The story is a staple of 20th-century scientific biography: brilliant researcher, oppressed by political restraints on scientific activity and expression, leaves a restrictive nation in search of an open academic atmosphere in which to perform groundbreaking work that expands the horizons of his or her field. In the previous iterations of this story, the scientist would settle in New Jersey or Massachusetts or California, prosper in the freedom and latitude given to scientific research, and become a proud citizen of the United States.

The 21st-century version of the same story may be shaping up quite differently.

Biomedical technology is one area in which current debates among politicians, religious groups, ethicists, and researchers have caused serious doubts about the ability of the United States to remain at the forefront of innovation in genetic technologies and their myriad applications. Already, restrictive requirements on stem cell research and widespread speculation about additional regulatory restraints have caused several noted researchers to depart to countries that welcome and support this promising scientific area. Warnings about the possible results come from academia and from concerned legislators. William Keye, MD, president of the American Society for Reproductive Medicine, cautions: "If all cloning technology is made illegal in the United States, other countries, some of which have already approved this technology, could benefit, attracting our leading biological scientists in a 'brain drain.' As a result, America could relinquish its place as the leader in biomedical research, and Americans could lose access to cures developed for diseases." Senator Arlen Specter (R-PA) notes that proposed legislation to ban cloning and severely restrict stem cell research would "tie the hands of medical science in the 21st century" and "create an enormous brain drain out of the United States to Europe."

Is the possibility of a "reverse" brain drain real, or is this merely one of the rhetorical weapons brought to an increasingly heated debate? Will international political considerations now play a part in career decision-making for biochemists working in the broad range of high-tech genetic applications and for those thinking about entering these fields? What are the likely practical outcomes to an ongoing war of words between opponents and proponents of cloning and stem cell research? JobSpectrum.org takes a closer look at the very rapidly changing international career landscape in the biosciences.

Taking the Lead…Elsewhere

In August 2001, President Bush restricted federally financed stem cell research to 64 existing stem cell lines taken from embryos discarded by fertility centers. No lines created after that moment could be used for research by any institution receiving federal funds of any sort—and it soon became clear that less than 20 of these 64 existing lines were suitable for research. In April 2002, Bush announced his strong support of a Senate bill that would ban somatic cell nuclear transfer, the basic process that facilitates cloning and the creation of embryonic stem cells. Although supported in this effort by conservative lawmakers and a large segment of the American public, Bush's description of cloning as "a nightmare scenario" in which embryos would be created and grown for spare body parts or custom-tailored to the demands of affluent parents brought grim responses from the scientific and medical community. Forty Nobel laureates issued a joint statement in which they noted that restricting nuclear transplantation technology would have "a chilling effect on all scientific research in the United States."

But the signs of a U.S. chill—and an increase in activity elsewhere—have been evident since the first fierce ethical debates that accompanied the quest to elucidate the human genome in the 1990s. The widely publicized birth of Dolly, the cloned sheep, put Great Britain at the cutting edge of scientific investigation in applied genetics. In 2001, Great Britain became the first country to allow the creation of human embryos as a source of stem cells. In February 2002, the House of Lords approved research on human embryonic stem cells cultured from surplus embryos from fertility clinics. The Human Fertilisation and Embryology Authority (HFEA) both regulates and supports this research at a number of institutions throughout Great Britain. A stem-cell bank is being planned by the Medical Research Council (MRC) to maintain a diverse supply of stem cells for new research, and British scientists are already referring with some pride to a coming "brain gain." "The climate for this kind of research is enormously better in Britain than in the U.S.," says Professor Chris Higgins, director of MRC's clinical sciences center at the Imperial College in London.

The "brain gain" is being supported by an influx of funding from both private and government sources. MRC is providing fast-track grants for international researchers who want to come to Great Britain, and other government agencies there are earmarking more than $60 million a year to support fellowships and training in embryo-related research. Universities across Great Britain are working actively on all phases of stem cell investigation and potential beneficial medical applications. Private endeavors, such as ReNeuron (Guildford, UK), a biopharmaceutical company developing stem-cell applications for neurological disorders, are springing up to produce marketable products from these innovative technologies.

A Noted Departure

British scientists and legislators were pleased to report in July of 2001 that their efforts to create a net brain gain for their country were paying off. In that month, Roger Pedersen, one of the United States' most accomplished and internationally honored stem cell researchers, left his position as director of the Reproductive Genetics Unit at the University of California, San Francisco (UCSF), and took his research to a handsomely funded situation at Cambridge University (UK). Like researchers in universities across the U.S., Pedersen had seen his range of activity increasingly limited by restrictive government proscription. In April 2001, a National Institutes of Health (NIH) ruling on "indirect" costs (including pencils, paper, and computers) indicated that even privately funded stem cell research at universities might still be determined to be tapping into government funding and, therefore, be proscribed. Pedersen temporarily suspended some research in his lab. Other universities entered into complex (and sometimes clandestine) agreements with private concerns to take stem cell research off campus.

