Alleged Gift of Tissue Taints Embryo Research

What renowned University of California fertility specialist Ricardo H. Asch allegedly handed to a Wisconsin zoologist was, by any measure, a precious gift.

In a country where relatively few couples donate their reproductive tissues for experiments, Asch bestowed 21 freshly inseminated eggs and three frozen embryos on Gerald Schatten from 1993 to 1994, UC San Diego officials say. The well-known scientist then used them to probe the mysteries of why some fertility treatments fail.

There was just one problem: The eggs and embryos were stolen, UC San Diego officials say. Last month, the university announced that, unbeknownst to Schatten, Asch had not obtained patients’ consent to give away their viable eggs and embryos. Nor had he obtained approval from the university.

Whatever promise the tissues held for science, some researchers fear Asch’s alleged gift will be best remembered for the taint it brought to the entire field of embryo research.

Worse, the accusation--the latest development in a long-running UC fertility scandal--has heaped more controversy on a scientific enterprise imperiled by political opposition. Some worry it has given fresh ammunition to abortion foes who object to tampering with incipient human lives.

“This is the last thing we want, to have this [Asch’s case] reflect on all the clinical and basic research that is being done,” said Dr. Mitchell Karlen, a Beverly Hills surgeon who is part of an American Medical Assn. task force now establishing guidelines on assisted reproductive technology.

The stain on embryo research may grow: Two former patients at Asch’s UCI clinic have sued the doctor, alleging he sent their embryos, without permission, for study at a Cornell University lab. UCI’s investigations of possible research misconduct at the Orange County clinic are not finished.

Through his attorney, Asch has denied he gave any embryos to Schatten and blamed any mishaps at UCI and UC San Diego clinics on university employees.

UC San Diego’s accusations against Asch came just days after Congress passed a law virtually banning federal funding for research on human embryos for the rest of the year. Though research on embryos created outside the womb has not been federally funded since the 1970s, the formal action sent a chilling message to scientists who had been hopeful of federal dollars under a Democratic administration.

The Asch affair and the federal ban are “a very serious one-two punch” to embryo research, said Arthur Caplan, an ethicist at the University of Pennsylvania. “On the one hand you’ve got questions raised about the integrity of the field; on the other hand, you have limits put on fundamental research . . . [that were] tossed in as a pawn in a big political game.”

The ban, critics argue, is counterproductive.

The UC fertility scandal--which also involves allegations Asch and his partners implanted stolen embryos in scores of patients--has raised a cry for a greater level of scrutiny in the field. In the research arena, funding from the National Institutes of Health brings federal oversight--and researchers face the risk of losing the money if they don’t toe the line.

Yet the federal government has stepped back just when circumstances suggest it should take a leadership role, some critics charge.

“Private researchers can do whatever they please and whatever they can get away with, and it can go on anywhere,” said Dartmouth College ethicist Ronald M. Green. “You can do it in your kitchen.”

While many political conservatives hope the absence of federal support will curtail research, the lack of federal oversight leaves privately funded researchers too much to their own devices, he said.

“People fail to realize there are two reasons for wanting federally funded research,” said Green, who sat on an NIH panel that recommended federal funding for limited embryo research in 1994. “The research is important medically and clinically. But also, in the absence of federal funding, the research goes on anyway . . . without review.”

The congressman who sponsored the ban argued that even if the government funded such research, officials still could not exert control over those who rely on private dollars. Rep. Jay Dickey (R-Ark.) stopped short of endorsing a ban on privately funded research, but he drew a clear line at anything smacking of a federal endorsement.

“It starts out with a base of respect for the sanctity of life,” Dickey said. “Some of us have the perspective that at conception, life begins. . . . We’re just saying we don’t want federal funds to go to experimenting with that life, terminating it or causing risk or harm to it.”

Most embryo research in the United States takes place in a few dozen centers and is privately funded. The portion done at universities is sometimes--but not always--reviewed by internal boards, with varying degrees of vigilance.

