Trickle-Down Genomics: Reforming ""Small Science"" As We Know It

if (n == null) The Scientist 13[15]:19, Jul. 19, 1999 Opinion Trickle-Down Genomics: Reforming "Small Science" As We Know It By Edward J. Smith Each generation attempts to develop programs and activities that help it fulfill the ancient Chinese wish "May you live in interesting times." These are indeed interesting times from the perspective of the biologist: The complete genomes of the worm Caenorhabditis elegans and of the yeast Saccharomyces cerevisiae have recently been sequenced,1 and the human genome is expected to be completely sequenced by the year 2003. Underlying these exhilarating developments are advances in technology that have emerged from the core discipline of genomics.2 As this millennium draws to a close, genome technology is changing the pace at which biological questions are being answered. Although access to this technology is greatly facilitated by the Internet, research-level access for many scientists working in biology remains limited. Private interests are now actively engaged in genome sequencing; this raises the question of whether the unraveling of the genetic code, especially that of the human genome, should be a private- or public-sector endeavor.3 There is no longer an argument about the need for and justification of the Human Genome Project (HGP) or about its emphasis on large-scale and data-production-oriented science. The relevance of this project is beyond question. I contend that the existing public-sector-based infrastructure for sequencing the genomes of human and model organisms provides the preferable platform for genome scientists to launch their efforts. This argument is based on my observation of the impact the HGP has had on agricultural sciences and on research carried out at smaller and minority educational institutions. A search of the World Wide Web using the keywords "genome project" provides a list of about 50 unique or species-specific Web pages. Half of the projects are devoted to the study of plants and animals of agricultural interest. At my home institution, Tuskegee University (TU), at least two agricultural genome initiatives are under way. As expected at the home institution of George Washington Carver, there are budding plant genome projects involving sweet potato and peanut. A related work in my lab involves the development of a microsatellite-based turkey genome map that will be useful in the use of this species as a model for understanding hypertension.4 To conduct these projects efficiently, an infrastructure supportive of science and a critical mass of scientists and engineers are needed. At smaller institutions, including TU and other historically black colleges and universities, both are lacking and not likely to appear in the immediate future. Life sciences research at historically black colleges and universities and other smaller institutions is most likely to benefit from the current public-sector infrastructure of the HGP. Our progress at TU in developing a first-generation turkey genome map is due in part to the ready availability of genome mapping technology on the Web and here, as we have neither the funds nor the personnel to support a large-scale genome- mapping program. We have been dependent, for example, on the Web-based Primer 3 and CLUSTAL W5 programs for primer design and sequence editing, respectively. More recently, we initiated a project to develop single nucleotide polymorphisms (SNPs) in expressed sequence tag sites in the chicken genome. This animal is not only a significant agricultural species but has long been a model organism for biomedical research and for studying compact eukaryotic genomes. The search for SNPs has been made easier by sequence analysis programs such as PolyPhred, Phrap, and Consed, developed at the University of Washington Genome Center in Seattle.6 Will such essential programs be available in the future if they are developed in private-sector alliances? If they are available, will investigators at smaller institutions be able to afford them? Prior to the era of million-dollar science, new methods and whole modes of new thinking trickled down to the rest of the scientific community. Investigators at smaller institutions needed only access to information contained in the library to be able to duplicate breakthroughs and apply newly published techniques to their work. Such trickling down also had the distinct advantage of increasing student exposure to novel technologic advances. Things have changed. To be competitive, laboratories involved in genomic research need equipment costing hundreds of thousands of dollars. This is an expense that smaller institutions simply cannot afford. In what seems a strange coincidence, in the same week that Science again addressed the issue of "Minorities in Science," a Newsweek "My Turn" article described the disproportionate number of African Americans in U.S. prisons.7 The Newsweek article advocated, as have administrators at historically black colleges and universities, a national effort to reverse the problem of a disproportionately high number of black males in prison. The Science article revealed that the 20-year effort to increase the number of minorities in science has met with little success. A simplistic conclusion drawn from the two articles could be that reducing the number of black youths headed for prison will increase the number of black youths pursuing socially accepted careers, including those in science. A tougher but more realistic solution is to open and maintain a new pipeline that supplies minority scientists. The old pipeline involved recruiting African Americans into science, educating them to the highest possible levels, and then relying on their employment by the highest bidder, often majority institutions, to integrate them into the scientific community. This had the advantage of increasing the number of minority science faculty and employees at majority institutions. However, it left a void in the pipeline that supplies top African American scientists to historically black colleges and universities, where a large number of them obtained