Harvard teams want OK to clone Human — cell work would be first in nation

Boston GlobeOctober 2004

Two separate teams of Harvard scientists are preparing to produce cloned embryos for disease research, and one has officially applied for permission from the university’s ethical review board.

If granted permission, the Harvard scientists could be the first to clone human cells in the United States. Worldwide, only one team of scientists in South Korea has successfully grown cloned human cells.

The cloning experiments proposed at Harvard represent the next step in the evolution of embryonic stem-cell research, a controversial field that has emerged as an issue in the US presidential campaign. The two teams want to use cloning to produce embryonic stem cells that precisely match the genetic material of patients with juvenile diabetes, Parkinson’s disease, and a range of other maladies.

Researchers believe that comparing the development of these cloned cells with healthy cells will give them a powerful new tool to study disease and possibly suggest new avenues for treatment.

Both teams are part of the recently formed Harvard Stem Cell Institute, set up by the university earlier this year to fund embryonic and other types of stem-cell research.

“This is exactly the kind of work that we envisioned for the Harvard Stem Cell Institute,” said Harvard biologist Douglas Melton, the senior researcher on one of the teams. “We want new ways to study and hopefully cure diseases.”

Cloning is legal in the United States, but the experiments cannot proceed without first passing through an institutional review process, which could take months or longer to complete, according to Melton. The other team is based at Children’s Hospital and has not yet applied for the hospital’s permission.

The proposals will probably add to the national debate around research using stem cells taken from embryos.

The tiny cells, grown in only a handful of laboratories, have already proved a divisive point between President Bush, who believes that life begins at conception and that harvesting stem cells from embryos can be seen as taking a human life, and Senator John Kerry, who does not agree that embryos constitute lives and believes that the potential for cures outweighs the cost.

Even the death this week of actor Christopher Reeve, who lobbied for more stem-cell research to treat spinal cord injuries, has become a part of the debate.

None of the proposed experiments involves “reproductive cloning” or attempts to produce a cloned person. Such experiments are illegal in many countries, though not in the United States, and would be considered both irresponsible and scientifically worthless by most disease researchers.

However, even cloning strictly for research raises more ethical questions than the embryonic stem-cell research currently conducted in the United States. To gather embryonic stem cells, scientist must pull apart an embryo that is several days old, a step that critics have argued is equivalent to taking a life.

Typically scientists have used frozen embryos, left over from fertility treatments, that would otherwise be discarded.

For cloning, however, scientists insert the nuclear material from a donated cell into an egg, producing an embryo from which they gather the embryonic stem cells.

“This crosses the line of creating life in the laboratory solely to destroy it,” said Richard Doerflinger, deputy director of the Secretariat for Pro-Life Activities at the US Conference of Catholic Bishops. “This is the ultimate reduction of human life as an object for others to use.”

The Harvard scientists, however, say that animal experiments show that most embryos produced this way are not capable of forming a life and that the work could open important new scientific vistas.

The team at Children’s Hospital, which includes Dr. George Q. Daley and Dr. Leonard Zon, is particularly interested in studying diseases of the blood, such as sickle cell anemia and immune deficiencies.

For example, researchers might be able to clone a cell from a sick child and then produce a line of embryonic stem cells that are genetically identical to the child. The genetic problem that causes the disease could be corrected, and the cells could be directed to grow into blood cells, providing a replacement for the patient’s faulty cells.

All of these steps have been shown to work in mice, in an experiment Daley’s team performed.

“This is a fresh approach,” Daley said. “But obviously there are many steps between where we are and clinical applications.”

In scientific circles, cloning is called nuclear transfer. The nucleus of a donor cell, which contains its genetic material, is transferred into an egg cell that has had its own nucleus removed. Researchers then prompt the egg to grow for several days, until it forms a ball called a blastocyst, typically a few hundred cells. From this blastocyst, scientists can then extract embryonic stem cells, which have the ability to become any cell in the body.

To date, only a team in South Korea has successfully performed nuclear transfer with human cells. In the United Kingdom, one team of scientists has been granted permission to conduct the experiments, and another has applied for permission.

At Children’s, Zon and Daley said they are interested in doing nuclear transfer experiments, but have not yet worked out all the issues they need to in order to apply for permission, Zon said.

Melton and Harvard biologist Kevin Eggan have formally applied to the stem-cell research committee at Harvard for permission to do nuclear transfer work. The team is specifically interested in juvenile diabetes and neurodegenerative diseases such as Parkinson’s, Melton said.

Harvard provost Dr. Steven E. Hyman said the university is considering all of the ethical and other issues that such experiments raise.

“We are being extremely careful about this,” Hyman said.

Hyman said that he did not know when the university would reach a decision on the Melton experiments and that he could not speak for the situation at Children’s Hospital.

Though based at Children’s, Zon and Daley both hold faculty appointments at Harvard Medical School, and both are members of the Harvard Stem Cell Institute.

No federal funds would be used in the work, according to the scientists. Under federal policy, laid out by President Bush on August 9, 2001, the government will not fund research that produces new lines of human embryonic stem cells, because this involves the destruction of human embryos.

Melton, who is the codirector of the Harvard Stem Cell Institute, said he was generally reluctant to discuss publicly experiments that he has yet to perform, but described his plans because of the public interest in the issue.

“This is cutting-edge research,” Melton said. “Nobody can know if it will be successful, but my intuition is that it will be important.”