UA Prof locks horns with Science

Marlys Witte fancies herself a rebel.

In June 1994, challenging world-leading AIDS researcher Robert Gallo and America's premier science journal, the riot-prone professor of surgery extended a personal tradition as old as her school days.

"I grew up in New York during the sixties. Greenwich village. I don't like gates," says Witte, flashing her trademark question mark pendant.

Profiled by publications including The Los Angeles Times, The Chronicle of Higher Education, and the Tucson Weekly, the unorthodox and outspoken physician, scientist and teacher, made her name in the 1980s marketing an unusual approach to medical education she calls, "The Curriculum on Medical Ignorance."

"Honestly, the response of professional philosophers has been lukewarm," she says. "They're too busy working on epistemology, the theory of knowledge, when really ignorance is much more interesting."

Drawing on the offhand advice of her mentor, physician-essayist Lewis Thomas, Witte began a mission to spike debate into a process one of her former students called, "an intellectual death march."

Writing in the journal, Medical Education, Witte and philosopher Anne Kerwin suggested that the information explosion in medicine demanded an alternative to "rote-memorization."

"I think we should be searching for black holes in knowledge," says Witte. "I was talking to [philosopher] Jay Garfield about looking for new fields, emerging fields in cyberspace, areas where research needs to be done."

Witte and Kerwin proposed a program that "emphasizes medicine's current . limited insight (i.e. ignorance)," but also provides students with tools to investigate and heal "in the face of fragmentary understanding."

"'Ignorance' was a trouble-word at first," says Witte. "People thought we were talking about failure. But later the word became an asset. The word had shock value. It had humor."

In response to the exams and the fact-drilling of traditional medical education, Witte and Kerwin offered doubt.

"We work through questioning. It's sort of like Socrates' dialogics, but I don't think Socrates went far enough. Well, O.K., he killed himself, but ."

Witte's entry last year into a debate over scientific integrity in AIDS publishing created surprise among some of her colleagues, while others saw the controversy as typical Witte.

"I think AIDS is an example of a disease where ignorance is the content. We can treat only tangential problems," says Witte. "I've had AIDS patients who see my ignorance pin, and they find that encouraging."

Tom Lindel, a professor of molecular biology and a colleague of Witte's, says, "I have known Marlys since we began work at the College of Medicine in 1970. She speaks her mind. She is a principled person, and I respect that."

When a major scientific journal rejects criticism of one of its peer-reviewed articles, the journal's review board usually has the last word.

But when the Science refused to publish indictments of systemic research error from Witte's group at the UA Department of Surgery, Witte took her work to the Journal of the American Medical Association.

"I wanted to make the science speak for itself. I didn't want to go outside the space of scientific journals," Witte says.

Describing research findings from AIDS guru Gallo's laboratory as "dubious," the article also criticized Science, arguing that, "the validity of the peer review process and the self-correcting nature of scientific inquiry [had been] called into question," when Science rebuffed their concerns.

The original Science paper, published by Gallo's group in March 1992, suggested that a low-toxicity compound produced by bacteria, SP-PG, could restrict progression of Kaposi's sarcoma.

KS, an AIDS-related cancer, affects more than 30 percent of people with AIDS, producing the skin lesions popularly associated with the disease according to a report from the Treatment Action Group, a lobbying organization that focuses on AIDS research.

Science expressed hope for SP-PG, which S. Zaki Salahuddin, one of Gallo's co-authors, described as part of his dream, "to bring into tumor biology nontoxic drugs."

The Chicago Tribune reported that Daiichi Pharmaceuticals, the Japanese firm that owns SP-PG, gained six points on the Tokyo stock exchange the day the Science article appeared.

Witte says when her group read the Gallo paper, they noticed irregularities in photographs of experimental mice.

When the group could not reproduce the article's results, they submitted their findings to Science.

After two rounds of review, Science rejected the Witte group's concerns as "without serious merit," and called their experiments "an extraordinary waste of time and effort."

JAMA's June 1994 decision to override the opinion of its sister journal Science and print the Witte group's findings has brought criticism from scientific publishing and cheers from some bioethicists.

"We were taken aback because JAMA did not contact us before publishing the article," says Monica Bradford, managing editor of Science. "It is always risky to second-guess editorial decisions. You do not always have access to all the information. You have to judge fairly, weigh both sides ... We bent over backward to make sure this group [Witte et al] received fair treatment. Their comments went through two rounds of review."

Jerome Kassier, editor of the New England Journal of Medicine, told the Chicago Tribune, "I think it [overruling Science] is an odd thing to do, and certainly something we would not do."

Judith Swazey, president of the Acacia Institute, a non-profit research center, told the Boston Globe, "I think it is appalling that Science was not willing to air these questions ... It is absolutely fascinating that JAMA published this. I would hope it would make a journal that is reluctant to publish criticism more willing to do so."

Reacting to the uproar in September 1994, JAMA printed a series of response letters from Gallo's group.

Shuji Nakamura, the lead author on the Gallo paper, wrote, "We ... are mystified by their [Witte et al's] failure to deal with the science and by their zeal to reach negative conclusions from the very beginning."

Gallo, who has had to struggle with charges of scientific misconduct surrounding his relationship with a French AIDS research group, left his post at the National Institutes of Health in May 1995 to start a virology institute at the University of Maryland.

"I went through a period of hell, which made it easier to break the cord," Gallo told the Los Angeles Times.

Witte, who proudly calls herself the "Ignorama Mama," has spoken for more controls on the peer-review process.

"It's very hard to take a paper and know what went on in the lab . We need to realize as scientists what a long road we have to travel," she says. "Physicians deal with ignorance on a daily basis, but we don't talk about it to the public. We promise more than we can deliver."

Refusing to deliver armchair polemics on her JAMA piece, the self-mocking Witte jokes, "I am an expert in ignorance. My brother is an expert in nothing. My friend Charles Crittenden, a philosopher, is an expert in unreality."

Marlys Witte will teach an honors freshman colloquium at the UA next Fall. Titled "Introduction to Medical and Other Ignorance," the course will touch on topics from pancreatic cancer to analytic philosophy.

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