their degrees. In addition, it removed role models and mentors with significant scientific accomplishments from minority institutions. As a result, there is the perception by students at historically black colleges and universities that science is a career for low-paid, underappreciated employees. If the HGP is to have a beneficial impact on the next generation of African American scientists at small institutions, this has to change. The nurturing of relationships between scientists at HGP-funded centers and faculty at minority and smaller institutions will go a long way toward effecting such a change. This approach will replace the current outreach programs that recruit minority students as summer interns. It will provide an opportunity on their own campuses for an increased number of minorities to become proficient at genome science so as to pursue independent careers in genomics. This approach makes it more likely that faculty at smaller and minority institutions might incorporate genomic science into their curricula and class discussions. The publicly funded HGP has the infrastructure but needs the funding and motivation to develop these relationships. Our collaboration with the Genome Center at the University of Washington provides a successful model for how this approach can work. With the support of the National Human Genome Research Institute, I spent the summer of 1997 at the University of Washington Genome Center working with Maynard Olson. The experience gained there has helped us initiate a genomics research program at TU to address questions in both agricultural and biomedical sciences. We now have resources at TU for high-throughput computing and production sequencing. Using these resources, we were the first to evaluate the multipopulation genetic characteristics of several human genes. For example, along with Edith Powell, a member of the Nursing and Allied Health faculty and a faculty apprentice in our laboratory, we evaluated allele frequencies of novel and known SNPs in the MICA gene in three ethnic populations, including African Americans.8 Together with other ongoing projects,9 these activities have had a positive impact on student experiential learning programs and faculty and graduate research at TU. At the 1998 Minorities in Biomedical Research Support Forum in New Orleans, for example, the third-place award went to a high school student whose project involved resequencing to illuminate the basis for the polymorphism revealed by the single-primer microsatellite genotyping procedure developed by our laboratory in 1993.10 Now an undergraduate student at TU, this award winner and five other undergraduates, including two who are headed for medical school in 1999, have had significant training in genomics. Also, through our collaboration with our colleague in Nursing and Allied Health, that program has had the opportunity to incorporate genomics into its teaching and research program. The reality that TU is the only historically black nonmedical school to develop a significant program in genomics indicates that the HGP can increase its impact on science and related activities at minority and smaller institutions. The partnership approach advocated here requires and assumes several conditions. These include the willingness of funding agencies to support the development of these relationships, the willingness of scientists at genome centers to commit precious time to these relationships, and the vision of administrators at both the host and guest institutions to nurture and reward such relationships. It is difficult to envision a for-profit program that would be willing to assume these commitments. Therefore, irrespective of how long and whom it will take to sequence the human genome, the United States government's continued involvement is necessary if we hope to have a significant impact on "small science." Such a pipeline-opening approach is needed to increase the number of minorities that contribute to the conduct of science in the next millennium.11 Edward J. Smith (edsmith@tusk.edu), Ph.D., Visiting Scholar at the University of Washington Genome Center, Seattle, is associate professor, Comparative Genomics Laboratory, College of Agricultural, Environmental, and Natural Sciences, Tuskegee University. "Genome sequencing of the nematode C. elegans: a platform for investigating biology," Science, 282:2012-8, 1998; A. Goffeau et al., "Life with 6000 genes," Science, 274:546-67, 1996. D. Botstein, J.M. Cherry, "Molecular linguistics: extracting information from gene and protein sequences," Proceedings of the National Academy of Sciences, 94:5506-7, 1997. M.D. Lemonick, D. Thompson, "Racing to map our DNA," Time, 153:44-50, Jan. 11, 1999. H.B. Huang et al., "Development and characterization of genetic mapping resources for the turkey (Meleagris gallopavo)," Journal of Heredity, 90:240-42, January-February 1999. S. Rozen, H. Skaletsky, 1997. Code available at http://www.genome.wi.mit.edu/genome_software/other/primer3.html D.A. Nickerson et al., "PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing," Nucleic Acids Research, 25:2745-51, 1997. D. Evans, "Lost behind prison bars," Newsweek, 132:20-1, Sept. 7, 1998. E.J. Smith et al., "Frequency and distribution in three ethnic populations of single nucleotide polymorphisms in the MICA gene," American Journal of Human Genetics, 11:A1270, 1998. See the Web address: agriculture.tusk.edu/genome2/genome.html E.J. Smith et al., "Simple sequence repeat-based single primer amplification of genomic DNA in random-bred populations of turkeys and chickens," Animal Biotechnology, 7:47-58, 1996. Comments and suggestions by Maynard Olson and Susan Lamont are gratefully acknowledged. Editorial assistance provided by Marie Loretan, Ursula Petralia, and Jaimie Foster is also gratefully acknowledged. Support for my collaborative work with the University of Washington Genome Center is provided by the National Human Genome Research Institute.

Trickle-Down Genomics: Reforming ""Small Science"" As We Know It

Trickle-Down Genomics: Reforming "Small Science" As We Know It

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