Category Archives: Myriad Genetics

Myriad Genetics Patent Struck Down!

As I’m sure most of you have heard, the US Supreme Court issued its ruling on the Myriad Genetics case today. There were no real surprises to speak of in the decision, as the court ruled exactly along the lines the executive branch asked it to. In an amicus curiae brief, lawyers for the US Department of Justice argued that whereas DNA sequences ought to not be eligible for patent protection, modified or so-called “complimentary” DNA does not qualify as a product of nature and is therefore patentable. The Supreme Court’s ruling, authored by Justice Thomas, towed exactly this line.

We’ve covered this case previously on this blog (here, here and here) so I won’t go into all of the details now.  But there are a couple of things worth pointing out.

Myriad’s argument that gene sequences are patent eligible because the act of isolating DNA turns a product of nature into an invention is a stretch, to say the least. Still, there was widespread concern that invalidating Myriad’s patents would strike a serious blow to the biotechnology industry, with major repercussions for America’s post-industrial economy. This helps to explain why the court went out of its way to emphasize the distinction between gDNA and cDNA (the latter is basically regular DNA with all the introns cut out).  As Eric Lander, the head of MIT and Harvard’s Broad Institute argued in his own friend of the court brief, the decision to uphold patents on cDNA helps to ensure the future profitability of biotech.

Second, my earlier prediction–the court’s ruling would hinge on the ontological question of whether genes are physical objects or informational entities–turned out to be right. Writing for the court, Clarence Thomas insists that Myriad’s patent claims “focus on the genetic information encoded in the BRCA1 and BRCA2 genes,” not their “chemical composition.” Hence, the fact that isolating these genes for sequencing required breaking covalent bonds in the DNA molecule is of no legal significance.

In the end, though, there were no real surprises in the court’s legal reasoning. Still, there was at least one major surprise (to me anyway).  It was the fact that the court issued a unanimous ruling today! I had predicted the court would strike down the patentability of gDNA but uphold the patentability of cDNA, but I had no idea which judges would vote which way. And I never would have guessed they would all agree on this issue. (Especially given the many differences of opinion on the circuit and appeals courts.)

Finally, and somewhat ironically, perhaps the most interesting part of the court’s decision turned out to be Justice Scalia’s concurring opinion, which I’ll reproduce here in full.

Is Scalia just being his usual snarky self, insisting that he have the last word? Or is he making a much more substantive argument about how Supreme Court justices ought to approach legal questions whose resolution requires taking a stand on technical issues that hinge on extra-legal expertise? Or, is Scalia actually saying that he’s unwilling to legislate ontology from the bench?

The Ontology of the Patent Law, Part II

Illustration of “native” DNA in the human cell, from the majority opinion in Ass. for Mol. Path. v. Myriad Genetics, United States Court of Appeals for the Federal Circuit

A few weeks ago, I wrote a post about a case the US Supreme Court will hear on April 15th concerning whether genes can be patented. As we get closer to that date, I want to pick up the thread where it was left off.

As a quick reminder, the case before the court now concerns the validity of a patent that was granted to Myriad Genetics on a pair of genes (BRCA 1/2) whose presence has been shown to confer an increased risk of developing breast cancer. Here, I want to examine how this case turns on a difficult ontological question, namely: what kind of things are genes?

A number of people who support Myriad’s patent argue that human genes ought to be understood as a molecule like any other. They are a material object, nothing more and nothing less.

Others, including the co-discoverer of DNA’s molecular structure, Jim Watson, have urged the court to endorse a divergent vision. In a friend of the court brief, Watson argues that although genes are indeed a chemical molecule, they are also something more.

According to Watson, a gene is primarily an informational object. “It is a chemical entity,” he writes, “but DNA’s importance flows from its ability to encode and transmit the instructions for creating humans.” Watson goes on to cite some of the terminology commonly used in molecular biology, such as “transcription” and “translation” as evidence for this claim. He then makes the following, totally fascinating, statement:

“The myopic viewpoint thinks of a human gene as merely another chemical compound, composed of various bases and sugars. But history and science teach us otherwise. … The human genome’s ability to be our instruction book on life distinguishes it from other chemicals covered by the patent laws. No other molecule carries the information to instruct a human zygote to become a boy or a girl, a blonde or brunette, an Asian, African, or Caucasian.”

The reason this distinction between genes-as-molecules versus genes-as-information matters so much is that it speaks directly to the question of whether genes are patentable. According to the United States patent law, any “new and useful machine, manufacture, or composition of matter” can be patented. That language is extremely broad, and it is designed to encourage innovation. But there is also an important exception, which states that a product of nature is not patentable. So the Myriad Genetics case crucially turns on whether the BRCA 1/2 genes are a product of nature.

