U.S. INQUIRY DISCREDITS GALLO ON AIDS PATENT
Diagnostic test claims were riddled by holes, probe says

By John Crewdson

Chicago Tribune 19 June 1994

A two-year inquiry by the inspector general's office of the Department of Health and Human Services has found no evidence to support Dr. Robert C. Gallo's claim that he was the original inventor of the widely used diagnostic blood test for AIDS.

Nor has the inquiry, a summary of which was obtained by the Tribune, provided support for the government's position that it is entitled, on the strength of Gallo's AIDS test research, to the lion's share of the millions of dollars in annual royalties paid by companies that make and sell the test.

Although the summary, like most federal investigative reports, contains no conclusions, it notes that the patent examiner who granted HHS the 1985 patent on Gallo's AIDS test told investigators she would not have done so had she known that French scientists already had developed such a test.

The patent examiner was among more than 50 scientists and former and current government officials questioned during the most extensive inquiry thus far into the circumstances surrounding the Franco-American dispute over Gallo's decade-old claim of having invented the AIDS test and discovered the virus from which it is made.

According to the summary, the patent examiner acknowledged that "had she been aware of (the French AIDS test research) at the time she examined the blood test application of Gallo, she would have suspended prosecution of the Gallo application interference" between Gallo's application and one filed months earlier by the French.

The summary notes that Gallo, who heads a research laboratory at the National Cancer Institute, failed to tell the Patent Office that scientists at the Pasteur Institute of Paris already had performed "extensive work" with the AIDS virus and had used it to make an AIDS blood test of their own.

Despite a legal obligation to disclose all information "material" to his claim of inventorship, the summary says, Gallo failed to inform the Patent Office that his laboratory had cultured the French AIDS virus, called LAV, "for an extended period and used it for many of their experiments."

According to the summary, Gallo later told investigators his assertions were untrue. "There is a point where I say I didn't grow LAV," Gallo is quoted as having acknowledged. "And, of course, LAV was grown."

The 35-page inspector general's summary, which provides a detailed chronology to "bring focus" to Gallo's statements and actions, includes a number of key statements attributed to Gallo -some made under oath-that are contradicted by evidence gathered in the inquiry.

According to the summary, after the dispute arose in 1985, HHS officials insisted that Gallo, not Pasteur, had been "first to identify the virus and to describe the virus antibody test."

The inquiry leaves little question, however, that Pasteur scientists were first to discover the AIDS virus, to isolate it successfully from several AIDS patients, to describe it in a scientific article, and to use it to make a diagnostic blood test for antibodies to the AIDS virus.

The summary also notes that more than a month before Gallo applied for the patent, another HHS agency, the Centers for Disease Control, informed Gallo that the French AIDS test was as accurate as his own at detecting AIDS virus antibodies in blood samples from AIDS patients.

In briefs filed with the Patent Office, HHS lawyers later dismissed the fact that Pasteur had sent Gallo a sample of its newly discovered AIDS virus as having had "no significance" for Gallo's research.

The summary asserts, however, that someone in Gallo's lab simply renamed the French virus, changing its designation from LAV to MOV, and continued to use it in the experiments that led to the development of Gallo's blood test.

The AIDS isolate Gallo later called HTLV-3B, the virus with which the U.S. version of the AIDS test is still manufactured, also has been shown to be the French virus LAV.

The AIDS test, one of the government's few lucrative inventions, has produced at least $20 million in royalties for HHS since 1987, compared with $14 million for Pasteur during the same period. Gallo has so far received more than $700,000 from the sale of the AIDS test in addition to his government salary.

The French first began to seek an expanded share of the AIDS test royalties in 1991, after Gallo admitted that HTLV-3B is really LAV-the result, he said, not of any misappropriation but of an "accidental contamination" in his laboratory.

The inspector general's report, however, states, "The claim that 3B was contaminated by LAV comes into question since there appears to be no evidence there ever was a 3B to be contaminated."

The formula for dividing the AIDS test royalties, which the French want to redraw, was worked out as part of a settlement announced by President Ronald Reagan and French Prime Minister Jacques Chirac in 1987, when far less was known about Gallo's AIDS test research.

In its chronological presentation of facts, for example, the inspector general's summary confirms a central complaint made by the French, most recently in a letter sent last week by Maxime Schwartz, the Pasteur Institute's director, to Dr. Harold Varmus, who heads the National Institutes of Health.

"The French test kit was developed in the absence of any input from the American scientists," Schwartz told Varmus, "whereas there is no evidence that the American test could have been developed if the American scientists had not received the French virus."

The French, initially angry that Gallo took credit for their discoveries after they provided him with their new-found virus and related materials, now assert that they were deliberately misled by the Reagan administration about the facts of the case.

In last week's letter to Varmus, Schwartz declared, "A cover- up of the true facts was deliberately undertaken so that we would settle." He said the French could no longer "abide by a sharing of royalties based on what would appear as a previous administration's deliberate fabrication."

Although HHS has so far refused to entertain the French appeal, that position may become more difficult to maintain in the face of the inspector general's summary. An NIH official said Varmus could not be reached for comment on his reaction to the inspector general's report.

