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The next big stem cell fight: mixing cow and human DNA

By Sharon Schmickle | Tuesday, July 22, 2008
CAMBRIDGE, ENGLAND—Scientists here are trying to mix cow and human DNA, something they say they must do to advance stem cell studies. Debate over this step has reverberated across the Atlantic, and Sen.

At the center of the latest stem cell debate: A cow grazes at sunset in central England.
REUTERS/Darren Staples
At the center of the latest stem cell debate: A cow grazes at sunset in central England.

CAMBRIDGE, ENGLAND—In Gary Larson’s wacky Far Side world, cows and humans swap traits with hilarious results.

Nobody is laughing, though, over a real-world bid to mix cow and human DNA, something scientists here say they must do in order to advance stem cell studies.

Debate over this step in the exploration of stem cells already has reverberated across the Atlantic. Sen. Norm Coleman, R-Minn., is a co-sponsor of a bill that would ban the research in the United States.

From the first test-tube baby to the first cloned animal, scientists in this part of the world have led a biological revolution that set off an uproar in the United States but met relative calm here.

Now, though, the research is crossing a line that has shattered the calm and ignited fiery debate all the way up to Prime Minister Gordon Brown’s cabinet.

The line at issue is the notion that the human animal is fundamentally different from all other creatures on Earth — in a sacred sense for many people of many faiths.

“From a Christian viewpoint, the teaching is, of course, that we are made in the image of God, and there is something special about human life in relation to divinity,” said Sir Brian Heap, a prominent Cambridge University biologist who has helped his government shape stem cell policy.

Heap is one of many scientists, though, who are ready to cross the line for the sake of research that could save lives and solve the mysteries behind deadly diseases.

Blurring human-animal lines

It isn’t religion alone that triggers revulsion to the notion of stirring animal DNA in with human genes, said Jeffrey Kahn, who directs the Center for Bioethics at the University of Minnesota.

Throughout the centuries, humans have drawn a bright line around themselves, relegating other animals to a lower order. We used animals to pull our plows, test our medicines and fill our dinner plates — and, with notable exceptions, we slept at peace with our moral sensibilities.

Now, though, scientists are blurring that line. Genomic studies are revealing that chimpanzees and humans are separated, at most, by 5 percent of their DNA. The cow is a more distant genetic cousin, but it too shares genes with humans.

Sir Brian Heap
Sir Brian Heap

Beyond the genome, scientists are finding that some animals possess intellectual and emotional capacity far greater than previously believed. They create tools, feel pain, recognize a sense of themselves as individuals, use language and experience some emotions.

The upshot, Kahn said, is a fresh encounter with the fundamental question that has roiled American politics throughout the abortion debate: What defines personhood?

That question in the United Kingdom right now turns on the eggs nurturing human cells that form embryos.

To understand the debate, let’s begin at the beginning.

The magical ‘master cell’

The research that led to this explosive step began in Cambridge, inside the brick and stone walls of a stately Victorian building. In 1981, genetic scientists, experimenting with mice, discovered a seemingly magical “master cell” that could give rise to all of a body’s parts from a beating heart to a perceptive eye.

The cell was an embryonic stem cell. It wasn’t until the late 1990s that scientists in Wisconsin isolated the same cells in human embryos, and set off a race for cures that have the potential to revolutionize medicine.

Jeffrey Kahn
Jeffrey Kahn

One major thrust is unlocking the mysteries of deadly diseases. Scientists envision a day when a line of stem cells — from, say, a cancer patient — could reveal clues to what went wrong and lead the way to cures.

Another promising potential is growing replacements for damaged or diseased tissue — ideally from a patient’s own cells so that rejection would not be a problem. A burn patient, for example, could grow new skin for grafting.

Egg shortage
There is a practical hurdle, though. The hope for replacing diseased tissue and eventually whole organs rests on a process that requires eggs. 

Researchers have relied on small supplies of eggs donated from fertility clinics. But now the studies are at a point where scientists need a much larger array of stem cell lines, Heap said, “to understand the basic mechanisms that are involved in producing let’s say a liver cell as opposed to a nerve cell as opposed to a skin cell.”

Women can’t be expected to donate enough eggs to satisfy that need.

Any woman who has undergone infertility treatment knows it is not a simple matter to deliver the eggs needed to expand one family let alone stock a major research facility. Egg donation can require many clinic visits and minor surgery to extract eggs from the ovaries.

Harvard University recently spent tens of thousands of dollars on newspaper ads in an unsuccessful campaign to recruit egg donors for stem cell studies, the Boston Globe reported.

“Hundreds of women have responded to the ads, but none has followed through with donations for a variety of reasons,” the Globe reported.

What’s true at Harvard is true in the UK and around the world. With inadequate egg supplies, the studies are lagging.

The controversial alternative is cow eggs.

The genetic swap
The process starts with cow eggs, so small that a pile of 50 looks to the naked eye like a tiny dust ball. From each egg, lab workers extract the nucleus, the DNA payload that would have developed into a calf had a bull’s sperm penetrated the egg. In its place, they insert the DNA package from a human cell.

Next, workers use laboratory techniques to trick the egg into thinking that it has been fertilized by sperm. Within about a week, the single-celled egg has morphed into a ball of cells that make up an early embryo from which stem cell lines can be extracted.

