The interim president of the California Institute of Medicine (headquarters behind this drawbridge) hopes to span breaches between board and institution Credit: Jessica Kolman

The California Institute for Regenerative Medicine (CIRM) is a strange beast. It was voted into existence through a state ballot initiative in 2004 and is financed through California bonds to promote stem-cell research. Charged with disbursing US$3 billion, the institute could spend more on human embryonic stem-cell research over the next decade than any single country. Other states are copying it in miniature: nine have proposed or allocated funds for stem-cell research.

Many people are watching CIRM, says Mary Woolley, head of Research!America, a health-research advocacy group in Virginia. With other investments in research flat, the institute is “in a vanguard”, she says. “It's really important for CIRM to get it right.”

CIRM watchers have reason to be concerned. In December 2006, its first president, Zach Hall, announced plans to retire after a rocky relationship with the chair of CIRM's governing board. His replacement, Richard Murphy, former president of the Salk Institute in La Jolla, California, took the job this month only after making clear that he would not stay past March 2008. He will not take the permanent position because he plans to start a consultancy on the East Coast where his children and grandchildren live. In August, CIRM's chief science officer Arlene Chiu announced that she too would step down.

CIRM leaders point to several difficulties in the search for a permanent president. The proposed annual salary of around $400,000 has been called too low (Table 1). Recruiting prominent scientific leaders is slow, and some candidates were scared away by legal threats to CIRM's existence that were resolved in the institute's favour only this May.

Table 1. Except for CIRM, salaries are as reported in 2005 tax filings. CIRM's current interim president will be paid $50,000 a month for six months and will not receive health benefits. The salary is officially capped at $412,500.

Manager, leader, or scientist?

If the board hires a good search firm and knows what it is looking for, Research!America's Woolley thinks finding a president should take about six months. That's a big “if”, however. “Failed searches happen all the time,” she says. Without a clear consensus about what they are looking for, she continues, a board could go through a search three or four times, each ending in disappointment. Robert Klein, the chair of CIRM's governing board, doesn't believe the search is taking longer than could be reasonably expected. Academic searches often take 18 months, he says, and the right candidate is worth waiting for.

The two CIRM presidents so far have been scientist-administrators nearing the close of their careers. Hall led the Zilkha Neurogenetic Institute at the Keck School of Medicine in Los Angeles until joining CIRM in 2005. Murphy announced his retirement as president of the Salk Institute at the beginning of this year. Whether the next president will also come from academia is unclear.

Board member Jeff Sheehey, an AIDS patient advocate, thinks experts with an industry background might be most adept at transforming research into therapies. “My pill bottles don't say 'UCSF',” he explains. “Someone from the foundation world or the business community might be an interesting choice,” agrees Research!America's Woolley.

At the presidential search subcommittee meeting on 31 August, Klein announced that a number of highly qualified candidates were under consideration. The board is looking for someone with both academic and industrial experience, an established commitment to moving medical science to patients, and, ideally, a track record of interfacing with government groups. The right candidate also needs extremely strong scientific and medical credentials.

Klein says some attractive candidates have refused to consider the position because they would no longer be able to run their own laboratories, a task that CIRM watchers and board members generally agree would be too distracting. However, there are numerous examples of scientist-administrators who maintain laboratories. These include Harold Varmus, the president of Memorial Sloan-Kettering Cancer Center, Paul Nurse, the president of Rockefeller University, and Michael Bishop, chancellor of the University of California, San Francisco.

Tom Cech, president of the Howard Hughes Medical Institute, says he would not have assumed leadership of that organization if he hadn't been able to remain an active scientist. Moreover, having a lab helps him craft better policies for advancing science, he says. “It's a constant reminder of the slow pace of research, of the exhilaration of discovery followed by many months of lack of progress.” Maintaining a lab drives home how destructive large drops in funding can be, he says, and keeps him aware of the time needed to build up reagents and infrastructure.

Some arguments against a CIRM president's ability to maintain a lab fall flat, as many scientist-administrators exert greater control over larger budgets and staffs than CIRM's president will. A guaranteed supply of bond funds eases the burden on CIRM's president to raise money for the institute. However, unlike other scientific institutes, CIRM has no mechanism to support its president's labs, and competing against other scientists for grants could create conflicts of interest.

Not only must the president forgo running a lab, he or she will also be accountable to numerous disparate groups. CIRM's public and private sector constituencies offer unprecedented means to advance science, but they also make the organization particularly difficult to run, says Hamilton Moses, a biomedical consultant in Virginia who focuses on non-profit governance. “CIRM operates at the nexus of the Political (with a capital P), scientific, institutional, and business forces of an aggressive state that views economic development as a priority.” Its organization, he adds, doesn't help. “'Noah's Ark' boards, where each member is appointed to represent a constituency, rarely work.”

