Supreme Court Justice Antonin Scalia admitted he doesn't really understand it. Justice Clarence Thomas wrote an entire court opinion implying—unconvincingly, to scientists—that he does. And, as of right now, there's still nothing stopping you from filing patents on it. Meet complementary DNA (cDNA), the confusing molecule at the heart of the recent Supreme Court ruling on DNA patents.
The case, ruled upon in june, was hailed as a victory over efforts to turn the human genome into corporate property. But the ruling may not be the smackdown of gene patents that it appeared to be, and cDNA is where much of the uncertainly lies. Big questions remain: What is cDNA actually being used to do? Why does it matter who owns it? And what do scientists think this debate is really about?
Steinbeck Without the Turtle
On a functional level, cDNA really isn't all that different from plain old DNA. In fact, it's just a slimmed down copy — the Reader's Digest Condensed Book version. DNA is made of up of paired sequences of nucleotides. Some of those sequences—exons—are critical to making a functioning, living thing. They provide the coding instructions that tell cells how to make proteins, and proteins do everything: muscle is made from proteins, proteins help cells communicate with one another, and they do the chemistry that turns food into energy.
Other sequences in the DNA, though—introns—just sort of sit there. You could snip them out and still make a protein, just like you could cut the chapter about a turtle crossing the road out of The Grapes of Wrath without losing any important parts of the plot. (Insert angry Steinbeck fans here.)
Essentially, that's all cDNA is: Steinbeck without the turtle. DNA without the introns.
In the Supreme Court case, a company called Myriad Genetics attempted to patent genes known as BRCA1 and BRCA2. Mutations in these genes have been linked to an increased risk of breast cancer. Myriad developed a test to look for those mutations. But the Court threw out the company's claim of ownership over BRCA1 and 2, ruling that Myriad couldn't patent the naturally occurring DNA that made up those genes.
But here's the catch: The BRCA genes code for proteins. In fact, that's what makes mutations on those genes a cancer risk. Healthy BRCA genes make a protein that repairs damaged DNA, and destroys cells whose DNA can't be fixed. Mutations prevent that protein from being made, thereby allowing damaged cells to grow unchecked. Like all protein-making genes, you don't need the introns from BRCA1 and BRCA2 to make a functional protein. When you're looking for potentially deadly mutations, only the exons matter. The Court said that Myriad can't patent the DNA that contains both introns and exons, but the company can patent the exon-only cDNA.
In fact, it already claims that patent.
A Process, Not a Product
The Myriad story makes cDNA sound like it's just a backdoor to DNA patents without actually patenting DNA. But there's more to it than that. Christina Agapakis is a postdoctoral research fellow at UCLA, where she studies synthetic biology. While working on her Ph.D. at Harvard, she helped her colleague Jake Wintermute create hydrogen-producing bacteria.
Wintermute made a pathway of enzymes, proteins that act as nature's chemistry sets. By taking protein-coding genes from organisms such as spinach and corn, and stringing them together in just the right order, his team could create the enzymes necessary to convert sugar into hydrogen. Those genes all contained introns and exons. But, Agapakis told me, bacteria don't really know what to do with introns. If you took a bacteria and gave it the foreign DNA, it would run into those introns and just get confused — kind of like what would happen if you took somebody who only spoke English and gave them a set of instructions written in a mixture of English and Japanese.
To keep the bacteria from throwing up its tiny metaphorical hands, Wintermute first converted the DNA into cDNA. No introns, no "confused" bacteria, no problem. Now, you've got a bacterium that can, theoretically, help you produce hydrogen fuel.
Eric Gaucher, associate professor of biology at Georgia Tech, offered another example of why cDNA is important to science. In 1882, his great-great grandfather Philippe identified a genetic disease that's known as Gaucher's disease. People with Gaucher's lack the ability to make the enzyme that breaks down glucosylceramide, a naturally occurring fatty acid. These people end up with vast stockpiles of this chemical compound, which can lead to liver malfunction, anemia, seizures, and early death.
Thanks to cDNA, though, many people with Gaucher's disease can be successfully treated. Scientists use cDNA to make protein-coding copies of a healthy, non-mutated version of the gene, which produces the enzyme that Gaucher's patients lack. The people still can't make the enzyme on their own, but if they take injections often enough, they can live symptom-free.
