A bridge next to Kevin Eggan's laboratory overlooks one of the most concentrated square miles of scientific fire power in the world: North Yard, the science hub of Harvard. The bridge, a recent construction in glass and steel, was intended to facilitate collaboration between two research teams.
On one side is the lab run by Dr Eggan, an assistant professor of molecular and cellular biology who specialises in human embryonic stem cell research; on the other is the Bauer Centre for Genome Research, which focuses on genes.
Working together, the teams started devising projects to analyse the genetics of human embryonic stem cells, with Dr Eggan's team generating the cells on one side of the bridge and their DNA being analysed on the other side.
But on August 9 2001 a metaphorical shutter came down that closed the bridge as effectively as if it had been bricked up. George Bush issued a presidential decree banning the use of federal funds for research on new human embryonic stem cell lines.
He delighted anti-abortionists and the Christian right, who oppose what they see as scientists making life and death decisions. This is despite the fact that most stem cell lines derive from surplus fertilised eggs from IVF treatment that would be destroyed in any case.
Dr Eggan and his team were able to carry on their work only because Harvard was committed to it and wealthy enough to fund it privately. But overnight, the ban turned them into the equivalent of dogs suspected of carrying rabies. Everything they did or touched, from high-tech equipment down to paperclips and the electricity used in the building, had to be quarantined from federally funded labs around them.
The joint project between the Eggan lab and the Bauer Centre was an immediate casualty. It was suspended to avoid "contamination" with the centre, which does receive federal funds.
Kafkaesque
Over the past five years the imperative of segregating all stem cell research has created a jumble of red tape. This has allowed collaboration to restart, but at a price. In the Eggan lab each piece of equipment is marked with a sticker: green for privately funded machines that can be freely used; red for those bought by the National Institutes of Health, the federal funding body, which must not be used in stem cell research.
The most Kafkaesque is the yellow sticker. This is applied to equipment that is federally owned but where a deal has been reached: whenever a scientist uses the machine they record it in a book and the NIH is reimbursed.
In one room there are two cryostats, used to prepare tissue for the microscope, standing side by side. One has a green sticker, the other red. Someone has put a label above the red machine, showing Mr Bush pointing straight out and saying: "You there! No human ES cell sectioning on this machine!"
For Dr Eggan, a young scientist of 32 who is itching to get on with research, the result has been agony and frustration: "I've spent the last three years of my life trying to get this sorted. At least a third of my time is still spent keeping the accounts and equipment separate."
No one yet knows where stem cell studies might lead, but most experts in the field believe there is huge potential for discovering new ways of treating diseases including diabetes, Parkinson's and Alzheimer's, or the cruel wasting disease spinal muscular atrophy.
Embryonic stem cells are the basic building blocks created when an egg is fertilised. About 100 cells cluster to form a ball known as a blastocyst, and at this stage each cell is capable of turning into any organ or tissue of the body. In Dr Eggan's laboratory, the computers show stem cells that have just transformed themselves into heart cells, pulsating under the microscope.
The Holy Grail for researchers is to control that process so that cells can be instructed to turn into different parts of the body. That could allow more accurate and humane ways of testing drugs on diseased cells grown in Petri dishes rather than on patients, and pave the way for a new generation of medicines.
None of this can be realised, scientists say, unless there is concerted and collaborative effort, with the US as the world's research engine. "This work is so hard and so in its infancy that to be counting paperclips because of a federal injunction is, to put it politely, unfortunate," said Susan Solomon, chief executive of the New York Stem Cell Foundation, a privately funded research body.
The Bush administration has sought to disarm criticism by allowing experiments to go ahead on supplies of cells created before the decree was issued in 2001. But, beside what some scientists point to as questionable logic, several of these "presidential lines" have proved faulty or been contaminated by being grown in animal culture. As a result, stem cell research in the US is now largely confined to a small number of prestigious establishments such as Harvard and the New York foundation, which can pull in sufficient private money to generate their own lines.
Other institutions, more dependent on federal funding, have been dissuaded from entering the field.
Paul Nurse is the president of the Rockefeller University in New York, which has seven Nobel laureates. Like Harvard it has the private funds to support stem cell research, but he is aware of several institutions unable to take the risk. "In theory if we used one plastic test-tube bought with just one cent of federal money for stem cell research we could jeopardise our entire research programme of $100m (£52m). That has created a climate of fear," he said.
The worst effect of the ban, he believes, is that it is pushing away a generation of young scientists. He knows people who have been inhibited from taking on stem cell research because of the bureaucracy.
Scientists' hopes are focused on the incoming Democrats who take control of Congress in January. But with a majority of two-thirds needed to overturn a presidential decree, Mr Bush is likely to be able to block any attempt to lift the ban. Few expect any change until he leaves the White House in two years' time. Until then Dr Eggan and his colleagues will carry on wrestling with their stickers and double accounting.
Explainer: Gains could be huge
Stem cells can divide to produce a variety of cell types, such as those in the blood or brain. The most useful to scientists are embryonic stem cells, from human embryos that are a few days old. These cells go on to produce every cell and tissue type in the body.
It is this ability that has scientists so excited. Already adult stem cells are used in, for example, bone marrow transplants for leukaemia, and if the power of stem cells to grow new tissues can be harnessed, doctors might be able to treat diseases such as Alzheimer's by using stem cells to replace missing structures in the brain. One day it might even be possible to regrow limbs or organs.
These clinical applications are a long way off. In the short term, studying embryonic cells will help scientists understand how structures in the body are formed and how congenital diseases develop. That could lead to treatments. Drugs will be tested on stem cells that mimic features of genetic diseases, so fewer animals will be used.
Progress is being made. A recent study published in the journal Nature successfully tested a stem cell treatment for muscular dystrophy in dogs. The researchers are next moving on to human trials.
James Randerson
