The main purpose of biomedical publishing is to convey the evolving scientific understanding of living organisms and the use of that understanding as the basis of health care among researchers, practitioners, and (increasingly) consumers. Published papers also serve as an archive of scientific knowledge, documenting both successful and unsuccessful results. Biomedical journals serve other purposes as well, such as providing benchmarks for academic promotion and revenue for professional societies and publishers. While MEDLINE has become ubiquitous and an increasing number of journals are available electronically, the fundamental model of publishing is unchanged. However, a number of challenges to that model are emerging. Boyd and Herkovic1 describe four challenges to scholarly publication: Cost. Publishers are charging increasing amounts of money for universities and academicians to access work that the latter created. Access. This high cost in turn is leading universities to decrease the size of their library collections, which in turn reduces access. Peer review. As more new journals, conference proceedings, and other forms of publication are introduced, the standards for peer review are diluted. Archiving. The growing use of electronic formats raises challenges to the long-term record of scientific publication. It is not altogether clear in what ways electronic publishing will improve or worsen this situation. On the one hand, the use of Internet-based management of the submission and dissemination process may reduce costs and increase the efficiency of peer review. On the other hand, if copyright laws and electronic protections hinder access, then costs could continue to go up, leading researchers to bypass peer review or reducing the incentive for high-quality scientific publication. We agree with Roberts2 that the World Wide Web provides at the same time both the possibilities for un-precedented dissemination of the fruits of scientific research and a brave new world where the price of obtaining such fruits remains high. As academicians who collaborate increasingly over the Internet, publish, read the works of others, and use such works in research, care, and teaching, we are attracted to the potential benefits of digital technologies. We idealize a world of free-flowing information adequately protected by reasonable intellectual property laws. But we fear the downside, whereby information becomes an expensive commodity surrounded by barriers that lock out individuals with lesser resources, such as students and those from developing countries. In summary, we share Roberts' “cautious optimism” about this new medium. This special issue of JAMIA is devoted to the topic of electronic publishing of scholarly information in the biomedical sciences. We sought both original research as well as perspective papers that addressed how electronic publishing affects the use of health and medical information by researchers, clinicians, consumers, and publishers. We have assembled a collection of seven papers that sample some of the important issues confronting the medical informatics community with regard to electronic publishing. Three papers present viewpoints on the economic and scientific ramifications of this new approach to disseminating scientific information. Two papers provide case studies, high-lighting specific experiences with this new medium. Another two papers present formulations for models for specific aspects of electronic publishing that may become prominent in the future. Coiera's viewpoint paper frames electronic publishing on the Internet in an economic light.3 He demonstrates the uncertainty we alluded to from Roberts' paper, noting that we cannot yet know how effective this new medium will be. Markovitz4 and Jacobson5 provide point and counterpoint views on the value of PubMed Central, the new initiative at the National Institutes of Health to create a freely available archive of scientific research papers built on top of the National Library of Medicine's PubMed system. Their papers highlight what are really two distinct issues in publishing: How do we handle preliminary and non-peer-reviewed research reports in this age of rapid information dissemination? Can we achieve a model of archive that still allows publishers reasonable revenues from a business standpoint? Anderson6 and D'Alessandro et al.7 provide two case studies of electronic publishing and share their results and perspectives. Anderson draws on the experience of the journal Pediatrics, which has been among the innovators in electronic publishing in medicine. He provides insight into the economic challenges facing academic publishers and concludes that while the Internet is a “disruptive technology,” there are feasible economic models for sustainable revenues. D'Alessandro et al. provide an examination of issues challenging the development of a well-known medical Web site, the University of Iowa Virtual Hospital. Their paper describes how they handle issues of content ownership, access, and archiving. Lehmann and Goodman8 and Tarczy-Hornoch et al.9 give us a glimpse of the future, showing how the Web has the potential to enhance access to and use of health information beyond being a store and dissemination medium. Lehmann, well known for advocating the use of Bayesian decision making by practicing clinicians, presents a model of how this technique could be made available in a practical way. Tarczy-Hornoch et al. focus on access to information on genetic testing. As we uncover more of the genome and the results of these studies make their way into clinical information, it will be increasingly important for frontline clinicians to have access to that information in synthesized forms. Clearly, these papers are but two examples of a great deal of work in progress that explores the potential of information in a digital world. We unfortunately did not have room for more. We conclude that an exciting era of publishing of scientific information is at hand. We do recognize that information quality control and dissemination have real costs and truly can never be “free.” But we also share the alarm over the growing cost and inaccessibility of information for economic reasons. The new digital technologies are profoundly changing the relationships between producers, middlemen, and consumers of information in all aspects of our lives—including commerce, finance, education, health care, government, and entertainment. Biomedicine is no different, and we are optimistic that models will emerge that allow effective symbiotic relationships among the players and stakeholders. This should, in turn, usher in a new era of unprecedented means of facilitating scientific collaborations and access and interaction with health information that will benefit society overall.

