Despite the fact that I myself am the co-Inventor of 6 US patents, 2 of which are patents that describe and protect human gene sequences, I am going on record to say that I think that the ability to patent human genes is wrong and should never have been allowed.
And tomorrow, the United States Supreme Court is being asked to wade in to see if they agree or not.
In what, by any reckoning, will be a landmark case, the Court will begin oral hearings in “the Association for Molecular Pathology vs. Myriad Genetics”. According to the website of the American Civil Liberties Union (ACLU) who is really the main plaintiff in the case:
The lawsuit, Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., was filed on behalf of researchers, genetic counselors, women patients, cancer survivors, breast cancer and women’s health groups, and scientific associations representing 150,000 geneticists, pathologists, and laboratory professionals. The lawsuit was filed against the U.S. Patent and Trademark Office, as well as Myriad Genetics and the University of Utah Research Foundation, which hold the patents on the genes, BRCA1 and BRCA2. The lawsuit charges that patents on human genes violate the First Amendment and patent law because genes are “products of nature” and therefore can’t be patented.
Gene patenting is not new. As I alluded to above, I personally am the co-inventor of two such genes, and the patents (US Patent 5576205 and US Patent 5614406) both describe isolated polynucleotide sequences (genes) from the human central nervous system, in this case genes for the so-called excitatory amino acid receptors , EAA1 and EAA2 (receptors in the human brain that are part of the neural transmission pathway). These patents (more on this later) were both filed in the early/mid-90’s and were issued in 1996 and 1997, i.e., both are almost 2 decades old.
But gene patenting goes back well before that, all the way back to at least 1972 when a scientist named Ananda Chakrabarty, then employed at General Electric developed a “man-made” strain of bacteria that was able to “eat” oil in oil spills, and the same US Supreme Court held then that the patent was valid because the bacterial strain thus created did not occur in nature but was created in the laboratory to perform a function that was innovative and new.
In a similar argument of being “man-made as opposed to “naturally occurring” the famous Harvard Oncomouse was protected by a patents filed in the mid 80’s. This was a mouse that had been purposely genetically altered by introducing an activated oncogene (a Ras gene), the net result making the mouse line susceptible to cancer and therefore a real innovative boon to aid in studies on the origins of cancer.
At the heart of both of these patents, it seems to me at least, are 2 tenets that we should keep in mind. The first of these is that patents cannot be issued for substances that are found in nature, and also that there has to be a test of “inventiveness”, i.e., the patent must describe and protect something where there has been some demonstrable innovation.
My About Face
So why, if I am the co-inventor of 2 gene patents, am I now against gene patenting? First of all, at the time I was working for a biotech company and they were the assignees of the patent so not only was it company policy but it also means that I would never have received a plugged nickel for any of the work. But more importantly, the state of knowledge and the environment in the late 80’s early 90’s when I did this work bear no resemblance to today. At that time, we really were not interested in the gene sequences themselves, at least not as describing a unique composition of matter. We wanted to take the copies of the CNS receptor genes so isolated and express the receptors in a cell line in the laboratory. The goal was to create a pure source of receptor protein that we could use in novel assays as we searched for drugs that could interact specifically with these receptors, hoping to create therapeutics for such diseases as depression, migraine, Parkinson’s and so on. It was the receptor cell lines and the receptors themselves we were interested in. That was what had value to us.
But you could not do that if you did not have the gene first, and if you couldn’t protect the gene sequence then you couldn’t protect any of the downstream work derived form the sequence. Or so the supposition.
And make no mistake about it – isolating those genes was HARD work – it took my team of several scientists several year to bring that all to fruition. There was real inventiveness in the processes used to isolate the genes, and especially to express the genes, even if we didn’t “invent” the genes themselves.
Fast forward over 20 years and oh how times have changed.
As I wrote about in this very blog, the age of genomics is up on us. The Human Genome Project and enterprises like the International Cancer Genomics Consortium (see previous post) mean the human gene sequences are literally being spewed out at rates unimaginable at the time I did my work on the human EAA receptor genes. And companies, universities and individual researchers have been quick to secure as much patent protection as the law will afford on as many of these genes as possible. It is my understanding that one still cannot simply patent a gene sequence – one has to know WHAT the gene encodes – and have some bone fide claim as to its usefulness.
But that doesn’t mean that the floodgates are not open. It is estimated that perhaps as many as 4000 genes are under patent protection right now. That represents about 15-20% of the human genome. That number is staggering and it is only going to grow, and quickly if the technology advances are any indicator. Many (most) of these (like mine!) will end up not being all that important in the overall scheme of things.
