The attempt to break the hold that Myriad has on key patents for cancer genes has reopened the debate on who can own rights to biology.
At the press conference held to announce success in transplanting a synthetic genome into a living cell, scientist and cofounder of Synthetic Genomics J Craig Venter claimed: 'I have never been quite comfortable claiming patents on discoveries.'
Yet Venter's name was prominent on the bundle of patents filed during his work on the Human Genome Project.
In his autobiography, Venter claims he became the scapegoat for the patents filed in the 1990s - patents on fragments of DNA uncovered during the sequencing work - as part of a plan by the National Institute of Health to secure rights over the DNA before private researchers. But the company he founded and later left, Celera Genomics, sought patents on hundreds of potentially significant human genes despite not knowing what most of the DNA did.
Even after Celera, Venter went on to help put together a wide-ranging patent to support his synthetic biology based on subsets of a natural bacterium.
Celera was not alone. Incyte Genomics and Human Genome Sciences did the same. But it was Monsanto, already widely criticised for its approach to intellectual property (IP) in the biosciences, who triggered a lawsuit that changed the way that agencies such as the US Patent and Trademark Office viewed DNA patents in the mid-2000s. After that case, the USPTO decided that only genes with a known function could be patented, not just fragments of DNA that seem to come from individual genes found during mass sequencing efforts.
Even that view could change again if another biotechnology company, Myriad Genetics, fails in its appeal to put its name against sequences of DNA that have existed in humans for millennia. It is the latest battle in the war to gain control over chunks of the genome, most of which is taking place in the United States of America but which has seen skirmishes in Europe and, more recently, in Australia.
An analysis of patents carried out five years ago found 20 per cent of the human genome has been patented in some way. Large parts remain unclaimed but the study turned up hot spots of patenting activity, with some genes turning up in a number of patents. One patent claimed more than 3,000 individual genes. The most heavily patented genes were key to a number of diagnostic patents. Diagnostics lie at the heart of the Myriad case and, aware of the trouble they were causing, a report by the Nuffield Council on Bioethics called for gene patents in diagnostics to be outlawed early in the past decade.
There are two parallel strands in the war over whether any part of the genome should be patented. The first strand is the emotive, triggered by speeches such as the one given by Michael Crichton in 2006: 'At the moment, Hepatitis C, HIV, hemophilus influenza, various diabetes genes, are all owned by somebody. They shouldn't be. Nobody should own a disease. The idea is so ridiculous I can hardly bring myself to discuss it.'
Californian congressman Xavier Becerra introduced a bill in 2007 that sought to ban gene patents in the US. The bill did not make it into law but Becerra, helped by organisations such as the American Civil Liberties Union, aims to reintroduce a similar bill in case the US courts accept Myriad's appeal. Becerra says: 'I have long believed that gene patents hurt patients by limiting access to life-saving tests and preventing scientists from conducting cutting-edge research; that is why I have sponsored legislation banning gene patents.'
The second strand is about the nitty gritty of legal detail and economic analyses of the effects of these patents. Critics of the anti-patent movement point out that no one holds a patent on the DNA inside our bodies. The patents that exist are for 'isolated DNA' - genetic segments that have been separated from the rest of the genome, copied and sequenced to find their precise combinations of nucleic acids.
The judgement from Robert Sweet in late March that, pending an appeal launched only in the past few weeks, effectively struck out the idea of gene patents in the US concentrated heavily on the precise meaning of 'isolated DNA'.
Sweet wrote in March: 'Plaintiffs' challenge to the validity of these claims, and the arguments presented by the parties and amici, have presented a unique and challenging question: 'Are isolated human genes and the comparison of their sequences patentable?'
The judgement would have real-world consequences. Myriad aggressively pursued its ownership of a number of patents that covered two genes that have proved to be important markers for women likely to suffer from breast and cervical cancer. Myriad was not alone in filing for patents that dealt with the BRCA1 and BRCA2 genes but it placed itself at the centre of battles over the ownership of patents like them.
Doctors Haig Kazazian and Arupa Ganguly of the Pennsylvania School of Medicine developed their own tests to screen the BRCA1 and BRCA2 genes to find if they carried the mutations that would significantly increase patients' risk of cancer.
They did this analysis for 500 women per year from the mid-1990s until a cease-and-desist letter arrived from Myriad. Other researchers could perform experiments with BRCA1 and BRCA2 using a de facto research exemption - not an exemption that is codified in law - but could not use their results to inform patients who came in for tests of their likelihood of developing cancer because of Myriad's position.
Myriad wanted to protect its business of testing for cancer risk, for which it charged approximately $3,000 per patient. In Canada, where public health authorities have effectively ignored Myriad, similar tests are available for a third of the price. The monopoly position and the apparently high cost of testing, together with the lack of an alternative provider to whom doctors could go for a second opinion, helped drive opposition to Myriad's position not just in the US but in Europe.
The European Patent Office (EPO) received a large number of complaints against the BRCA1 patents that were granted and many of the opponents were not competitors but organisations and institutes keen to call the existing system into question, according to Niklas Mattsson, patent attorney at Scandinavian legal group Awapatent.
Although the EPO at first rejected the key BRCA1 patent and then allowed a much more restricted patent to stand - with the claims on the gene sequence itself removed - the reason was more one of the specific circumstances surrounding the work by Myriad rather than a more general ruling on the viability of gene patents themselves. The company's original filing contained mistakes in the sequence and a correct version was published later, preventing Myriad from patenting its own amended version.
In the US, Sweet's decision went much further, going to what a gene patent means. Myriad was keen to present isolated DNA as being distinct from that found in the middle of the genome of a living cell. But Sweet argued that there is no appreciable difference between the isolated form and natural versions. As a result, Sweet wrote: 'It is concluded that DNA's existence in an 'isolated' form alters neither this fundamental quality of DNA as it exists in the body nor the information it encodes. Therefore the patents at issue directed to isolated DNA containing sequences found in nature are unsustainable as a matter of law and are deemed unpatentable.'
The question remains whether patents such as those claimed by Myriad have slowed science. Kenneth Huang of Singapore Management University and Fiona Murray of the Massachusetts Institute of Technology (MIT), who worked on the project to uncover how many human genes had been patented, found almost 10 per cent fewer research papers published after patents held by companies were filed. The reduction after patenting by public institutions was lower, perhaps indicating a greater willingness by companies to send cease-and-desist notices.
However, cases like Myriad are rare and one survey indicated only 1 per cent of scientists reporting they had to delay work because of patents. It's hard to find a bioscience experiment that does not use green fluorescent protein (GFP), the discovery of which won scientists a Nobel Prize. And its IP brings in substantial royalties. But the core patent is not many years from expiry, transferring the gene to the public domain.
If Myriad loses, then the value of patenting genetic discoveries will not just be uncomfortable, as Venter finds it, but unprofitable. Whatever happens, it is only temporary ownership anyway.