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Harvard launches effort to clone human stem cells

A troubled field gets a big boost

Harvard scientists announced yesterday that they are beginning an ambitious attempt to create the world's first cloned human embryonic stem cells, bringing the university into one of science's most ethically charged fields.

The goal of the research, they said, is to create a powerful new tool to explore the biology of, and hopefully find treatments for, a number of devastating diseases: juvenile diabetes, genetic blood disorders, and ALS, also known as Lou Gehrig's disease.

These goals are distant hopes because there is no assurance that cloned human embryonic stem cells can even be made. Although cloning has been used successfully in many animals, each species presents a unique set of technical challenges. Beyond the biological puzzles, there are practical obstacles, such as finding women who are willing to donate the eggs needed for cloning.

The research is controversial because scientists destroy days-old embryos, which some opponents say is essentially taking human lives, and because the research uses human eggs, which can place donors at a slight risk of side effects.

But at a press conference yesterday, Harvard Provost Dr. Steven E. Hyman said the university had concluded that the research was ethically justified, following extensive reviews by eight committees over two years. Hyman said the scientists will be required to follow strict guidelines governing how eggs are obtained and what experiments can be done -- but he said the work is too important to not do.

``We are convinced that work with embryonic stem cells holds enormous promise for developing treatments for a host of presently intractable adult and childhood diseases," Hyman said. ``We have approved this work after the most extensive ethical and scientific review in recent memory here at Harvard."

The announcement represents a high-profile boost for a field marred by scandal. In 2004, Korean scientist Hwang Woo Suk claimed he had created the first cloned human embryonic stem cells, raising the hopes of patients and bringing worldwide attention. By the end of 2005, his claim had collapsed in a dramatic case of scientific fraud, leaving scientists to wonder whether the technically challenging feat is even possible.

But now, in addition to the Harvard project, at least eight other teams in the United States and abroad have said they will attempt to create cloned human stem cells.

The Harvard project is particularly large, with two independent teams of top scientists -- one at Harvard University's main campus in Cambridge, one at Children's Hospital Boston -- each working with its own network of collaborators. The Harvard scientists have laid extensive groundwork, including building laboratory space and getting all the necessary approvals, and one group has already begun its experiments. This places Harvard ahead of several of the other teams.

The project also constitutes a statement from Harvard, an institution that generally shies away from controversy, that it intends to aggressively pursue a course set by outgoing president Lawrence H. Summers. Summers has been a champion of the Harvard Stem Cell Institute, arguing that stem cell technology will prove to be an enduring force in science, medicine, and business -- and that researchers from across the sprawling university should cooperate to make Harvard a world leader in the field. The cachet of the Harvard name will mean that the project will draw close attention, both from advocates and critics of the work.

``Science has to recognize that it has a huge power in our day and age, and that power, if it goes off the rails, will become a very exploitative and dangerous power in our midst," said Rev. Tadeusz Pacholczyk, director of education at the National Catholic Bioethics Center in Philadelphia. ``This is an example of moving directly toward that end."

Embryonic stem cells have the ability to become virtually any cell in the body, making them a valuable tool in scientific research. In the past, embryonic stem cells have been harvested from frozen early embryos -- microscopic balls of several hundred cells -- obtained from fertility clinics that would discard them otherwise. But these stem cells do not have the DNA that contributes to certain diseases, such as juvenile diabetes, which limits their usefulness in researching those diseases.

Cloning, also called somatic cell nuclear transfer, would allow new types of experiments by creating embryonic stem cells that have the same DNA as a patient with a particular disease.

To do this, the Harvard scientists will extract DNA from a patient's cells and place it into a donated egg cell that has had its own DNA removed. This new egg cell is then prompted to grow for several days in a laboratory dish, yielding the early embryo needed for embryonic stem cells.

These cloned stem cells can then be grown in the lab and in theory be manipulated to become different types of human tissue, such as the neurons that make up the brain. Scientists know how to coax embryonic stem cells to become neurons and only a few other types of cells.

The embryos will be used to create cells only, not cloned babies -- a step that would be biologically challenging to take, and that virtually all scientists oppose. Using nuclear transfer for reproduction is a crime under a Massachusetts law passed last year. The same law makes it legal to do nuclear transfer for research.

Most of the opposition to stem cell cloning in this country has come from political conservatives who object to the destruction of human embryos. But nuclear transfer has also generated some criticism from liberal, abortion rights supporters, who say donors should not be subjected to the risks involved in egg extraction for research.

