CAMBRIDGE -- A top Harvard University official has approved the cloning of human cells to make embryonic stem cells, bringing scientists here closer to launching an audacious -- and controversial -- effort to battle juvenile diabetes, Parkinson's disease, and other maladies in powerful new ways.
The Harvard project, which Governor Mitt Romney and others have attacked on ethical grounds, cannot proceed until a university committee finalizes a protocol for protecting the volunteers who will provide cells. But Dr. Steven E. Hyman, Harvard provost, said that after more than a year of review, the university has concluded that the work is ethically sound and scientifically important.
''This research holds the promise of important benefits for the understanding and treatment of serious human diseases," Hyman said. ''I want to see the science progress within acceptable ethical boundaries."
The project comes at a crucial time, when the Massachusetts government is considering new stem-cell legislation and some, including Romney, are seeking to outlaw the very research Harvard plans to do. If Romney fails and the Harvard team, led by Kevin Eggan and Douglas Melton, begins the experiments, it will be the only active group at an American university, and one of only a handful in the world. The approval, which was quietly given in January, also puts the Harvard name solidly behind the cloning of human cells, which will probably encourage other US scientists to follow their lead -- and sharpen the national debate.
This is not the first time that Melton, who has been spearheading a remarkable challenge to President Bush's stem-cell policy, has found himself in the spotlight.
On Aug. 9, 2001, the president declared that scientists could only use federal funds to work on human embryonic stem cells that had already been created. But last year, Harvard announced that it was forming an ambitious new stem-cell research institute using millions in private money, with Melton as co-director, and that the institute would do the work the president objected to. That institute has now raised $26 million, according to a Harvard official.
Last year Melton also announced that he had used private money to create 17 new batches of human embryonic stem cells and would offer them for free to researchers. That number has since grown to 28 batches, more than the entire list of cells available to researchers under the current Bush policy.
For the new work, Eggan and Melton were asked to submit their plans to a Stem Cell Research Committee, set up by the university to review all work with human embryonic stem cells. It was the job of this committee to review all the broader ethical and scientific issues and advise the provost, according to Richard Losick, who chairs the committee and is a professor of biology at Harvard.
In November of 2003, Eggan and Melton submitted their proposal to the the committee, which is made up of ethicists, scientists, and public policy experts from the Harvard community. Melton also said he had at least two lengthy conversations with Harvard President Lawrence H. Summers about the proposed work.
Then, in a detailed three-page letter dated Jan. 11, 2005, Hyman informed the scientists that Harvard supported the work, provided the human subjects committee approved.
The letter laid out a set of specific restrictions on the work, according to Hyman. For example, the scientists may only use embryos in their first days of development, and they may not place the embryos into a human -- a move that would cross the line into reproductive cloning.
The scientists are also prohibited from paying women who donate eggs for anything more than their expenses, Hyman said, a restriction that will ensure that women will not choose to participate for financial reasons.
The permission extends until January 2006, and the scientists must apply for annual renewals after that, Hyman said. The letter also states that Harvard considered the passionate objections to the work.
''The university acknowledges that a blastocyst holds a special moral status for many," said Hyman, reading from the letter. ''Therefore we should accord it appropriate respect by ensuring that it is only used for [important] research."
Before the research can begin, the team will need the approval of the Standing Committee on the Use of Human Subjects in Research. This committee is charged with ensuring that the volunteers understand the risks of participating, and that every effort is made to protect them. The greatest risk, scientists said, will be for the women who volunteer to donate eggs, though those risks are small.
To collect eggs from the ovaries, women are given a general anesthetic and then a tube is threaded into the vagina. A tiny needle is used to pierce through the back of the vaginal wall, guided by ultrasound, and the eggs are collected.
These women will face the chances of complications that come with any surgical procedure, mainly infection, internal bleeding, or a reaction to the anesthetic. Another risk is a condition known as ovarian hyperstimulation syndrome, a potentially serious reaction to the drugs used to encourage the production of eggs.
At Boston IVF, a fertility clinic where the egg donation work will be done, doctors do about 3,000 cycles of in vitro fertilization per year, and about 200 of those are women who are donating their eggs to others, according to Dr. Michael Alper, the medical director. Alper said that in 20 years of practice, he could not remember a case of a woman suffering from infection or internal bleeding because of an egg retrieval surgery.
In the past, Alper said, Boston IVF experienced about 10 hospital admissions per year for hyperstimulation syndrome, though typically just for observation, as a precaution.
Two years ago, though, the clinic started using an outpatient procedure to drain fluids from the abdominal cavity, and this seems to reverse the condition quickly. Since they started doing this, they have had no hospital admissions for hyperstimulation syndrome, he said.
The Harvard scientists will be studying Parkinson's disease and juvenile diabetes, but they are interested in using the technique to study other diseases as well.
The Harvard research will probably cost millions of dollars, to be paid for by the Harvard Stem Cell Institute, the Howard Hughes Medical Institute, the Russell Berrie Foundation, and possibly others, according to Charles Jennings, executive director of the stem-cell institute. The fund-raising, he said, has not been finished.