Copyright: © Todd A. Gibson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

In 1988, Disney released Oliver & Company, their first animated movie to feature widespread use of computer-generated imagery (CGI). The use of CGI in films was entering the mainstream of Hollywood, and it marked one of the few places at the time that had a demand for artificial intelligence (AI) researchers and the large computing facilities to support them. Lawrence (Larry) Hunter had just graduated with a PhD in artificial intelligence from Yale, and was familiar with Hollywood, having grown up there. But rather than pursuing an AI career in cinema, Hunter went on to gather a small group of like-minded scientists, and together they established what has become the largest international conference in computational biology: Intelligent Systems for Molecular Biology (ISMB). Since its inception, ISMB has held meetings on four continents and published proceedings papers from researchers in 34 different countries. This year, ISMB celebrated its 20th annual international conference in Long Beach, California. Through interviews with many who played prominent roles in the formation of ISMB, we look back at the early days of the field from which ISMB was born. Their reflections provide insight into the early meetings, and the growth and maturation of both ISMB and the field it represents over the last two decades.

At the same time, the United States National Institutes of Health (NIH) was in a political battle with the Department of Energy (DoE) over the Human Genome Project (which began in October of 1990). Though today nobody would question the province of NIH to control the Human Genome Project, at the time GenBank was run by the DoE's Los Alamos National Laboratory, and the DoE had experience breaking up genomes using radiation hybrids. The NIH sought to strengthen its argument to control the Human Genome Project by establishing its computer and engineering skills. In March 1989, Hunter was one of the first, if not the first, computer scientist hired as a staff scientist at NIH's National Library of Medicine (NLM).

I knew what the film business was like, and I knew I did not want to do that…. It sounded sexy except that no job lasted more than 6 months and it's a constant scramble. I had a lot of friends who wanted to go into the film business. I knew what kind of suffering those kids went through, how miserable it was to try and get those jobs, how brutal the competition was and how unfair.

Hollywood was a natural fit for Hunter's skills. Computer animation was taking off and there was a strong demand for AI skills which could reduce the human labor required to animate a film. However, despite having grown up there (or perhaps because of it), Hunter avoided it:

I was pretty systematic, starting in around the middle of 1988, trying to figure out where I was going to get a job that wasn't going to make me feel miserable or how I was going to make a living.

I was no longer afraid of walking around in a hospital, I was no longer terrified of being mistaken for a patient. I got used to looking at gross photographs of bits and pieces of people (they don't call it gross anatomy for nothing!), and I'd learned a certain amount of medical terminology. I wasn't motivated by medicine in those days, I wanted to stop doing lung tumor pathology pretty badly. Lung tumor pathology, especially in the '80s, there really wasn't very much we could do. If you had lung cancer, you were pretty much out of luck. Everybody died in six months-ish…. I spent all this time trying to get a computer program to make these distinctions that had absolutely no clinical significance whatsoever. So that was really depressing, the fact that everybody died, and the therapies were miserable to undergo and didn't really help very much…

In the fall of 1988, Lawrence Hunter completed his doctoral dissertation, which included case-based reasoning to diagnose lung tumors from histological slides. It's precisely what you would expect for someone enthusiastically pursuing the intersection of biology and computation. Only Hunter wasn't enthusiastic:

[The November 1991 workshop] group was mainly interested in bootstrapping an approach to computational biology that was more grounded in AI. At the same time, I don't think we wanted to tie ourselves to AI because the purpose of AI is machine intelligence, and our interest was in aiding biology, or the application of computers to biology. We didn't want to put the focus on intelligence, but rather on the methodologies that we used in AI…. I think Larry felt that it was time to establish a meeting that would serve as the touchstone for this whole approach that we were thinking about.

What was really missing from all that was the AI attitude, which is basically symbolic processing and associated things like machine learning and databases, and so forth.

It's worth remembering that there were people working on computational applications in structural biology…and also phylogenetics…. The algorithms community, computer science community, had started to get involved, mainly with string algorithms.

You have to understand how new this was at that time. There really wasn't much there so they sponsored…a workshop to try to bootstrap infrastructure in this field.

