by M. William Lensch, PhD Children’s Hospital Boston and Harvard Stem Cell Institute
It’s been some 30 years since the first funding limitations were placed on research involving human embryos (1), but what has this situation meant practically as far as scientists are concerned? How have the actual prohibitions as well as their attendant secondary issues impacted life in the laboratory? I know many scientists and what’s happening in their labs doesn’t sound much different from my own. Ultimately, however, I can only speak to my own experience where I can confidently tell you that it’s been difficult.
For a scientist dedicated to probing the mysteries of rare congenital diseases using human embryonic stem cells (hESCs), the current situation is as frustrating as it is exciting. Excitement comes from having the ability to ask and answer previously inaccessible questions about the earliest stages of development. Human ES cells are the reason why new strides are being made into very old questions about human biology. The frustration stems from a litany of reasons including:
Lack of financial resources
The need for new systems of research oversight and approval
Political uncertainty including the legality of certain research collaborations
“Being in the crosshairs”
Money: Science and art depend upon patronage. Both fields have contributed enormously to the betterment of humankind though neither would be possible without individuals and organizations willing to bankroll risky projects. Private research dollars have been tremendously important to science, especially given the current federal restrictions. However, privately funded research plans tend to be much more task-oriented and of a shorter time period compared to those receiving public funding. For some projects, setting strict performance goals can be enormously beneficial, but I would argue that it shouldn’t be the only path, especially when considering innovative research at its earliest stages. It’s difficult to run most laboratories like a business. Part of this is because “surprises” or unexpected laboratory results have enabled some of the most amazing discoveries and taken things in a new direction. Surprises are difficult to factor into a business plan.
For my own work, the largest supplier of research funding in the entire country (the NIH) is immediately unavailable to me. I am currently a junior faculty member who would like to have my own lab one of these days and yet I have no federal funding record whatsoever. Not good. Beyond this, the current policy demands that when working stem cell lines created after August 9, 2001 (2), I cannot use existing (and often expensive) equipment that was purchased using NIH money for what otherwise may be identical work. This means that I have to have separate centrifuges and microscopes for cell A versus cell B, different pipettes for culturing cell A versus cell B, and even a different pencil for taking notes on cell A versus cell B, thus wasting money, space, and time.
Oversight: In order to ensure that scientific research is conducted in a manner that is consistent with ethical principles (including considerations for safety and personal autonomy) the federal funding system has implemented systems of oversight, which come to bear upon scientists using public money.
Unfortunately, when federal funding is off the table, many of the rules and regulations for appropriate research oversight vanish as well, leaving researchers somewhat uncertain as to what the rules are and how to proceed. Institutions are uncertain too and in many cases have had to engineer processes for maintaining oversight from scratch. Some help has come from the National Academy of Sciences (NAS) and the International Society for Stem Cell Research (ISSCR), which have drafted voluntary guidelines to aid in considering questions of research oversight. However these are only well-intended suggestions, lacking the enforceability of an oversight process linked to federal funding. Institutions are left to interpret these guidelines locally and determine how (or if) to let scientists work with hESCs.
What are institutions to do? What should the rules be? Who should make them? How will they be enforced? When I was a post-doctoral fellow, I spent an unusual amount of time helping answer such questions. And though I think that it was important work, it was time spent away from the bench where the fact is the policy recommendations that I have authored or co-authored cannot replace peer-reviewed research articles in my curriculum vitae.
Legislative uncertainty: At any given point over the last few years, I wouldn’t have been able to tell you which way I thought things would turn out as far as the future of hESC research was concerned despite my trips to Beacon Hill and Washington D.C. to talk to lawmakers about stem cells. It would be a fib to say that there weren’t times, and many of them at that, when I wondered if it was all worth it.
Today, the two major presidential candidates seem to support some sort of easing of government restrictions on hESC research though there remain some important differences between them, including the use of hybrids and chimeras in research. Pro-stem cell legislation has passed both houses of Congress, only to be vetoed (more than once) but I am nevertheless optimistic that things will change for the better. Beyond federal policy, the current patchwork of state laws present both benefits and challenges. The answer to the question, “Who can work with whom?” can depend on your zip code.
Scientifically, there’s not much low hanging fruit left these days and as the old saw goes, what does remain is probably rotten. Complex, difficult questions are before biomedical science where collaborative work is one of the best ways to tackle them. Collaborations are reflected in the authorship of journal articles where it is quite common for a big project to draw on the talents of scientists at several different institutions and not uncommonly, other countries. Some states including California, New York, Connecticut, and a few others have set aside state funding to promote work on stem cells as a matter of public health and economic growth. To other states, it has meant establishing strict rules, such as Michigan’s law criminalizing the derivation of hESC lines within the state’s borders (3). What does it mean for a scientist to collaborate with a colleague in a “prohibitive” state? Does the colleague face some sort of recrimination for being part of a research project disallowed in their home state, but perfectly legal or even encouraged within their collaborator’s home state?
Being in the crosshairs: Some can be quite vociferous in their opposition to our work. It’s disappointing to read that hESC research is listed among the “seven modern social sins” (coming in at number two above things like drug abuse, polluting the environment, and creating poverty) (4), to hear that all but one of the entire cadre of United States’ Catholic Bishops condemn hESC research as being “a gravely immoral act” (5), as well as to face the occasional outspoken member of the public who during an event will compare hESC research to infanticide or articulate some other inflammatory position.
The polls that I have seen all indicate that a significant majority of people in the United States support hESC research though a very vocal minority often has the microphone. The unfortunate part about these sticks and stones is that the people who work with hESC all seem to be doing it for the same reasons: to ease suffering, to unravel the complexities of development, and to make the world a better place.
To conclude: I’ve mentioned just a few of the tangible difficulties that exist because my profession rests at a confluence of science and national policy. Coming to the laboratory each day presents terrific opportunities as well as enormous challenges. But these challenges pale in comparison to what a paraplegic goes through just to get dressed every morning, to the number of times a kid with diabetes will be jabbed with a needle, or to the daily erosion that comes from intractable leukemia. That’s what one has to remember in this business because it’s where the energy comes from to keep a person coming back for more.
Bibliography:
1. Hall SS. Merchants of Immortality: Chasing the Dream of Human Life Extension. 1st ed. New York: Mariner Books; 2003.
2. Bush GW. Fact Sheet: Embryonic Stem Cell Research. http://www.whitehouse.gov/news/releases/2001/08/print/20010809-1.html; 2001.
3. Act 368: Use of live human embryo, fetus, or neonate for nontherapeutic research; prohibitions; presumption. Public Health Code, State of Michigan. Vol 333.2685; 1978.
4. Krause-Jackson F. Vatican Lists Seven Social Sins, Including Drug Abuse. Bloomberg.com. Vol http://www.bloomberg.com/apps/news?pid=20601102&sid=aizlo DFbRPRM&refer=uk; 2008.
5. Liston B. Bishops condemn stem cell research. In: Reuters, ed. Reuters. Vol http://www.reuters.com/article/healthNews/id USN131220080613; 2008.