But some, like the BRCA1 and BRCA2 gene patents held by Myriad Genetics are huge, controversial and important, not only for the patent holders, but for patients and future patients and for researchers and future researchers. They are important for the precedents they set, and for the implications that spring from them.
The Canadian Cancer Society is concerned that patenting of genes may hinder accessible, affordable and reliable genetic testing. These tests are important for Canadians who have been advised by their doctors that such testing would be beneficial to them because of a strong family history of hereditary cancer. We also believe that these patents will have a negative impact on research as patents can hinder collaboration among researchers and can add to the cost of research.
We have spoken out about the patents on the BRCA1 and 2 genes which affect the risk of breast and ovarian cancers. Myriad Genetics Inc. holds the patents to the BRCA1 and 2 genes, as well as a patent for a specific test, called BRACAnalysis, which is used to detect abnormalities in these genes. As a result, all samples must be sent to the company’s headquarters in the United States for analysis. The high costs associated with this process limits Canadians’ access to genetic testing. As a result, the Canadian Cancer Society has called on the federal and provincial governments to ensure Canadians have access to high quality appropriate genetic testing.
The Canadian Cancer Society opposes patents on genes and gene sequences. We support patents for specific diagnostic, therapeutic or other innovations that derive from the knowledge of genes or gene sequences.
The Case at Hand
Although the case being heard starting tomorrow is about Myriad and BRCA1 and BRCA2 genes, at its heart it is actually all about the right to patent human genes at all.
If the decision goes against Myriad, the implications will be far reaching to each and every holder of a patent on human gene.
If the Myriad BRCA patents are struck down, what happens to these other 4000 gene patents already issued? Will they be ‘grand-parented” i.e., allowed to stand until they expire, but no NEW patents would be allowed from that point forward?
Or would they actually be declared invalid? If so, what happens to all of the companies/researchers/others who hold patents on genes? While some patient groups may say “tough beans” on them, this could be an economic disaster in the making for entrepreneurial health care companies whose failure we should neither relish nor wish for.
And if patents on genes are no longer permissible, either prospectively or retroactively, will we enter a new era where investments in genomic research simply will not get made the way they are now? Are we at risk of bringing the genomic revolution, if not to a screeching stop, at least to a slow down which would be counter-productive to patients needs and rights, and set back the whole burgeoning area of personalized or precision medicine?
These are difficult questions that we must grapple with and the the court will no doubt have to consider. In the run-up to this hearing, huge volumes have already been written. Not surprisingly some have taken the point of view that any patents on human genes are not proper and that they violate a basic tenet of being natural products that should not be eligible for patent protection. Anti-patent voices often cite how gene patents are restricting research and how that is not in society’s best interests. Other points of view take the exact opposite tack – that if we do not allow patents on genes then we will slow down innovation and advances in the very area where we do not ant to give up any momentum, namely personalized medicine and precision treatments.
In another excellent overview piece in the New Yorker Magazine Michael Specter asks Should Private Companies Be Allowed to Patent Genes?
In part, Specter writes:
“If these patents are enforced, our genomic liberty is lost,” Christopher E. Mason, of Weill Cornell Medical College, said. He and Jeffrey Rosenfeld, an assistant professor of medicine at the University of Medicine & Dentistry of New Jersey, published a study last week in the journal Genome Medicine demonstrating that, when one looks not just at entire genes but at DNA sequences contained within them, nearly the entire human genome is covered by patents. “Just as we enter the era of personalized medicine, we are ironically living in the most restrictive age of genomics. You have to ask, how is it possible that my doctor cannot look at my DNA without being concerned about patent infringement?” The biotechnology industry contends that if the patents aren’t upheld, entrepreneurs and many businesses, particularly pharmaceutical and agricultural companies that rely heavily on genetically-modified products, will have less incentive to innovate.
In her highly readable and informative article for NOVA, Are Gene Patents Standing in the Way of Personalized Medicine? Amy Maxmen give us this perspective:
With advanced sequencing technology, geneticists can now search for mutations in 40 genes related to cancer for less than the price of a BRACAnalysis test, which is estimated at $3,500. For about $2,000 more, researchers can sequence the genes that code for proteins, known as the exome. Or for roughly twice the price of Myriad’s test, all 22,000 genes in a person’s genome can be sequenced. But because of concerns about patent infringement, these tests usually do not reveal the status of BRCA1, BRCA2, and patented genes related to dozens of other diseases. Instead, doctors have to order multiple tests from various vendors, even though a single test is possible with current technologies. Expanded licensing could solve this issue, but that could significantly raise costs for clinicians.
