Culturing Support for Stem Cells

Just two weeks ago, stem cell researchers in Massachusetts won an important victory. A bill allowing scientists to conduct embryonic and adult stem cell research with fewer bureaucratic obstacles became law on May 31 after a long legislative battle.

Introduced in February by State Senate President Robert E. Travaglini, the bill immediately generated controversy—Mass. Governor W. Mitt Romney vowed to veto it, arguing that creating embryos for scientific purposes could destroy human lives. Yet the bill sailed through the House and the Senate, easily surpassing the two-thirds margin necessary to override Romney’s veto.

The passage of this bill marked a major victory for Harvard scientists and administrators, who in the face of ethical and political challenges have stubbornly persisted in promoting and developing stem cell research across the University.

Gathering a group of top-notch researchers, the University started the Harvard Stem Cell Institute (HSCI) one year ago in the hope of creating revolutionary medical treatments through therapeutic cloning and embryonic stem cell research in a centralized facility. Since then, the HSCI has garnered over $30 million in private funding.

And University President Lawrence H. Summers has thrown his full weight behind the HSCI, telling an audience at the Harvard Club of Washington this year that stem cells and the “revolution in the life sciences” offer Harvard “a historic opportunity.” He compared today’s Boston to Renaissance Florence, stating that the biological sciences hold the possibility of developing “a center of central intellectual activity of mankind” in the greater Boston area.

To support Travaglini’s bill, Summers submitted an op-ed to the Boston Globe on April 2—one of only three he has ever written in his career as University president.

“Recent history suggests that human embryonic stem cell research, once it becomes more prevalent, will become almost universally accepted,” he wrote, and compared it to the achievements of other doctors whose work had been considered “sacrilegious” by their contemporaries—such as the development of DNA research, which Summers wrote had been decried at first, but soon became a standard part of medicine and biology.

In addition to Summers’ efforts, Harvard scientists have also supported the political cause of stem cell research. Many lobbied and testified in support of the Travaglini bill before members of the Mass. state legislature—a fact which Travaglini’s office says was key to overturning Romney’s veto by a wide margin.

But Massachusetts is just the first step for Harvard’s lobbying efforts. Douglas A. Melton, Cabot professor of the natural sciences and co-director of HSCI, among others, has made a point of testifying to national committees, and remains emphatic that stem cell research cannot be conducted effectively without the financial support of the U.S. government.

Currently, federal guidelines only permit the National Institutes of Health (NIH) to fund embryonic stem cell research using cell lines created before August 2001. This creates significant hardship for scientists, limiting both financial and physical resources. Embryonic stem cell researchers are also prohibited from using any equipment purchased with federal funds.

And while the new Massachusetts law sanctions experimentation with both fertility clinic-derived cell lines and somatic cell nuclear transfer, it does not provide monetary support to researchers.

This means that Massachusetts researchers who wish to experiment with non-federally approved cell lines must rely exclusively on private funding.

But despite Harvard’s most valiant efforts to secure private support, researchers say that federal support is necessary to keep Harvard and other universities up to speed with research conducted worldwide, and Harvard researchers have become involved as both advocates and scientists.

PUSHING POLICY

Harvard researchers were heavily involved in the state debate about stem cells over the past few months.

They gave presentations, testified to committees, spoke personally with legislators, and even opened up their laboratories so that state senators and representatives could come to observe their work.

“We wanted to show state leaders and the congressional delegation that the unique assets Massachusetts can bring to the table—Harvard University, MIT, and also importantly the affiliated teaching hospitals—are all in a geographic proximity that cannot be replicated elsewhere,” says Kevin Casey, Harvard’s senior director of federal and state relations.

And according to Travaglini spokeswoman Ann C. Dufresne, Harvard scientists were “absolutely pivotal” in securing the passage of the recent legislation.

“With their Powerpoint presentations, their conversations, their meetings, [scientists] were successful in educating lawmakers so that they could feel comfortable about the ethical questions raised,” says Dufresne. “The more legislators understood, the greater the support grew. Education was vitally important—it was key to the success.”

And beyond researchers’ persuasion and Summers’ support, Harvard can influence policy through the various lobbying groups it has joined.