``The merit isn't such that these women should be asked to undergo these risks," said Judy Norsigian, executive director of Our Bodies Ourselves. Norsigian supports other forms of embryonic stem cell research.

Egg extraction is commonly used in the fertility business. The process can have side effects, including ovarian hyperstimulation syndrome, a dangerous condition that is serious in about 1 percent of women getting fertility treatment.

One of the Harvard teams, led by Douglas Melton and Kevin Eggan, will recruit volunteers to undergo egg extraction. The other team, led by Dr. George Q. Daley of Children's Hospital Boston, has already begun the work using eggs that failed to fertilize when combined with sperm during fertility treatment; these eggs would otherwise be discarded. Scientists suspect that these eggs will prove more difficult to spur into developing into an embryo. But their potential is unknown, and they are a natural byproduct of fertility treatment, so scientists can get them without subjecting women to any risk.

Finding egg donors could prove to be a serious obstacle. In Massachusetts women can be paid to donate eggs used for fertility treatment, but for research, women can only be reimbursed for expenses.

Dr. Robert Lanza said that Advanced Cell Technology, where he is vice president for research, has been trying unsuccessfully to recruit women to do nuclear transfer since December. Lanza said that about 100 woman have responded to ads but that they were dissuaded by the potential risks -- and the fact that they could earn thousands of dollars to do the same thing as an egg donor for fertility treatment.

``After six months of exhaustive effort, it seems like this is going to be problematic without some form of compensation," said Lanza.

Harvard's Eggan said he hopes that egg donors will be found among the relatives of those with the diseases the team will study.

The work is also complicated because it cannot be supported with federal money. In 2001, President Bush prohibited the government from funding any research that would create new batches of embryonic stem cells, though scientists can use federal money to work with embryonic stem cells created before the policy.

All of the Harvard research is being funded by private sources, which include the Harvard Stem Cell Institute, the Stowers Medical Institute, a Missouri-based research organization, and private donors contacted by Harvard University and Children's Hospital. Melton predicted the work could cost millions of dollars, but Harvard officials declined to say how much had been raised so far.

Both Harvard teams hope to find cures for diseases, using the tools of developmental biology, the study of how organisms grow and develop.

Nuclear transfer would give them new ways to explore how the process of development goes awry in certain diseases, and perhaps suggest treatments that make use of the natural developmental potential of human cells.

The team led by Melton and Eggan will initially focus on juvenile diabetes, but it also hopes to study neurodegenerative diseases such as Parkinson's and ALS.

For example, they hope to make batches of embryonic stem cells that have the DNA of patients with ALS. Researchers would coax the stem cells to grow into neurons, and compare the development of neurons made with the diseased stem cells to neurons made with embryonic stem cells produced with the DNA of a person without the disease.

``In essence, we can move the study of the disease from a patient to a Petri dish," said Melton, who is co-director of the Harvard Stem Cell Institute.

Melton and Eggan will be working with Boston IVF, a fertility clinic that will extract eggs from donors, the Naomie Berrie Diabetes Center at Columbia University Medical Center, and the New York Stem Cell Foundation, a privately funded laboratory.

The team led by Daley wants to find treatments for blood-based diseases such as leukemia and sickle cell anemia, which is caused by a genetic flaw.

Using nuclear transfer, Daley said, the team would hope to create embryonic stem cells that are genetically matched to a patient. These embryonic stem cells would then be grown into precursors of blood cells, like those normally found in bone marrow, providing the patient with a bone marrow transplant with a minimal risk of rejection.

In cases of genetic diseases like sickle cell anemia, the same procedure could be used, with an extra step to fix the genetic flaw in the patient's cells before growing the bone marrow cells for transplant.

But, he said, ``the research is very much in its infancy, and clinical applications may be a decade or even more in the future."

Daley, who is an associate professor at Harvard Medical School, will use eggs donated by patients in the Brigham and Women's Hospital Center for Reproductive Medicine. The work passed an ethical review at both Children's Hospital and Partners Health Care, which the Brigham is a part of.

In the United States, a team at the University of California at San Francisco has already begun cloning experiments. Also planning to do the work are a group in New York City and Advanced Cell Technology in Worcester, as well as scientists in the United Kingdom, Spain, Sweden, and China.

Gareth Cook can be reached at cook@globe.com.

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