Indeed, she quotes Dr. Francis Collins, former head of the Human Genome Program, who himself obviously has second thoughts as saying
“At the moment there is a good deal of uncertainty about whether individuals who wish to have their whole genome or exome sequenced are in legal jeopardy without paying a licensing fee to people who own patents on various pieces of the genome. If we end up with a $1,000 genome that comes with a $5,000 fee for royalties, that is not okay.”
In other words, It will soon (if not already) cost less to sequence a person’s ENTIRE genome than to have a single BRACAnalysis done by Myriad to look at but 2 of the perhaps 25,000 genes in a genome.
Do Gene Patents Really Restrict or Inhibit Research?
One only has to do a Google search for BRCA1 or BRCA2, or better still do a PubMed search and you will see hundreds or thousand of research projects that seem to be about one or other of these genes, directly or indirectly. If that is so, many argue that the “bogey man” of restrictions imposed by patents is just that, an artificial argument that holds no weight. I just did a quick PubMed search for “BRCA1 BRCA2” and here are the results: 4,885 hits. Obviously not every one of these is a world-beater, but that’s a lot of productivity in a field that some argue has been hampered by the Myriad patents.
On of my most esteemed and respected colleagues, Professor Tim Caulfield (Professor of Health Law and Policy at the University of Alberta) wrote an article in 2009 that suggested that gene patents in fact do NOT particularly inhibit research. In Do Gene Patents Hurt Research? The Data Say They Don’t Caulfield cites data to suggest that gene patents are not the destroyer of research that some make it out to be. But I must caution, this was an article written in 2009 and based on earlier data, and I think the world has changed rather dramatically since then in the area of rapid sequencing and genome sciences so I do wonder of that would still be true today. I suggest not.
Another noted journalist Sharon Begley (senior health and science correspondent for Reuters) wrote an article in 2010 for the Daily Beats/Newsweek entitles Why Patenting Genes Is a Bad Idea. In it Begley argues that
On the surface, the patents don’t seem to impede research. Thousands of BRCA papers have been published, and in surveys few scientists say patents are an obstacle to research. But few isn’t none. And the survey results may reflect the fact that many patents are cheap to license and are unrestrictive, says law professor Timothy Caulfield of the University of Alberta; that is, the patentholder allows anyone to work on the gene for only nominal payment. Because Myriad doesn’t, and has such a fierce reputation for enforcing its BRCA rights, these patents are different.
Thousands of BRCA tests, for instance, find “variants of unknown significance”—mutations that might or might not portend cancer. “Ordinarily, labs would test lots of people to determine the normal variation in a gene to see which variations are associated with disease,” says geneticist Wendy Chung of Columbia University. “But because of Myriad’s monopoly, that hasn’t happened. We haven’t been able to freely study how BRCA functions.”
But as Begley says, ‘few isn’t none’ and indeed she writes that at least some scientists have received “cease-and-desist” letters from Myriad about their research:
Arupa Ganguly of the University of Pennsylvania had been testing BRCA to elucidate the range of harmless and dangerous mutations. Scared off, she stopped. “The idea was to discover how mutations other than the common ones affect the gene,” says Penn’s Haig Kazazian. Rather than fostering innovation, he says, gene patents “inhibit biomedical research.”
Amy Maxmen in the article quoted above says “Above all, geneticists worry that gene patents prevent new DNA technologies from reaching the clinic. She related how even one of the “inventors” who contributed to the BRCA patents for Myriad has second thoughts:
[Sean]Tavtigian, the scientist who helped Myriad secure the patents, is now a molecular geneticist at the University of Utah. His position on intellectual property has changed as well. “Patents might have been useful in stimulating diagnostic development in the 1990s, but the technology has improved to the point that we can evaluate a person’s genome for close to the cost of testing BRCA1 and BRCA2,” he says. “Now, these patents are standing in the way of progress in personalized medicine.”
And there are other ways in which gene patents in general and the Myriad patents in particular cause harm. As noted science journalist Gina Kolata wrote just this week in her article DNA Project Aims to Make Company’s Data Public “No matter which way the patent decision goes, the company, Myriad Genetics, will still own the largest database that tells patients what various mutations mean”.
This is a HUGE issue. To wit, as she continues:
With 17 years of experience, millions of tests looking for thousands of mutations in the genes, and a $500 million investment, the company was able to amass a huge database that tells which DNA changes increase cancer risk and by how much, and which are inconsequential blips in DNA. And it is keeping that data to itself.
