Jim Ostell

I have always been amazed by the form and symmetry of living things and have enjoyed wondering how they came to be. During my undergraduate years at the University of Massachusetts (1968-72), I majored in zoology and found myself completely surprised by my course in invertebrate zoology, discovering that the diversity of body form and lifestyle solutions was vastly greater and stranger than I had ever imagined. However, much as I enjoyed the subject, I was afraid that in order to pursue an academic career in the field I would have to narrow my focus so much that I would lose sight of the breadth of life that I found so exciting. Voicing these concerns to a favorite professor, he assured me that it was not so, pointing out that "although his career had been built around the study of cestodes, he was also a world authority on an entire order of copepods."

Deciding against an academic career, in 1972 I took a job as a collector of live materials for a biological supply house. I roamed meadows and ponds collecting amphibians, plants, and invertebrates in western Massachusetts. However, this began to pall as I realized that I was denuding large areas of wildlife, which, although in the service of education, did not seem to be a positive thing to be about. There followed a period, perhaps typical of the times, in which I took a variety of jobs including picking apples, working my own small construction business, and finally working as a medical technologist in hospitals.

In 1976 I began to entertain ideas of going back to school. I tested the waters by taking an organic chemistry course and a computer programming course, which at that time meant Fortran on a Cyber 70 mainframe with punched cards. This experience convinced me that I should return to zoology, so in August I approached my histology professor, whose course I had loved, and broached the subject of applying to graduate school the following year. To my surprise, he informed me that they still had one opening, that he remembered me, and that the position was mine if I wanted it. Two weeks later I was teaching a laboratory section in cell physiology, and I have been in biology ever since.

Perhaps it was the precipitous nature of my entry into graduate school, but I had no plans for what my career goal after graduate school might be. While I do not necessarily recommend this as a career strategy, I felt tremendous freedom to pursue any avenue that looked interesting to me. I am grateful to the graduate department in zoology at the University of Massachusetts that they accommodated me. I ended up with a master's thesis describing the anatomy and late-stage development of the male cricket accessory gland, which goes from a small undifferentiated bulb to a large gland with hundreds of differentiated secretory tubules with a massive protein synthetic capacity in a single larval instar. I described the organ by reconstructing it from serial sections using a variety of histochemical staining techniques, verified by microdissecting individual tubules and characterizing their protein products by thin gel electrophoresis, and examining specialized regions using scanning and transmission electron microscopy.

As I was nearing completion of this project, I found myself wondering how all this complexity could arise from such a simple beginning. One of my advisers suggested that I should look into the new field of molecular biology for an answer by pursuing a Ph.D. I was not certain I wanted to do this, for my experience with biochemistry courses seemed to consist mainly of memorizing the Krebs cycle, but he eventually prevailed.

I was fortunate enough to be accepted into the laboratory of Fotis Kafatos at Harvard BioLabs in 1979. It was an exciting time to be there, and the BioLabs was full of stimulating people and challenging ideas. DNA sequencing and cDNA cloning were recent innovations, and gene organization of some viruses and phages had already been described. I was swept up in the excitement, and it didn't seem anything like memorizing the Krebs cycle. In time I had cloned and sequenced, but then found myself at a loss. What now? Then someone suggested that perhaps a computer would help to find some meaning in my sequence.

The Kafatos lab was very forward-looking to the new technology at the time. Not only did we have a 300-baud modem connecting an ASCII terminal to the MolGen project at Stanford University, but we also had a CP/M (8-bit) microcomputer with 48 kilobytes of memory and 8-inch floppy disk drives for our personal use. Of course the secretary had priority to use it as a word processor during the day, but those of us in the lab could use it for science at night if we wanted to. This computer was always breaking down, so the repair people were often there. I had been a ham radio operator and interested in electronics, so Fotis found me one day looking interestedly in the top as it was under repair and asked if I knew anything about computers. When I replied "A little," he smiled and said "Great! You are in charge of the computer."