In an earlier decision in favor of Myriad Genetics, the US Federal Circuit Court of Appeals argued that isolated genes do not occur in nature. As the majority opinion pointed out, “DNA in the cell … is packaged into twenty three-pairs of chromosomes.” (See the figure above.) That is, the genes on which Myriad Genetics holds a patent are always part of a larger assemblage. But Myriad Genetics did not seek patent protection over whole chromosomes. They only applied for a patent on a section of DNA that had been isolated and purified. As the court’s ruling noted, Myriad “cleaved” the BRCA 1/2 genes “from their native chemical combination with other genetic materials.” This rendered them a human invention, for “an isolated DNA molecule is not a purified form of a natural material, but a distinct chemical entity that is obtained by human intervention.”

(It is worth pointing out that in another friend of the court brief, Eric Lander argues that the Appeals Court’s decision rested on a factually inaccurate assumption. In fact, DNA in the human body is constantly broken and repaired. So much so that it is statistically certain that isolated versions of both the BRCA 1 and 2 genes have appeared in nature.)

Watson’s claim that genes are primarily informational objects throws a wrench in the Appeals Court’s reasoning. It also echoes the argument made by Judge Robert Sweet of the United States District Court of New York in the first hearing of this case. In his ruling to strike down Myriad’s patent, Sweet wrote that although certain chemical differences may distinguish DNA in the human body from DNA that has been isolated and purified in the lab, those differences are irrelevant to the case at hand. That’s because chemical differences alone are not enough: isolated DNA would have to be “markedly different” from the DNA sequences routinely found in nature to qualify as a genuine invention.

But what constitutes a marked difference? Answering this question is tricky and, according to Judge Sweet, requires taking the nature of the object in question into account. In fact, although Judge Sweet did not use the word himself, we might say that it requires taking the essence of the object into account. The question before the court, then, is whether purifying a stretch of DNA by isolating it from the rest of the genome changes its essential nature somehow.

Why would this be?

To see why this is the case, Federal Circuit Court of Appeals Judge Bryson asks us to imagine a baseball bat that has been fashioned out of an Ash tree. There is a real sense in which the bat is just a “purification” of the tree because you can fashion a bat simply by taking away the wood around it. The bat has been “extracted” from the Ash tree much like the BRCA 1/2 genes have been extracted from the genome. But in fashioning a tree into a bat we have changed its function and thus completely changed its nature. “The result of the process of selection is a product with a function that is entirely different from that of the raw material from which it was obtained.” The same is not true for the BRCA 1/2 genes.

In fact, exactly the opposite is true! The reason that Myriad patented the BRCA 1/2 genes is that they serve as a diagnostic tool. But for them to succeed on this score, it is crucial for the isolated sequences retain their homology to those regions of the genome that confer an increased risk of developing breast cancer. To quote from Bryson dissenting opinion again: “Biochemists extract the target genes along lines defined by nature so as to preserve the structure and function that the gene possessed in its natural environment.” For this reason, the process “does not result in the creation of a human invention.”

Let me just close with a couple quick observations. First, much like the case of Diamond v. Chakrabarty that I discussed in my previous post, this case again forces the court to wade into the deep waters of ontological deliberation. As you’ll recall, the Diamond v. Chakrabarty decision saw the court privilege one level of biological organization (whole organisms) over another (circular pieces of DNA) in deciding whether or not something is an invention or “nature’s handiwork.” This is surprising, and it links up with a controversy within biology about the levels at which evolution operates (usually referred to as the units of selection debate).

Now the court is again being asked to make an ontological decision. But this time, it’s not about whether we should privilege one level of biological organization. Rather, it’s about whether genes are just a chemical molecule or if they are something more; namely, an informational entity.

Of course, historians of science have been thinking about this question for some time. For example, Lily Kay’s book Who Wrote the Book of Life argues that molecular biologists during the 1950s and 60s adopted the DNA-as-code metaphor because many of them had a background in physics and mathematics and because research on computers and information-processing was taking off at the time. Philosophers of biology, too, have debated the utility of thinking about genes in this way. (Here is an excellent review by Peter Godfrey-Smith.)

Despite all the debates, almost every historian and philosopher agrees that when biologists like Watson talk about genes as informational objects they are speaking metaphorically. DNA is not really a set of instructions or a codebook, but it might be heuristically useful to think of it in that way.