Both these examples are different from the Myriad case because, here, cDNA really isn't the goal, in and of itself. Instead, it's a tool, a way of easily producing the thing you really want.
What You Can't Own
That fact, Eric Gaucher said, might make cDNA more patentable, not less—but in a way that's totally different from how the Supreme Court seems to have addressed it.
Gaucher runs a synthetic biology laboratory at Georgia Tech, so he's been following the legal precedents for gene patents, in order to understand what his team can patent—and how. There's a long history of legal rulings against the idea of simply taking a piece of DNA and planting your flag on it.
"You can't just extract taxol from a tree and patent the structure of the taxol," Gaucher said, referring to a chemotherapy drug that was isolated from the bark of Pacific yew trees in 1967. And he thinks that should apply to cDNA, just like it applies to DNA.
But what you can do—and what many people have done—is patent the process of synthesizing a chemical compound, like taxol, in the lab. And, as we've seen, that process can include cDNA. If you went this route, you wouldn't be patenting the cDNA, itself. Instead, you'd be patenting the way you used it to get to the product you really wanted.
What confuses Gaucher most about about the Myriad case is why Myriad didn't just patent the specific process, to begin with, instead of trying to patent the chemical structure. The former, he says, is fair game. The latter is a clear monopoly that inhibits other researchers' ability to be innovative.
After all, he said, think about what would happen if Myriad patented the DNA (or the cDNA) for BRCA1 and, later, somebody else figured out that a different mutation in the same gene affected the risk of some other disease totally distinct from breast cancer: say, Alzheimer's. That would have nothing to do with Myriad's business selling breast cancer tests, or with the work they did to find the mutations that increase the risk of breast cancer. But, if they owned the gene structure, with or without the introns, they could control discoveries they weren't involved with.
This, he says, is a key flaw in the way the Supreme Court was thinking about those cDNA patents. To him, it suggests the judges didn't really understand what they were ruling on and it's something he expects to see play out in courts, perhaps the Supreme Court itself, in the near future.
Luis Campos, a biomedical historian and associate professor of history at the University of New Mexico, also thought the Supreme Court ruling was weird and logically inconsistent. Patents on cDNA are already kind of a dying breed, he said. Labs have been more focused on patenting the process of getting to an end product, rather than the structure of a gene. By calling out cDNA specifically, as though it were an end product, the Court might end up reversing that trend, Campos said, something that could have a serious chilling effect on research.
Unlike Gaucher, however, Campos sees this ruling as part of an ongoing legal trend towards patenting living things and natural (or semi-natural) structures. Historically, those things were out of bounds for patents. The American botanist Luther Burbank actually complained about this fact in the 19th century when he found himself unable to exert any control over the unique plant hybrids — spineless cactuses, white blackberries — that he'd painstakingly developed. But in 1930, the United States began to allow people to patent plants that were asexually reproduced. In 1970, that was extended to certain kinds of sexually reproduced plants. And, in 1980, the Supreme Court ruled that you could patent a microorganism. That case involved a genetically modified bacterium that had been significantly changed in order to allow it to "eat" crude oil, and the Court specifically said the ruling should be read as narrow — meant to apply to that specific bacterium and situations that were very similar.
The case of cDNA is more complex. Is it something new that scientists make? It is, but it's also true that it contains no new information. Moreover, Gaucher points out, viruses make cDNA naturally, to make copies of their own genetic information within host cells. Sometimes, they accidentally make cDNA out of bits of their host's genes, as well. It's completely plausible that, in the future, somebody will patent a piece of cDNA, on the basis of having created something new that doesn't occur in nature, only to subsequently learn that a virus created the exact same sequence naturally. What will the courts say then?
From Gaucher and Campos' perspectives, it's likely the Supreme Court justices have absolutely no idea.
"You get the sense that they don't understand it," Campos said. "The fact that they called out this one kind of DNA, and felt compelled to repeat textbook details. It sounds like they were trying to get their heads wrapped around what [cDNA] was and, in the process, they completely missed the big questions."