The American College of Medical Informatics is an honorary society established to recognize those who have made sustained contributions to the field. Its highest award, for lifetime achievement and contributions to the discipline of medical informatics, is the Morris F. Collen Award. Dr. Collen's own efforts as a pioneer in the field stand as the embodiment of creativity, intellectual rigor, perseverance, and personal integrity. At most once a year, the College gives its highest recognition to those whose attainments have, throughout their careers, substantially advanced the science and art of medical informatics. In 1999, the College was proud to present the Collen Award to Joshua Lederberg, PhD. Biologist, geneticist, computer scientist, and scholar, Dr. Lederberg's lifelong contributions to biomedicine and science, as well as to medical informatics, make him highly deserving of the recognition embodied in the Collen Award. Joshua Lederberg was born in Montclair, New Jersey, on May 23, 1925, the son of a rabbi. His interest in a scientific career was mentioned in an essay that he wrote at the age of seven. His family moved to New York City when Lederberg was a child, and Lederberg was able to attend Stuyvesant High School, a school that allowed him to concentrate in the sciences. In New York, Lederberg was also able to take advantage of facilities such as the American Institute, which made laboratory space and equipment available to talented high school science students. On graduating from high school at 16, Lederberg took advantage of a local scholarship to attend Columbia University and, after completing his undergraduate degree, he began medical school there. He did not see combat service during World War II, but from July 1943 he was enrolled in the U.S. Navy's V-12 training program, which combined an accelerated premedical and medical curriculum with active service as a hospital corpsman in a U.S. naval hospital. As a medical student, Dr. Lederberg undertook a series of experiments with Edward L. Tatum, demonstrating sexual recombination in bacteria. With his growing interest in a career in laboratory science. Lederberg decided to leave medical school to pursue a PhD, which he received from Yale in 1948 at the age of 23. After graduate school, Dr. Lederberg joined the Genetics Department at the University of Wisconsin, which at the time was part of the University's School of Agriculture. He eventually helped form the Department of Medical Genetics and served as its first chair. In 1958, when he was but 33 years old, Joshua Lederberg received a telegram of the sort that only a handful of scientists ever receive. He was awarded the Nobel Prize for “his discoveries concerning genetic recombination and the organization of the genetic material of bacteria.” He shared the prize with George W. Beadle and Edward L. Tatum, who won “for their discovery that genes act by regulating definite chemical events.” Joshua Lederberg demonstrating that his informatics work was “hands on,” even in the era of Model 33 teletypes. The work that led to Lederberg's Nobel award had begun in 1945, when he was 20 and still a medical student. Work published in 1944 inspired Lederberg to investigate the possibility of sexual reproduction in bacteria, which at the time were thought to reproduce only asexually. Lederberg's work, which formed the basis for his doctoral dissertation, demonstrated that bacteria can in fact reproduce through sexual recombination, and opened up the genetics of micro-organisms to the traditional methods of the field. These methods are now central to the fields of biotechnology and genetic engineering. Lederberg's name is today mentioned in most text-books of genetics and microbiology, not only for his demonstration of bacterial conjugation but also for his discovery of transduction and for his coining of the term plasmid to denote extrachromosomal genetic material. His scientific reputation was already established by the caliber of his work, but the Nobel Prize extended his reputation to the general public and allowed him to pursue his interests at the intersection of science, policy, and society. Between 1966 and 1971, he wrote a series of more than 200 articles for the Washington Post, which converted into lay terms many of the pressing scientific issues of the day. Typical articles addressed such themes as “Russian computers are having delusions—or are they?” and the premonitory “Congress should examine biological warfare tests,” a topic that continues to interest and engage him at the national level to this day. In parallel with his genetics research, Josh has had a long interest in formalizing the intellectual processes of scientific investigation and discovery and using computer models to represent these activities. He had used card-sorting techniques to help analyze the bacterial reproduction observations that led to his Nobel Prize years earlier, but on coming to Stanford in 1959 to found the Stanford Department of Genetics, his study of informatics took on new dimensions. He took classes in programming and began a series of systematic investigations of computer use in biomedicine. He introduced one of the first LINC computers into the Stanford Medical School and became principal investigator of a school-wide computer resource called ACME (Advanced Computer for Medical Experimentation). By the mid-1960s, Lederberg was working on ways to systematize the enumeration of chemical