The gene patenting decision from a plaintiff’s point of view

Arupa Ganguly is pleased with the outcome of her day in court. “I’m ecstatic,” she says. “I feel like a tiger that has been released from a cage.”

Ganguly, who directs the Genetic Diagnostic Laboratory at the University of Pennsylvania’s hospital in Philadelphia, is one of numerous plaintiffs who sued a company called Myriad Genetics over patents the corporation held on genes that raise breast cancer risks. On Thursday the Supreme Court unanimously decided the case in her favor.

In 1995, Ganguly and Haig Kazazian, now of Johns Hopkins, began offering DNA tests to determine whether women carry faulty copies of the BRCA1 and BRCA2 genes, which raise the risk of developing breast cancer. In 1998, Myriad sent the Penn group a letter demanding it cease and desist the testing. Myriad owned the patent on breast cancer genes, the letter said, and nobody else had the right to examine those genes even if they were using methods different from those Myriad uses. In 1999, the group got another more strongly worded letter that Penn’s own patent lawyers urged them to heed. Ganguly and Kazazian stopped their testing.

“I hope no other lab director will ever get a letter like that,” Ganguly says. “It took the ground out from under my feet.”

Myriad’s patent claim meant that doctors could not look for mutations in the breast cancer genes except by ordering the company’s test. They also could not pass along information gleaned by accident when sequencing a person’s entire genome, unless they paid Myriad, says Ada Hamosh, a clinical geneticist at Johns Hopkins University. The company also locked away data on the mutations that strike the breast cancer genes, she says. Doctors need to know that kind of information in order to determine how a mutation is likely to affect a patient’s health.   

In 2008, Ganguly and Kazazian signed on to an American Civil Liberties Union lawsuit against Myriad, and other researchers followed.

This year on April 15, Ganguly hopped an early morning train to Washington and sat in the courtroom as the justices heard the case. “It was pretty clear to me that it would go our way,” she says. She never suspected it would go so far in her favor, though.

In a rare unanimous decision, the Supreme Court ruled June 13 that naturally occurring genes are not eligible for patent protection. The court also said that companies can patent synthetic versions of genes known as cDNAs. That bit of the ruling has researchers, investors and just about everyone else scratching their heads a bit.

In their natural form, genes are composed of DNA, the chemical units of which are designated by the letters A, C, G and T. Some combinations of those letters can produce proteins, which do much of the work inside cells. The strings of letters used to build proteins are arranged along a chromosome in chunks called exons, and interspersed by bits of DNA called introns, which don’t encode proteins. It is as if sheets of nonsense text were stuck between the pages of an instruction manual. Cells copy the entire gene — nonsense text and all — and then discard the extraneous information, stitching the exons into a coherent protein-building blueprint called messenger RNA, or mRNA. Other cellular machinery reads the mRNA and constructs proteins accordingly.

In the laboratory, scientists and technicians can isolate the mRNA and make a DNA copy of that molecule. The result is a cDNA, or complementary DNA. Because cells don’t normally make cDNAs, the court decided that those synthetic molecules are fair game for patenting.

Only Justice Antonin Scalia expressed any doubts about the decision — he agreed that genes can’t be patented but was a little fuzzy on the molecular biology.

It turns out that Scalia was right to express a little skepticism, says Kazazian. Nature makes cDNAs, too. Retroviruses, such as HIV, store their genetic information as RNA and then have to make DNA copies of themselves — for all intents and purposes cDNAs — that will then be inserted into the host’s genome. And the human genome contains more than 8,000 natural cDNAs, which are (mostly) now-defunct copies of genes known as processed pseudogenes.

The provision on cDNAs was probably included to appease the biotechnology industry, but it’s not clear how the decision will affect research on these quirky components of the genome or on retroviruses.

Striking down gene patenting opens the way for other companies and researchers like Ganguly to develop a wide variety of tests for breast cancer risks and other diseases. Many of the tests may be cheaper than Myriad’s $3,000 offering.

“Everybody gets to do business now,” says Hamosh. “It’s an open market.”

Meanwhile, Myriad still has protection for the methods it uses to test the genes, and probably gets to retain the database of information it has amassed about mutations.

“Because of that database it could be that Myriad won’t lose much business,” Kazazian says.

Although he is delighted that companies can no longer patent genes, the ruling doesn’t benefit him personally and he has no plans to test breast cancer genes again. “It’s been nearly 15 years. I’m not going to go back and do this.”

Both sides are claiming that the verdict as a victory (even though it is clear the decision breaks Myriad’s hold on the genes). But Ganguly says that people at risk of genetic diseases are the biggest winners because they will have more than one company to turn to for testing. And they may not have long to wait; the afternoon after the ruling came down, a company called GeneDX announced that it would begin BRCA1 and BRCA2 testing later this summer.