Both the HSCI and Harvard Medical School (HMS), as well as Harvard’s major teaching hospitals, joined the Massachusetts Citizens United for Research Excellence (MassCURE), a group which was created in March to battle Romney’s expected veto. Quickly gaining over 30 institutional members across the state, MassCURE pushed to remove “ambiguous language” about stem cell research from legislation and advocate for bills that would make Massachusetts “hospitable to embryonic stem cell research,” according to its website.

“The point of advocacy groups is to show a broad constituency to legislators—to let them know that it’s not just Harvard University,” says Casey. “Harvard is in a broad-range coalition with hospitals, patient advocacy groups, individual patients, and others that are all united in this promising area of research.”

Likewise, Harvard has tried to show state legislators that the development of stem cell research will benefit not just the University, but also the entire Boston-Cambridge area, turning it into the Florentine Renaissance that Summers mentioned at the Harvard Club of Washington.

“President Summers is promoting the concept that the life sciences in Massachusetts is a sector that is going to be the wave of the future—an important part of that sector is stem cell research,” says Casey.

FUELING THE RESEARCH

Not only did Harvard win a victory with the passage of Travaglini’s legislation, but following on its heels was a proposal last week that would earmark $100 million for stem cell research in Massachusetts.

This pales in comparison to funding in California, which recently decided to give stem cell researchers $3 billion over the next decade.

But representatives at Harvard and in Travaglini’s office say that not even California’s efforts are enough and that NIH needs to fund stem cell research.

“California is in a better situation if they can get their act together. But if you consider the $30 billion a year budget for the NIH, California’s stem cell initiative still doesn’t make up for it,” says Jane Corlette, Harvard’s associate vice-president for government, community, and public affairs. “That puts all of us in the U.S. behind.”

In order to lobby for funding nationally, Harvard’s researchers have had to take on the double roles of scientists and advocates.

Melton first testified before a U.S. Senate Labor, Health and Human Services Appropriations Subcommittee on Jan. 10, 1999 on behalf of stem cell research, acting as a volunteer for the Juvenile Diabetes Foundation International.

He referenced his own children, both of whom have juvenile-onset diabetes, in arguing for the necessity of developing stem cell therapies.

“I am here today because my seven-year-old son, Sam, has had Type I diabetes since he was six months old,” he said in the hearings, later adding, “The opportunities presented by human stem cell research offer us the promise of significant advances—and perhaps a cure—for diabetes.”

Melton has often reiterated that he wants the U.S. to loosen restrictions on how federal funds can be distributed—arguing that the ostensible license to conduct stem cell research is useless unless the government backs scientists financially.

“It’s like telling you that you can drive your car, but you can’t use gasoline,” says Melton. “Ninety-nine percent of research done in the U.S. is funded by federal funds.”

At the inauguration of the HSCI in April 2004, Summers said that the U.S. government was mistaken in its conservative stance on stem cell research.

“For reasons that are sincere, but that I believe are deeply misguided, the federal government has made a decision that, despite its traditional role as the major funder of basic research in the biomedical sciences, not just in the United States but in the entire world, that this is an area from which it will withdraw,” he said, adding that this decision put the burden on Harvard to fund and develop the HSCI.

Because the federal government will only fund experiments with embryonic stem cells from lines that existed before August 2001­—which amounted to $28 million in funding from the NIH in 2004—but does fund experiments with adult stem cells freely, scientists have felt particularly pressed to prove the necessity for research on the embryonic lines.

George Q. Daley, who is an associate professor of biological chemistry and molecular pharmacology at Children’s Hospital and HMS and a member of the executive committee of HSCI, testified before the U.S. Senate Commerce Subcommittee on Science, Technology, and Space in September 2004. He spoke about the limitations of adult stem cell research, saying that it had been successful in certain instances—exemplified by bone marrow transplants—but that scientists need to move forward with experiments on embryonic stem cells.

“Adult stem cells are not the biological equivalents of embryonic stem cells, and adult stem cells will not satisfy all scientific and medical needs,” he said to the Senate subcommittee. “Claiming that the study of adult stem cells should trump the study of embryonic stem cells is an opinion at the fringe and not the forefront of scientific thinking....Ultimately this will slow the pace of medical research and compromise the next generation of medical breakthroughs.”