structures, especially molecular isomers—families of molecules with the same chemical formulas but with different arrangements of the atoms. This early work would find expression later on in the DENDRAL project.1 Comments by Donald A. B. Lindberg, MD, Director, National Library of Medicine: It's hard to remember when I really first met Josh, but I can remember vividly the first serious conversation I ever had with him. It was 1964, it was my first meeting as a Markel Scholar, the group was in the Ahwanee Lodge in Yosemite, and the speakers had been Jacob Bronowski, Le Dubridge, and Josh Lederberg. And I remember seeing Josh in the sun at a coffee break, sitting alone at a table, sort of lost in thought, and I decided that he probably wouldn't mind being interrupted. So I asked him what was he thinking about? It seemed like not too impertinent a question, although it probably was. And he said well, he was thinking about this: that if he had a chemical molecule in his mind, and he could see it clearly, what would be the next one that logically should be considered? Well, that struck me as kind of an amazing thing to be thinking about. With the post-Sputnik start of the U.S. space program in earnest, one of Lederberg's new areas of attention was the exploration of outer space in search of life forms. He coined the term “exobiology” to describe this new field, dealing with the search for the origins of life, and established the Instrumentation Research Laboratory to explore the synthesis of analytic instrumentation and computers to devise ways of detecting molecular signatures of life-related processes in planetary environments. This required inventing new instruments, such as fluorescence-activated cell sorting, and applying evolving instruments, such as gas chromatographs and mass spectrometers, in novel ways. It is also required inventing new ways to represent information about molecular structures such as proteins in the computer so that they could be analyzed and compared with each other. Work he performed in 1964 may have represented the first time that a protein sequence was stored in a computer for analysis. Comments by Edward A. Feigenbaum, PhD, Former Co-investigator of DENDRAL and SUMEX-AIM, Professor of Computer Science, Stanford University: In 1964, when I first met Josh, he was writing his first large-scale computer program, in a dialect of ALGOL. The program was called DENDRAL, for dendritic algorithm, but the reference to dendrites was metaphoric. Josh was creating a complete system for the enumeration of acyclic chemical structures. The system included: A notation in which each unique chemical structure was represented by a unique symbolic expression in canonical form. A graph manipulation algorithm for generating structures from molecular formulas. The DENDRAL algorithm was capable of generating structures exhaustively and without redundancy. A computer program to put the DENDRAL algorithm to work. In 1964, this was a landmark program not only for graph manipulation by computer but for application of computers to chemistry and life sciences, especially application of symbolic processing methods. When I arrived at Stanford in January 1965, I discussed with Josh my goal of creating models of the thinking processes of scientists, especially the processes of empirical induction with which hypotheses and theories were inferred from data. What I needed was a specific task environment in which to study these issues concretely. Josh suggested a task of inferring organic chemical structures from mass spectral data and enthusiastically entered a collaboration. He suggested a generate-and-test approach, in which the DENDRAL program he had done would serve as the “legal move generator” in the heuristic search for plausible structural hypotheses. The program we built, with the help of Bruce Buchanan, was called Heuristic DENDRAL. We extended its performance greatly in both breadth and depth when Carl Djerassi joined the collaboration. Josh brought this about, conveying to Carl the importance of the work. Josh's enthusiasm was infectious. My sketch of Lederberg and DENDRAL is necessarily brief and leaves out many of his tangible contributions to our work in artificial intelligence and its applications. And it leaves out almost all his intangible contributions—the texture, if you will, of the day-to-day interactions with Josh. These interactions were full of wisdom and guidance on how to run substantial interdisciplinary projects of the kind we were doing in expert systems, insights on the nature of knowledge and cognitive processes in science, and creative ideas for getting us over today's hurdle and tomorrow's hill—in truth, a flood of creative ideas. If we had had the energy and resources, we could probably have done ten other projects with these ideas. Working with Josh on our common problems in modeling expert thought in science and biomedicine gave me the privileged opportunity to witness a great intellect at work, applying superb analytic thinking skills with the enthusiasm of a young hacker for how much fun it was to program a computer to do these things. And it was not only fun, but it was important in the history of computer science. The DENDRAL collaboration led Josh to devote a great part of his energies to computer science, including the underlying languages and tools necessary to express his ideas about molecular biology and genetics. Comments by Donald A. B. Lindberg, MD, Director, National