PERSPECTIVES Scientist 1 May (2000). Box 5 | European Parliament directive on patenting 12. Eisenberg R. S. Intellectual property issues in genomics. Trends Biotechnol. 14, 302–307 (1996). Directive 98/44/EC of the European Parliament and of the Council of the 6 July 1998 on the legal 13. US Code, title 35, § 102(a). 14. US Code, title 35, § 103. protection of biotechnological inventions, Official Journal L 213, 30/07/1998 p. 0013–0021 Article 5: 15. Parchomovsky, G. Publish or perish. Michigan Law Rev. • The human body, at the various stages of its formation and development, and the simple 98, 926–952 (2000). 16. Lichtman, D., Baker, S. & Kraus, K. Strategic disclosure in discovery of one of its elements, including the sequence or partial sequence of a gene, cannot the patent system. Vanderbilt Law Rev. (in the press). constitute patentable inventions. 17. Bishop, J. E. Plan may blow lid off secret gene research. Wall Street Journal 28 September (1994). • An element isolated from the human body or otherwise produced by means of a technical process, 18. In re Bell, 991 Federal Reporter, 2d series 781 (Court of including the sequence or partial sequence of a gene, may constitute a patentable invention, even if Appeals for the Federal Circuit, 1993). 19. In re Deuel, 51 Federal Reporter, 3d series 1552 (Court of the structure of that element is identical to that of a natural element. Appeals for the Federal Circuit, 1995). 20. Marshall, E. Drug firms to create public database of genetic • The industrial application of a sequence or a partial sequence of a gene must be disclosed mutations. Science 284, 406–407 (1999). in the patent application. 21. US Code, title 35, § 157(c). 22. US Code, title 35 § 102(e). 23. Shapiro, C. & Varian, H. R. Information Rules: A Strategic concern may motivate some institutions to ests might do more to enlighten public policy Guide to the Network Economy (Harvard Business School Press, Cambridge, Massachusetts, 1998). defer publication in precisely the circum- debates about the importance of the public 24. Venter, J. C. Clinton and Blair shouldn’t destroy our stances that it motivates other institutions to domain in genomics research than appeals to research. Wall Street Journal 21 March (2000). 25. Marshall, E. Talks of public–private deal end in acrimony. make prompt disclosure. The difference ethical imperatives. Science 287, 1723–1725 (2000). depends on whether they believe that pre- 26. Bentley, D. R. Genomic sequence data should be released Rebecca S. Eisenberg is the Robert & Barbara immediately and freely in the public domain. Science 274, empting future patents is good or bad. Apart Luciano Professor of Law at the University of 533–534 (1996). 27. Adams, M. D. & Venter, C. J. Should non-peer-reviewed from concern about preserving their own Michigan Law School, Ann Arbor, Michigan 48109, raw DNA sequence data be forced on the scientific patent rights, public research sponsors and USA. e-mail: [email protected] community? Science 274, 534–536 (1996). publicly funded research performers may 1. Venter, J. C. et al. Shotgun sequencing of the human Acknowledgements genome. Science 280, 1540–1542 (1998). This research has been supported by a grant from the United worry that premature public disclosure could 2. King R. T. Jr Code green: Gene quest will bring glory to States Department of Energy. prevent them from complying with their some; Incyte will stick with cash. The Wall Street Journal 10 February (2000). Links mandate under the Bayh–Dole Act to pro- 3. Healy, B. Special report on gene patenting. N. Engl. J. Med. 327, 664–667 (1992). mote technology transfer and product devel- 4. Eisenberg, R. S. Public research and private development. COMPANIES Celera | Monsanto | Merck | Incyte opment by patenting research results. Indeed, Virginia Law Rev. 82, 1663–1727 (1996). |Human Genome Sciences 5. Waterston, R. & Sulston, J. E. The Human Genome Project: this concern was cited by former NIH director Reaching the finish line. Science 287, 53–54 (1998). FURTHER INFORMATION Human Genome Bernadine Healy in support of the decision to 6. Marshall, E. Claim and counterclaim on the human Project | Joint statement by Bill Clinton and genome. Science 288, 242–243 (2000). Tony Blair | The SNP Consortium | The file patent applications on the first ESTs iden- 7. Nowak, R. The gold bug: Helicobacter pylori; claimed to tified by Craig Venter when he was at NIH25. be the first free-living organism genome fully sequenced. Bermuda rules | National Human Genome Science 267, 173–174 (1995). Research Institute policy on patenting of In fact, it does not seem that publication of 8. Wade, N. 10 Drug makers join in drive to find diseases’ human genomic sequence | Interim utility raw genomic DNA sequence will prevent the genetic roots. The New York Times 15 April (1999). 9. European Patent Convention, Article 54. guidelines and written description guidelines issuance of patents on genes that are subse- 10. US Code, title 35, § 102(b). 