In what is thought to be a first for the country, New York State has announced that women who donate eggs for research can be paid up to $10,000. Obtaining human eggs for research has been a huge hurdle for scientists attempting therapeutic cloning through somatic cell nuclear transfer (SCNT), the process used to create Dolly the cloned sheep. Non-binding guidelines put forth by the National Academy of Science prohibit paying women for eggs used in stem cell research. The issue--and the science--is so highly charged that most scientists working in the field have kept quiet about the details of their research, and it's unclear how many women have come forward to donate eggs thus far.

Scientists want to use SCNT to generate cloned human stem cells. In the process, the DNA from an adult cell, such as a skin cell, is inserted into a human egg that has had its DNA removed. The fertilized egg then begins to develop similarly to a regular embryo, and scientists can harvest stem cells several days later. The resulting cells are genetically matched to the adult tissue donor, and could therefore be used for cell transplants without the risk of immune rejection.

The creation of induced pluripotent stem cells (iPS cells)--a technique developed over the last few years to make stem cells from adult tissue without the use of eggs or embryos--has to some degree pushed the issue of egg donation to one side. These cells resemble embryonic stem cells in their potential to become many different types of tissue and are also genetically matched to the cell donor. But scientists say cloning is still important; they want to compare iPS cells and cloned cells, for example. In animal research, cloned stem cells have been studied much more extensively than iPS cells, which are still relative newcomers and appear to be highly variable in their ability to differentiate and self-renew.

Paying women for egg donation has been a highly controversial issue, with some opponents saying that payment will create a financial incentive for women to donate eggs. But supporters point out that women are already paid for egg donations for in vitro fertilization. Scientists working in the field say that recruiting women for egg donation--a potentially painful process with some risk--has been unsuccessful.

According to an article in the New York Times,

"There are many questions you can only answer by studying human eggs," said Dr. George Q. Daley, a stem cell researcher at Harvard and at Children's Hospital Boston. "I think it's a gold step for New York State, and it will mean a tremendous advantage for New York." Dr. Daley's research has so far used poor-quality eggs discarded after in vitro fertilization, a process he said has yielded modest returns but no stem cells.

Stem-cell scientists aren't the only ones celebrating today. In addition to signing an executive order that will lift federal funding restrictions for embryonic stem-cell research, President Obama signed a presidential memorandum aimed at restoring scientific integrity to government decision making. Hopefully, that will help bring an end to what has been broadly viewed as a dark time for science, with political and religious views hijacking high-level scientific discourse.

According to his statement, made earlier today,

This Order is an important step in advancing the cause of science in America. But let's be clear: promoting science isn't just about providing resources--it is also about protecting free and open inquiry. It is about letting scientists like those here today do their jobs, free from manipulation or coercion, and listening to what they tell us, even when it's inconvenient--especially when it's inconvenient. It is about ensuring that scientific data is never distorted or concealed to serve a political agenda--and that we make scientific decisions based on facts, not ideology.

By doing this, we will ensure America's continued global leadership in scientific discoveries and technological breakthroughs. That is essential not only for our economic prosperity, but for the progress of all humanity.

That is why today, I am also signing a Presidential Memorandum directing the head of the White House Office of Science and Technology Policy to develop a strategy for restoring scientific integrity to government decision making. To ensure that in this new Administration, we base our public policies on the soundest science; that we appoint scientific advisors based on their credentials and experience, not their politics or ideology; and that we are open and honest with the American people about the science behind our decisions. That is how we will harness the power of science to achieve our goals--to preserve our environment and protect our national security; to create the jobs of the future, and live longer, healthier lives.

You can read the full remarks here.

Doug Melton, codirector of the Harvard Stem Cell Institute, has been instrumental in pushing stem-cell research forward despite funding restrictions. In a statement issued this morning, Melton gives a personal perspective on the difficulties of the past eight years:

On a personal level, it is an enormous relief and a time for celebration. It is a relief from the bureaucratic and accounting nightmares that have slowed our work, discouraged young scientists, and delayed progress for nearly 8 years. It is a relief to know that we can now collaborate openly and freely with other scientists in our own University and elsewhere, without restrictions on what equipment, data, or ideas can be shared. Science thrives when there is an open and collaborative exchange, not when there are artificial barriers, silos, constructed by the government.