Because of its control over public funds, CIRM must also meet accountability and transparency requirements. Proceedings of many meetings must be made public, and if the president consults with two board members at the same time, a transcript might need to be made available. As a public-funded entity, CIRM is constantly called upon to divulge more information for public scrutiny, particularly because board members' institutions are eligible for CIRM funds. A decision not to disclose the names of scientists whose grant applications were rejected has been criticized, for example.

With the wrong person, these tasks would wear away the essential passion for developing medical uses for stem cells. “This is mainly a skilled management job, requiring wisdom, scientific expertise, and a good list of known contacts to go to for advice and help, but not necessarily a background in medicine or stem cells,” says Bruce Alberts at the University of California, San Francisco, who served two six-year terms as president of the US National Academy of Sciences. Management jobs require many tasks that scientists find boring, adds Cech. Only someone with tremendous skills at working with diverse groups of people could thrive in this job.

Who's in charge?

And then there's the issue of how the institute is led. “Proposition 71 [the legislation that led to CIRM] creates a two-headed monster where it's not clear who's really in charge,” says John Simpson, stem-cell project director for the California-based Foundation for Taxpayer and Consumers Rights, who describes himself as a constructive critic of the agency.

No one denies that the governing structure of CIRM is different from most grant-making institutions. “That was unquestionably one of my goals,” says board chairman Klein, the chief architect of Proposition 71. The institute's staff, currently around 25, is legally limited to 50. CIRM's board consists of 29 members appointed by an array of government officials and must include specified numbers of commercial entities, state universities, other biomedical research institutions, and patient advocates representing particular diseases. The board makes research standards and grant awards. Its chair's responsibilities include managing the board's “agenda and work flow, including all evaluations and approvals of scientific and medical working group grants” plus interfacing with government agencies, handling financing plans and leading negotiations for intellectual property and other contracts.

“Is it a board that has a staff, or an institute that has a board?” asks former CIRM president Hall. “That's the horns of the dilemma.” Confusion about the president's role was obvious by the end of 2005. Then-president Hall felt the need to ask for a clear resolution that he and his staff would be responsible for drawing up a strategic scientific plan for the institute in consultation with board members.

Many of the board members of CIRM have experience in private foundations and government commissions, where a board can chart an organization's course. At most scientific institutes, however, the board does not set the shape or scope of the institute's programs. It scrutinizes what's happening at an institute, but does not determine it. “We call it management here,” says Cech, when asked how the board and staff of his institute interact. He says the most apt description of a board's role comes from one of his own board members, Harvard chemistry professor and former dean Jeremy Knowles: “Noses in, fingers out.”

Despite the power of the CIRM board, it does expect its president to lead, says board member Sheehy. “The board doesn't really initiate anything,” he says. “We've gone along with everything put forward by the president or the scientific staff.”

Depending on whom you ask, Klein is either a self-sacrificing visionary with a knack for getting things done or an impulsive micromanager prone to over-reaching his skills.

Klein says that none of the presidential candidates has cited the board's or his own role as an obstacle. The skills necessary to run CIRM have “natural areas of division” explains Klein, a wealthy entrepreneur who took up patient advocacy after his son was diagnosed with diabetes. He can handle bond and tax issues, leaving the president more time to lead the scientific programme. How that plays out in practice is unclear. Depending on whom you ask, Klein is either a self-sacrificing visionary with a knack for getting things done or an impulsive micromanager prone to over-reaching his skills.

“Obviously, to work effectively the two people need to get along well,” says Murphy, who began his job as interim president this month. He describes his relationship with Klein as “very good” and “very candid”. Murphy advised Klein as he was writing Proposition 71 in 2003 and served on CIRM's board since its inception in 2004 until he stepped down from the Salk Institute earlier this year.

In 2000, when Murphy became president of the Salk Institute, that organization had had four presidents in as many years. By the time Murphy announced his departure in 2007, most of the Salk's board members had joined during his tenure. At the Salk and at his previous position, director of the Montreal Neurological Institute at McGill University in Canada, Murphy says he “spent a lot of time building the board,” with the result that both institutions ran better. At a governance subcommittee meeting in February, in which board members wrestled with the roles of the chair and president (and a few members suggested creating a nonexecutive chair), Murphy said the board should exert less control over the president. “We are a board. We are not an operations committee,” he said. “We should let the president do his job.”

But Murphy insists that CIRM's governance structure is sound: the diversity of the board is an asset, he says; basic scientists who value “curiosity-driven research” and patient advocates intent on clinical progress have much to teach each other. The trick, he says, is establishing mechanisms so groups work together. “I bring that experience, an understanding of how the board can interact effectively with the institution.”

But if there is one thing people agree on, it is that CIRM is an organization like no other. “CIRM represents an experiment,” says Moses. “It is too soon to know whether it will be successful.”