Here’s the hitch: Even after the cleanest genetic swap, the egg retains a trace of DNA which resides outside its nucleus. While most of our DNA is inherited from both parents, this mitochondrial DNA comes from the mother alone. And she passes it to her offspring.

Thus, the human embryo gets fragments of bovine DNA. And, thus the uproar.

Not a first
The process is not new, nor is the marriage of human and animal DNA. Several labs in the Upper Midwest have inserted human genes into cow eggs in efforts to induce the cows to yield milk laced with ingredients for human medicine.

The University of Minnesota and the Mayo Clinic in Rochester, Minn., have experimented for years with developing cells and organs in pigs for transplantation into humans.

In 1998, researchers in Massachusetts announced that they had fused human DNA into cow eggs, creating very early embryos that critics called “cowboys.” None of the embryos survived, and the aim was not to give birth to cow-human hybrids. Instead the scientists sought tissue for transplantation.

In 2005, the National Academies in Washington, D.C., issued guidelines, which are not legally binding, saying such experiments should be allowed if they are approved by special review boards.  

Meanwhile, some other countries, including Canada, banned human-animal embryo research.

Now, in reaction to the British experiments, some Congress members are pushing for a U.S. ban.

“What was once only science fiction is now becoming a reality, and we need to ensure that experimentation and subsequent ramifications do not outpace ethical discussion and societal decisions,” Sen. Sam Brownback, R-Kansas, said in a statement.

Brownback is the author of the bill Coleman and 17 other senators co-sponsored.

“As someone who has consistently protected the sanctity of human life, Senator Coleman will not support any research that would result in human-animal hybrids,” said his spokesman LeRoy Coleman. “This type of experimentation not only raises serious ethical concerns, but also public health issues. In Congress, Senator Coleman has been leading the effort to discover and promote ethical stem cell research, and he is certain that the creation of human-animal hybrids is not the answer.”

Last year the Senate passed a Coleman-authored bill which would expand federal funding for stem cell research that does not harm embryos.     

More visible in UK
There are several reasons why the UK’s move into the hybrid-embryo research has prompted such heated reaction even while similar studies have been conducted in American labs, Kahn said.

A major reason is that the British system regulates stem cell research in a way that makes it far more visible than in the United States.

The hullabaloo in American politics is over federal funding for stem cell research. That’s the tip of the iceberg. Much of the work is in privately funded labs, Kahn said, where scientists are free to experiment with human-animal combinations.

In the British system, the special authority regulating the research made public this year that it had granted licenses to two research teams for experiments with human-animal hybrids. One of the teams, at Newcastle University, announced in April that it had created the first part-animal, part-human embryos, the BBC reported.

Meanwhile, opponents of the research had moved in Parliament to ban it, while proponents pushed a bill that would affirm the right for scientists to continue the studies under strict controls.

It would be illegal to implant the animal-human embryos into women or any animal. In other words, no babies could be born from them. It also would be illegal to keep them beyond 14 days, which gives scientists time to extract stem cell lines, but stops the embryo short of a point many say defines the beginning of a person.

Opponents were not satisfied.

“We do not believe that regulation is enough,” Edward Leigh, a Conservative Catholic Member of Parliament, said in the BBC report. “In embryos, we do have the genetic makeup of a complete human being and we could not and should not be spliced together with the animal kingdom.”

Prime Minister Brown defended the research in a letter to members of his Labour Party.

Brown reminded them of a world-wide race for therapies that are expected to deliver lucrative returns to their developers: “The UK is at the forefront of this research and responsible for much of the worldwide progress.”

While stressing hope the research holds for patients, he also spoke to the moral dilemma: “Leading doctors and scientists . . . believe that theirs is an inherently moral endeavour, that they can save and improve the lives of thousands and over time millions of people, and that they can combine this work with a deep commitment to the highest ethical standards and a sincere respect for religious beliefs.”

Roman Catholics passionately disagreed, not only to the mixing of human and animal DNA, but also the notion of creating what they regard as a human life and then destroying it.

In his Easter sermon, Cardinal Keith O’Brien, the head of the Scottish Catholic Church, denounced the research as “a monstrous attack on human rights, human dignity and human life.” He accused the government of endorsing “experiments of Frankenstein proportion.”

O’Brien also posted an appeal on YouTube in which he says that the mixing of human and animal life “is abhorrent to us as Catholic Christians.”

The House of Commons defeated the proposed ban in May and passed the bill sanctioning the research. Three members of Brown’s own cabinet voted against his position.

Debate continues
Heap, the biologist at Cambridge, is one of many prominent British scientists who support the research but also call for a thorough airing of ethical and moral concerns. He is co-author of a definitive paper on the research published in June by the International Society for Science and Religion. The other author is the Rev. Dr. Ronald Cole-Turner of the Pittsburgh Theological Seminary.

Heap and Cole-Turner call for philosophers and theologians to join scientists in the “highest level” of analysis of issues that will continue to arise from the research “because they impinge on the significance of species boundaries and human dignity, as well as the capability to address serious medical conditions.”

Sharon Schmickle writes about foreign affairs and science. She can be reached at sschmickle [at] minnpost [dot] com.