Meri Firpo still laughs when someone asks her about the pens.

Last year, a Los Angeles Times article proclaimed that Dr. Firpo, a stem cell researcher at the University of Minnesota, required that workers in her two labs across the hall from each other and virtually identical except that one uses federal research dollars and the other does not to use different kinds of pens in order to avoid running afoul of government rules that prohibit any federal money from paying for embryonic stem cell research on lines not approved under President Bush’s stem cell policy. (That policy restricts research to about 20 lines that existed when Bush announced the policy in August 2001.)

“The pen thing was really a coincidence,” Dr. Firpo says. “When we were setting up the main lab, I let my lab manager make all the orders, and they like a pen I don’t like. So when we set up the new lab, I bought all the equipment myself and I thought I’d buy the pens I like. That’s how we ended up with two different kinds of pens.”

Figure 1. Plating stem cells in a University of Minnesota laboratory.

But although the federal government is unlikely to shut an embryonic stem cell research lab down for illicit use of federally purchased pens, the fact remains that keeping a lab the kind of “scientific kosher” required by the Bush administration’s policy can be a massive undertaking and no one’s entirely sure if they’re doing it right.

“Everyone is doing their own institutional policies around this,” says P. Pearle O’Rourke, chair of the Embryonic Stem Cell Research Oversight (ESCRO) committee for Boston’s Partners HealthCare. “Everyone relies on the same few items from the National Institutes of Health their frequently asked questions, for example to try to figure out what to do. But there are a lot of judgment calls. You go to meetings and ask other institutions what they’re doing. It’s pro-active damage control.”

In April 2006, the Association of American Medical Colleges sponsored a formal meeting on this conundrum, a forum that allowed leaders in bioscience research to share their experiences on legal, organizational, compliance, monitoring, and cost policy issues related to human embryonic stem cell research. The result was a report that many institutions are using as a road map for their own policies even though the NIH does not and cannot officially endorse it. (The report, Human Embryonic Stem Cell Research: Regulatory and Administrative Challenges, is available online for free download on the AAMC’s Web site, http://www.aamc.org; browse the Research section of the Publications page.)

Among the issues discussed:

• Space both lab space itself and the surrounding space. If you have a separate building for non-federally funded research, great, but most institutions don’t. Once you have labs in mixed-use buildings, institutions must monitor not only the division of assigned square footage, but shared space like cafeterias and lounges.

• Equipment many institutions “color code” equipment like microscopes and centrifuges with green, yellow, or red tags to indicate “immediately available,” “available in the future” or “not available at all” to embryonic stem cell research purposes.

• Supplies from pens to pipettes and test tubes, most of the participants at the AAMC meeting agreed that a separate storage policy is safest, even if the items are not necessarily separately purchased and are instead simply cost-allocated.

• Staffing staff time is usually allocated on a percentage basis, but this requires a very thorough assessment of scientists’ (and administrative staff) actual availability. For example, if a researcher is supported by an NIH training grant that pays 100% of his salary, he can’t touch non-federally supported stem cell lines.

Figure 2. Dr. Meri Firpo

Within these and many other areas, the questions raised are myriad. “For example, if you had a computer in your office that you bought with a federal grant, can you use that for any non-federally funded stem cell research? Some will say no, others will say that’s over-reading,” says Dr. O’Rourke. “The bottom line is that we are all trying to create policies that we feel will stand up to scrutiny, but without concrete guidance for understanding the minutiae of what to do. It’s a moving target.”

And many scientists take a “don’t ask, don’t tell” approach to these questions, opting not to call the NIH (or other federal institutions funding biomedical research, such as the Department of Defense or the National Science Foundation) with questions about what they can and can’t do so that they don’t get an answer they don’t want.

At the University of Minnesota, Meri Firpo knows she’s fortunate: the institution has established an accounting policy that makes it easier for her to track spending. There are specific cost centers allocated to her embryonic stem cell research on non-federally authorized lines, so that the code indicates that the purpose of the research is not federally fundable.