The question for most historians and philosophers of science, then, is not whether genes are informational entities, but whether the metaphor has been a useful and productive one. There is a deep irony in the fact that we are about to see the United States Supreme Court grapple with exactly this question, but that it will be doing so in a very literal way.

The Ontology of Patent Law, Part I

On April 15 of 2013, the Supreme Court of the United States will hear a case challenging the practice of patenting DNA sequences, including human genes. With the forbidding title of Association for Molecular Pathology v. Myriad Genetics, this case is all but certain to have a huge impact on the history of biotechnology, the patent law, and interactions between science and capitalism more broadly.
Today, I am posting the first of a two-part piece on the case, with some thoughts on patenting living things and parts thereof.

The case currently before the US Supreme Court concerns a biotech company called Myriad Genetics. During the mid 1990s, Myriad successfully filed for a patent on two genes (BRCA1 and BRCA 2) that dramatically increase a woman’s risk of developing breast cancer. Having sequence both of these two genes, Myriad Genetics developed a diagnostic test, which it currently markets for several thousand dollars. It is worth emphasizing that Myriad’s patent covers the genes themselves, not just the diagnostic procedure. In agreeing to hear the case, the Supreme Court explicitly signaled its willingness to address the question “Are human genes patentable?” 
(For more, see the Petition for a Writ of Certiorari. You can also read some commentary as well as download friend of the court briefs here.)
Rather than discuss the case in all its particulars, I’ll focus on what I take to be one of its more interesting dimensions: the extent to which challenges to what are called composition-of-matter patents can force the court to wade into the deep waters of ontological deliberation. At the risk of stating the obvious, I’ll remind everyone that ontology is a branch of metaphysics that studies the nature of being. Ontology is about what there is. In contrast, epistemology concerns how we come to know things. 
According to Title 35, Paragraph 101 of the United States Patent Code, any “new and useful process, machine, manufacture, or composition of matter” may be subject to patent protection. However, there is a well-known and longstanding exception to this extremely broad formulation: the so-called product of nature doctrine. It holds that naturally occurring entities such as physical laws or minerals cannot be subject to patent protection. As such, the court has often found itself in the position of having to decide what is and is not a genuine product of nature. In so doing, it has had to specify where nature ends and culture begins.
Patent law is often seen as a kind of bargain between society and individuals. The state agrees to give a monopoly over a new and useful invention in exchange for its disclosure or publication. The granting of a monopoly over an intangible good is not to be taken lightly because it hinders other people’s access to it. But the practice is usually seen as justified by the fact that doing so not only discourages the keeping of trade secrets, it also incentivizes discovery and thus acts as a spur to technological progress. 
If the patent law represents a kind of bargain or balancing act between the interests of individuals and the society, it makes sense to think carefully about where to draw the line between patentable and non-patentable subject matter. In particular, I think most people would agree that the law would no longer be fulfilling its proper function if it allowed someone to privatize whole swaths of the natural world simply by describing them and thus claiming an ownership right. It can’t be right that whoever discovers coal’s ability to release thermal energy when lit on fire therefore has a right to stop anyone else from digging up and burning hydrocarbons. (Although the latter might not be such a terrible turn of events in this day and age!)
The product of nature doctrine goes back to ex parte Latimer from 1889, in which the United States Patent Office ruled that a new fiber produced from pine needles was not patentable subject matter. Its most canonical expression, however, was articulated by William O. Douglas, Associate Justice of the United States Supreme Court. Writing the majority opinion in Funk Brothers Seed Co. v. Kalo Inoculant Co. (1948), Douglas declared that a mixture of naturally occurring bacteria was not patentable because these, “like the heat of the sun, electricity, or the qualities of metals, are part of the storehouse of knowledge of all men. They are manifestations of laws of nature, free to all men and reserved exclusively to none.”
Justice Douglas’ opinion continues to influence legal arguments about the proper scope and interpretation of 35 USC § 101. Part of its remarkable staying power is due to the fact that Chief Justice Warren Burger relied on it extensively for his 1980 decision in the case of Diamond v. Chakrabarty. As I’m sure most of you are aware, this was the case in which the United States Supreme Court ruled that genetically modified organisms were eligible for patent protection because they are products of human ingenuity rather than nature.
Chief Justice Burger’s argument in Diamond v. Chakrabarty explicitly contrasted the latter’s invention to the one under dispute in Funk Brothers v. Kalo Inoculant. To get Burger’s reasoning straight requires a passing familiarity with the details of both cases. 
