Is Commerce Blocking Science?

Dr. Robert Cardiff, a researcher at UC Davis, holds a 6-week-old genetically engineered mouse used to study breast cancer on 10/29/03, in Davis, in rubber-glove covered hand (left)
Each year, millions of mice are genetically engineered to precisely mimic human cancers - a technology that could lead to the swift development of new and targeted treatments.

But many researchers complain that progress is being slowed by commerce. That's because E.I. duPont de Nemours and Co. lays broad intellectual-property claims to drug discoveries made with just about any animal genetically engineered to be prone to just about any cancer.

DuPont and Harvard claim the terms are typical of such arrangements between industry and academia and aren't particularly onerous. But many researchers and other university patent officials allege that DuPont charges high fees, sets strict conditions and aggressively polices its broad rights, often to the detriment of science.

Critics of such intellectual property deals between industry and schools fear medical advances will be hamstrung as companies gain control of patents not of just animals but also individual human genes and other biological functions.

Dr. Lewis Chodosh is a University of Pennsylvania scientist who can control a cancer's spread in many of the mice he's engineered - a technique that gives him insight into how and why the disease progresses.

Chodosh said he recently approached a duPont competitor with one of his mice creations in hopes of experimenting with the company's approved cancer drug, which he believes would show good results in his mice. The company declined because it didn't want to become embroiled in a patent dispute with duPont, Chodosh said.

"This is a terrible thing for cancer research and is becoming exponentially more so," Chodosh said. "It clearly prevents research that could benefit the public."

DuPont didn't actually create the mouse, now known by its trademarked name OncoMouse, that forms the basis for its patent claims. Dr. Philip Leder and another colleague at Harvard University did, by placing into a mouse a human gene known to cause breast cancer. They did so with partial funding from duPont.

In 1988, Leder's mouse was patented as a "non-human mammal" genetically engineered to be cancer prone. It was the first time an animal was patented. Since then, 383 more animals have followed.

Harvard quickly struck a deal with duPont, assigning the company all exclusive commercial rights to the patent and control over licensing terms.

DuPont claims the patent and related ones control rights to most genetically engineered animals used in cancer research. But the battle has boiled down to a fight over genetically modified mice, which are widely used in drug research because of their availability and genetic similarity to humans.

"I immediately saw that this could be a very useful tool and that has turned out to be the case," said Leder, adding that he didn't have an opinion on the controversy swirling around his creation. "I'm just one of the inventors."

But many others in Leder's field immediately complained about the deal Harvard struck with duPont, saying it overly restricts their work. Their complaints were given scant attention at first because few in the cancer field were working with genetically engineered mice.

Yet as genetic engineering moved from the novel to the commonplace, and a push for better animal disease models intensified, work with modified mice has exploded in recent years. And so have the clashes with duPont.

Earlier this year, duPont's demands prompted the University of California system to refuse to sign a licensing agreement that would have let genetically engineered mice be widely used - without each researcher having to worry about individual arrangements with the company.

The state university's Davis campus did, however, agree to the company's licensing requirements after one of its researchers bred genetically engineered mice without duPont permission and received a warning letter, said UC Davis patent chief Larry Fox.

The OncoMouse was to be a major topic of discussion at the five-day 24th Congress of the International Association of Breast Cancer Researchers that was to start Saturday in Sacramento. Frustrated researchers hoped to persuade duPont to loosen its restrictions.

The researchers seeking change appear to have their work cut out for them. DuPont officials say their licensing terms aren't as strict as portrayed. The company allows nonprofit researchers with no commercial ties to obtain licenses for free and freely exchange mice with similarly situated colleagues.

"We have a hard time seeing how we are being viewed as not supporting research," said Charles Murray, duPont's business director for intellectual assets. "We are very supportive of this."

Murray said the company has 170 licenses with nonprofit outfits and another 24 commercial agreements in place. He declined to discuss financial terms.

Still, there's growing discontent among scientists who see duPont as an obstacle to turning their basic research into something that can actually help cancer patients.

"Most of us do go ahead and do our thing with the mice and not worry about duPont because we aren't for profit," said Robert Cardiff, a UC Davis Medical School professor. "But when we want to go from the lab to the bedside, we all know we have to go through the private sector."