“It makes it easier for them to track, and easier for me too,” she says. “The university makes sure that no federal or state funds get mixed in. It makes separation of funds for salaries, supplies, and equipment very transparent. If you’re paid off a salary with this type of code, some of it is non-federally funded. I just have to make sure that if you have 10% of your time paid with non-federal funds, you don’t work more than 10% of your time on non-federally authorized stem cell research.”

Figure 3. Pipettors must be color coded or in some way be identified in facilities where federally funded embryonic stem cell research is being conducted.

So far, straightforward. But even such an institutional system requires Firpo to spend a lot more time on lab minutiae than most investigators. “Say we’re ordering pipettes. I want to be the one in charge of saying that these pipettes go in this fund, and these pipettes in another,” she says. “That means that instead of my lab manager ordering the pipettes, I have to do it: look at all orders for the day, see who needs what, officially assign the funds, send the order through, and sign for it when it comes in. That’s a significant amount of time, but if there’s any question as to who ordered this stuff and put it in this cost center, I’m the one accountable.”

The segregation of equipment is a big challenge in a research culture that thrives on shared resources. “It’s ‘I borrow from you, you borrow from me,’” says Firpo. “If I run out of this enzyme, I go to the lab next door and borrow 10 microliters. It’s like borrowing a cup of sugar from your neighbor. But there are things in my lab that, if someone borrows them and doesn’t bring them back, we’re in big trouble.”

While it’s perfectly okay for someone doing federally funded research to borrow something Firpo bought with non-federal dollars, the opposite isn’t true. So when a $250 pipettor used for measuring very small quantities sprouted legs and walked away, her lab couldn’t just borrow someone else’s. “I’ve had to say it over and over again: you can’t borrow things or let others borrow from our lab,” Firpo says. Her lab uses a similar color-coding system to the one described in the AAMC report: red and purple ice buckets in the main lab designate whether or not they are for federally-funded projects.

Figure 4. Test tubes ready to be filled with stem cell samples.

This necessary approach often stifles the open communication that researchers have come to expect. “Say you’re a scientist in a lab that was just totally redone with NIH funds. You come down and are chatting with a colleague who’s doing embryonic stem cell research with non-NIH cells,” says O’Rourke. “You’d love to look at those cells with your new cell sorter or imaging technique. With any other project, that would be encouraged, but here, you can’t. You have to keep reminding people that they’re only allowed to use these cells within this footprint of space, time commitment, people and supplies.”

Each institution’s approach to, and concerns about, embryonic stem cell research funding and policy differs slightly. “Take space, for example. At a recent meeting, a participant from California pointed out that the Federal Emergency Management Agency has put a lot of money into buildings at a number of institutions for earthquake preparedness,” says O’Rourke. “They wondered if those institutions can allow embryonic stem cell research in buildings funded by FEMA? If it’s completely built with federal dollars, probably not, but what about if it was partially supported that way?”

At Partners, says O’Rourke, the organization created an ad hoc group to deal with the full range of hESC issues, including financial policies. The group includes vice presidents of research, lawyers, investigators, regulatory experts, public affairs staff, and research finance staff, and has met on a monthly basis for the past three years to develop best practices how to deal with space, personnel time, equipment, and “expendables” like paper, pens, and test tubes. Each time a new laboratory or scientist decides to do non-federally funded embryonic stem cell research, the research finance expert from the committee must spend hours with the head of the lab, going through space, salary, equipment and supply allocations, and create a file on every protocol.

“I’m always surprised at how much work people have to go through to make this research go forward,” Firpo says. “We have to make sure that all the funds that come to our embryonic stem cell program have never included any funds from the NIH, Medicare, Veteran’s Administration, National Academy of Science, USDA the streams of money they would normally put into a big pile have to be monitored separately to make sure they’re pristine.”

“Institutions have spent an inordinate amount of time and energy trying to figure out, with vague directives and shifting guidance, what to do about these issues,” agrees O’Rourke. “And I feel like it’s been a real resource drain putting color codes on machinery. It’s a quagmire.”