WASHINGTON

Harold Varmus, the director of the US National Institutes of Health (NIH), came under heavy fire from a congressional subcommittee last week because of lapses that had allowed an NIH-funded researcher to conduct human embryo research in alleged contravention of US law.

“It appears that some in NIH believe they are above the law. They are wrong,” said Joe Barton (Republican, Texas), chairman of the oversight and investigations subcommittee of the House of Representatives Commerce Committee, which oversees management of NIH. Barton accused NIH of “slax oversight, miscommunication and an utter lack of sensitivity to the social and moral issues involved”.

But Varmus, the only witness at the hearing, said that “We too have a very large respect for law… This episode was highly unusual and unlikely to recur”.

The hearing focused on the case of Mark Hughes, a reproductive biologist with whom NIH severed its relationship last autumn on finding that he had breached a congressional ban on federal funding for human embryo research (see Nature 385, 190; (1997).

Hughes is a specialist in single-cell genetic analysis, which can be applied both to non-embryonic cells, such as cancer cells, and to early-stage embryos. DNA from 8-cell embryos produced at in vitro fertilization (IVF) clinics is analysed and, if it is found to be abnormal, the embryos are not implanted. This technique is called preimplantation genetic diagnosis (PGD).

Hughes, who did not testify at the hearing, said in a subsequent statement that he had felt that the federal ban did not to apply to his work, because he was working with DNA from embryos, not the embryos themselves.

“I studied and tested only DNA samples obtained from embryos by technicians at non-NIH funded programs at clinics and universities around the country,” he said in a written statement. “It was my belief that this in no way violated any prohibitions against government-sponsored embryo research.” The statement adds: “Many people at NIH… knew of my single cell work. I think this demonstrates that I believed, in good faith, that I was permitted to continue my PGD research.”

Varmus maintained at the hearing that NIH recruited Hughes in 1994 only to do non-embryonic work, unless an NIH policy then in place forbidding embryo research was changed. He said NIH believed that Hughes was doing embryo research only in his own time and with his own resources, at a separate facility, while doing non-embryonic work at the National Center for Human Genome Research (NCHGR, now the National Human Genome Research Institute (NHGRI)), to which he was recruited by NIH from Baylor University in Houston, Texas. Varmus said that Hughes was repeatedly told of existing prohibitions on embryo research. “He knew what the rules were,” Varmus said.

But the politicians produced NIH documents that appeared to contradict Varmus. For instance, the agreement Hughes signed with NCHGR in 1994 states, “pre-implantation genetic diagnosis will also be provided by blastomere biopsy and single-cell [polymerase chain reaction] technology”. And an NCHGR publicity book outlining the work of its lead researchers describes Hughes' work as including “genetic diagnosis of the 8-cell preimplantation embryo in vitro”.

Varmus told the politicians that the book was “without any obvious implication that that research was being done at the NIH”. He added that, when Hughes was hired, NIH had a “reasonable expectation” that the existing prohibition on human embryo research would soon be lifted. The documents simply reflected that expectation. But Ron Klink (Democrat, Pennsylvania), the senior subcommittee Democrat, declared, “We are very troubled by this. It appears to be considering something” that was forbidden. He demanded that Varmus produce earlier communications to Hughes proving that “there was not a wink and a nod” when Hughes was hired.

The congressmen also distributed a recent report by an internal NIH inquiry committee on protection of human subjects. It concluded that preimplantation diagnosis “was a prominent feature of Dr Hughes' activities, as well as those of at least two [NIH-supported postdoctoral fellows] and one Visiting Fellow throughout their association with NHGRI”.

The report says that at least one case of preimplantation diagnosis was handled on the NIH campus. It adds that “the work of the Hughes laboratory was presented at in-house NHGRI research retreat days and in the published abstracts of the American Society of Human Genetics in 1995 and 1996. Thus, it appears to the committee that the research activities of the Hughes laboratory were conducted and communicated in an open manner within the NHGRI and general genetics communities.”

The federal law pertaining to Hughes' particular embryo work was clear from January last year, when Congress banned federal funding for research on spare embryos from IVF clinics in which embryos are harmed or destroyed.

But when Hughes was hired in 1994, a legal obstacle to federally funded human embryo research had recently been lifted, and NIH was operating, according to Varmus's testimony, with the expectation of revising its own policy to reflect this and allow some embryo research. An NIH expert panel — which included Hughes — concluded in December 1994 that federally funded human embryo research was allowable in certain carefully controlled conditions.

While President Clinton immediately blocked an NIH panel recommendation that some creation of human embryos for research purposes be allowed, his order did not address work on ‘spare’ IVF embryos. This was banned thirteen months later by Congress.

A document provided by NIH but not produced by the congressmen at the hearing supports NIH's version of events. Jeffrey Trent, the scientific director at NCHGR, wrote to a colleague in August 1995 that he had talked to Hughes about his non-NIH embryonic work at nearby Suburban Hospital. “I told [Hughes] that I am not willing to place federal personnel, etc., at Suburban within an IVF facility,” Trent wrote.

The NIH also provided letters from Hughes assuring NIH that he was not using NIH-funded staff or equipment at Suburban Hospital — statements later shown to be false, according to an NIH investigation.

At the hearing, Klink also asked Varmus about “all these postdocs that were doing the same thing (that is, preimplantation genetic diagnosis) under Hughes”. Did they not “give a damn”, he demanded, or were they “intimidated” by Hughes? “I am concerned about a deficiency in mentorship” by Hughes, Varmus responded.

The charge that Hughes intimidated his postdocs into doing work they suspected might be illegal is contained in notes made by Kate Berg, an NIH official, when NIH investigated Hughes in October last year. But Scott Gant, a lawyer representing Hughes, said that Hughes “denies having intimidated anybody.”

The NIH human subjects inquiry committee also concluded that Hughes conducted the embryo work at NIH without the required approval of an NIH ethics board, and without meeting the standards for commercial diagnostic laboratories required by law.

Varmus said that NIH was taking corrective actions to reduce the risk of a recurrence, including ensuring that no other similar research was being conducted, and contacting researchers most likely to stray into the area banned by law.

Hot seat: Varmus (left), seen here at an earlier hearing on cloning, says events surrounding the controversial research are “unlikely to recurr”. Credit: AP/DOUG MILLS

Other management gaffes surfaced during the hearing. The congressmen grilled Varmus about how Hughes was allowed to load a lorry with more than $1-million-worth of NIH equipment, including some boxes marked “Suburban Hospital” — on loan to Georgetown University — and leave NIH with it, without a completed loan agreement or inventory. Some of the equipment was diverted to Suburban Hospital.