The new lab rats

Embryonic stem cells divide in more ways than one. They've famously split the political community into camps over whether to support scientific research on the cells, taken from frozen, days-old embryos. And thanks to their ability to multiply endlessly in lab dishes, they've caught the attention of medical companies interested in creating cell banks and marketing stem-cell-based products.

Two such companies: GE Healthcare and Geron Corp., which in June formed an alliance to create a drug-testing product derived from human embryonic stem cells (hESCs) that potentially could replace the animals currently used for research. The agreement-nearly coinciding with the approval of broader federal funding rules for hESC research-may indicate an emboldened interest in the field among medical and pharmaceutical industry leaders.

GE Healthcare is a $17 billion unit of General Electric Co., the business birthed by an American icon of genius, Thomas Alva Edison. Today GE towers as the 12th-largest company in the world by revenue. Besides stamping its ubiquitous blue emblem on fridges and stoves everywhere, GE has business ventures in aviation, energy production and distribution, financial services, media (NBC), theme parks, and as ever, light bulbs. GE's healthcare unit specializes in making imaging and diagnostic equipment for hospitals, along with IT systems for handling medical records and other data. Working with hESCs is a new step for the company.

Geron towers in a different way. The California-based company, a world leader in hESC research, in January became the first corporation ever to obtain FDA approval for a clinical trial of hESC-based therapy. (The trial, intended to treat spinal cord injuries, has yet to reach the stage for patient participation.) Geron does not itself harvest stem cells from embryos, but it funded the original work resulting in the isolation of hESCs in the late 1990s. In exchange, Geron received embryonic stem-cell lines and several exclusive research rights, and today holds more than 110 patents for lab technology related to the cells.

Geron's exclusive agreement with GE stipulates that the two companies will work together to develop a biological product made from hESCs that pharmaceutical companies can purchase and use to test new drugs. The result could be that animal trials are largely replaced. Konstantin Fiedler, GE Healthcare's general manager of cell technologies, said soon after the announcement, "Once you have human cells and you can get them in a standardized way-like you get right now your lab rats in a standardized way-you can actually do those experiments on those cells."

Here's how it will work: Geron's technicians have created ideal conditions that allow their stem cells to multiply and form large cell banks. Groups of these cells can be coaxed to begin growing into specialized tissue types-in this case, heart muscle cells and liver cells. Geron will share these cells and patented technology with GE, which will manufacture and market the cells as a testing product. Drug developers who purchase the biological tests will use them to predict whether their drugs will produce toxic effects on the human heart or liver-a major reason clinical trials for new drugs are halted. In theory, this will speed up the drug-development process and help pharmaceutical companies save money.

Because animal cells are physiologically different from human cells, and because human heart and liver tissue (from cadavers) can be difficult to obtain, Geron claims hESCs are ideal for drug testing.

Some disagree. Michael J. Sleasman, the managing director of the Center for Bioethics and Human Dignity, said he continually hears of scientists who are making advances with stem cells from nonembryonic sources, like induced pluripotent stem cells from adults or cells from umbilical cord blood. Since no embryo is destroyed in the process of deriving these stem cells, Sleasman calls these "ethically appropriate" forms of research-research that "doesn't sacrifice life for the improvement in quality or the saving of another life."

The stem-cell lines Geron works with were originally harvested from leftover fertility clinic embryos and were among the few existing lines approved for federal funding under the Bush-era "ban" on federal hESC research grants. President Obama repealed that ban in March, and in July the National Institutes of Health, responsible for administering such grants, released new guidelines governing how federal tax dollars can be used for hESC research. (The NIH expects to spend $91 million on the research for fiscal year 2009.)

Sleasman said the funding guidelines offer a "slightly more flexible framework" than that which was previously available and will allow new hESC lines to be inducted into federal research. Although neither Geron nor GE Healthcare receives NIH funding, their alliance will probably benefit indirectly from the attitude of acceptance the relaxed rules have helped create. "I think what you're seeing is a wager that this new NIH guideline has provided somewhat of a legitimation of research now that is moving forward," said Sleasman.

Pharmaceutical companies are already moving forward. In my survey (see sidebar below) of the stem-cell policies of the world's top 10 pharmaceutical companies, seven were either already working with hESCs or had guidelines in place for doing so. (One company responded that it did not conduct stem-cell research; another wished to review its current research programs before verifying a nonembryonic stem-cell policy; a third didn't respond in time for this story.)

The Obama administration's friendly approach toward work on hESCs may encourage many U.S. pharmaceutical and medical companies to accelerate the development of their own hESC-based therapies and products. Geron and GE plan to have their first drug-testing product, incorporating heart muscle cells, ready by early 2010.

The process

1. Sperm and egg are joined by in vitro fertilization at a fertility clinic.

2. After about three days, the embryo grows to eight cells. The parents may decide to implant it, freeze it indefinitely, destroy it, or donate it for research.

3. Scientists take a donated embryo, grown to the blastocyst stage (about 5 days old), and remove stem cells, destroying the embryo in the process.

4. In Geron's lab, the stem cells are encouraged to divide and reproduce themselves indefinitely, resulting in large cell banks.

5. The stem cells are coaxed to developing into specific tissue types: (A) heart muscle cells (cardiomyocytes), and (B) liver cells (hepatocytes).

6. GE Healthcare packages the heart or liver cells in a final testing product and sells it to pharmaceutical companies.

7. Researchers at the pharmaceutical companies who are developing new drugs test the drugs on the heart or liver cells and watch for toxic effects. The cells may die, become diseased, or remain healthy.

Stem-cell policies

Most of the world's top 10 pharmaceutical companies (by revenue) either conduct research on embryonic stem cells or have guidelines in place for such research, including: • Johnson & Johnson • Pfizer • GlaxoSmithKline • Roche Group • Novartis • AstraZeneca • Merck

Only one of the top companies-Abbott Laboratories-would confirm that it does not conduct such research. Sanofi-aventis had a policy against using embryonic stem cells but did not verify that the policy remains in place. Wyeth, which is being acquired by Pfizer, did not respond.