Library of Medicine: I was walking across the lovely campus of Stanford with him, following a morning in which I don't remember the real circumstances, but a whole lot of very nice research was reported at Stanford. I must confess, while I liked it all, I was sick and tired of hearing about LISP and list-processing languages. So as we hiked off to the commissary or the faculty club or wherever we ate, I said to Josh, “Josh, what would happen if some malignant deity just all of a sudden destroyed, eliminated, LISP. There isn't any more LISP. What would you do?” And he said “Oh, well, I guess, Don, I'd take FORTRAN and write LISP.” Lederberg insisted on participating first-hand in the development, testing, and use of the computing systems that fascinated him, no matter how cumbersome the early human—computer interfaces were. The breadth of Josh's biological, chemical, and computer science knowledge allowed him to serve as the bridge or glue among the interdisciplinary teams he assembled. Comments by Carl Djerassi, PhD, Former Co-investigator of DENDRAL, Professor of Chemistry, Stanford University: When I came to Stanford in 1960, Josh was probably my closest friend, professionally and personally, and within about two years we started to collaborate, I as a chemist, he as a person who works in every field conceivable, including even chemistry. At that time he was interested in exobiology and unmanned flights to outer space and felt that whatever information we needed would get back through telemetry and that, in order to determine if there was any life in outer space, we had to look for certain evidence of life out there. I was involved at that time in the area of mass spectrometry and, precisely, materials that would be related to things in outer space. Steroids, of course, are an example of something that you are unlikely to find up there. So we got together with Ed Feigenbaum, who had been working on artificial intelligence in general, to see what we could apply to chemistry, in particular the structural elucidation of organic compounds, which was precisely my area. And then they came to me and said, “Look, can we just simply try to simulate in a computer how Carl Djerassi thinks?” And that was really the beginning of a very fruitful collaboration for well over a dozen years in which a lot of other people were involved—Tom Rind-fleisch, Bruce Buchanan, and others. And we published a lot of papers in which we did try to simulate a chemist's thinking in computer-intelligible language. Note that was just the time when other chemists were working on simulating synthetic strategies. We did just the opposite. We talked about how one establishes structure rather than how one synthesizes it. That was unique at that time in the chemical field. What was most interesting, it stimulated us to do a lot of chemical research to fill gaps, intuitive gaps, in our own thinking, which the computer picked up because the computer program wasn't that intuitive yet. And that was really quite interesting, because chemists don't really wonder how they are thinking, they just do it. That really taught us an element of intellectual rigor. And it was a wonderful collaboration of people in medicine and computer science and chemistry. That was a large part of what at that time was called the DENDRAL program, which led to a number of other important algorithms and software projects that were eventually even commercialized. Lederberg has maintained an active laboratory to this day. Josh's contributions included very practical insights, such as designing a highly system for computing the of molecular whose are precisely from mass As the DENDRAL and made modeling the thought processes of chemists working to molecular structures, Josh's interests to the of computer applications. The of computer systems in the and the of computer led Lederberg to of scientists, and not just computer scientists, on research by of these new The resource that he in the early many systems that were the of artificial intelligence research for years to Comments by Former of and Director, Medical Stanford University: one of the most important of Josh's many contributions to medical informatics was his use of and help scientific and collaboration. I came to Stanford in to the DENDRAL At that time there was already a computer resource called ACME that Josh, Ed Feigenbaum, and had in the This resource was the use of computers for in biomedicine and for the of software and information among the and This system was for its It had a very to a system and an that in the and of the that were part of the ACME a after I came to a group of led by Josh Lederberg, the ideas from ACME and DENDRAL in the form of a to the called two ideas at the The first was to a national of artificial intelligence in medicine application and the was to using that was just then by the in the form of the I have to you that the of this was very in of the at It took a and a with and two very long and for us to get for this at the of we did get for and the of a of projects at and a was the first research resource on the In we were number among a of on the in that for about years and was the for more than 20 projects that were the in that the work was the of of but Josh's was in the of the Josh as a as a of as a of that and as a and was Josh wrote a very important essay in that these ideas. It was and the of The New I'd like to a brief from this In it he discussed how of