Breast cancer gene patents: the Canadian story

How did SickKids Hospital end up in the midst of a nasty U.S. court battle to controlpatents on human genes?It's a long story that goes back to the 1990s when scientists were racing to find the gene mutations that caused breast and ovarian cancer incertain families.

Last week,a Salt Lake City-based company, MyriadGenetics, filed patent infringement suits in Utah court alleging two other U.S. companiesare infringing on its patents forBRCA1 and BRCA2, human breast cancer susceptibility genes. The court documents exposeda little-known Canadian fact.

It dates back to thedays before rapid gene sequencing when isolating a gene was challenging and painstaking research.

Dozens of scientists were feeling their way along human chromosome 17 and later chromosome 13, drawing up the roadmaps as they went. In the process, they inventedgenetic cloning techniques and followed their hunches in a frenzied search for the mutation that cursed some women.

• SickKids Hospital dragged into U.S. breast cancer gene suit

At the time, several Canadians were at the forefront of this pioneering gene mapping and cloning. So it was natural that they would team up with international collaborators.

'You have to ask the question how come we don't have better tests to find mutations or how come we can't offer women with ovarian cancer better options? Is it possible the number of people working on these genes is limited because of these patents?' Prof. Patricia Tonin

Back then Myriad Genetics did not exist. Founder Mark Skolnick was a scientist at the University of Utah, leading a team of collaborators at other universities, including McGill University in Montreal andLaval University in Quebec City.

McGill Universityprofessor Patricia Tonin in Montreal was part of the original team trying to find BRCA1, a gene mutation they knew existed somewhere along chromosome 17 and increased therisk ofbreast and ovarian cancer.

At the time, Tonin said she didn't realize her Utah collaborators wereintent on commercializing the findings.

"What I didn't know at the time was that the Utah team had formed a company, Myriad Genetics," Tonin said."We weren't aware of the magnitude of what they were trying to do.

"At most we thought what would come out of this was a genetic testing kit, but that's not what the patent was about. It was about ownership of a particular region of human genome, which contains the BRCA1 gene and surrounding regions.The implications were quite broad."

Race to find gene mutation

When the McGill scientists were offered a chance to have their names on the BRCA1 patent, Tonin said she and her colleague Steven Narod refused, and began working with a U.K. research group on the hunt for BRCA2. Narod could not be reached for comment.

"There was no question in our minds when it came out, we refused to participate," she said. That decision meant McGill University would receive no royalties from the patenting of BRCA1.

The year was 1995, and the race was on to find the second gene mutation. By now, Myriad Genetics had been created and Skolnick, the scientist turned CEO,made no secret of his intentions to find the second gene mutation and create a commercial test for both of them.

"We did it to win the race. The group that was in that laboratory workingseven days a week were doing it to beat the other team. Period. And we won," Skolnick said in a U.S. documentary titled In the Family.

But the issue of patenting human genes had become controversial,Tonin said. "By then, yes, there was controversy about their ambition. So it became very well known, a huge issue" she said.

Still, researcher Johanna Rommens at what was then the Hospital for Sick Children inTorontoand Laval researcher Jacques Simard continued to work with Myriad to help them find BRCA2.

Did they know they were on a team that intended to profit from the gene?

Rommens declined to be interviewed. Simard refused to comment, citing a confidentiality agreement he signed with the Quebec research institution Endorecherche Inc., which is also named as a plaintiff in the Utah court injunction.Endorecherche also refused to comment.

Australian lawyer and author Luigi Palombi researched the BRCA2 race as part of his PhD thesis, which he later turned into a book. "Anyone that got into bed with Myriad knew the company was going to make money or they would have gone somewhere else or they would have refused to collaborate with Myriad, which was an option that was available to them," he said.

"It brings forward this whole issue of just how far publicly funded researchand research institutions can collaborate with private industry," he said.

"It is all well and good for politicians to say that we need to encourage commercialization and we need to encourage public institutions to partner with commercial institutions.

"But at the end of the day the taxpayers are funding a very serious aspect of the research and then they get involved in commercial enterprise and then of course the results of that research are being denied the public.

"So where is the public interest in all of this? I think this is a big issue that the Canadian politicians and the Australian politicians and politicians everywhere are going to have to come to grips with."

Were there public health consequences of havingpatents on BRCA1 and BRCA2?

It's a questionTonin would like someone to research."I was asked a few years go by Ovarian Cancer Canada, 'Do you think this has had an impact on research?' Probably yes, but how to prove it?

"You have to ask the question how come we don't have better tests to find mutations, or how come we can't offer women with ovarian cancer better options? We need better models to study these genes.Is it possible the number of people working on these genes is limited because of these patents?"

Patent chill hangs over labs

Palombi says the costs of the test have remained high because of the patents. "If the patents weren't there they would have dropped a long time ago, and if they weren't as broad in what they were claiming the prices would have dropped," he said.

What's more, the lack of competing tests has reduced options for women. "I mean if you are a woman who has been told you are potentially in line for breast cancer, you want more the one opinion," says Palombi.

"Are you going to rely on Myriad's test or don't you want a second or a third or a fourth opinion? These are big issues that are not being answered by these sorts of patents."

Richard Gold, a McGill University law professor and patent expert, says innovation is also being slowed by these patents.

"So if women want real access to their entire genetic risk, rather than just from a gene or two genes, then this is a real concern."

Ambry, a smaller California company that is trying to develop a cheaper genetic test forBRCA1 and BRCA2 related cancers "is part of what we call the next generation of genetic testing," says Gold. "If Myriad and other companies that own patents in this area are able to block that type of test then we are really going to lose out on all of the benefits, or many of the benefits from genetic testing in the future."

What is the effect of this patent litigation in Canada?

"So far Myriad has left Canada alone," Gold said. "There was a big fight in 2001-2002. All the provincial governments ganged up against Myriad and Myriad kind of left with its tail between its legs."

Although Myriad so far hasn't tried to protect its Canadian patents on BRCA1 and BRCA2, Gold says thatremains a possibility.

"It's this sword hanging over all the labs. They're unwilling to do testing in the area, at least in some provinces, because of the fear of patents. At the same time there is a cloud of uncertainty, because of the U.S. ruling.

"Even though it only applies to the United States, Canadian patent laws are similar, so there is a cloud of uncertainty sitting on top of Canadian patents in this area," Gold said.

"So we kind of get the worst of both worlds. We're not getting the investment that patents are supposed to bring and yet the chilling effect that patents have over subsequent entrants is being felt fully here."

Gold hopes the current experience will encourage public institutions to approach commercial agreements differently.

"There's always been a relationship obviously between industry and hospitals and universities. And it's not all bad because, of course, universities do basic research.But you want to make sure the research you do actually helps save people. I would hope that now universities and laboratories will be wiser in the way they set up their agreements where they have a choice whether to be involved in litigation, where they can impose somekind of obligation to negotiate first," he said.

"I'm hoping that the community of researchers and labs and hospitalshave learned from their experience, including unfortunately this experience, and will put more protection in the agreements so they won't get dragged along as SickKids appears to be."