Scouting around my new domain, I discovered that we had a Fortran compiler for it, complete with Xeroxed documentation from some little company in Washington called Microsoft. Having been disappointed with my experiences using MolGen, I started writing my own sequence software on this little machine, adding such user-friendly innovations as asking the user questions in English, reporting the cut sites of restriction enzymes instead of their recognition sites, and so on, all of which facilitated my own work as a biologist. Soon others in our lab were using the software, then others in the building. With a little prodding, I wrote up a description of the software that had evolved this way and published it in the first special issue on computers in Nucleic Acids Research. I offered copies to anyone who wanted them. To my surprise, it turned out to be one of the more complete packages of molecular biology software available at the time, and one of the only ones that could run on a microcomputer.

I was deluged with requests for software, for all sorts of different machines. I soon found myself with hundreds of installations all over the world. This led to more suggestions and collaborations with other scientists. Soon I was doing nothing but maintaining this software package and working on computer analyses of DNA sequences. It gradually became apparent that it would be very helpful to me if my committee would accept my work on the computer in combination with the bench work and collaborations I had been involved with as the basis for my thesis. The committee was split on whether this work was appropriate for a Ph.D. in molecular biology, and it did not seem that any resolution was in sight.

About this time, I was approached by International Biotechnologies Inc., who wanted to base a commercial product on my software. Harvard agreed to allow this, and I became self-supporting although still a graduate student. The software came out as the IBI/Pustell Sequence Analysis Package and became one of the most widely used packages for microcomputers. This introduced me to a much higher level of software development, maintenance, and reliability than I had ever had to meet with public-domain software. I also continued my scientific collaborations during this time. Eventually, following my wife's medical career, I was living in an 1862 farmhouse in Vermont on 7 acres of land with a view of mountains and writing molecular biology software. There I completed a version of the software for a new computer, the Macintosh, which would eventually become the MacVector product which is still sold today. I even finally got my Ph.D. from Harvard in 1987.

Idyllic as this sounds (and it was idyllic), I was aware that I was becoming ever more distant from molecular biology as it surged ahead. There were discussions of the Human Genome Project, and it was clear to me that great changes would have to come to what is now called bioinformatics and I felt they would pass me by. About this time, I was approached about joining the newly formed National Center for Biotechnology Information (NCBI), at the National Library of Medicine of the National Institutes of Health. It was an opportunity to bring my decade of experience supplying software to working molecular biologists to a new endeavor at a national level. In an awesome act of self-sacrifice, my wife agreed to sell the farm in Vermont and move with me to a much more expensive and vastly smaller house around Washington, D.C. I sold all my rights to my commercial software package and became a public servant in November of 1988.

In the few years since then, NCBI has grown into arguably the premier institution in the area of bioinformatics in the world. We have created such widely used resources as BLAST and Entrez. We now produce GenBank and provide the computer support for OMIM. We are involved in many new projects and a great many scientific collaborations. As the chief of the information engineering branch at NCBI, it has been my privilege to provide some of the vision for what we have realized and to have been able to work with such an outstanding group of scientists and software developers as we have at NCBI.

I find that my career does touch a very broad spectrum of biomedical research and that my student fear of a path with too much focus in a narrow area is not my problem. Rather, keeping up with computers and biomedicine is a bit like trying to ride two charging horses at the same time. If you are still standing at the end of the day you are a success. The frantic pace of events does not permit me to delve as deeply into the emerging biology as I might prefer, but I am not alone among modern biologists in feeling the pressure of time and resources. However, my position does place me in contact with the many excellent scientists who are actively pushing the biology forward, and they kindly keep me from becoming hopelessly out of date as I, in turn, attempt to fill their information needs. While not always pleasant or easy, I am thrilled to be riding on this unruly tidal wave of biological information thundering out of the scientific community and attempting to turn it into a powerful and well-behaved tool for understanding the living world.