with tools would the of both in time and space, and how this the of in the and use of and scientific in many As I the not how much we have made in the use of but it is with the form of the that have the science is Joshua Lederberg the Morris Collen Award at the in Josh Stanford in to of The University in New the of one of the research he to explore the synthesis of computing and tools with scientific research on many and to serve as a for young in the field of medical informatics. Comments by Edward MD, PhD, Former of SUMEX-AIM, and Professor of and of Computer Science, Stanford University: When I first came to Stanford in the early I was of Josh Lederberg's there. I came with an interest in biomedicine and computer science and so was to such as Josh, Ed Feigenbaum, and Bruce who had the DENDRAL at that Josh, as principal investigator on the new was of having a on the not only because of his work on DENDRAL but also because he a kind of scientific from which I as a young a great I would that Josh an environment in which I was taught to computer science as science, and not simply the of The scientific to one to be that the can the is to and there is an on were in the environment and the in which I computer science because of the of people like Josh. I was very of Josh's even I did not work with him It was He taught me about the of collaboration among scientists of and their to together to new and ideas that are even than the of their He me that there are still In of his in molecular biology and he was contributions in computer science. He was creating an environment in which great computer science work could be done and was also with the and beginning to how they science in the I a mind in and I in him an interest in all things intellectual and an to in very There was much to in Josh Lederberg and his After he moved to Josh to have a at Stanford on our computing environment and on the scientific that we to He was an to the even after his as well as on the He has been a of personal for is available from Josh, and I have found that I can for him for just the that can help me make a He has an for years in and that are to information I don't who is more at using for it with and coming up with ideas for how a environment to and other Josh continues to be a in that area. this Josh Lederberg a and of computing and to his work and to his at the national and The informatics him a great Josh was highly in the University its in the new era of biological science, research, and the of He became of in and to his as a His insights have been as he as an to and a of to his and He has been active in applying scientific to the of research, to public and to As was he has hard at the public and about the of biological and warfare and on and Josh has his active research laboratory at working on the and of on the computer modeling of scientific and on exobiology and the search for the origins of A of the of Joshua Lederberg has been by the Library in their in The is and Josh's papers as a to the history of science. Josh's career in medical informatics, this is available on the Josh's work in informatics is a and he continues to for the field. Comments from an history with Joshua Lederberg, PhD, Former of DENDRAL, and SUMEX-AIM, The University: I'd like to have my name Lederberg's is that really only when they can the and some time in the real the of the is what determine out there. As long as we have to by to be evolving in a very cumbersome and It is with and that the American College of Medical Informatics Joshua Lederberg as of the Morris F. Collen Award. The the of and in the of this award and the also to and the American for for to from their history of Dr. Lederberg, of which are available on the at

Even though medical informatics is most often viewed from the perspective of its host disciplines in clinical and biologic medicine, it has an identity and agenda of its own. This paper is an attempt to promote discussion about the long-term role and agenda for medical informatics as a discipline into the next decade. The discussion has two main lines of argument, one about the "engineering" goals of informatics and the other about the "basic research" goals. These are, of course, influenced by ongoing of developments in computing, communications, and software infrastructures, but informatics is now mature enough that many of its goals transcend these changes.

Medical informatics is defined largely by its host disciplines in clinical and biological medicine, and to project the agenda for informatics into the next decade, the health community must envision the broad context of biomedical research. This paper is a sketch of this vision, taking into account pressures from changes in the U.S. health care system, the need for more objective information on which to base health care decisions, and the accelerating progress and clinical impact of genomics research. The lessons of modern genomics research demonstrate the power of computing and communication tools to facilitate rapid progress through the adoption of open community standards for information exchange and collaboration. While aspects of this vision are speculative, it seems clear that the core agenda for informatics must be the development of interoperating systems that can facilitate the secure gathering, interchange, and analysis of high-quality information and can gain leverage from worldwide collaboration in advancing and applying new medical knowledge.