Duke Finds a Second Alzheimer’s Gene—What Does It Mean?

Genetic CodeThe recent discovery of a gene linked to Alzheimer’s disease provides a timely context for revisiting the significance of gene patents. Researchers at Duke University Medical Center recently announced that they have identified a second gene (called TOMM40) associated with an increased risk of late-onset Alzheimer’s, which affects people over the age of 65. A team of Duke gene hunters originally identified the first Alzheimer’s gene (APOE) in 1993. Although the announcement prompted warnings about the need for further confirmation, the Duke researchers hope that the analysis of which versions, or alleles, of the two genes that people carry will significantly sharpen geneticists’ ability to predict susceptibility to Alzheimer’s. Those predictions might prove especially useful in both diagnosing Alzheimer’s disease and in developing future Alzheimer’s drugs.

One of the first questions on everyone’s mind, particularly in light of the high-profile lawsuit by the ACLU and others against Myriad Genetics, is whether this newly discovered Alzheimer’s gene could be patented. In principle, yes.  Going back at least to the early 1980s, the U.S. Patent and Trademark Office (US PTO) and the federal courts have repeatedly taken the position that genes in isolation from their natural environment (that is, outside the body) are patentable subject matter, just like any other chemical compound. Individual cases have turned on such specifics as whether others had previously identified the gene, or whether and when the patent applicant or others had first disclosed the gene. But there is no general prohibition against patenting genes.

On the contrary, a recent draft report on gene patenting (pdf) prepared for the Secretary of Health and Human Services by the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) estimates that about 20% of human genes are covered by patents, including such controversial examples as BRCA-1 and 2, which are linked to susceptibility to breast and ovarian cancer and are the subject of the ACLU’s suit against Myriad Genetics.

What is the practical significance of patenting a gene sequence? A patent allows the holder to prevent others from making, using, or selling the patented invention for twenty years. There is no meaningful research exception, nor any obligation to permit any particular use. To do research on a patented gene outside the body, or to perform a genetic test, is to use the patented invention—and that requires the permission of the patent holder. So researchers who want to study the genes, or doctors who want to have their patients tested to determine which versions, or alleles, of a patented gene they possess, must first seek permission, usually at some financial cost.

If Duke or a spinoff were to patent TOMM40 and/or APOE, the outcome could be the same: the patent holder would control access to the gene for both research and diagnostic testing, and be permitted to set whatever price the market (in most cases, insurance companies) would bear. (This is, of course, illustrative only: there is no indication that Duke is or has any intention of pursuing such a strategy.)

There are all kinds of horror stories surrounding gene patents, including claims that they stifle important research and commercial innovation, or that they result in the denial of essential medical tests to the poor and uninsured. (Last week Dan Vorhaus and I discussed the effects of gene patents on the emerging whole-genome sequencing industry.) The most frequently cited concern is the case of the BRCA-1 and 2 alleles, the patent rights to which are owned by Myriad Genetics, a University of Utah spinoff. (Myriad also has obtained patents on a variety of related diagnostic and testing methods, which is a common practice among gene patent holders.) As the patent rights holder, Myriad can choose whether, and on what terms, to permit research, and it performs (or licenses others to perform) the majority of the BRCA-1 and 2 genetic tests itself for fees that the SACGHS report calls “midrange.” Myriad’s gene patents are the subject of a recent and highly publicized lawsuit brought by the ACLU alleging that the patents are both illegal and unconstitutional.

But how accurate are these claims? The SACGHS report reviews the range of studies on the effects of gene patents and reaches no firm conclusion. There are reports of problems in conducting research, and tests on patented genes are sometimes more expensive that they might be otherwise, but in the aggregate the evidence seems equivocal. As the SACGHS report puts it:

Based on its review of the literature, case studies, and review of international policies regarding gene patents, SACGHS found little in the way of broad or consistent evidence that indicates either positive or negative effects of gene patents on patient access to diagnostic tests.

Regardless of effects, gene patent proponents retort that the promise of a patent monopoly is essential to lure private capital and motivate researchers. This claim, however, is particularly hard to test, since we’ve never tried it any other way.

A final thought concerns the future of gene patents. I suggested in my previous post on the ACLU-Myriad litigation that the ACLU’s frontal attack on genes as patentable subject matter was a long shot at best. But I also noted a number of other cases that seemed to be chipping away at the margins of gene patents by finding them obvious or inadequately described. The Supreme Court has also decided to review a business method patent case from the Federal Circuit, In re Bilski (pdf), that may have implications for patents on diagnostic techniques. So gene patents would appear to be here to stay, but the impact of gene patents on both research and commercialization is still very much up in the air.