I got a little money from both [NIH and NSF] to invite people in for a two-day workshop. The invitations were based on the database. That was the meeting that created the first ISMB. We decided at that meeting that we needed a journal, a conference, a summer school, and a scientific society. That's what a “real field” has…. It was a really interesting meeting, it felt really heady. It felt like we were really onto something.

At NLM Hunter maintained a database of AI researchers interested in molecular biology, and with it the groundwork was laid for ISMB in November, 1991:

The Early Meetings

A tremendous amount of effort goes into organizing and running the ISMB meeting each year. But whereas recent ISMB meetings benefit from the experience and organization that has built up over the many years of running the meeting, the early meetings had no such scaffolding to rely on. In July 1993, the first ISMB meeting was held where Hunter worked, at the Lister Hill Center, which was the basic research arm of the NLM. Searls recalls:

We all wrote a grant…to run the meeting. It wasn't much. We did it on a shoestring…. The program covers one sheet, both sides, which I folded into three and made a nice, neat schedule, complete with the poster session. I kind of remember, now, putting that together on my early Mac. We did things pretty much on the cheap. We didn't have meeting organizers. There were people milling around in the lobby [of the hotel]. I sat down at a table, and just started registering people. We went to the Lister Hill Center, the auditorium there, to actually conduct the meetings. At that time, I think we could just hike across the field into the NIH grounds. Nowadays, it's a walled fortress so you can't get in, but in those days, we just hiked over to the Lister Hill Center, to the auditorium there, and ran the meeting.

Jude Shavlik recalls the ad hoc feel as well:

We were turning people away because there wasn't enough room. We spent a lot of trouble [planning for] an overflow room…. It was pretty high demand right away…. Of course, some people didn't want to come because we said that late registrants could only go to the overflow room. By the time the conference really happened, maybe the first morning, people had to go in the overflow room. Then after that, with people hanging out in the halls or leaving early or whatnot, we were fine using the regular room. But it was an immediate sell out, at least at a couple hundred.

Searls remembers some elation after the first ISMB:

It was very exciting. It was hard work…. I think we were exhausted. I remember after the meeting, Larry and Jude and I decided to go out to lunch to unwind and sort of bask in the glory. We went to a place in Bethesda, a local place that Larry knew. I think, first of all, we breathed a sigh of relief to have it over with, but…I think we were very excited that this meeting had been successful and it showed promise of continuing and growing. There was a sense, even at that point, of a birth having occurred and that something good was happening. There's an emotional element to it at the time. It was exciting to have this happening at the same time that the idea of the genome project was now on the horizon. There was a sense that the data was just going to keep on coming, and the challenges were going to keep on coming, along with new technologies, and that we had the computational tools to grow in tandem with the demand…. We called it the “First Annual” meeting, and we expected it to be annual from then on. I was pretty optimistic at that time that that was the expectation. We wanted to have the signature meeting for this community of computational biologists.

All of the early ISMB meetings were challenging to prepare and run. Hunter finds the second ISMB particularly memorable:

I think the most memorable was 1994, the second ISMB meeting. We had planned to hold it in Seattle…. We announced the Seattle ISMB at the conclusion of the first meeting in July '93. Then, by November of '93, we discovered [that the Seattle organizer] was organizing a competing meeting just a month before when ISMB '94 was to be, and he had basically stopped talking to us. In a panic, we cast about for some other location where we could hold the meeting with only about 6 months lead time to get organized.

Russ Altman picks up from here:

I got a pretty late call from Larry saying, “Russ, we don't have a venue for the next meeting and it's not going to happen unless we put it together.” And I said, “Well, why don't we try to have it at Stanford? I can get an auditorium.”

Hunter continues:

By the beginning of December he had space reserved, mailing lists set up, Stanford's financial folks on board, and the call for papers out—everything went surprisingly well, and in the end, very few people knew that we had done such drastic mid-course corrections.

Chris Rawlings recalls how hectic it was organizing the third conference at Cambridge:

[At the second conference] we basically said, “Well, we should organize one in the UK. It shouldn't just be a US thing.” So we put our hand out and said, “Yeah, OK, we'll do the next one.”…it was done on a shoestring. That was the real challenge, doing it without any huge support from your organization, who didn't really know why you were doing it and were worried that you were going to make a financial loss, and therefore have to underwrite it. It was just all the practical things that got in the way, and underestimating the amount of work that was needed.