UC San Diego alleges Asch skirted the university’s oversight process. University officials assert the doctor failed to get approval from the university’s review board, as required, then lied to the Wisconsin researcher, Schatten, saying he had. Asch also is accused of falsely assuring Schatten, in writing, that patients had approved the transfers. A board at the University of Wisconsin approved Schatten’s research based on those misrepresentations, officials there said.

For his efforts, Asch got his name, with those of Schatten and others, on two research papers in scientific journals, officials said.

The misconduct accusations leveled at Asch were not the first blot on the field. In 1993, researchers at George Washington University Medical Center conducted a cloning experiment, using embryos left over from in-vitro fertilization procedures to create 48 genetically identical human embryos. The experiment--which was approved by the university--raised moral outrage among everyone from medical authorities to the Vatican.

Coming about two years later, the research misconduct allegations against Asch--a giant in the fertility field--struck a raw nerve.

As legislators vow to address the field’s problems with new laws and regulations, many research advocates protest Asch’s alleged misconduct was an aberration. If the doctor was so unethical as to sacrifice patients’ rights for scientific glory, no law or regulation was going to stand in his way, they argue.

“The solution . . . is not just to ratchet up the regulations,” said Norman Fost, who heads the review board at the University of Wisconsin but made it clear he was expressing his personal views. “Every time you do that, you inhibit good researchers. . . . Much of the regulation we have now does nothing to prevent misconduct. It just adds paperwork. More regulation doesn’t prevent somebody from lying or cheating.”

Others say more self-policing within the industry is a must. Some labs already have tightened procedures in response to the Asch case. And committees have convened at several campuses and hospitals--including a panel at UCI--to consider improving oversight of human subject research.

Greater regulation might very well slow the pace of research, one UCLA professor said--but so be it.

“The $64,000 question is: How rapidly does this area of research have to move?” said Dr. Joseph Gambone, director of the fertility program at the UCLA School of Medicine.

“People in science tend to want zero regulation so science can move along as rapidly as possible. . . . But this is a branch [much like atomic research] that has enormous ethical and moral and legal considerations. Maybe it should move along more slowly. Maybe it’s good to take pause.”

Many of Gambone’s colleagues fear the combination of strict regulation and no federal funding will leave important research at a standstill.

“This ought to have been the decade of the human embryo,” said Dr. Roger Pedersen, a professor and researcher at UC San Francisco dismayed by the federal ban. Instead “we know less about human fertility and early embryology than about any other species we’ve studied as a model. . . . It’s a dismal situation, given human beings are the most important species on the planet, at least to us.”

It is but one of many ironies stemming from the country’s ambivalence toward embryo research, researchers said.

Here is another: The country is stockpiling a huge number of frozen embryos--some of which will never be used to impregnate women--yet most are unavailable for research. Patients who might benefit from the findings often are not inclined to donate them for that purpose.

“It’s very hard to obtain eggs for experimental purposes because women pay a large price in terms of time, effort, risk and expenditure to have eggs available so they can try to achieve a pregnancy,” said Dr. Joseph Massey, a fertility specialist in Atlanta.

“We’ve got 15 huge tanks of embryos, about half of which are in limbo. Women want the option to decide two, three or four years down the road what to do with them, and really, who’s gonna give up their eggs? What incentive do they have?”

Caplan, the University of Pennsylvania ethicist, speculated that the shortage of embryos for research has created a small black market among researchers.

Meanwhile, he said, clinicians are creating many more embryos than they actually use because not enough research is being done to make the fertilization process more efficient.

“It is bitterly ironic that . . . the absence of research in this area is part of the reason why there is an overproduction of embryos, with no one certain what to do with them. The research hasn’t been done to make the treatments work better.

“The longer we don’t do research, the more we create excess embryos--and the more the temptation [on the part of clinicians] to circulate them sub rosa.”