Sources familiar with the inspector general's inquiry said that although Gallo, as a prospective inventor, had a legal obligation to tell the Patent Office about the Pasteur's research on the AIDS test and his own work with the French virus, the Patent Office had to share responsibility for improperly granting Gallo the patent.

The examiner who handled the Gallo patent, one source said, told investigators she hadn't known until after the Gallo patent was granted that the French had filed their own application months ahead of Gallo. The examiner blamed the mix- up on a breakdown in Patent Office tracking procedures.

Among the items never brought to the examiner's attention, the sources said, was a scientific article, published two weeks before the Gallo application was filed, in which Pasteur scientists provided the first description of the blood test for AIDS.

Earlier this year, federal prosecutors decided not to bring criminal charges against Gallo, citing what the inspector general's summary calls "several obstacles, jurisdictional concerns and procedural rules governing criminal prosecution," including the five-year federal statute of limitations.

The prosecutors advised the inspector general in the same letter, however, that their decision did not mean they believed Gallo "should continue to receive . . . annual royalty payments" from the AIDS test. One source close to the prosecutors said the language had been added to the letter "for a reason."

The inspector general's inquiry, which encompasses events from 1983 to 1994, was far broader than an earlier HHS investigation that had been limited to a single 1984 article in which Gallo reported his discovery of the AIDS virus.

That investigation concluded Gallo deliberately "misstated the role that the French virus . . . played in his work with the AIDS virus" by removing all references in the article to his assistants' use of LAV and then inserting a sentence claiming that LAV had never been successfully cultured.

Those investigators reluctantly withdrew their misconduct charges last November, saying that, while they had not changed their opinion about the facts, they did not believe they could get a fair hearing from the government appeals board that decides cases of science fraud.

Despite the withdrawal of the misconduct finding, the Gallo case has continued to smolder "like an underground fire that won't go out," as the authoritative newsletter, Science & Government Report, described it last month.

The publication quoted Frederick Richards, the Yale University professor who headed a blue-ribbon committee of scientists that oversaw the misconduct investigation, as calling for a reopening of the misconduct inquiry based on evidence that had emerged since the withdrawal.

Among other items, Richards referred to the recent discovery by congressional investigators of a 1987 computer analysis, by scientists at the Los Alamos National Laboratory, showing that Gallo's HTLV-3B was merely Pasteur's LAV by another name.

A memo from those scientists, written to senior NIH officials just nine days after the Franco-American settlement was announced, said the government's assertions that Gallo had made an independent discovery amounted to a "double fraud."

"The major purpose of this whole investigation," Richards was quoted as saying, "was to find out whether they stole the virus. The answer is, they stole the virus. But we didn't know that at the time."

The first indication that the Gallo matter was not concluded in the eyes of NCI and NIH came last April, at a congressional hearing on fraud in government-sponsored breast cancer research.

The NCI's director, Dr. Samuel Broder, who had earlier ordered the removal of Dr. Bernard Fisher of the University of Pittsburgh as chief of the nation's largest breast cancer research group, was asked whether he applied the same standards of fitness and suitability to NCI's own scientists, particularly Gallo.

Broder replied that "the issues involving Dr. Gallo have until recently been complicated by a formal inquiry process," a reference to the misconduct investigation. Broder said he had been "awaiting the results of that process" before reviewing "the situation and the facts of Dr. Gallo's case."

Last month Broder sent Gallo a list of questions about his early AIDS research that had not been addressed by either the misconduct investigation or the inspector general's inquiry. Broder gave Gallo until the end of May to produce the answers.

One question concerned an article Gallo published in 1985, just as the dispute with the French was taking shape, in which he claimed to have produced his first confirmed isolate of the AIDS virus in "the fall of 1982"-several months before the French first isolated their AIDS virus in January 1983.

In addition to asking Gallo to provide data supporting that claim, Broder asked him to document the source of the AIDS virus isolate which Gallo called MOV, and which the inspector general's summary says merely was a new name given to LAV.

A source close to Broder and Gallo, who spoke only on condition of anonymity, said Gallo had been unable to provide the requested documentation for his purported 1982 discoveries, to identify the origin of MOV or to answer many of the other questions.

Last Monday, the Charleston, S.C., Post and Courier reported that Gallo was being "courted" by the Medical University of South Carolina, which has its headquarters there.

The university's cancer research center is headed by Dr. Peter Fischinger, one of Gallo's former NCI superiors. Fischinger is mentioned in the inspector general's summary as one of the officials who helped delay publication of data showing that Gallo's HTLV-3B was genetically identical to LAV.

The article quoted Gallo as saying he was "listening" to offers from the university and had "cut the umbilical cord with the National Institutes of Health," which he described as "not quite what it used to be. There is not quite the joy of life there now."

The university's president, James B. Edwards, who served as secretary of energy in the Reagan administration, told the newspaper he would "like very much" for Gallo to work there. I would like him to be working in our lab when he gets the Nobel laureate," Edwards said.

The newspaper noted that the university currently is cutting back on staff, but suggested that lack of funds would not be an obstacle to its recruitment of Gallo. It said Edwards noted that " Gallo's HIV test patent alone brings in millions, and his work would quickly pay its own way." *