The international character of ISMB has been important from the outset. In the preface to the proceedings of the first ISMB, the full name of the gathering is stated as the “First International Conference on Intelligent Systems for Molecular Biology”. The preface continues:

The word “international” in the title reflects the observation that outstanding work in this field takes place in many countries around the world. Not only was the program committee drawn from Europe, North America, and Asia, but a gratifying fraction of the submissions were as well.

The commitment to an international conference has only grown stronger over the years. Thirteen of the conference's 20 years have been held outside of the US. In recent years, the rotation of conference venues has formalized, with a European country hosting every other year, and North America hosting on intervening years. Also, since 2004, ISMB has been held jointly with the European Conference on Computational Biology (ECCB) during each European meeting.

Beyond the organizational challenges of the early conferences, the format of ISMB was an issue as well. Peter Karp recalls:

One thing about our field is we were really starting a new science, and there were a lot of decisions that we got to make about how to shape the field in a number of different ways. For example, how would conferences be run. Some of the choices we were making were, for example, would we have refereed proceedings from our conferences or not? We decided, yes, we would do that. That's how computer science works, but it's not how biology works. The way biology works is most of the speakers are usually invited. That's not how we did it because we kind of wanted to give everyone a chance with setting up their ideas and have reviewers decide what seemed to be the best ideas. That seemed to be a more open way to run things.

Initially, the refereed papers were presented in a single track. It wasn't until the 2004 meeting in Glascow, Scotland, that the conference moved to parallel tracks for paper presentations. Rawlings:

That was quite controversial in the history of the conference. There were a lot of people who wanted to keep it more strongly in the AI intelligent systems model and have a meeting where everybody would go to everything. But it just grew too big. We just couldn't…. The other thing that was unique amongst conferences in the early days was that we followed a tradition from computer science conferences of having the tutorials before the meetings.

By 2007, ISMB had expanded so dramatically that each attendee could choose from among 23 pre-conference offerings, including special interest group meetings, tutorials, and a student symposium. The main conference had expanded to more than 150 talks spread over eight parallel tracks.

Altman remarks on growth and specialization of the conference as well:

I could go to ISMB '93 or '94, and I could sit in on every talk and understand every word of every talk because it was a new field. There wasn't differentiation yet. We all were generalists. Then you fast-forward 20 years, and we now have areas of specialty and expertise. And I can go to a talk where I may understand the rough idea, but I haven't worked in that field, and a lot of the basics are not immediately familiar to me…it's just a very natural evolution of any [new] field. But there's always a certain bit of sadness, because you yearn for the days when you could sit in a room and understand every talk. And right now that's getting harder and harder.

Alfonso Valencia identifies ISMB meetings that marked important milestones:

The [1995] conference in Cambridge was the year where the conference changed from a computer science-based conference to a point where everyone realized that, if you want to make progress, there has to be more focus in biology. So this is where there was a significant change in the spirit and the orientation of the conference. The [1997] one in Greece was important because it was the first time we realized that we needed a professional [society]…and where we founded ISCB. [It established the conference as] part of our professional activities, as the conference for bioinformaticians and computational biologists. The [2004] one in Glasgow was the one where we realized we were really big because, for the first time, the numbers were over 2,000 people. And it was the first one where the balance between Europe and the States became an important part of the conference. It was here that we established the rules and the ways and the spirit of collaboration between the Americans and the Europeans.

Valencia further emphasizes ISMB's substantial contribution to forming the identity of the computational biology profession. Searls agrees, summing up the road ISMB has traveled:

There were no grizzled veterans back in the early days. There were no gray eminences, no old-timers. It's not a question of age…. It's a field that started out without any infrastructure, without any standard curricula, without any good journals, and without a meeting series like ISMB. That's something that's all been addressed, one by one. The field has developed an infrastructure, for lack of a better word, which makes it an authentic scientific field, and now you do have a sense that there are standard curricula, that you know what you need to learn in order to be educated in this field now.

The proceedings papers from the first ISMB meeting are affiliated with eight different countries. One sign of ISMB's maturity is that 34 country affiliations have now appeared in the ISMB proceedings over the last 20 years (see Figure 1). The conference's growth is also evident in the increasingly competitive acceptance rate (see Table 1).