Mahendra Rao Credit: Invitrogen

In March, work began on 540 square meters of new laboratory space at the Buck Institute for Age Research in Novato, California. About a quarter of this will be for Mahendra Rao who took an unusual faculty position at the Buck in January. He will spend two to three days there a month, but he will not draw a salary, as he is retaining his current post as vice-president of stem-cell research at research-tool giant Invitrogen. Although the situation is unprecedented at the Buck, it is not Rao's most unusual career move.

Outside the stem-cell community, Rao is probably best known for quitting his job as stem-cell section chief at the US National Institutes of Health's National Institute on Aging in October 2005. He simply said that the policy that prohibited him from working on newly derived human embryonic stem (ES) cells meant that he couldn't do the job he was hired to do, and so he left.

Rao recalls that people were surprised. “You don't just leave the NIH,” he says. But Rao has a history of big transitions. He completed his MD in Mumbai, India, in 1983, then worked as a resident and neurologist before giving up those positions to become a doctoral student at the California Institute of Technology in Pasadena in the late 1980s.

Still, few would have predicted that he would take a position at Invitrogen, based in Carlsbad, California, upon leaving the NIH. He could have returned to academia or gone to a start-up. Rao had held academic positions at Caltech, the University of Utah, and Johns Hopkins (where he had students and a lab, but didn't take a salary because he was also working at NIH). In 2004 he co-founded the company Q Therapeutics, based in Salt Lake City, Utah, which develops cell therapy for neurodegenerative diseases.

There is a huge lacuna going from lab to clinic, and that is developing proper tools and reagents. Mahendra Rao

When Invitrogen approached Rao about joining the company, he said he wanted to create better tools for stem cells. “There was one reason I thought working for Invitrogen would be important,” he says. “There is a huge lacuna going from lab to clinic, and that is developing proper tools and reagents.” He explained to Invitrogen how he thought that should be done. Invitrogen formalized a stem-cell group. “They decided they would take that risk, and I thought that would be exciting,” says Rao, who brought over a handful of scientists from his NIH lab when he became vice-president of stem cell research at Invitrogen, where he is based at the company's Frederick, Maryland, facility.

At Invitrogen, he oversees work in the company's labs in the United States and other countries, but much of his job is to figure out what labs throughout the world are doing, the better to collect and evaluate ideas for future products. Rao is considered one of those people who knows what's going on in the stem-cell world: he has been invited to speak on how stem cells are being used in hospitals and cell-banking companies in Asia; he is on the International Society for Stem Cell Research's task force on clinical translation of stem cells; he chaired the FDA's Cell and Gene Therapy Advisory Committee and worked closely with Story Landis, head of the NIH Stem Cell Task Force. And with Arlene Chiu, the first chief scientific officer for the California Institute for Regenerative Medicine, Rao has co-authored a book on embryonic stem cells.

The position at the Buck came about through a collaboration between Rao and Buck scientist Xianmin Zeng. The two first worked together at the NIH, and when Zeng received a grant to train young stem-cell scientists at the Buck, she asked Rao to help her teach the week-long courses. That is how Rao met Dale Bredesen, founding president and then chief executive officer of the institute. Bredesen, an MD, was charged with keeping an eye out for commercial opportunities and with expanding stem-cell science at the institute.

Rao's appointment set a precedent for the Buck, says Bredesen, as he is the first person with a faculty appointment who also works in industry. Interestingly, it's a precedent that Bredesen followed in reverse in February, when he stepped down from his executive officer role to devote more time to a disease prevention start-up he co-founded. He will continue to run his own lab at the Buck.

Bredesen recalls being impressed with Rao's commitment to turn his work in the laboratory into widely used applications. “The thing that stands out in my mind was that he came in and said ‘I'm an MD, and I got into this research because I wanted to do more for patients',” says Bredesen. Of course, it must help that the Buck hopes to expand its young stem-cell group and Rao has extensive contacts throughout the field.

Rao describes deciding whether to come to the Buck in very simple terms. "They asked me if I would be willing to spend time here with colleagues I knew already, and I thought that would be nice." Nevertheless, agreeing on the terms of the deal took about two months of wrangling between Invitrogen and Buck lawyers.

The terms of the arrangement are unique for both organizations: if Rao discovers something using funds and infrastructure from the Buck, the Buck will generally own the patents. Although the Buck will cover Rao's cross-country airfare and expenses, he will not, by Invitrogen's wish, draw a salary for the two to three days a month he spends at the Buck. This makes the licensing agreements easier to work out.

Although both Zeng and Rao have their own labs and employees, Zeng will supervise much of the day-to-day operation of Rao's lab. Rao and Zeng are working on differentiating human ES cells into dopamine-producing neurons with an eye to therapies for Parkinson's disease. Rao is also collaborating with Buck researcher Judith Campisi on a more basic research project: how co-culture of ES cells with other cells promotes either stemness or differentiation.

Campisi says Rao is unusual because he is both enmeshed in the demands of commercializing tools and committed to understanding basic biology. “Very rapidly those areas tend to conflict,” she says. “It tends to be difficult to keep both of those focuses in your head.”

In addition to practical applications and basic biology, Rao clearly spends much time thinking about the state of the field. He believes that political forces have driven scientists working with adult stem cells to interpret data less rigorously than they might, whereas scientists working with ES cells underestimate how long it will take for their work to yield clinical benefit. “It's been a huge problem. When you tailor your results to a particular political agenda, you've lost sight of what science is all about,” he says.

Rao says his “pet peeve” is not the fractured funding situation created by the NIH's inability to fund research on many human ES cell lines, but the abdication by the United States of its role as a leader in stem-cell research. The country demonstrated its strength in pushing forward efforts like the Human Genome Project, he says. “When the US took the lead, it was like making sure that people listened.” Even if other sources spring up with funding resources, he says, there's no strong, unifying force to coordinate efforts. “That loss is going to be huge and people haven't appreciated that.”