SEPTEMBER / OCTOBER 2004

FORUM

Master plan for the master cell: Stem cell potential unites Harvard scientists

Dr. David Scadden: Stem cell research is “by nature an inter-disciplinary and inter-departmental activity.”

For all its promise to cure several diseases and repair injuries once thought to be only “treatable,” stem cell research has been woefully fragmented on the world stage, as pockets of researchers from around the world continue to forge ahead in potentially groundbreaking research, but without a central hub for sharing and disseminating information. To answer the call, Harvard recently announced its ambitious plans for the largest ever effort to break new scientific ground, raise needed non-governmental funds, and take a leadership role in connecting stem cell researchers around the world. HMI World takes a look at this new initiative, and puts stem cell science under the microscope to learn where this exciting—and controversial—research is heading.

What began as a discussion about the science, ethics, and future of stem cell research resulted in the assembling of an executive committee, and eventually, in April of this year, the announcement of the creation of the Harvard Stem Cell Institute. Dr. David Scadden, a stem cell researcher with Harvard-affiliated Massachusetts General Hospital, and one of the early conceivers of the idea for the Institute, said that a key driver for its development was a “groundswell of interest in developing a way to coordinate activity. [The researchers] wanted to interact more formally, and that would require something more than departmental structure. Stem cell research, he said, is “by nature an inter-disciplinary and inter-departmental activity.”

Now, with seven Harvard schools, seven Harvard-affiliated teaching hospitals, and almost 100 researchers and scientists (with 25 principal investigators) joining forces, it is, to date, the country’s ninth privately funded stem cell research center.

Dr. Leonard Zon: “There are many, many people at Harvard who have been working on [a host of different stem cell research applications] and what’s happened now is that a large group of people who haven’t been together in the past now have a chance to come together.”

“What you have here is the entire brain trust of Harvard,” said Dr. Leonard Zon, a hematologist at Children’s Hospital, and the president of the International Society for Stem Cell Research (ISSCR). “There are many, many people at Harvard who have been working on [a host of different stem cell research applications] and what’s happened now is that a large group of people who haven’t been together in the past now have a chance to come together.”

Presently, it is a “virtual” Institute that supports research and serves as a central point of contact for scientists working in affiliated laboratories in the Boston area, and sponsors symposia and seminars focused on various scientific issues. (Though a physical location—including laboratory facilities—is a long-term goal, no specific plans are currently in the works.)

The master cell
With almost daily media coverage—of the lastest research findings, as well as the political and ethical debates the research has inspired—stem cells and stem cell research have become household terms, especially for those who suffer from, or care for someone who suffers from, the many ailments for which this research holds promise. But what exactly are stem cells, and why have they come to find themselves at the center of such fierce debate?

Stem cells are, as the name implies, cells from which the development of various tissues and organs stem. Their value lies in the fact that they can renew themselves, as well as contribute to the growth and development of various organs and tissues.

Much of the scientific research to date deals with “tissue stem cells,” also known as “adult stem cells.” These cells are undifferentiated “blank cells,” meaning that they don’t yet serve a specific function, and can sustain and self-replicate for extended periods while awaiting a command to develop into specialized tissues and organs, such as blood, nerve, or muscle. Various forms of therapy using these adult stem cells have been effective when there is an opportunity for like-for-like transplantation. Blood stem cells are already being used in treatments, particularly for leukemia and other blood cancers, and stem cells harvested from bone marrow have long been used in transplantation procedures.

The other type of stem cell is more promising—and more controversial. The embryonic stem cell, which is removed from a human embryo, is not bound to be programmed for only one specific function. It can be programmed to become any type of cell in the body, a fact that has excited many researchers and rankled some ethicists (because embryos must be destroyed to harvest the cells) with its far-reaching potential to effectively treat several major ailments.

Today in the United States, due to stem cell legislation, researchers who receive federal funding (which includes most researchers affiliated with the Institute) may conduct research only on the 18 “cell lines,” or generations of cells created from a single embryo, that were created before August 19, 2001. (Once an embryonic stem cell is successfully harvested, it becomes a ready and indefinitely renewable source of identical stem cells.)

Treatment potential
Though potential treatments are wide ranging, the Institute is focused on researching five major types of organ and tissue failure, which affect nearly 150 million Americans: diabetes, neurodegenerative diseases (such as Parkinson's), blood diseases (such as leukemia) cardiovascular disease, and musculoskeletal diseases like muscular dystrophy.

Scadden says these five were chosen for two specific reasons: first, to take advantage of the areas of focus already existent within the Harvard faculty, and second, because researchers are optimistic that these diseases have relatively near-term solutions. “And as we learn about ways we can manipulate cells, we can expand that list,” he said.

Obstacles ahead
Researchers face no shortage of roadblocks in their research, not the least of which is the limited number of cell lines available to federally funded researchers. The fact that each existing line is capable of renewing indefinitely doesn’t solve many problems. The issue isn’t quantity, but variety, says Scadden. “General characteristics are shared, but distinct features are different among cell lines,” he said. “Some are better at growing, some are better at becoming other kinds of cells. Unfortunately, they’re not all equivalent.” The Institute is using private funding to develop 17 new cell lines.

But aside from legal, ethical, and financial obstacles, what concerns researchers most is making the scientific breakthroughs that are yet unmade, and which hold the greatest potential for new and effective treatments.

One in particular, says Zon, is learning how to drive stem cells into becoming what the scientists want them to become—not only how to do it, but how to do it efficiently. “In all cases, the major avenue is ‘how do you get them to self-renew?’” he said, “and how do you get them to make the tissue you want them to make. We need to discover the biochemical pathways that make a cell turn into another cell.”

The U.S. has enjoyed a long history of work with adult stem cells, and was the first nation to work with embryonic stem cells. The world’s first cell lines were harvested in the U.S. Now the pace of stem cell research is quickening globally, as Singapore, the United Kingdom, Israel, Australia, and South Korea have all been very aggressive in recruiting scientists, and are making a concerted effort to enhance their own research portfolio. Scadden notes that the Institute has collaborative efforts in place with investigators around the world.

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