In a unanimous decision last month, the Supreme Court ruled that naturally occurring genes are not patentable. But, said the Court, cDNA, a man-made copy of the genetic messenger in cells, is patentable. As a geneticist, I have my own opinions about this ruling. But the potential outcomes are important enough that all members of the public, not just biologists, should be equipped with the knowledge to evaluate it. The ruling may significantly affect patients’ access to genetic testing, and it sets an important precedent for future developments in the biotechnology sector.
The company that applied for these patents is Myriad Genetics. Building on the work of researchers around the world, Myriad identified the location and sequence of two genes that are sometimes mutated in breast cancer, known as BRCA1 and BRCA2 (collectively, BRCA1/2). Myriad filed patents for the genes in 1994 and 1995.
People can have their risk of breast or ovarian cancer assessed by finding out if they have mutations in BRCA1/2. Then, one can use this information to increase preventative care measures, like increased screening, or even having both breasts completely removed (a double mastectomy)—an elective surgery recently made famous by Angelina Jolie.
Myriad Genetics is the primary distributor of the BRCA1/2 test, which costs upwards of $3000. Because Myriad owned the patents on BRCA1/2, it was the only company that could administer the test for cancerous mutations.
The Supreme Court ruled that genes cannot be patented because “natural phenomena” are not patentable. That’s good news for doctors, researchers, and anyone who doesn’t like the idea of a company owning patent rights to pieces of your body. It also opens up BRCA1/2 testing to labs other than Myriad. But, the Court also ruled that cDNA, an edited man-made copy of the gene, can be patented. Ruling that cDNA can be patented will have important consequences for research, including research to discover new disease treatments and create new genetic tests.
Few people outside of biology research have heard of cDNA. In order to understand the critical distinction between DNA and cDNA, some background is necessary. Genes, which are made of DNA, contain the information required to make proteins. DNA is double-stranded, like a ladder. The familiar DNA nucleotides A, C, T, and G each have a complementary partner they always pair with: A always pairs with T, and C with G.
To make protein from DNA, several steps must happen (illustrated in the accompanying schematic). First, the DNA pulls apart into two separate strands and a copy is made. Instead of DNA, this copy is made of RNA. The copy, called pre-RNA, is not identical to template DNA. It’s a complementary copy. Next, that pre-RNA is edited so that only the parts that encode protein (the exons) remain. This exons-only version is called mRNA. The cell then uses the mRNA to assemble proteins.
For scientists, working with RNA is difficult; it is unstable and degrades quickly. So it is sometimes advantageous for researchers to extract mRNA and convert it back to stable DNA. The new DNA that’s created from the mRNA is called cDNA (see DNA to cDNA schematic). Just like pre-RNA is a complementary copy of the DNA template, the cDNA is a complementary copy of the mRNA template. It’s worth mentioning that cDNA can occur naturally; certain viruses can copy mRNA to cDNA (in fact, this is where scientists learned the technique).
cDNA is an edited version of the original gene. The naturally occurring gene contains exons, introns, and other genetic material; the cDNA contains only exons. Those exons are the same exons as the original DNA, and appear in the same order (illustrated in schematic).
Myriad did not create the sequence of the BRCA1/2 cDNA; the sequence is a complementary copy of patients’ mRNA. But, because physically making the cDNA meant the scientists created something new, the Supreme Court held that cDNA was eligible to be patented. This is a bit like taking a copyrighted photograph, cutting several chunks out of the middle, and calling the result a new product that is eligible for copyright. On one hand, the new photograph may have significantly different artistic merits than the original one, and wouldn’t have existed without your intervention. Yet, the existing parts are exactly the same as something that was already there.
Why do Myriad’s patent rights to cDNA matter? There are several reasons. First, cDNA is an important research tool. For example, the edited cDNA sequence, not the longer DNA sequence, is often used to create animal models of diseases. Those models are essential for researching new treatments and cures. Without the licensing to BRCA1/2 cDNA, certain cancer research may be restricted to Myriad. Next, cDNA is critical for developing new diagnostic tests for genetic disorders. Since the BRCA1/2 genes themselves are not patented, it may be possible for other companies to develop new genetic tests— but the patented cDNA will make this process much more difficult. Myriad’s current control over BRCA1/2 testing artificially inflates the cost, because they’ve closed out all of the competitors. Also, without other labs to study the BRCA1/2 mutations and testing methods, there is no way to independently verify the results. This is analogous to getting a diagnosis from a doctor, but then being forbidden to seek a second opinion from anyone else. Finally, the issue is about access to information. By sharing the rich dataset Myriad has collected from patients, collaborative research efforts from many labs could lead to better cancer detection and treatments. It may also help to make testing more affordable.
Researchers are quite concerned about the implications of cDNA patents. Our lab uses fruit flies to study neurodegenerative diseases. We’ve created fruit flies with cDNA disease genes in order to study how the disease kills neurons, with the eventual goal of finding new therapeutic targets. Fortunately, cDNA sequences that have already been presented at conferences or in research papers will not be eligible for patent by someone else. But unpublished cDNA in ongoing research is vulnerable. What if we were to discover that some company has patented the cDNA for the disease we’re studying? Would all of our research suddenly be shut down, unless the company agreed to license the cDNA (that my lab created, which we already use)? Knowing that our lab and thousands of others depend on access to cDNA, should we all stop and file patents to head off opportunistic companies that might try to privatize invaluable research tools?
Vague language in the cDNA patent decision stirs additional concerns. The rationale for allowing cDNA to be patented is that it is synthetic. But scientists are increasingly turning to artificial DNA synthesis as a research tool. If a machine synthesizes a segment of DNA, but it’s the same sequence as gene found in nature, would that be patentable? What if you changed just a few letters in the DNA sequence, but the resulting protein was unaffected? How many modifications would you have to make to a BRCA1 cDNA sequence before it was different enough not to infringe on Myriad’s patent?
While the Supreme Court’s ruling that genes cannot be patented has been widely regarded as good news, little attention has been paid to the potential impact of cDNA patents. The results of this ruling are expected to result in significant patent protection for the pharmaceutical industry. Without patent protection, there is little incentive for pharmaceutical companies to invest in basic research to develop treatments for cancer and other diseases. But, we incur the risk of over-commoditizing property on the boundary of patentable. In this case, patenting the cDNA itself—rather than just the method of using BRCA1/2 in genetic testing— seems to be an overreach of what one can really “own.” Whether or not cDNA should have deemed eligible for patent is worth deeper consideration, and sets a precedent for increasingly complex distinctions between what is natural and what is man-made.