The sequencing of the human genome and the genomes of several pathogens clearly predicts a future for medicine in which molecular biology will be increasingly important. For this reason, it is critical to understand the principles of molecular biology, how we came to discover these principles, how future discoveries are likely to be made, and how we can best structure our research endeavors to make these discoveries. This monograph provides us with exceptionally readable answers to these questions.
Operators and Promoters is an affectionate, almost loving description of the field and many of its participants by a leading researcher in molecular biology, the late Harrison "Hatch" Echols. Tragically, Hatch died before the book was completed. It was finished by his wife, Carol Gross, also a distinguished molecular biologist, with the help of many of Hatch's and Carol's friends and colleagues.
On one level, this book is a survey of the important discoveries leading to our current understanding of how genes operate to determine the structure and function of cells (and organisms). As described by Hatch, the key philosophical approach of this science is the application of the principles of physics (through genetics) and chemistry (through biochemistry) to the study of biology. These principles were used to study relatively tractable, simple systems (bacteria and the viruses that infect bacteria). An assumption was made that there was sufficient universality in the molecular mechanisms underlying biology that these studies would be relevant to higher, more complex organisms such as Hatch, Carol, you, and me. In essence, biology was demystified. The book traces the sometimes chaotic and surprising and at other times straightforward and predictable discoveries that revealed the basic principles of gene expression, gene regulation, DNA replication, DNA recombination, and repair of DNA damage. Also described is the amazing world of RNA and the advent of genetic-engineering technology.
Even though this book would be valuable and timely as a survey of the field of molecular biology, it is really a vehicle for describing the participants and, more important, for describing how the field functioned as a mini-society. I suspect that all the main participants were known by Hatch personally. In little snippets, he captures key characteristics of many of them. In most cases, these descriptions vividly brought back my own memories. He is never particularly critical. Hatch was perhaps a bit too positive, but this is in keeping with his warm view of others.
The development of the science was uneven and sometimes chaotic. Creativity -- often among a few key people -- luck, and technological developments had major roles. Competition was there, too, but there is no doubt that Hatch favored a type of open, collaborative competition in which various investigators each wanted to succeed but also took great joy in the advancement of others in the field. Hatch describes this type of competition as follows: "At the first level of competition, all scientists want to think of the best ideas and the best experiments and to advance their field through telling others of our findings. In an atmosphere of open exchange of ideas and mutual trust and appreciation, the competition to be creative accelerates new understanding; the situation is somewhat analogous to trying to be the most valuable member of an athletic team." This first level of competition is followed by a desire for recognition outside the field and then by a quest for complete dominance of the field in the eyes of the outside world. Of course, some scientists skip the first stage or the first two stages. One of the missing analyses in the book is how the grant funding system may skew these different types of competition. In certain research areas, the participants consider it very difficult to obtain funding unless one is approaching the stage of complete dominance of the field.
Hatch also captures other features of our scientific culture. For instance, his description of scientific meetings is a gem: "The [meeting] is designed to exchange information and ideas through formal talks and informal discussions. The meeting is also a grown-up version of show and tell, in which scientists try to convince everyone else that they are doing the most interesting and exciting work and have the best ideas about how it all works. Each meeting also has a certain ambiance, which changes with the time and the particular cast of characters." Hatch is right. My third-grade show-and-tell experiences were good training for the meetings.
We should take seriously Hatch's views on scientific creativity as it relates to the structure of the scientific enterprise. He strongly favors the American system, in which young investigators can have independent laboratory groups and investigators feel that they can collaborate as well as compete. I believe that Hatch is correct in his analysis, but I am not at all sanguine that the current funding and university climates are going to continue supporting this type of scientific culture.
The book also reminds us that key discoveries are often surprising side products of research projects. These discoveries are not always the anticipated goals of experiments, nor will they be found in the specific aims of grant proposals. An important example is the discovery of type II restriction enzymes by Hamilton Smith while he was setting up the reagents for studying DNA recombination in Haemophilus influenzae.
Although the entire book is excellent, the sections that dwell on Hatch's direct experiences have an exciting and illuminating quality that are really inspiring. There are a few things that I feel are missing. First of all, it was a great tragedy that Hatch died before the book was completed. This is not just a personal statement -- there are issues that are missing that I would have liked the book to address, such as the use of genomic information in societal decision making. Hatch undoubtedly had opinions on this and other important issues that the editor could not and should not have tried to add to the book. Second, in keeping with Hatch's positive personality, it is hard to sense the pain that some scientists have felt during various competitions. This is unfortunately also an aspect of our scientific culture.
I strongly recommend this book for a wide variety of audiences. It will be enjoyable reading for everyone. Those who participated in the development of this field will take great joy in recalling specific events or participants. Young students contemplating a career in science often think that science is a hyperrational matter of finding the right equations or cloning the right gene. This book shows that science is an unpredictable and inescapably human enterprise, wrapped up in the personalities and interactions of its practitioners. For established scientists, it should give us pause to consider what is best about our enterprise and how to save it.
William S. Reznikoff, Ph.D.
Copyright © 2002 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
