Closing in on human cloning

Introduction

Although two successive presidents have publicly opposed human reproductive cloning, the federal government’s aggressive funding of experiments in cloning technology in nonhuman primates is bringing human cloning closer to reality.

Since 1991, the Center for Public Integrity has found, the National Institutes of Health has given more than three dozen grants for cloning-related research in nonhuman primates such as rhesus monkeys, which are genetically close to Homo sapiens. And the agency is currently supporting—to the tune of $6.4 million—a five-year experiment specifically intended to remove obstacles in monkey cloning.

The research is relatively unregulated and has little public oversight. Some experts warn that it will ultimately bring human cloning closer to reality—unless clear laws are enacted to ensure that the knowledge gained from primate-cloning research is not replicated in human beings.

“People have to be aware of how close [cloning of nonhuman primates and human beings] are to each other,” said Stuart Newman, a professor of cell biology and anatomy at New York Medical College.

“The animal cloning science is having a complete free ride,” said University of Pennsylvania bioethicist Autumn Fiester. “Sky is the limit [for the science]—there is no regulation, no limitations placed on the science at this point.”

The bulk of the government’s largesse went to three researchers: Gerald Schatten, who helped produce the first genetically altered primate and received the five-year, nearly $6.4 million NIH grant mentioned above; Don Wolf, known for the creation of sibling rhesus monkeys from cloned monkey embryos; and James Thomson, one of the scientists who first isolated stem cells in human beings.

All three have strong ties to either of two NIH-funded National Primate Research Centers, one in Beaverton, Ore., and the other in Madison, Wis.

According to Schatten’s grant proposal, one of the goals of his project is “to produce at least ten cloned [non-human primates] by overcoming unanticipated hurdles” that he “discovered during primate cloning.”

Schatten declined to be interviewed for this report.

The Center for Public Integrity identified cloning-related grants for experiments on nuclear transfer in primates—which involves replacing the nucleus of an unfertilized egg cell with material from the nucleus of another cell, a procedure used for cloning—or for general support of laboratories doing such research.

Federal ban

President Bill Clinton prohibited federal funding for human cloning research in 1997, just after Scotland’s Roslin Institute announced the creation of the sheep Dolly, the first successful cloning of a mammal from a single adult cell. Clinton noted that the new technology potentially represented huge “breakthroughs” and offered great medical and agricultural benefits, but “also raises profound ethical issues, particularly with respect to its possible use to clone humans.”

Clinton’s successor, President George W. Bush, not only kept that ban, but expanded it to limit government funding for embryonic stem cell research.

But while the federal move substantially cut off money for research in humans, federal dollars fueled many breakthroughs in animal cloning and related areas of genetics.

NIH money— specifically, the National Center for Research Resources’ investments in primate centers—in fact, made possible many critical discoveries in primate genetics.

These centers maintain more than 24,000 nonhuman primates and supply nonhuman primate cells, tissues, organs, and biological fluids to researchers around the country and the world, according to the NIH.

The branches in Oregon and Wisconsin are leaders in primate reproductive techniques and stem cell research. For example, the first major successful application of the cloning technology in primates was recorded in Oregon in 1997, when a team led by senior scientist Wolf produced sibling rhesus monkeys from cloned monkey embryos. The breakthrough came a week after the announcement of the birth of Dolly.

Both Wolf and James Parker, a spokesman for the Oregon facility, stressed that the rhesus monkeys were not clones. Parker told the Center for Public Integrity that the experiment was not cloning because the cloned primates were not genetically identical to any adult monkey. Parker insists, in fact, that Wolf does not engage in cloning research. He used, rather, “cloning techniques” (Thomson’s spokesman, Terry Devitt, also says that Thomson does not do cloning research).

Under Schatten’s leadership, the Oregon center created the first genetically engineered monkey. ANDi, born in 2000, was the first primate to incorporate a foreign gene, a green florescent protein from jellyfish.

In their experiments on so-called nuclear transfer technology Schatten, Wolf and their colleagues were aided by Thomson, who derived new rhesus embryonic stem cell lines and shipped them to Oregon week after week. Stem cells, which are primordial cells, possess the potential to become any part of the body. According to his proposal, Thomson began supplying the cell lines in 1997.

Thomson isolated and cultured embryonic stem cells from nonhuman primates in 1995 following some 10 years of research on monkeys. Three years later, Thomson grew human embryonic stem cells in a privately-funded laboratory for the first time.

All of the research conducted at the primate centers is federally subsidized. The Wisconsin National Primate Research Center received more than $25 million worth of federal grants between 1996 and 2002. During that time, the NIH gave Thomson grants to conduct his stem cell experiments on nonhuman primates in the center as well as experiments that used “nuclear transfer strategies to generate genetically identical rhesus monkeys.”

From 1996 to 2002, Wolf and his colleagues at Oregon received more than $30 million in federal grants.

The National Center for Research Resources has supported nuclear transfer research by private companies as well. Government documents reveal that, as early as 1991, the center gave a grant to a Granada Biosciences Inc. researcher for “nuclear transfer in non-human primates.”