Research advocates say the hundreds of centers doing in vitro fertilization procedures in this country--and the millions of dollars invested by patients in these procedures--dwarf the resources invested in improving the process through applied research. Ultimately, they say, that is unfair to infertile patients.

“We have to fight for the important research that’s needed,” said Diane D. Aronson, executive director of RESOLVE, a nationwide advocacy group for infertile people. “Infertility is . . . a heartbreak for a lot of folks.”

For a while, researchers’ hopes were high. In 1993, Congress quietly lifted a long-standing moratorium on federal funding for in vitro fertilization research. The NIH, in response, convened a panel--including Aronson and Dartmouth’s Green as members--to develop detailed recommendations for funding.

In 1994, the panel released a report endorsing limited research for such purposes as improving the likelihood of pregnancy, identifying genetic abnormalities, developing contraceptives and understanding chromosomal abnormalities associated with cancer.

One promising line of research discussed in some detail was the possibility of cultivating eggs outside the body so women wouldn’t have to undergo sometimes painful and risky hormonal treatments.

The panel termed “unacceptable” such endeavors as cross-species fertilization--involving the mixture of human and animal reproductive materials--and combining material from two human embryos into one.

But, to the disappointment of panel members, the recommendations went unheeded.

In late 1994, President Clinton banned funding for research on embryos created exclusively for research purposes. And last month, Congress approved the more sweeping ban in a concession to conservative Republican legislators. The president accepted the provision--part of a larger spending bill-- “under duress,” an administration official said.

“The 103rd Congress was doing everything it could to disregard the life of the child,” countered Dickey, the congressman who sponsored the ban. “We’re bringing it back into focus.”

He said he has seen no evidence that experimentation on human embryos would help infertile couples. And the potential for genetic research--theoretically allowing for selection of embryos based on sex and other characteristics--made him squeamish.

“It worried me somewhat that we were getting into what occurred in Nazi Germany,” he said. “Any of that stuff where we start experimenting with gene selection, it all bothers me.”

Dr. Robert D. Visscher, executive director of the American Society of Reproductive Medicine, lamented that the research debate is largely limited to people in the fertility field and conservative political adversaries. The attention of the public at large, he said, has yet to be fully engaged.

“In the United States, we have a very difficult time dealing with reproductive health issues and anything to do with sexuality--including contraceptives, embryo research, fetal tissue research--anything to do with having babies.

“We just are not able to have a discussion on it because it gets tied in with the abortion debate, and you get visceral responses. There aren’t the appropriate discourses that give rise to popular consensus.”

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Areas Proposed for Embryo Research

In 1994, a panel convened by the National Institutes of Health recommended the federal government fund limited research on human embryos that are up to 14 days old and created outside the uterus. At that point, an embryo is about as big as a period at the end of a sentence. Last month, Congress approved a virtual ban on federal funding for such research. The work, if it is done, most likely would have to be privately funded.

Some areas endorsed by the NIH panel for funding:

* Studies aimed at improving likelihood of successful outcome for pregnancies

* Research on process of fertilization and new contraception techniques

* Studies on various roles of paternally derived and maternally derived genetic material in embryo development

* Studies on egg maturation that panel said might help female patients avoid sometimes painful and risky hormone treatments

* Genetic diagnosis of embryos--before and after implantation--to determine possible defects

* Research involving use of embryonic cells that could serve as basis for therapies such as bone marrow transplants, repair of spinal cord or skin replacement

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Some proposals the panel found unacceptable:

* Cloning or “twinning” of human embryos, followed by transfer into the uterus

* Research involving fertilization of fetal eggs with intention of transferring them to a uterus

* Mixing materials from two or more embryos

* Genetic diagnosis for the purpose of sex selection, except for sex-linked genetic diseases

* Human-animal combinations and implantation of human embryos into animals

* Implantation of chemically or mechanically activated human eggs that have not been fertilized

Source: National Institutes of Health

Researched by LISA RICHARDSON / Los Angeles Times