Some genetics researchers are furious and have now figured out a way to get the data anyway. Every time Myriad sends out a report on a gene test, it specifies not just the mutations it found but also what they mean. As a result, Myriad’s data on each of the mutations is scattered in millions of reports in the hands of doctors and patients. If the geneticists could just gather those reports, they say, they can recreate Myriad’s database.
So they started a grass-roots project, Sharing Clinical Reports, and are asking cancer clinics and doctors to provide them with all the Myriad data they have from patients who have been tested.
It will be interesting to see if this grass-roots initiative can work.
For Many, This is Personal
Not surprisingly, some of the most vocal opponents of Myriad’s patents (and the right to patent human gens at all) comes from breast cancer survivors and breast cancer advocates, and from those who have a high familial risk of breast cancer (i.e., the ‘target’ market for BRACAnalysis). In a moving analysis Nancy Stordahl ( the Nancy behind the Nancy’s Point website) wrote a piece for Huffington Post Healthy Living. In her post entitled BRCA1 and BRCA2 Gene Patent Debate Reaches the U.S. Supreme Court: Why Everyone Should Care she wrote:
For me this case is personal. Breast cancer risk lurks in my family’s DNA, so genetic testing was called for at the time of my breast cancer diagnosis in 2010. My entire treatment course depended on my test results. Knowing the results of my BRCA gene analysis test before making decisions about my course of treatment was crucial, perhaps even lifesaving for me.
I want every other person in a situation similar to mine to have affordable access to this life-altering information about their genes, to be able to get a second opinion if they want one and to get definitive test results so that they’re not left hanging in limbo. When the resources are available, as they could be if not for Myriad’s patents, anything less is just plain wrong. Equally importantly, women who do not have cancer yet but are deemed to be at high risk for developing breast or ovarian cancer based on results of BRCA testing (or would be so deemed if they had the opportunity to be tested) have preventative options that they may or may not choose to take in an attempt to avoid getting cancer. Lives are at stake here.
Michael Specter (article quoted above) said it well:
Moreover, when a company patents a gene, it also patents the rights to what that gene (or any fragment of its DNA) might tell us about our health, including our chances of living or dying. A woman who inherits a harmful version of either of the genes that Myriad has under patent, for example, is five times more likely to develop breast cancer than a woman who does not. She is also at significantly greater risk of developing ovarian cancer. Women who want to know whether they possess those harmful mutations have just one way of finding out: by taking a three-thousand-dollar blood test offered by Myriad Genetics. To seek a second opinion on such a critical issue, their only option is to pay to take the test again. This is because Myriad, as is its right under patent law, has prevented laboratories from performing the test or developing alternative versions. It is important to remember what is at stake: breast cancer kills more women in the Western world than any other kind of cancer. Even the best tests are sometimes wrong; second opinions save lives.
Whether or not gene patents cause harm to research, or whether or not they create unnecessary hardship for patients, or whether or not they are incentives for innovation and future research, it is my view that gene patents are just plain wrong.
I do believe that diagnostic tests derived from the gene sequences should be patentable if they are inventive, and I do believe that processes by which the DNA is itself isolated can be patented *if* it is innovative and inventive. But I do not believe that the distinctions being made, namely that the existing gene patents are NOT on the NATURALLY-occurring genes, but are actually only on isolated DNA material. To me that argument is specious and holds no real logic or value. It is a fudge – a workaround, and even for me, a molecular biologist by training, I do not believe that a copy of a gene, once isolated, should be considered to be any less a product of nature than the version of it in each of our cells.
To me , it is just wrong.
Perhaps I will leave the last word to Michael Specter:
In arguments before the appeals court, lawyers for Myriad compared the use of the genes that the company has patented with efforts to extract minerals from the ground. Without the man-made process of extraction, the minerals are useless. When Judge William Bryson of the United States Court of Appeals for the Federal Circuit asked Myriad’s attorney Greg Castanias if that meant that simply getting an element out of the ground ought to be considered an invention—he used lithium as an example, but he could have chosen anything from the periodic table of elements—Myriad’s lawyer said yes.
… if the Supreme Court buys Myriad’s argument, the sun, along with the carbon, hydrogen, and oxygen contained within it, will indeed be up for grabs. And so will every gene in our bodies, as well as all the DNA that scientists have mined, with increasing success, in their efforts to overcome the diseases that plague us all.