Human applications

The NIH said its allocations of resources are well within the laws.

“We are going to follow the president’s Executive Order against human cloning,” an NIH spokesman told the Center. “Concerning animal cloning, we will follow our assurances for the care and protection of animals.”

Wolf disputed the notion that cloning of primates would necessarily lead to human reproductive cloning. “First of all, you need to say that the reason we are trying to perfect the technology is because you want to use it in nonhuman primates.”

“There is no rational justification for cloning nonhuman primates predicated on the interest in humans,” he said. “Fact of the matter is we have far more experience in humans with doing test-tube babies and assisted reproductive technology than we do in monkeys. I wouldn’t buy the argument that establishing cloning technology in monkeys is going to impact reproductive human cloning technology in humans.”

But Wolf agrees the research has human applications. “As a spin-off, it seems reasonable to extrapolate that the more you learn from experience in mammals, and nonhuman primates, specifically, the more information you bring to the problem or to the challenge if you are going to clone humans,” he said.

The reasons aren’t hard to find. In biological terms, humans share some 93 percent of their DNA with rhesus monkeys. “Humans and monkeys bear a close genetic relationship, reflected in many anatomical, behavioral, developmental and physiological similarities,” notes the Web site of the California National Primate Research Center, the federally funded biomedical research facility housed at the University of California, Davis. “Monkeys are the only mammalian animal model with menstrual cycles and hormonal patterns comparable to humans.”

The embryonic cell cloning from an undifferentiated cell, carried out in Oregon under Wolf’s supervision, was described as “the closest application” of cloning technology “yet to a species related to humans.”

Schatten’s and Thomson’s work also show the close connection between primate and human research. For example, Schatten turned to human stem cells last year after fine-tuning the work on embryonic stem cells in monkeys. Thomson used research on nonhuman primates to successfully isolate human stem cells.

Thomson’s spokesman, Terry Devitt, acknowledged that the scientist’s work in primates was key to the scientist’s ultimate success with humans. “There are a lot of similarities between embryology in nonhuman primates and humans. I would say that [work with nonhuman primates] was essential ultimately to his success with human cells.”

NCRR Director Dr. Judith Vaitukaitis concurs. She wrote in the Fall 2002 edition of the NCRR Reporter that research done at “the NCRR-funded Wisconsin National Primate Research Center enabled the first isolation and culturing of ES [embryonic stem] cells from nonhuman primates in 1995. Using knowledge gained from these studies, Dr. James Thomson and his colleagues took the conquest forward in 1998 when they isolated and propagated human ES cells.”

Private money

The federal government’s ban on using its resources for human cloning-related experiments does not apply to privately financed research in the area, either.

Although most mainstream scientists oppose human reproductive cloning, some have vowed to pursue it, most notably Kentucky-based fertility expert Panayiotis Zavos and Italian embryologist Severino Antinori.

The scientific infrastructure in the United States, which promotes public-private partnerships, allows research with private funding at the point where federal support ends.

In fact, scientists often seek to build on their federally financed basic research using private sponsorship, or by joining private firms that do such research.

A case in point is Thomson’s research on stem cells.

Shortly after his team isolated stem cells in nonhuman primates, the University of Wisconsin scientist turned to human stem cells. Since federal funding could not be used for the same research with human cells, the lab was funded by Geron Corp. and Wisconsin Alumni Research Foundation.

In 1999, following Thomson’s breakthrough in human stem cells, a separate company, WiCell, was created to commercially provide human stem cell lines.

“[The lab] was set up in a way that the work was completely isolated from any federal funding,” Devitt, the Thomson spokesman, told the Center for Public Integrity.

Such arrangements between universities and private companies have become popular around the country. A university’s patenting powers makes it an attractive lure for companies, which in turn can provide extra funding for badly needed research.

A powerful incentive for such so-called technology transfer offices is the Bayh-Dole Act of 1980. The law encourages the commercialization and utilization of therapeutic applications that arise from research funded by the federal government.

The transfer of resources to the private sector isn’t limited to technology. Private firms sometimes employ researchers hitherto working at public research facilities.

Bioethicist Fiester said that the government could thwart some of the criticism by having strict regulations. “I don’t believe that the reason the government is supporting this kind of cloning, and other animal cloning, is because they want to see human cloning,” she said. “But one of the things they need to do is create a ban—a very clear ban, not one that’s got such a murky language nobody knows what is outlawed and what is supported—but a ban on doing the parallel work on human beings that they are doing on nonhuman primates and animals.”

But Fiester is also a realist. Given the furious pace of scientific advances in the field, she says, even with proper regulations in place, a human clone is a very real possibility. “Whenever the primate [cloning] technique has been perfected, it will propel someone somewhere in the world, maybe the Chinese, maybe the Koreans, who will try to clone a human being,” she said. “I don’t see pragmatically how there’s any stopping it. Maybe in the United States, maybe somewhere in the world, someone is going to do it, if [the primate cloning technique] gets perfected in nonhuman primates.”

Alexander Cohen contributed to this report.