But this is to me a day that marks an important change in spirit, in our national outlook. I think sometimes of how August 9, 2001 was a dark day for science and for America because political ideology was used to define how science should be done. I am going to gather my lab at 11:45 in our tea room to celebrate. And here I mean celebrate listening to our nation's leader, President Obama, state forcibly that science should guide policies, scientific facts should inform our thinking and decisions. Science as a way of knowing is a very powerful tool for good and it is liberating to hear that science, not political ideology, will guide the Obama Administration in its decisions. I was always uncomfortable being put in the position of being an opponent to my own government, being set up in opposition to what the previous Administration implied was an ethical approach to science when in fact it was not an ethical decision made on 8 August, 2001, but a political decision. I am deeply happy to say that those days are done.

The image shows the development of a human-bovine cloned embryo (top) and a human-rabbit cloned embryo (bottom). Credit: CLONING AND STEM CELLS, 2009 Mary Ann Liebert Inc.

A shortage of human eggs has been the major impediment to human cloning, so scientists have been trying to use animal eggs instead, a controversial approach that has raised fears of human-animal hybrids. Now new research suggests that using animal eggs as surrogates won't be successful.

In therapeutic cloning (or somatic cell nuclear transfer), scientists transplant DNA from an adult skin cell into an egg that has had its DNA removed. Unknown factors in the egg reprogram the adult DNA to resemble embryonic DNA, and, in theory, the cell begins to develop like a normal embryo. Scientists would like to create stem cells from cloned human embryos, both for research and potentially for therapy: the cells would be genetically matched to their human donors and thus could be transplanted without fear of rejection. But no one has yet accomplished this with human cells and eggs.

The creation of human-animal hybrids has been a subject of great debate in the United Kingdom, where scientists won permission to use rabbit and cow eggs in human cloning experiments in 2007. (This Q&A with Ian Wilmut, the biologist who spearheaded the cloning of the now renowned sheep Dolly, explores the controversy.) Similar research involving rabbit eggs has taken place in the United States, but with little government regulation here, there has been much less public debate.

A paper published today in Cloning and Stem Cells could make the debate moot. A comparison of gene expression in human cells transplanted into both human eggs and animal eggs suggests that animal eggs simply don't have the power to reprogram human DNA. Here's an extract from a press release issued by Advanced Cell Technology (ACT), which sponsored the research.

Although human-to-human clones (human clones) and human-to-animal clones (hybrids) appear similar, the pattern of reprogramming of the donor human cell is dramatically different. This study . . . shows for the first time that the donor DNA in the cloned human embryos is extensively reprogrammed through extensive up-regulation ("turning on" of genes) with similar expression patterns to normal human embryos. Nearly all of the key differentially-expressed genes were activated in the human clones. In distinct contrast, the majority of these genes were down-regulated or silenced in the human-animal hybrids.

Wilmut, who edits the journal, said in a statement, "This very important paper suggests that livestock oocytes are extremely unlikely to be suitable as recipients for use in human nuclear transfer. This is very disappointing because it would mean that production of patient-specific stem cells by this means would be impracticable."

In the last year, scientists have been experimenting with a new method of reprogramming, which skips the egg altogether and instead uses several genetic factors to directly modify DNA. The ACT researchers also examined expression of these key genes and found that they were activated in both normal and cloned human embryos but not in the human-animal hybrids. "The human-animal hybrids showed no difference or a down-regulation of these critical pluripotency genes--effectively silencing them--thus making the generation of stem cells impossible. Without appropriate reprogramming, these data call into question the potential use of animal-egg sources to generate patient-specific stem cells," said Robert Lanza, chief scientific officer at ACT, in an e-mail.

Some say that the characterization of reprogramming in human clones is the most interesting aspect of the research. According to an article in the Scientist,

The gene expression profiles now "lay the foundation" for other detailed molecular analyses of human-human clones with an eye toward isolating embryonic stem cells, said [Keith Latham, a developmental biologist at Temple University School of Medicine, in Philadelphia, who was not involved in the research]. [Justin St. John of Warwick University] agreed that the paper's most important finding was the detailed characterization of human-human embryos, not the limited human-animal hybrid data. "That in and of itself is a success," he said. "I'm not sure why they weren't selling that point more . . . They seem to [be] spinning a negative result instead of spinning [a] positive result."