HIGHLIGHTS ETHICS WATCH GENOMICS The $1,000 genome: ethical and legal hurdles Sea squirt There is much buzz these days about 24-hour, whole-genome genome released genotyping of individuals for under US $1,000. Craig Venter has announced that he will tackle this ‘$1,000 genome’,and some The sea squirt Ciona intestinalis is an futurists are thinking of how it might be used in medicine1. unusual organism with an unusual Although the technology for rapid whole-genome genotyping is history. For more than a century, biol- not yet developed, the tools for doing so might soon be available2. ogists have pored over this marine Solving the technical problems fortunately gives us time to invertebrate due to its peculiar resolve the ethical, legal and social issues (ELSI) that this anatomical features and controversial endeavour presents before it is ready for ‘prime time’.Take the taxonomy. It is now widely accepted Adult sea squirt, image courtesy of Nori Satoh. question of ownership of one’s DNA, still an unresolved issue in that this species is a primitive chordate many jurisdictions. Individuals have the right to decide whether — that is, it has a cartilaginous col- development that are absent in the fly tissue that contains their DNA is removed from their body, but few umn resembling a spine — and so, it and worm genomes, such as thyroid personal legal rights have been established over the genotyping or is suitably placed to tell us about the hormone production and detection, testing of DNA that is legally acquired or sloughed off a person. evolutionary steps leading from inver- and heart development. To gain public acceptance of sequencing an individual’s whole tebrates to vertebrates such as our- As well as shedding light on the genome, and the testing that this will make possible, legal selves. The draft sequence of the origin of the vertebrates, interesting protections for consent and privacy are essential. However, at C. intestinalis genome — which has evolutionary insights can be gained present, only 15 US states explicitly protect the rights of consent been 18 months in the making — has from unique features of the Ciona to testing, and Canada, Australia and most European countries do now been published by Dehal and genome. This is the first animal that not explicitly protect an individual’s rights to refuse testing and to colleagues and represents the first has been found to have genes involved have privacy in their test results3. genome of an invertebrate chordate to in the synthesis of cellulose. A putative We also need to make clear rules about when genetic be published. In their paper, the cellulose synthase has been identified information might, or might not, be used in job and insurance authors present a preliminary analysis that is likely to be involved in the pro- decisions. To support a ban on genetic discrimination is easy, but of the gene content of Ciona and how duction of the outer tunic of the adult there are some legitimate uses of genetic testing in both settings. it compares with those of other sea squirt. This gene shares homology A more balanced solution is needed, but we have yet to identify sequenced animals. with those found in nitrogen-fixing what it would be. The 160 million bp Ciona genome bacteria and so might have been Finally, holders of patents on genes and DNA sequences could was sequenced using a whole-genome acquired by an ancestor of Ciona block rapid sequencing of the whole genome of an individual by shotgun approach and is freely avail- through horizontal gene transfer from making excessive royalty demands or refusing to license those uses4. able on the web. It was found to con- a bacterial genome. Also of interest is Changes in the patent system, to allow freer use of gene patents tain ~16,000 protein-coding genes. a new family of receptors that contain while protecting incentives for innovation, are also needed. This is similar to the number of genes two domains — a caspase domain All is not lost, however. Attention to the ethical, legal and social in Drosophila melanogaster (~14,000) and a region with homology to pro- issues raised by the human genome project has identified most of and Caenorhabditis elegans (~19,000), teins involved in Notch signalling — the relevant issues, and this has helped to shape a consensus about but around half the number esti- that have never been observed before how ethically to tackle many issues, including research with stored mated to be present in puffer fish in a single protein, thereby providing samples, biobanking, testing minors, setting standards for genetics (~31,000) and human (~30,000). It an example of domain shuffling. counselling and the need to rethink patent law. has been argued that extensive gene This paper illustrates the power of The prospect of a $1,000 genome is a welcome prod for legal duplication was important in the evo- genome projects to give insight into authorities to finish the work that the genomics, medical and lution of the vertebrates. Comparative evolutionary processes. Sea squirts bioethics communities have done on ELSI questions. It is time for studies of gene families in Ciona and might be only distantly related to clear, legal recognition of people’s rights to control the acquisition, the vertebrates support this idea, as humans, but their genome sequence testing, use and privacy of their most of the genes that are present as adds another perspective to that given DNA. The $1,000 genome has the multiple copies in vertebrates only by other sequenced vertebrate and potential to increase greatly access have a single representative in Ciona. invertebrate genomes. Undoubtedly, to the medical pay-offs of genomics. The two physiological innovations the release of the sea urchin genome, To get there, we will need to get our that characterize vertebrates are their expected in the next ten months, will ethics and laws straight as well. complex central nervous system and complement this work and will pro- John Robertson their adaptive immune system. A vide more information about meta- major evolutionary question is how zoan evolution. REFERENCES 1Pollock, A. Genome pioneer will and when these features arose. Genes Catherine Baxter start center of his own. New York Times A18, 15 required for these functions are absent References and links 2 August 2002 | Nature Science Update. 24-hour from the Ciona genome, suggesting ORIGINAL RESEARCH PAPER Dehal, P. et al. Genome Dawns [online] <http://www.nature.com/ The draft genome of Ciona intestinalis: insight into nsu/o20923/020923-2.html> (24 September that they originated specifically in the chorate and vertebrate origins. Science 298, 2002) | 3Roche, P. A. & Annas, G. J. Protecting vertebrate lineage. By contrast, there 2157–2167 (2002) genetic privacy. Nature Rev. Genet. 2, 392–396 WEB SITE Diptych: ‘Yin/Yang sienna’, by Jacques (2001) | 4Merz, J. F. Patents limit medical potential are Ciona homologues of genes Ciona genome project: http://genome.jgi- Deshaies (2002) (detail). of sequencing. Nature 419, 878 (2002) required for other aspects of vertebrate psf.org/ciona4/ciona4.home.html 82 | FEBRUARY 2003 | VOLUME 4 www.nature.com/reviews/genetics © 2003 Nature Publishing Group.