Pedersen had seen enough. He announced, "after working for 5 years in this field in the US, I have become increasingly frustrated at the prospects for public funding." His decision to go to the UK went with the understanding and support of many at UCSF. Haile Debas, dean of the UCSF School of Medicine, said, "We consider embryonic stem-cell research to be very important. Dr. Pedersen is obviously seeking an opportunity where he can do his work with less difficulty than he faces in the United States." Pedersen was welcomed to Cambridge with an instant MRC grant of £1 million to continue his work. Sir Keith Peters, professor of physics at Cambridge, noted, "They [MRC] saw that there was a research opportunity for the UK to take advantage of this more liberal legislation to secure a high-quality scientist."

Whether large numbers of scientists will follow Pedersen, whose move to the UK was covered extensively in the US and British press, remains to be seen. Many researchers in the US are waiting, working in what one has termed "an ill-defined netherworld," as debates about government support and restrictions continue. At UCSF, Debas notes, "If federal support for stem cell research is not forthcoming, the risk exists that talented scientists will leave….This would be a tragedy of the greatest proportion." Pedersen believes that the most rational and ultimately productive route is for the US to implement guidelines—including ethical standards—that will govern stem cell research while allowing the derivation of necessary additional stem cells. "It is critically important to avoid laws preventing any aspect of stem cell research, such as [proposed] legislation that would…criminalize genomic replacement studies," he says. "The potential benefits of stem cell research promise to transform healthcare and stimulate economic growth. But they will accrue to countries where the policies and funding encourage, rather than hobble, the stem cell enterprise."

Biotech Expansions Across the Globe

A Customer Country?

Where does this leave the US? Among other confusions, it means that US researchers are in need of more stem cells and new stem cell lines that are permissible under the narrow restrictions in place after the August 2001 curfew set by President Bush. On April 12, 2002, NIH announced an agreement to purchase embryonic stem cells produced by ES Cell International, which is based in Australia but maintains laboratory facilities in Singapore, The Netherlands, and Israel. ES Cell holds 6 of the viable stem cell lines that would be permissible under the August 2001 restrictions . The stem cells would be provided both for research at NIH and at nonprofit organizations supported by NIH grants. Ruth Kirschstein, acting NIH director stated that, "The cell lines being offered are genetically diverse and, as such, will expand opportunities for researchers to explore important differences among cell lines." Other NIH staffers viewed the purchase as a "make-do" effort to bridge a substantial and growing gap in available research materials. "We are merely purchasing this as a product, while at the same time our ability to do meaningful research is being threatened," said one NIH administrator. "Can we really blame those who look to countries with less restrictive research environments and a more scientifically sophisticated assessment of the beneficial potential for this technology?"

Who's Away from Home?

Interestingly, no one can say definitively how many scientists have opted to leave the country. The US Department of State does not maintain reliable figures on the numbers of Americans working overseas. "We have people working in other countries while they're on sabbatical, as 'guest scientists', in locum tenens [temporary fill-in] positions, or on loan agreements from universities in the US," said one State Department official. "These people certainly don't renounce their US citizenship when they take these positions, so we have no way of knowing the nature and extent of their commitment to their new jobs." Pedersen, for example, maintains ties with UCSF while working at Cambridge. Other American scientists have taken temporary positions outside the country to continue their work as these issues are sorted out back home. University career counselors contacted for this story reported no increase in recruitment efforts from other countries among biology or biochemistry majors and graduate students.

American Industry: Optimistic But Bags Packed

Private concerns and institutions continue to perform stem cell research in the US, some quite successfully. Advanced Cell Technology (Worcester, MA), through its subsidiary Cyagra LLC, sells its cloned dairy cows for $20,000 each. The leading company in the field is Geron Corporation (Menlo Park, CA), which also owns Roslin Bio-Med Ltd., holder of the patents to the technique that created Dolly the cloned sheep. Other big players are Infigen (DeForest, WI) and the Anthrogenesis Corporation (Cedar Knolls, NJ), which recently acquired Atlantic Stem Cells, Inc. Each of these companies has contacts and sometimes-structured relationships with university labs, and many hire new recruits from university programs.

Despite their relative freedom from some of the more rigid restrictions that regulate government-funded research, these companies are facing significant challenges. One is in the area of patents, in which current disputes have reached a crisis. Several of the core patents that govern much of cloning technology are under scrutiny by the U.S. Patent & Trademark Office. The result, says Infigen president Michael D. Bishop, can be financial headaches. "Anytime there is confusion in the marketplace over who owns the rights to what, raising capital becomes a challenge," he says. "If we can't clear up the ambiguities of these base patents, we won't be able to move forward with the technology." Efforts by some companies to license specific stem cell lines have caused others to go overseas to look for new lines. With some of the most innovative research progressing overseas, the very real possibility of researcher flight, and the availability of productive cooperation between academic institutions and private business, several of these companies are looking at the possibility of expanding--or moving--some of their U.S. activities abroad. Geron, for example, spends more than $4 million each year supporting researchers at the Roslin Institute in Glasgow. Thomas Okarma, Geron CEO, has told several news sources that the company is open to a possible move. "We can grow that or not, depending on where the political winds go," he said.

