Masters Of The Disease Masterswitch

Under conditions of low stress NF-κB (Nuclear Factor-κB) remains safely bound by IκB (Inhibitor κB) proteins in the cellular cytoplasm. However, when stress does strike, NF-κB is thought to be released by its IκB minders. Once free, NF-κB homes in on a cell's nucleus, where it binds a particular consensus sequence (5'GGGACTTTCC-3') of certain genes and promotes their transcription. thereby plays an important role in regulating vital cellular processes, such as programmed cell death (apoptosis), tumor production (tumorigenesis), inflammation, autoimmune reactions, and replication of viruses. In short, NF-κB is a master regulator of many diseases.

The regulatory importance of NF-κB was discovered by research groups led by David Baltimore (MIT), Phillip Sharp (The Whitehead Institute), and Tom Maniatis (Harvard University). Their host institutions successfully obtained U.S. Patent No. 6,410,516 ("the '516 patent"), whose claims cover various applications of their discovery, and licensed it to ARIAD Pharmaceuticals, Inc.. Previously, ARIAD successfully sued Eli Lilly & Company for infringing claims of the '516 patent with its osteoporosis drug, Evista® (raloxifene HCl), and its septic shock drug, Xigris® (drotrecogin alfa).

Now ARIAD and its licensors have decided to sue Amgen, Inc., and Wyeth, whose cytokine-derived drugs, Enbrel® (etanercept - a tumor necrosis factor (TNF) blocker) and Kineret® (anakinra - an interleukin-1 (IL-1) receptor antagonist), for infringing other claims of the '516 patent.

The pioneering biological research that elucidated the regulatory activities of NF-κB was elegant and masterful. The resulting '516 patent, some of whose claims have already survived judicial validity challenges, has given ARIAD and its licensors commanding roles as keepers of the biological gate through which many drugs must, or will have to, pass to be therapeutically effective: NF-κB regulates hundreds of genes, which in turn play roles in hundreds of human diseases. Providing that the validity of claims of the '516 patent continue to be upheld, the patent masters of NF-κB will continue to wield their power for years to come: the '516 patent will not expire until at least 2019.

Nonreproductive Rights

This week Natallie Evans, a British cancer-survivor, was told by the Grand Chamber of the European Court of Human Rights ("Grand Chamber") that she would never be a mother. Evans, whose eggs were harvested prior to her 2001 treatment for ovarian cancer, sought the right to implant frozen embryos despite opposition from the former boyfriend whose sperm had fertilized her eggs. The Grand Chamber held that a British law requiring the consent of both genetic parents before such embryos could be implanted in a mother did not violate Evans' human rights under European law.

Four of 17 judges disagreed, in part characterizing the dispute as follows:

The applicant underwent surgery to remove her ovaries (26 November 2001). Therefore, the eggs that were extracted from her for IVF treatment were her last chance to have a genetically related child. J not only knew this fact very well, but also gave her an assurance that he wanted to be the father of her child. Without such an assurance, the applicant could have tried to seek other ways to have a child of her own. In [the relevant part of] the judgment, where the majority tries to strike a balance between the rights and interests of the applicant and of J, no weight is given to this “assurance” element, that is, to the fact that the applicant acted in good faith, relying on the assurance given to her by J. The decisive date was 12 November 2001: the date when the eggs were fertilized and six embryos created. From that moment on, J was no longer in control of his sperm. An embryo is a joint product of two people, which, when planted into the uterus, will turn into a baby. The act of destroying an embryo also involves destroying the applicant's eggs. In this sense too, the British legislation has failed to strike the right balance.

Having exhausted all avenues of legal appeal, Evans has now thrown herself upon the mercy of her former boyfriend, whose consent would allow implantation, and the British government, whose statute requires double consent. Neither appears likely to relent.

Esse Est Fervescere

Today Working Group II ("WGII") of Intergovernmental Panel on Climate Change released a "Summary for Policymakers" of their upcoming fourth assessment report on "Climate Change Impacts, Adaptation and Vulnerability". Based on a staggering 29 000 data series, WGII concludes that

the consistency between observed and modelled changes in several studies and the spatial agreement between significant regional warming and consistent impacts at the global scale is sufficient to conclude with high confidence that anthropogenic warming over the last three decades has had a discernible influence on many physical and biological systems.

Conspicuous by their absences are observations made in the developing world. As the first diagram in the Summary shows (Figure SPM-1, entitled "Changes in physical and biological systems and surface temperature 1970-2004"), observations were missing for the increasingly prodigious greenhouse gas producers, China, India, and Brazil, and the fossil fuel megaproducers spanning the entire oil-producing Middle East. Perhaps these countries hope that, by adopting a Berkeleyan esse est percipi perspective, avoidance of scientific eye contact will make global climate change bypass their territories. Alas, the report predicts just the opposite for almost all of them: a hotter, drier, and much less pleasant future.