The Funk Brothers case concerns a patent that had been granted on a mixture of various Rhizobia, bacteria that fix nitrogens after becoming established in the root system of plants. Farmers had long known that inoculating their plants with bacteria helped them to grow, but each plant required its own, specific strain. The patent under dispute in Funk Brothers was for a *mixture* of many bacteria that could successfully inoculate a whole range of plants, which made the mixture more widely applicable and thus economical than what was currently available on the market. 
Justice Douglas struck down the patent under dispute in Funk Brothers because making a mixture of exiting bacteria, he reasoned, did not qualify as a genuine invention. Rather, it represented “no more than the discovery of some of the handiwork of nature.” “No species acquires a different use,” he went on to argue. “The combination of species produces no new bacteria, no change in the six species of bacteria, and no enlargement of the range of their utility. Each species has the same effect it aways had.”
Chakrabarty’s patent claim was in many respects similar, but in others quite different from that under dispute in Funk Brothers. Whereas the latter concerned a mixture of pre-existing bacteria, Chakrabarty claimed to have engineered a whole new organism. He did so by introducing several small pieces of naturally occurring circular DNA molecules–called plasmid–into a species of pseudomonas bacteria. It is worth emphasizing that Chakrabarty did not claim to have manufactured any new pieces of DNA. All that he did was to introduce existing DNA molecules into a new organism. In the “Summary of the Invention” section of his original patent application, Chakrabarty wrote, “Having established the existence of (and transmissibility of) plasmid-borne capabilities for [breaking down petroleum molecules into more simple chemical compounds], unique single-cell microbes have been developed containing various stable combinations of [those plasmids].”
Despite their many similarities, Chief Justice Burger went out of his way to draw a stark contrast between Chakrabarty’s patent and the one under dispute in the Funk Brothers case. In Chakrabarty’s case, he wrote, “the patentee has produced a new bacterium with markedly different characteristics from any found in nature and one having the potential for significant utility.” Because the “discovery is not nature’s handiwork, but his own,” Burger concluded, “it is patentable subject matter.”
What I find so remarkable about this case is that in trying to decide whether a genetically engineered organism is patentable subject matter, the United States Supreme Court was not just compelled to decide what is and is not a product of nature. Rather, by way of trying to answer that question, it had to address an antecedent question about the level of biological organization at which nature produces its handiwork. That is to say: different strains of bacteria remain a product of nature even when they are brought into a new mixture with one another (and thereby acquire a new efficacy), whereas a new mixture of circular DNA molecules is a product of human ingenuity.
As an exercise, you can re-read Justice Douglas’ decision above and replace each instance of the word “species” and “bacteria” with the word “plasmid.”  I admit the phrasing sounds awkward, but the effect is pretty compelling nonetheless.
What is going on here? The answer, of course, is quite a lot. But let me just close with one thought and then take the issue up again in my next post, where I will examine the legal reasoning in the Myriad Genetics case itself.
The patent law is designed to encourage innovation and it does so by rewarding technological breakthroughs. I suspect that one reason we balk at the idea of patenting products of nature is that we don’t want to reward the mere act of describing something that was previously created via some other means, whether it is evolution or God or what have you. Reading Douglas’ decision, one gets the sense that he took *moral* offense at the notion that someone could receive financial rewards for doing no more than harnessing “nature’s handiwork.” 
Of course, nobody thinks that discovery is an easy or straightforward process. But patent law does assume that it is fundamentally different from the act of invention. One way in which the two are kept separate is that both are governed by different reward systems. Whereas a new discovery brings with it an accrual of credit, inventions bestow a more material kind of reward. 
My aim here is not to *endorse* a clear-cut distinction between invention and discovery. I am well aware that discoveries often come with financial and other kinds of material rewards. Similarly, it need hardly be pointed out that inventors are routinely given significant credit by the scientific community for the work they have done.
What I would like to suggest, however, is that one reason we are so invested in making a distinction between invention and discovery, products of nature and human ingenuity, is that doing so helps us keep alive an even more fundamental distinction, namely the one with which I began. That is the distinction between ontology and epistemology, between the nature of things in themselves and how we experience, know, or represent them. Seen in this light, it is no surprise that questions about patenting things like live organisms and human genes should elicit such strong emotional and moral reactions. After all, to give up the dream of drawing a hard line between acts of description and intervention would force us to revise a great deal more than just Title 35, Paragraph 101 of the United States Patent Code.
In the next post, I will link these issues up with more fine-grained concerns about giving ontological primacy to certain levels of biological organization and characterizing genes as informational objects.