New approach reported in stem cell creation
Gains seen without destroying embryos
Two teams of Massachusetts researchers announced yesterday that they have made progress creating embryonic stem cells without destroying embryos, suggesting that scientists might someday find a technical solution to one of the nation's most highly charged ethical debates.
The experiments are remarkable because they were done primarily to answer ethical criticism, not to investigate major biological questions, marking a new stage in the ongoing debate over stem cell research. They are a measure, scientists said, of the intensity of the frustration researchers now feel with federal restrictions on their work. But they are also a sign of the increasing interest in finding a new, less controversial way to make embryonic stem cells, and perhaps the beginnings of an unusual dialogue between leading stem cell scientists and their critics.
''I am very encouraged," said Tadeusz Pacholczyk, a prominent critic of embryonic stem cell research who is director of education for the National Catholic
One team, working at the Worcester-based biotech company Advanced Cell Technology, created embryonic stem cells by removing a single cell from a growing embryo, without seeming to harm the embryo. Another team, based at the Whitehead Institute for Biomedical Research in Cambridge, tried another approach that used genetic manipulations. The two teams worked separately, but reports of their work, describing experiments done with mice, were both published yesterday by the prestigious journal Nature.
A number of specialists said that neither of the techniques, in their current forms, represented a way of making stem cells that would be widely accepted because they still faced technical hurdles and ethical questions.
Still, the new research, which was published online to make it available faster, is politically charged. The US Senate is considering legislation, already passed by the House of Representatives, that would overturn some of the Bush administration's restrictions on funding stem cell research. Supporters of the legislation fear that talk of potential alternatives -- all of which are at least years away -- could sap support for the measure.
''If you are supporting these alternatives at the expense of the proposal to expand access to the stem cells that are available today, you are essentially voting to delay the research," said Dr. George Q. Daley, a stem cell scientist at Harvard Medical School and Children's Hospital in Boston.
Scientists are interested in embryonic stem cells because they have the ability to form any cell in the body, giving them a powerful tool to study diseases, and perhaps find cures. Embryonic stem cells are typically obtained from frozen human embryos, donated by women who have been through fertility treatments and no longer need them. But these embryos, which are virtually formless balls of several hundred cells, are destroyed in the process, prompting charges that the scientists are taking human lives.
On Aug. 9, 2001, President Bush said the federal government would not fund any research that used batches of embryonic stem cells created after that date, saying the government should not be encouraging the destruction of human embryos. The experiments announced yesterday were aimed at finding a way around this restriction, which scientists say has been holding back stem cell research in this country.
The scientists at Advanced Cell Technology, led by Dr. Robert Lanza, sought to show they could create embryonic stem cells without harming the embryo. They built on a technique that is commonly used to test embryos for genetic abnormalities at fertility clinics. In this technique, called pre- implantation genetic diagnosis, or PGD, a technician delicately removes a single cell from an eight-celled embryo. If the cell is genetically normal, then the embryo is placed in the mother. The procedure does not appear to harm the embryo, according to the paper in Nature.
Lanza's team, working with mice embryos, showed that this single cell can be used to make embryonic stem cells. In an interview, Lanza suggested that a fertility clinic doing PGD could remove a single cell, as it normally does, but then allow it to divide once in a dish. One cell could be used for the genetic testing, and the other could be used to make stem cells.
But scientists and ethicists identified several potential problems with the approach. Pacholczyk said Catholic teaching does not approve of PGD, because it is a violation of the embryo and is not aimed at helping the embryo. It is also possible that the removed cell has the potential to become an embryo, meaning that its destruction would also be viewed as taking a human life.
There are also practical problems, according to Douglas Powers, chief scientific officer of Boston IVF, a fertility clinic. For example, he said, there is the chance that the removed cell could die in its dish -- meaning it could not be tested for genetic abnormalities -- while scientists were waiting for it to divide. This could interfere with the patient's care, and perhaps mean that she would have to delay her attempt to become pregnant.
''When you start mixing the obtaining of research material with a clinical test, you get into a very tricky area," Powers said.
The other research, conducted by Rudolf Jaenisch, a Whitehead scientist, and his graduate student Alexander Meissner, is a test of a concept proposed last year by Dr. William Hurlbut, a member of the President's Council on Bioethics who teaches ethics at Stanford University. The idea is to create a genetically modified egg cell that is able to create embryonic stem cells, but is not able to develop into an embryo.
The technique gets its name, ''altered nuclear transfer," from the fact that it is a variation on nuclear transfer, also known as cloning. In nuclear transfer, the nucleus of an adult cell, which contains its DNA, is placed into an egg cell that has had its own nucleus removed, and the new cell is prompted to grow.
This can grow into an embryo genetically similar to the adult who donated the original cell. With altered nuclear transfer, the aim is to alter the genes of the nucleus before they are placed into the egg cell, to ensure that it is unable to become an embryo.
In the experiment, which was done using mice, the team showed that when they prevent a particular gene from functioning, the egg cell can create embryonic stem cells but is unable to become a viable embryo. In the experiment, the cells appear to divide and develop normally for several days, but it is then unable to develop a crucial outer layer of cells that eventually becomes the placenta.
But Pacholczyk said he has reservations about the particular gene used because it seems that the procedure creates a ''crippled embryo" -- which he considers to be a life that is quickly extinguished -- instead of avoiding the creation of an embryo.
He said that he and others were more hopeful about a variant on the idea that targets different genes. This idea was proposed by Dr. Markus Grompe, who is director of the Oregon Stem Cell Center and a professor at the Oregon Health and Science University in Portland.
Grompe said that he plans on doing experiments to test the ideas using monkey embryos, but that he does not yet have funding for the work.
Gareth Cook can be reached at cook@globe.com. 