The issues confronting lobbyists at the national level can be more complicated than those at the Massachusetts state level, according to Corlette.

“It’s hard for Republicans, who depend on a right-wing base. If you know that 25 to 30 percent of people believe that life begins at conception, then it’s tough to vote for stem cell research,” says Corlette.

Melton himself has begun to collaborate with South Korean researchers, who have relatively unfettered access to government funds. He says that with that kind of support, they have quickly surpassed comparable American research in recent months.

GRASSROOTS SUPPORT

In the meantime, Harvard has secured $30 million in private funding for the HSCI, and one of Harvard’s teaching hospitals, Beth Israel Deaconess, received a grant of $6 million earlier this year to support its own stem cell initiative.

“Our position is clear: we believe that stem cell research—including embryonic stem cell research and somatic cell nuclear transfer—holds great promise for treating serious illnesses and should be conducted at Harvard,” says University Provost Steven E. Hyman.

Yet as the policy battles continue, the year-old HSCI has become a hub for scientists across Harvard.

It boasts 659 members—not all of whom are scientists, but who are interested in either the research or its societal implications and bioethics—and a core group of about 50 to 100 conducting research in the field.

“What you need to turn research into clinical application is talented people, and we have that in unparalleled numbers,” says Charles Jennings, executive director of the HSCI. “Our first challenge in creating this intellectual community is to get them talking to each other.”

To do this, the HSCI holds symposia where researchers discuss their projects and “promote interactions between scientists in different subject areas,” according to Jennings.

HSCI researchers can receive three types of funding—seed grants, core grants, and program grants.

The program grants will allocate money to developing cures in distinct disease areas, and Jennings says that working groups and plans for these disease areas will be finalized this fall.

Seed grants support individual projects. Twelve researchers across the University have been awarded these grants—five of which involved embryonic stem cell research, while the others worked with adult stem cells or partially differentiated progenitor cells.

“We tended to focus on young researchers, particularly those engaging in new research,” says Jennings. “The NIH is pretty conservative in funding new projects.”

For researchers such as Mathew W. Lensch, a stem cell research fellow at Children’s Hospital, the HSCI grant will be the predominant source of funding.

“This grant directly affects my ability to do research for the next two years,” Lensch explains. “I’m just one guy working on one project. This money allows me to be funded independently from federal sources.”

Yet the use of private funding can put tight limitations on researchers.

For example, core facilities, which are usually funded by NIH grants, contain shared equipment—tools which many researchers need to use but are too expensive for any one person to purchase.

Yet the researchers who are privately funded cannot use the equipment purchased by federal funds, meaning that expensive items such as cell sorters need to be purchased privately as well.

HSCI’s core grants are intended to cover the cost of buying and maintaining this equipment—but the division between researchers will remain.

“NIH funding, which supports essentially all other avenues of biomedical research, is prohibited except for the small number of lines that were in existence prior to August 2001,” says Hyman. “These funding rules create substantial burdens for our scientists because it means that equipment and supplies purchased with federal funds cannot be used by our stem cell scientists.”

In addition, researchers have been faced with the question of streamlining the ethics of stem cell research—and whether Harvard should impose a uniform code across all its hospitals and institutes, or whether each organization dealing with stem cells can be autonomous.

According to Kathleen M. Buckley, assistant provost for science policy, Harvard

researchers will try to unify their ethical regulations within the next few months.

“As independent institutions, the hospitals are working with Harvard University to figure out how to deal with embryonic stem cells, and what form of cooperation that will take,” Buckley says. “We want to stick together in this. We’re not exactly set up, I think that’s going to take us the summer.”

But through the variety of challenges that the researchers have faced—whether that be the obligations of political testimony or the pressure exerted by private funding—scientists have been able to rely on unflagging support from the highest administrators.

As Summers said at the inauguration of HSCI, “We have the potential to make this place, right here...the center of research in one of the most important and significant, if not the most important and significant areas, of the life sciences, one of the most significant, if not the most significant, areas in all of intellectual life.”

—Staff writer Risheng Xu can be reached at xu4@fas.harvard.edu.