Stem cell strides may help resolve ethical dilemmas

New methods preserve viable embryos, but some opponents skeptical of tactics New processes don't kill viable embryos -- opponents say moral issue s
- Carl T. Hall, Cornelia Stolze, Chronicle Staff Writers
Monday, October 17, 2005

Scientists are reporting two new ways of creating embryonic stem cells without killing viable embryos, potentially reshaping the biggest bioethical debate of the Bush administration.

In one case, embryonic stem cells were made from a genetically abnormal embryo designed to be incapable of developing. The other method was an attempt to fashion stem cells from an embryo without damaging it.

The new methods, detailed in separate research reports released online Sunday by the British journal Nature, are intended as laboratory answers to the moral questions raised by the destruction of human embryos. If the strategies work, one result could be the availability of more federal grants for one of the most promising fields of biomedical research.

A White House spokesman said it was premature to speculate on any potential change in administration policy. But William Hurlbut of Stanford University, a member of a White House bioethics advisory council, called it "a starting point for an important new dialogue" on possible "technological solutions for the moral problems surrounding human embryonic stem cell research."

The new techniques raise their own questions about just what sorts of laboratory creations deserve human status. The latest research is "right there on that boundary between what I would consider ethically permissible and potentially ethically troubling," said biochemist Fazale Rana at Reasons to Believe, a Christian group in Southern California opposed to human embryonic stem cell research.

Much of the debate centers on the precise definition of "embryo," because it is considered by some people to have the same moral status as a human being. In one of the new sets of experiments, researchers crafted stem cell lines from lab creations characterized as "nonviable" entities.

Others dismissed such arguments as semantic quibbling.

"This is an attempt to solve an ethical issue through a scientific redefinition that really doesn't solve the issue," said Jaydee Hanson, director of human genetics at the International Center for Technology Assessment, a Washington, D.C., nonprofit organization that opposes some kinds of cloning and stem cell research on moral grounds.

In August 2001, President Bush made the production of any new stem cell lines ineligible for federal grants because such work involves the destruction of human embryos. Bush also objects to cloning embryos, which scientists advocate as a way of creating specialized stem cell lines carrying disease genes or the DNA of an individual patient.

Those restrictions helped inspire California's $3 billion Proposition 71 initiative, which state voters approved in the 2004 general election specifically to pursue research banned from receiving federal support.

On Sunday, stem cell researchers Rudolf Jaenisch and Alexander Meissner of the Whitehead Institute at the Massachusetts Institute of Technology showed how embryonic stem cells -- the flexible early-stage cells that can mature into all the cell types of the body -- can be produced from a type of research cloning known as "alternate nuclear transfer."

The researchers devised a way to block the activity of a gene from an adult cell that would have allowed the cell to develop into an embryo once in the uterus. With that activity blocked, the cell is nonviable because it lacks the ability to "establish the fetal-maternal connection" in the uterus. This abnormal DNA then was inserted into the nucleus of an egg whose own DNA had been removed.

The idea was to create something akin to a cloned embryo but that would be inherently incapable of developing beyond the pre-implantation stage. But the researchers showed they could still generate a specialized stem cell line, which would have the same DNA as that of the adult cell used to produce the cloned embryo. Thus, it could be considered a strategy to make "patient-specific" embryonic stem cells without destroying any potential life.

A separate team of researchers led by Robert Lanza and Young Ching of Advanced Cell Technology, a Massachusetts biotech company, used yet another method to obtain stem cells.

Experimenters used a single cell, known as a "blastomere," snipped from a developing embryo at the eight-cell stage. This is sometimes done as a type of biopsy in fertility clinics when would-be parents are concerned about implanting an embryo carrying a genetic disorder. Known as "pre-implantation genetic diagnosis," the goal is to screen out disease-carrying embryos. Previous clinical evidence suggests that removing one or sometimes even two cells for diagnosis leaves a viable embryo.

The latest study showed that a cell removed for diagnosis can be coaxed into replicating itself overnight. The copy then can be used to generate a line of stem cells, the researchers reported, while allowing the original cell to be subjected as usual to pre-implantation analysis.

The new approaches so far have only been tried in laboratory mice, and there's no guarantee similar results can be obtained in humans. They were described as proof of principle for ideas long championed by those opposed to embryo destruction.

He insisted that an entity such as that produced in the MIT experiments has "no inherent principle of unity, no coherent drive in the direction of the mature human form."

But the new methods do not assuage all ethical concerns.

"The tinkering doesn't change the essential nature of the cloned entity," said Hanson, of the International Center for Technology Assessment. "The only reason it's not an embryo is definitional."

Douglas Melton, a renowned stem cell scientist at Harvard University, said he doubted critics of stem cell research will be placated by the alteration of a single gene. An altered embryo, he said, may still be considered an embryo.

As for using a biopsied cell, several studies in mice, rabbits, sheep, swine and primates have shown that single cells transplanted into the uterus of the respective species are capable of propagating viable offspring. Thus, even if removing a single cell doesn't interfere with the developmental potential of the embryo, the isolated cell itself could be considered capable of embryo status.

Jaenisch said this human potential argument shows how "absurd" the theoretical discussions can get in stem cell biology.

"If one used this argument to protect cells developed through nuclear transfer because with further manipulation they might become a living clone, then every cell of our body would deserve the chance to become a human being," he said. "In not cloning them, each of us would be barring millions of individuals from getting a chance to live."

Despite all the arguments, Jaenisch said it's still conceivable that special cloning or other techniques might be an acceptable compromise to allow expanding the federal role in stem cell research.

If so, he said, "We would have made a big step forward."

So far it is not clear if stem cells created by either of the new methods would qualify for federal grants, according to James Battey, head of a stem cell task force at the National Institutes of Health.

Bernard Lo, a prominent bioethics expert at UCSF who also advises the California Prop. 71 program, called on those who object to stem cell research to make their views on the alternative derivation methods clear at the outset.

"This work is really driven by a desire on the part of scientists to address the moral concerns some people have. So those people should say now if it doesn't settle the problem," to avoid a lot of wasted effort, he said.

E-mail the writers at chall@sfchronicle.com and cstolze@sfchronicle.com.