Friday, June 14, 2013

The problem with biotech patents

There's a big swirl of confusion today as folks try to make sense of the Supreme Court's decision over the patents claimed by Myriad Genetics for variant sequences of the BRCA genes. What Myriad wanted to do was patent the use of natural sequences of those genes (including naturally occuring variants) to diagnose breast and ovarian cancer risk. The court said that you can't do that; patenting native DNA is not permitted because it is a "product of nature". In other words, you can't just take something natural and claim a patent monopoly on its use. That's clear, and to many folks helpful; Myriad was charging something like $3000 per test (which, to be clear, is a massive profit compared to the actual cost of the laboratory work; Myriad would claim that profit is reward for discovering the connection between the BRCA genes and breast and ovarian cancers). If that were the end of the case, things might be reasonably clear...but of course it isn't.

Myriad also held patents on cDNA sequences derived from the naturally occurring BRCA sequences. That means they had isolated mRNA, the version of the gene that leaves the nucleus and provides the template for making proteins, and had then created a DNA version of that mRNA (that's what we call cDNA). Why would you want to do this? Well, for one, there are stretches of DNA in eukaryotes (basically, everything but bacteria and viruses) which are not used to make protein, and these introns are spliced out of the mRNA before it leaves the nucleus. If, for example, you wanted to make a lot of one of the BRCA proteins, you might put a cDNA copy into a bacterium and use it as a protein factory. You have to have cDNA to do that - the introns would screw up the final protein, because the bacterium would treat them like DNA that is supposed to be translated into protein. This is all pretty routine in a molecular biology laboratory.

The Court held that Myriad is able to patent cDNA sequences made from the BRCA genes. The thinking appears to be that because there is human work and manipulation going on, the cDNAs are no longer naturally-occurring. In a strict sense, the court is correct; there are unlikely to be human cDNAs of the BRCA genes floating around in nature. Most folks who understand biology are shaking their heads, however, as creating a cDNA is hardly an innovative thing; again, it's pretty routine. In fact, to convert mRNA back into cDNA, you use an enzyme (reverse transcriptase) that was isolated from retroviruses. Why? Because retroviruses make cDNA all the time - cDNA made from their own genetic material, which is held in RNA form. Retroviruses need to convert that back to DNA if they are going to get the host they infect to make more retrovirus from that DNA (getting the infected cell to make more copies of a virus is the way viruses reproduce). So making cDNA is routine, and the heavy lifting is done by an enzyme "invented" by retroviruses. Most of us think that through and wonder why the cDNA is patentable when the native DNA was not.

What the Court was trying to do, I think, is distinguish between natural DNA and synthetic DNA. One can easily order up a batch of short DNAs made in any combination of bases you would like; indeed, this is routine in a modern laboratory. The Court would surely like to protect with a patent the researcher who comes up with a completely new DNA sequence that does something cool that is not done in nature. One could also imagine someone combining sections of existing genes in a new way that was useful, and granting that invention a patent. In the first case, the product is a totally new DNA; in the second, it is a new combination of existing DNAs.

The fundamental problem, however, is that most biotech patents rely heavily on information derived from nature. The Myriad DNA patents were about using genetic information from DNA to predict disease. The production of recombinant insulin uses human DNA sequences to make insulin in bacteria; nobody "invented" insulin, but instead invented a way to make it in bacteria using the same DNA information. The Polymerase Chain Reaction, which was successfully patented, relies both on unique human ideas (using a fluctuation of temperature to progress through cycles of DNA duplication) but also on a version of the DNA polymerase enzyme that is stable at 95ÂșC. The enzyme that could handle that high temperature was not invented; it was isolated from bacteria that live in hot springs, and natural selection did the "inventing." That's what most molecular biology really is - cleverly finding ways to use natural processes to do stuff that doesn't happen outside the lab. We use natural enzymes to duplicate DNA, to cut it in specific places, and to link it back together when we're done. We use bacteria to convert DNA into protein, to store chopped up pieces of a genome, and to replenish our stores of particular DNA sequences. We isolate mRNA from bacteria into which we have cloned the corresponding DNA, then use retroviral enzymes to turn the mRNA back in to cDNA. The heavy lifting in molecular biology relies on agents that are "products of nature." At least for now, the human ingenuity is not in designing new things from scratch, but rather in finding out how to get natural agents to do new, useful things.

This fundamental property of biotech just doesn't play well with patent law. Patents were designed to protect inventors designing new things (from the French dessiner, to draw). Indeed, drawings are traditionally a big part of patent law, and previous examples of a principle that make a patent invalid are called "prior art." Nature, in these cases, is a source of materials, while the form comes from human imagination. Edison did not invent tungsten, but he did draw it in to a filament, enclose it in a vacuum, and run a current through it to produce light from electricity. Patent law is great at protecting Edisons.

In biotech, however, we tend to draw not just material substance, but information from nature; a DNA sequence is nothing, really, but a convenient and durable way of storing information around which living things have built a whole set of processes. Most biotech work is discovery rather than invention, discovery of what is already out there in natural genes or non-coding DNA, or in the times and places in which the information in those genes is turned into protein, or in the ways in which those DNA sequences interact. That doesn't mean that there is not a lot of ingenuity and creativity involved, but the biotech researcher is really partnering with nature, and drawing a line between the ingenuity of natural processes and the ingenuity of researchers manipulating those processes in new ways is not going to be easy. We still need patents to encourage innovative research in biotechnology, but nature holds a heck of a lot of prior art.

1 comment:

  1. So seems very Lockean. You can't own property that you haven't done anything to. Property emerges when you do anything. So if you pick an apple, then that is your property for Locke (ceteris paribus).