As an indicator of the ever-shifting political landscape, Tommy Thompson, Secretary of Health and Human Services, announced in late April that four new infrastructure enhancement grants for human embryonic stem cell research would be awarded through NIH. The grants are designed to jump start basic research in the field by providing funds for expansion, testing, quality assurance, and distribution of existing cell lines that meet the President's criteria for federal funding of research on stem cells. Two of the awardees are Australian-owned companies, ES Cell International and BresaGen, Ltd., which hold stem cell lines not previously available in the United States.

Scientific Superstition?

At the root of the current difficulties in the United States, say some observers, is a deep and intransigent misunderstanding and miscommunication about the terms and techniques under discussion.

President Bush has referred to cloned embryos, which usually contain no more than 16 stem cells, as "individuals" and has indicated that therapeutic applications of these cells would "require the destruction of a nascent human life." Michael West, president and CEO of Advanced Cell Technology, said of Bush's recent descriptions of the consequences of cloning: "I'm not proud to be an American when our leadership doesn't take the time to get the science right." In November 2001, ACT scientists announced that they had cloned a six-cell human embryo as a source for embryonic stem cells for transplantation.

The root of the misunderstanding is a failure on the part of many to differentiate between the use of the new technology to create a cloned human being and the application of specific cell lines to the treatment of medical conditions and disease. Despite a recent announcement by an Italian physician that a cloned embryo had been successfully implanted in female patient, almost no scientists favor the creation of cloned humans. "The cloning of a human being should be prohibited," said Paul Berg, who won the Nobel Prize in 1980 and spoke on behalf of dozens of other Nobelists. "Nuclear transplantation technology, however, is meant to produce stem cells, not babies."

The American public clearly opposes cloning and has problems with the whole area of stem cell research, according to a recent poll by the Pew Research Center for the People & the Press. According to the results of the poll, American are united in opposition to both human cloning and experimentation in human cloning by more than four to one (77% to 17%). The position on stem cell research is less clear-cut. Half (50%) of those who "have been paying at least some attention to the issue" favor government funding for stem cell research, but a substantial minority (35%) are opposed. Well-educated respondents were much more likely to favor stem cell research. Opposition by religious groups to stem cell research remains strong and well organized.

The rift between those who support and oppose stem cell research is unlikely to heal soon. Many researchers who entered what they once believed to be the value-neutral field of scientific research find themselves facing their own ethical quandaries in deciding how and whether to pursue such new lines of inquiry. For others, the choice is clear. Peter Hintze, a German conservative politician, has called opposition to stem cell research "the ethics of the healthy." For many who have family members or relatives with previously untreatable diseases or degenerative illnesses that might be cured by stem cell technologies, the potential benefits are compelling.

Professions Without Borders?

In a press release from the prestigious Gairdner Foundation in Great Britain, Joseph Martin, dean of the Harvard Medical School neatly summed up the situation: "The U.S. is going to end up being the most recalcitrant about coming to any kind of conclusion that the public at large will be able to accept. So, we have this situation evolving where science will become regionalized, where people who do work in this area will, to some degree, have to decide what their work is going to be and, therefore, where they're going to live."

Does the current political climate mean that in the future planning a career in bioscience will involve a sort of rubric in which "allowable" areas of scientific investigation will be plotted against a list of appropriate host countries? No mass exodus is predicted, but with the current climate and pending legislation, it is difficult for American science to move confidently forward in this area. For many researchers, the decision to stay, leave, continue their research, or seek another line of inquiry hangs in the air. "The waiting is killing us," Jennie Hunter-Cevera, president of the University of Maryland Biotechnology Institute, told The Scientist.

It is a wait that has implications across the board for government, academic, and private research across the United States.

Nan Knight is a freelance science writer and editor whose credits include Smithsonian exhibits, Discovery Channel Web sites, and a wide range of publications on radiation in medicine.

Editor's Note: In future articles, JobSpectrum.org will look at some of the practical aspects of working in the new international biotechnologies:

Working overseas:
How to position yourself if you want to go.
How to respond if you're assigned to work outside the US.
What you need to know about overseas scientific work environments.

Ethics in the scientific workplace:
How to respond when you have ethical questions about your company's research directions.
How to deal respectfully and responsively with coworkers whose ethical concerns about work differ from yours.

Related Reading

For more information on stem cells and the debate surrounding their use in medical research, see:

National Institutes of Health Stem Cell Primer
Basic information and a constellation of links to other resources on stem cells

American Association for the Advancement of Science
The AAAS position on stem cell research, along with links to supporting materials and sites

CNN's Stem Cell Debate and Resources
An in-depth news report on stem cells, along with links to other CNN stories and background site.