Harvard Teams To Use Cloned Embryos

Harvard stem cell scientists were humbled in 2004 when South Korean scientist Hwang Woo Suk announced that he had created stem cell lines from cloned human embryos.

“Without question, the South Koreans are the world leaders in this research, hands down,” said Cabot Professor of the Natural Sciences Douglas A. Melton at the time.

But with Hwang’s advance came new resolve.

“Harvard scientists are a competitive lot,” Harvard Medical School professor George Q. Daley told The Crimson at the time. “We should be a leader in what could be one of the most revolutionizing fields of medicine.”

Harvard countered Hwang’s Feb. 12, 2004 announcement by unveiling plans for the Harvard Stem Cell Institute (HSCI) two weeks later.

And with last December’s discovery that Hwang had fabricated the results of his research, Harvard has made a final push to regain its place at the forefront of the revolutionary and controversial field.

Yesterday, the University announced that Melton and Daley, now top officials at HSCI, will each lead a team of researchers in an attempt to use a process called Somatic Cell Nuclear Transfer (SCNT) to create disease- and patient-specific stem cell lines from cloned embryos.

The research was approved after more than two years of intensive ethical and scientific review by eight separate boards, said University Provost Steven E. Hyman at a press conference yesterday.

If successful, the research will represent one of the most significant advances in the field. While preliminary SCNT work has been done at the University of California-San Francisco and by Advanced Cell Technology, a private biotechnology company, Daley said at the conference, “no one has published a credible paper reporting the derivation of a [human embryonic stem cell] line by SCNT.”

“We’re setting the bar for the rest of the country and the world,” said Leonard I. Zon, the chair of the HSCI’s Faculty Executive Committee. “We hope the advances in this field can help thousands of patients.”

Melton and Harvard biologist Kevin C. Eggan will lead one team, focusing at first on diabetes research. Daley’s team, which is based at Children’s Hospital, has been conducting preliminary SCNT experiments on malignant blood diseases for the past two months.

CUSTOM-TAILORED CELLS

In SCNT, the nucleus of a fully differentiated cell is inserted into a de-nucleated egg and developed into blastocysts, which can be used to create stem cell lines.

Melton and Eggan will be using skin cells harvested from diabetes patients.

The long-term goals of the research will be both academic and clinical, the researchers said.

By creating stem cell lines using cells from patients with diseases such as diabetes, Alzheimer’s, and sickle-cell anemia, researchers can “move those patients’ diseases into the petri dish” and more effectively study them, said Daley at the conference.

“The fact that these embryonic stem cell lines will carry the genes of that sick person is a remarkable opportunity to study the disease the person is carrying,” Eggan said.

And since patient-specific stem cells allow for precise gene repair and would not be rejected by the patient’s immune system, the research may pave the way for more effective clinical treatments, Daley said, though he added that “clinical applications may be a decade away or more.”

UNDER THE MICROSCOPE

Embryonic stem cell research has been a highly-charged ethical issue, not least due to Hwang, who, in addition to fabricating the results of his research, admitted that he had harvested eggs from two of his subordinates and that he had paid other women for their eggs.

Some speculated that Hwang’s subordinates might have felt pressure to donate their eggs. And payment for egg donations has since been banned by South Korea.

The Harvard researchers acknowledged yesterday that in the wake of the scandal in Korea, the eyes of the entire scientific community would be on their work.

“There is going to be an extra degree of scrutiny,” Daley said. “We’ll be held to an exceedingly high standard.”

Daley said that the HSCI’s network of collaborators, which include the Columbia University Medical Center and the New York Stem Cell Foundation, would serve to provide independent validation of research methods and strategies.

In addition, the researchers said yesterday that they would be using “fail-to-fertilize” eggs from in vitro fertilization clinics. They added that they are in the process of taking the necessary regulatory steps so that they can begin to harvest fresh eggs from donors on a strictly voluntary basis.

The research is complicated further by government regulations in place since 2001 that prohibit the use of federal funds for human embryonic stem cell research that uses new cell lines.

To ensure compliance, Hyman said, the HSCI has a set of “very detailed business and accounting processes to ensure that no federal funds are used for this research.” The rules cover everything from the purchase of equipment to what scientists can and cannot touch, Hyman wrote in an e-mail Monday night.

Daley called the logistical protocols a “Herculean effort.”

Harvard and Children’s Hospital have turned to private donors—including the Howard Hughes Medical Institute and several individuals—to help fund the research, which if successful will require “millions of dollars over the next few years,” according to Melton.

—Staff writer Laurence H. M. Holland can be reached at lholland@fas.harvard.edu.