition 71 before the voters. He has given an additional $750,000 since it qualified for the Nov. 2 ballot. Other wealthy donors, including several friends of Klein’s, have boosted the total to more than $20 million so far. Recent polls have shown the measure headed for approval.

Klein, who has a background in public financing, said he quickly realized that state bonds could provide the needed resources far more effectively than private money. After speaking to top scientists, Klein said, he determined that $3 billion would be needed to finance both new facilities and grants.

Weissman, among the scientists who consulted with Klein, said the figure “made my jaw drop.”

The large sum also has become a central argument for opponents of the proposition, who argue that even if research using embryonic cells is ethically justified, the state should not lock itself into spending billions on a prospect that remains uncertain.


‘Therapeutic Cloning’

Among the most controversial parts of the initiative is a provision specifically providing funds for a procedure sometimes called “therapeutic cloning.”

Cloning is the process by which genetic material from a nonreproductive cell is inserted into an egg. The egg is then tricked to start developing as an embryo, which will have the same genetic makeup as the person whose cell provided the DNA.

Stem cell scientists, who prefer to use the term “nuclear transfer” to describe the procedure, say they are opposed to cloning to produce babies. Instead, they want to use the technology to create embryonic stem cell lines with carefully chosen genetic makeups.

This might help them create tailor-made tissues for patients. It would also allow scientists to create an array of stem cell lines from people with such diseases as schizophrenia, sickle cell anemia and Alzheimer’s. The cells could be studied to see what is wrong with them, thus helping to illuminate the underlying chemical problem.

Another point of contention is a claim that the benefits of stem cells could be realized by using cells from adults. In California, some churches opposed to Proposition 71 have distributed material to congregants saying that adult stem cells are as promising for researchers as embryonic ones.

Scientists know that some adult organs (brain, blood and skin, for instance) have stem cells. Unlike embryonic stem cells, these cells will not grow indefinitely and are usually limited in what kinds of tissues they can become. Moreover, scientists do not yet know if every organ in the body has a stem cell.

Adult stem cells have been used successfully for many years in some types of therapy: cells from bone marrow, for example, have been used to rebuild blood in patients.

Some researchers hope that adult stem cells can be used more broadly. A few years ago, several groups reported that the cells, when treated the right way, seemed to develop a new flexibility -- a blood stem cell, for instance, could be coaxed to become a heart muscle cell.

These claims have come under serious question. Scientists trying to repeat the work have reported that the cells did not change their fate at all. Instead, a blood stem cell would fuse with an existing heart cell, giving the semblance of change.

“A lot of that literature ... has just turned out to be wrong,” said Dr. Leonard Zon, professor of pediatrics at Children’s Hospital Boston and Harvard Medical School and president of the International Society for Stem Cell Research.

Other researchers continue to hope that somewhere in the adult body resides a cell that has the potential to turn into many different tissues, the way an embryonic stem cell can.

Dr. Catherine Verfaillie, director of the Stem Cell Institute at the University of Minnesota, thinks she may have found it: a rare cell in the bone marrow that is devilishly difficult to grow and that in her group’s hands can make bone, fat, muscle, blood, liver, lung, gut and brain-like cells.

Her work, too, is proving hard for others to replicate, although she is training scientists in her lab in how to grow these difficult cells. Their medical potential, she said, is unknown.

Amid federal restrictions, threats of cloning bans and the hope of a massive infusion of money, stem cell scientists are continuing to explore both embryonic and adult stem cells, expanding the list of cell types they can make and testing those cells for their curative potential in animals. They are not sure where their experiments will lead them or how the political winds will work to slow or hasten their endeavor.

“We have a lot more research to do until we know what stem cells can do and what they can’t do,” said Nobel Prize winner David Baltimore, president of Caltech. “We need to get on with this work.”


Times staff writer Megan Garvey contributed to this report.