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At the time of this writing, we are in the midst of celebrating several significant anniversaries for Jim Watson. It was 50 years ago that Jim, as a young graduate student working with Salvador Luria, first arrived at Cold Spring Harbor to spend the summer with that year's phage group. Twenty years later, in 1968, Jim, returned to the Laboratory as its new Director and began the remarkable revitalization of the Laboratory's facilities and research activities. By choosing to study the cancer-forming DNA tumor viruses, simian virus 40 (SV40) and adenovirus, Jim placed the Laboratory and its scientists in an excellent position to make seminal contributions to cancer research and to fundamental aspects of eukaryotic cell and molecular biology. Jim arrived here with his new bride, Liz, and together they have perfected one of the most attractive centers for research in the world, combining historic and architectural taste with an unparalleled love for the beauty and history of Cold Spring Harbor and its environs. All of us owe a great debt to both Jim and Liz, and we are happy that they continue to devote much of their time to the continued success of the Laboratory.
Science has changed profoundly in the past 30 years. The year 1997 marks the 25th anniversary of the publication by Paul Berg and his colleagues of the first joining together of DNAs from different sources; they combined SV40 DNA with either bacteriophage l DNA or Escherichia coli DNA. The next year, Stanley Cohen, Herb Boyer, and their colleagues reported the first functional recombinant DNA. Twenty years ago, Fred Sanger and his colleagues reported the sequence of the complete genome of bacteriophage fX174 (5375 nucleotides), and they published the new chain-terminating method for sequencing DNA. Today, this technique is the basis for sequencing the entire genome of many organisms, including the human genome, which consists of about 3 billion base pairs. These accomplishments, together with the innovative use of restriction endonucleases by Kathleen Danna and Dan Nathans to map the SV40 genome in 1971, heralded a new age in biology. Soon, Cold Spring Harbor Laboratory scientists, quick to master the new science, made important advances that contributed to the emerging recombinant DNA age. Biologists were no longer limited by techniques, but only by their imagination.
One of the significant developments to come soon thereafter was the establishment of the first biotechnology companies, which used the new biology to produce contemporary pharmaceutical products and reagents more effectively. The biotech companies, with their significant resources provided by venture capital, would soon produce recombinant human growth hormone, recombinant insulin, blood cell growth factors, and other important new drugs. Company scientists realized that they had to be in the business of basic research to be the first to discover new drug targets and proteins. The initial successes of the biotech companies attracted collaborations with increasing numbers of academic researchers because their biotech colleagues often had equipment and facilities that were the envy of the academic community. Collaborations to sequence proteins and clone cDNAs that encoded important cell surface receptors and other signaling molecules became the norm. Often, the biotech companies won the race with academic laboratories to obtain key genes. But even with all its resources, the biotech industry did not surpass the quality of research in the universities and institutions like our own, for it was not always obvious where the next important and useful discovery would emerge. With few exceptions, the great discoveries in biology during the past 20 years emerged from academic laboratories, including Cold Spring Harbor Laboratory.
The relationship between academic research and biotech research has evolved over the years, and today, a happy synergy exists that greatly benefits society as a whole. Publicly funded academic research is still governed by peer review, is published for all to see, and is focused primarily on the issues that society and individual scientists deem important. A large percentage of public funds continue to support fundamental, rather than directed, discovery. For example, many of the dramatic advances in the development of combinations of drugs against HIV relied on basic studies of many retroviruses and their interactions with the cell. Techniques and facilities for protein crystallography that ultimately played an important role in the development of the HIV pharmaceuticals were developed to understand the structure of proteins that had little if any medical or commercial value. And without recombinant DNA technology, it would have been far more difficult to develop strategies to fight the AIDS epidemic. There remains much to do in HIV research, but it is already clear that because of the vigorous support of basic academic research, scientists had the tools to deal with HIV when it surfaced. Basic research had provided an infrastructure on which to build, and although it was often frustrating that progress was not faster, the pace of dealing with the disease was relatively rapid when compared to epidemics of the past.
Biotechnology companies now play an important role in the larger biomedical research enterprise. In addition to their contributions to basic and applied research programs, they have become a very effective conduit for translating the basic research discoveries made in academic laboratories into drug discovery and, ultimately, clinical uses. In the past, basic research discoveries that might have languished for many years are now rapidly picked up by the biotech industry and incorporated into their own research programs.
Many biotech companies, in turn, seek collaborations with the much larger pharmaceutical companies that have the financial and technical resources to develop promising leads into the clinic or to the market. In a sense, the pharmaceutical industry can choose from the large number of projects put forward by the smaller biotech companies and have greater confidence that a project may go all the way to the clinic. Collaborations between the biotech and pharmaceutical companies are important because the cost of developing a new drug that will become an FDA-approved pharmaceutical is extraordinarily high, often running into the hundreds of millions of dollars. As a result of the academicbiotechpharmaceutical collaborations, completely new approaches for the treatment of cancer are entering clinical trials at unprecedented rates, with real expectations that significant inroads to treating the disease may occur in the not too distant future.
Collaborations between academic institutions such as Cold Spring Harbor Laboratory and the biotech industry can also fulfill another need that large pharmaceutical companies may not address. many diseases, although devastating to patients and their families, are not economically feasible for large pharmaceutical companies to pursue, principally because the market will not be large enough to justify the expense. Biotech companies, particularly the newer enterprises, are more likely to pursue these targets because they offer an opportunity for a biotech company to achieve its first independent clinical success. In some cases, where the clinical need is demonstrable but the economic incentive is absent, public funds from the National Institutes of Health and other government agencies might be money well spent. Thus, the relationship between the biotech industry and public funding might come full circle to yield clinical success.
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