No: And Anyway, The HGP Isn't `Big Science'

Molecular biology is sophisticated conceptually, but the routine tasks are repetitive, manual labor. The human genome project is developing many automated techniques for molecular biology, including those for mapping and sequencing. In addition, thanks to the project, critical new computation-al tools for biology are being invented and the most sophisticated approaches in mo- dern computer science are being applied to biology. The technology imperatives of the HGP require interdisciplinary efforts, bringing together the techniques of chemistry, computer science, engineering, applied math, physics, and biology. The complex problems of modern biology demand these interdisciplinary collaborations, and the HGP has been catalytic in this regard. Moreover, the HGP is training a new type of interdisciplinary biologist who understands technology as well as biology. I believe these multidisciplinary biologists will be among the scientific leaders of the 21st century. America currently is the world leader in biotechnology. This leadership is being threatened by the Japanese. The HGP, through both its technology and the creation of a powerful biological infrastructure, will help ensure this world leadership in the future. In this regard, let me make two points. First, biotechnology offers an opportunity to redress America's failure in industrial competitiveness and the negative trade balance. Let me give you an example: In 1981, a small venture capital-supported company, Applied Biosystems Inc., was initiated to commercialize several instruments for molecular genetics that our laboratory had or was developing. This company now employs 1,300 people. It is the world leader in instrumentation for molecular biology. Its profits last year were $19.3 million. Sixty percent of these profits came from abroad, primarily from Japan and Europe. Hence, where we are technologically competitive, we can generate a positive trade balance. The HGP promises to develop a variety of new biotechnology tools and technologies that will in turn spawn new industrial opportunities, both as new companies and new directions for established companies. Indeed, I would predict that biological computing will generate striking new industrial opportunities in the future. The second point is that the biotechnology industry will not mature until the second or third decade of the 21st century. Hence, the growth potential of the biotechnology industry, in my view, is virtually unlimited--particularly keeping in mind the potential for agriculture, animal medicine, and the environment--certainly well above the $100 billion range. The HGP will prime the American economic pump. It is a critical time to develop new biological technologies. If we decline to do so, we can all rest assured that our competitors will fill the vacuum. The HGP is about building an infrastructure for biology and medicine--first, assembling an ordered array of DNA fragments across the human chromosome (called the map); second, deciphering the genetic messages of the chromosomes (called the sequence); and finally, developing the automated technologies and computational tools necessary to create the map and the sequence. The map will allow biologists and physicians to find more rapidly and much less expensively the thousands of genes causing disease. For example, it is estimated that it cost $150 million to isolate the gene for cystic fibrosis. With a detailed map of the human genome, this cost could essentially fall below $5 million--a 30-fold savings. With the sequence, it would cost considerably less. Also, the map will allow small laboratories to compete with large labs in the mapping of human genes. The sequence will allow the identification of the 100,000 or so human units of information (genes), and will allow the identification of specific genes that predispose to cancer, autoimmune disease, heart disease, and nervous diseases. Moreover, the identification of all the human proteins will give us the tools to understand how the immune system, cardiovascular system, and eventually the nervous system function. These understandings will lead to new therapeutic strategies, so that DNA fingerprinting, which will allow us to predict disease susceptibility, can be joined to therapeutic approaches to prevent the corresponding disease--thus ushering in an era of preventive medicine. Our investigations of human autoimmune disease lead us to suggest that in 15 years we will be able to predict from DNA fingerprints who will be susceptible to diabetes, rheumatoid arthritis, or multiple sclerosis, and then to prevent, by manipulation of the immune system, the onset of these diseases. Since rheumatoid arthritis alone costs Americans approximately $1 billion per year, the savings of preventive medicine will be enormous. New Tools The automated technologies and computational tools will free biologists and physicians for more creative activities. For example, au- tomation allows a single biologist to sequence DNA approximately 1,000 times faster today than just 12 years ago. Thus, young scientists can gain access to far more information and free up more time for creative thinking or interactions. The naysayers to the HGP argue that it is bad science, big science, an inappropriate educational environment for young scientists, and that it competes with traditional biology for support. Those that argue the HGP is bad science misunderstand its goals. The creation of powerful new automated technologies and computational tools as well as the infrastructure provided by the map and the sequence of the human genome is good science. Most opponents argue that sequencing is expensive and hence it would be ridiculous to sequence the entire genome now. This is true. Realize that most of the human sequence analyses will be carried out only after we have sequencing tools 100 to 1,000 times more rapid and about 100-fold less expensive than contemporary methods. Then, sequencing the human genome will become an incredible biological bargain. The HGP primarily funds single investigator-sponsored research. It is not big science. Rather, by making the human chromosomal map and sequence available to small laboratories, it allows them to compete with large laboratories. Hence, the HGP is the guarantor of small science. Equally important, it encourages a new type of biology that employs technologies from many other sciences. Rath- er than big science, it is interdisciplinary science. Thirdly, the HGP offers exceptional training opportunities. It will free young scientists from the drudgery of molecular biology by furnishing automation and new computational tools. Young scientists will have access to enormously increased amounts of information; hence, they will have more opportunity for thoughtful and integrative activities. The young interdisciplinary scientists will lead biology and medicine into the 21st century. The naysayers view the HGP as inappropriately competitive with conventional biology. This situation is similar to the view many biochemists had toward the emerging field of molecular biology in the late 1960s. The biochemists were by nature conservative and felt uncomfortable with the changes molecular biology represented. Moreover, they failed to understand the power of molecular biology and completely failed to envision the revolution in biology arising from mol- ecular biology. In the end, molecular biology and biochemistry reinforced and enriched one another. Both are essential to contemporary biology. So, the HGP promises to enrich contemporary biology through revolutions in technology and the creation of a powerful biological infrastructure. It is time for biology and the HGP to grow together and become mutually complementary, leading biology and medicine into the 21st century. Leroy E. Hood is Bowles Professor of Biology at the California Institute of Technology and director of the National Science Foundation's Science and Technology Center for Molecular Biology.

No: And Anyway, The HGP Isn't `Big Science'

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