Michael Crichton weighs in on patenting and the Genomic Research and Accessibility Act

In yesterday's New York Times, Michael Crichton (author of "Jurassic Park" and "Next") wrote in favor of the Genomic Research and Accessibility Act, which would ban the patenting of genes found in nature. He correctly points out that genes are not inventions and attributes the fact that they can be patented to "a mistake by an underfinanced and understaffed government agency, The United States Patent Office." I note that the bill, as described by co-sponsor Xavier Becerra, is not retroactive, so, while it's a no-brainer that the patent office should not be granting patents for the discovery of natural phenomena, this bill won't do much to facilitate the promise of personalized medicine (because most of the genes that matter have already been patented). I have discussed the possibility that we might find relief in the courts before (regarding EBay Inc. vs. MercExchange, LLC and Labcorp vs. Metabolite Laboratories). Certainly, gene patents disserve the public interest, but that is not enough, and the prospect of understanding the law in these cases is daunting.

Science Blogs listed on the OMMBID blog

The OMMBID (Online Metabolic and Molecular Bases of Inherited Diseases) blog has published a list of science blogs and related websites. It's nice to have been included. When I get some time I will browse that list and update my own lists of favorites on Connotea and my summary page.

Shared bookmarks for the literature -- what to do?

After some initial skepticism, I agree that "social bookmarking" is nice. It's very useful to put bookmarks to the literature online and see what articles others have cited, and the old approach of journal-specific browsing (associated with hard-copy volumes, but also including eTOCs) is certainly outmoded. I'm experimenting now with del.icio.us (as both ongenetics and RNAinfo) and Connotea. An RNA Society survey generated a few votes for CiteUlike, which looks great, although it is not easy to get it to accept an article from PubMed (in order to get the correct URL active you have to select the article you want from a list; if it is only result of your search, PubMed continues to display the URL for the search). A user named Cortel has lots of relevant citations, so I may continue to keep track of him, whether I settle on CiteUlike or not. I also created my parallel blog, "Quick Notes on Genetics," primarily with the idea of citing articles, and I keep a list of especially relevant articles tied to my lab's web page (the Mount lab reading room). Finally, it's worth mentioning the Faculty of 1000 in this context. This is all way too much. It's not clear what I will settle on, but most of these will be forgotten once I stop exploring and develop a routine for finding and sharing the articles that interest me.

The genetic architecture of complex traits: significant differences can involve noncoding DNA and can be epistatic

Clark et al., in "A distant upstream enhancer at the maize domestication gene tb1 has pleiotropic effects on plant and inflorescent architecture," describe a significant QTL residing in noncoding (and largely repetitive) DNA far upstream of the affected gene (PubMed, Nature Genetics). I am reminded of the graduate genetics course given by Michael Freeling that I sat in on while a postdoc at Berkeley (in 1984, while studying the effects of transposable element insertions on gene expression in Drosophila in Gerry Rubin's lab). He emphasized epigenetic phenomenon and truly expected that novel molecular mechanisms (such as transposon instability) would reveal "a molecular clock that really ticks." From his web page it looks like he's continuing on the same tack today.

A paper in the previous month's issue of Nature Genetics (Carlborg et al., "Epistasis and the release of genetic variation during long-term selection," PubMed, Nature Genetics) reported a genetic network of four interacting loci affecting chicken growth ("Growth4, Growth6 and Growth12 had a significantly larger effect on growth in homozygous Growth9 individuals than [others]"). This kind of genetic interaction is precisely what any developmental geneticist would expect, yet breeders and population geneticists often cling to simple linear models. This paper will certainly help, not least of all because it involves a method for the detection of epistatic QTLs.

From HapMap to selection map

It was the article by Nicolas Wade in the New York Times ("Still Evolving, Human Genes Tell New Story") that alerted me to the new article in PLoS Biology by Voight et al. ("A Map of Recent Positive Selection in the Human Genome", from Jonathan Pritchard's group at the University of Chicago). I've been anticipating a list of human genes under selection for some time, and it's exciting to see this published. This paper, perhaps more than any other, marks the transition to a new and controversial era in genetics. On the positive side, we're going to learn a lot very quickly about the genetics of human differences. This will provide many benefits and engage curiosity in satisfying and useful ways.

On the other hand, the uncritical acceptance of results that are statistical in nature (and have a real possibility of being wrong) is disturbing. A recent visitor to Sarah Tishkoff's lab (Jeff Jensen, from Cornell, where he works with Aquadro and Bustamonte) gave a talk about the statistical problem of distinguishing selection from certain demographic phenomena that made me think the interpretation of selection maps is going to be extremely uncertain. It is surprising that none of those issues were addressed in Wade's article, especially so because the New York Times typically fills their science articles with quotes from others in the field. I felt the same unease a few weeks ago when watching a PBS documentary "African American Lives," in which famous African-Americans were given overly specific information about their ancestry without appropriate statistical disclaimers.

I suppose that we will all be talking a lot more about selection and race with my friends who are not geneticists, and putting a lot more population genetics into my graduate genetics course. Clearly, the idea that population genetics is passé is now passé.

Alternative splicing and host defense in flies and plants

In an article appearing online in Science this week, and discussed in The Scientist, Watson et al. (PubMed) implicate the Drosophila Dscam gene in host defense. They detect secreted forms of the protein in hemolymph and show that the gene enhances phagocytosis of bacteria by hemocytes. They also demonstrate conservation of the potential for extreme isoform diversity across insect taxa, an extension of earlier work from the Graveley lab (Graveley et al. 2004; PubMed, RNA journal). Isoform diversity due to alternative splicing is therefore implicated in the generation of adaptive variation in host defense molecules. It is interesting that isoform diversity due to alternative splicing of Toll-like proteins has likewise been implicated in plant defense (reviewed by Kazan 2003 and Jordan et al. 2002; an example is Zhang & Gassmann 2003).

What kind of adaptation does this make possible? Certainly, extreme variability allows rapid adaptation on a population level. Furthermore, the presence of membrane bound and secreted forms of the same molecule presents the possibility of adaptive immunity through clonal selection of hemocytes that see antigen. Louisa Wu pointed me to an article in Nature Immunity (Little, Hultmark and Read 2005) making the point that neither memory nor specificity has been ruled out in invertebrate immunity. True adaptive immunity in insects would be very exciting, but we're a long way from that. How could variation in isoform production among hemocytes in Dscam isoforms be heritable? Through epigenetic silencing of splicing factors? We're just at the beginning of this story.

The authors say this:

broad conservation of receptor diversity strongly suggests important
functions and future studies will have to further address
whether the presence of diverse immune receptors in
invertebrates increases the effectiveness of immune responses
of individual animals. Alternatively, given the relative short
life span of many invertebrates, it may be that immune
receptor diversity is less important ontogenetically but rather
enhances the adaptive potential of animal populations to
changing environmental and pathogenic threats.