Harvard University researchers announced an ambitious, privately funded plan yesterday to create human stem cell lines from cloned embryos, an ethically charged endeavor that could yield treatments for diabetes, sickle-cell anemia and other disorders.
The scientists said the stem cell lines, created in part from DNA taken from sick patients, would also enable them to observe how diseases develop at the earliest stages of human life - long before symptoms are evident.
"We hope to move the study from patients to the petri dish," said Dr. Douglas Melton, whose research shifted to Type-1 diabetes several years ago when both of his children were diagnosed with the disease.
Embryonic stem cells are master cells that develop into every tissue type in the human body. Researchers worldwide are hoping to harness them to produce replacement tissues for patients suffering from a variety of afflictions in which tissues die.
The Harvard scientists, joined by researchers at Columbia University in New York, will use private donations to circumvent the Bush administration's ban on the use of federal funds to produce new stem cell lines.
The first step is creating cloned embryos and extracting stem cells from them. A South Korean scientist claimed to have done that almost two years ago, but his work was exposed as a fraud.
Noting that the Korean fiasco will put their work under close scrutiny, the Harvard scientists said they have crafted safeguards to ensure that their results are authentic and that human subjects are treated ethically. The work has been approved by institutional reviews at Harvard, two affiliated hospitals and a fertility clinic. A review panel at Columbia University also approved it.
So far, no other institution has reported producing a stem cell line from cloned embryos, and the Harvard scientists said it could be years before they show results.
"This research is very much in its infancy, and clinical applications could be a decade or more in the future," said Dr. George Daley, associate director of the Boston Children's Hospital stem cell program. Daley was one of several scientists who briefed reporters over a telephone link.
Elsewhere, scientists have begun similar work. Researchers at the University of California San Francisco are studying human eggs in preparation for cloning experiments, a spokeswoman said yesterday.
Also, an institute in the United Kingdom reported success in creating a cloned blastocyst - an early embryo - but not in producing a stem cell line from it.
The Harvard program is not likely to rest well with religious conservatives, who object to embryonic stem cell research in general because it requires the destruction of embryos they regard as human life.
Cloning research is even more contentious because it raises the eerie possibility that embryos could be raised to create an exact replica of a person. But scientists across academia have steadfastly denied they have any intention to do so.
Yesterday, Richard Doerflinger of the U.S. Conference of Catholic Bishops said he also objects to the recruitment of female egg donors for the project. He argued that they could face health risks for experiments that might or might not yield results.
"They could be made sick for what the researchers admit that for many years will simply be a scientific experiment," said Doerflinger, the group's deputy director for pro-life activities. "I have additional ethical objects to creating and destroying embryos."
So far, scientists have derived stem cells from surplus embryos donated by couples treated at in-vitro fertilization clinics. These cells, however, stand a good chance of being rejected if transplanted into unrelated patients.
Many scientists believe that compatible stem cells can be derived from cloned embryos made by joining a patient's own DNA with a donated egg emptied of its genetic contents. In theory, the resulting stem cells would be accepted once they were implanted back into the patient, since they would be a perfect genetic match.
To this end, the Harvard scientists are planning several experiments.
In one, Melton will lead an effort to create stem cell lines that could ultimately be used to treat Type-1 diabetes. Patients at a Columbia University diabetes clinic will donate skin cells, from which scientists will extract the nuclei, he said. The nuclei, containing the patients' genetic material, would be inserted into eggs donated by women at a Boston fertility clinic.
Once the embryos are about eight days old, they will have produced a pocket of stem cells that can be extracted and grown in a dish.
"We hope to create a disease-specific stem cell so we can understand what is the primary cause of this disease with the long-term goal of finding new treatments for it," Melton said.
To treat diabetes, the scientists will have to isolate stem cells that can generate the insulin-producing cells of the pancreas, he said. Scientists will also study how to correct genetic defects so the transplanted cells do not trigger the same disorder.
Melton said he does not know how many women will volunteer to donate eggs.
"Women who are members of families affected or afflicted with particular diseases might step forward," he said. "Or it might be an entirely different group of women who might participate." The donors would be compensated for their time, transportation and medical expenses, but would not be paid enough to profit, he said.
Dr. Kevin Eggan plans to work with Melton on diabetes, as well as focusing on neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Meanwhile, Daley plans to study sickle-cell anemia and various bone marrow disorders.
Ultimately, Daley plans to take skin biopsies from children suffering such disorders and implant their DNA into eggs that didn't fertilize at a Boston in-vitro fertilization clinic.
Dr. John Gearhart, who heads the cell engineering institute at the Johns Hopkins School of Medicine, said one of the chief benefits of the research would be the ability to study the underpinnings of disease.
"You'd have an ALS patient and the whole medical history of that patient, and an embryonic stem cell line from that patient," he said. Scientists, in effect, would be able to study the processes that went awry when the patient was just a collection of cells.
He said Hopkins is not planning to produce cloned embryos anytime soon, and he doesn't expect many additional academic centers to become involved until a few groups have succeeded at some level.
For now, Hopkins plans to generate stem cell lines from regular (rather than cloned) embryos, from which much still needs to be learned, he added. Earlier this year, the Maryland General Assembly enacted legislation providing $15 million for stem cell research, including some that might not qualify for federal money.
"We've still got to demonstrate that we can generate cells that are effective and safe," Gearhart said. "We have a tremendous amount of work to do."