11. Palevitz, B. A. Rice genome gets a boost: private for Patent Examiners | European Parliament quently found to lie within that sequence sequencing effort yields rough draft for the public. The directive on patenting under United States law. The situation in Europe is less certain and awaits clarification of national laws in response to a 1998 directive of the European Parliament on the legal protec- OPINION tion of biotechnological inventions (BOX 5). Although the patent system has not yet resolved many of the legal issues that will determine what portions of the human Evo-devo: the evolution genome may be patented, for the time being there seems to be little threat that disclosure of of a new discipline the human genome in the public domain will leave future researchers who identify and char- Rudolf A. Raff acterize genes with nothing left to patent. The history of life documented in the fossil of development, and how the process Conclusion record shows that the evolution of of development itself biases or constrains Complex and interrelated strategies for complex organisms such as animals and evolution. A revolutionary synthesis of endowing the public domain are at work in the plants has involved marked changes in developmental biology and evolution is field of genomics. These strategies arise out of morphology, and the appearance of new in progress. the varied plans of different institutions for features. However, evolutionary change extracting value out of genomic information, occurs not by the direct transformation of Developmental and evolutionary biology complicated by the interplay of the public adult ancestors into adult descendants are two disciplines that explore morpholog- domain with the patent system. Public disclo- but rather when developmental processes ical change in organisms over time. sure of genomic information advances some produce the features of each generation However, the processes involved are differ- interests while harming others, with no simple in an evolving lineage. Therefore, ent. Development is genetically pro- distinction between the interests of public and evolution cannot be understood grammed and cyclical. Evolution is non- private institutions. Understanding these inter- without understanding the evolution programmed and contingent. Although a 74 | OCTOBER 2000 | VOLUME 1 www.nature.com/reviews/genetics PERSPECTIVES link between the two processes was recog- mental biologists. But palaeontology pro- phylogenetic distance, making genes identi- nized in the late nineteenth century, an vides insights available in no other way. For fied by developmental mutations most use- effective connection of evolutionary and example, the discovery that the earliest (fos- ful in comparisons of related taxa. developmental biology awaited the appear- sil) TETRAPODS had feet with eight toes rather ance of developmental data that contained a than five2 was a complete surprise, and was The contribution of phylogenetics strong and marked evolutionary signal. This important in providing us with a new view Evolutionary biology is comparative, and happened in the 1980s, when the growth of of what ancestral limbs were actually like, requires tracking events over long time developmental genetics established a link and for giving us clues as to how limb devel- frames, and across phylogeny. Although phy- between genes and development. As devel- opment evolved. logenetic relationships have not been regard- opmental regulatory genes were cloned and Finally, evolutionary biologists are faced ed as important for the study of develop- sequenced — notably those of the Hox gene with understanding how small genotypic mental mechanisms, they become crucial family, which are important in specification once we begin to consider the evolution of of the identity of insect segments — it was developmental processes3. New analytical realized that the same regulatory genes were “Development is methods provided by CLADISTICS and the shared by animals with different body plans avalanche of gene sequence data have revo- (for example, insects and vertebrates). More genetically programmed lutionized phylogeny. importantly, shared regulatory genes have and cyclical. Evolution Phylogeny imparts three important kinds conserved roles in development, which of information. First, we can determine the some have taken to indicate homologies in is non-programmed direction in which developmental features the development of body architecture and contingent.” are evolving. Second, knowing the diver- among different animal body plans1. gence times of branches in a tree allows evo- Developmental biology has once again lution rates to be inferred. (There is, at pre- become relevant to understanding both modificationsEPIGENETICS are translated into phenotypic sent, controversy about using extrapolations evolutionary mechanisms and the patterns changes during evolution, and how micro- of rates of gene evolution to determine of evolutionary history that are revealed by evolutionary changes contribute to the important divergences that pre-date visible palaeontology and PHYLOGENETIC studies. MACRO-EVOLUTIONARY events on the timescale fossil evidence; the divergence among ani- observed in the fossil record.