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The creation of the Basic Neurochemistry Textbook
George J. Siegel

C.F.B.: We will now hear about the way the Basic Neurochemistry textbook came into existence. Not only is this textbook an amazing source of neurochemical information, but it is also a major moneymaker for the ASN. Without money the ASN could not accomplish most of its objectives. So here is the Editor-In-Chief of Basic Neurochemistry: George Siegel

The creation of the Basic Neurochemistry Textbook - George J. Siegel

Thank you, Claude. I've never really thought of myself as a banker before and I can tell you that my wife does not think of me as a banker, because she keeps the books.

This is a session for history and certain facts have to be stated. I have a special privilege here because I really come here as a student. The Talmudic sages speak about the ways in which students are supposed to honor their teachers. For example, if your teacher and your father are both in prison, and you can only ransom one, you are supposed to ransom your teacher first. I say this by way of introduction because some of my teachers actually are still in this room and have been contributors to Basic Neurochemistry. It is said that necessity is the mother of invention, and in certain respects, this book came about because of certain things that I had to do, and the fact that I had teachers that actually helped me do it.

In terms of specific history, two important facts need to be mentioned - that the National Institute of Neurological Diseases and Blindness (called the NINDB in those days) had a conference on training and clinical neurochemistry in 1968. In June of 1968, the NINDB council passed a motion to emphasize support for neuroscience teaching programs. At that time, I didn't know anything about that. What I knew was that in 1968, I had finished training with Wayne Albers who was my mentor at the NIH where I was working as a research associate in his lab. I had gotten there - this is a bit of history that's important - through a route, which included Jerry Lehrer as my teacher in neurochemistry at the Mount Sinai Hospital in New York. While I was a neurology resident with M.B. Bender as my neurology preceptor I worked in Jerry Lehrer's lab at night in studying kinetics of acetylcholine esterase using L-naphthol acetate as a histochemical stain. There I started learning to compartmentalize myself: neurology and neurochemistry. After residency, I went to work with Wayne Albers as a research associate in his lab, studying sodium, potassium-activated ATPase and the mechanism of ouabain inhibition of the enzyme. While I was at NIH, I heard a speaker who was very impressive to me because he was studying a subject that really had to do with brain function, neurochemistry and behavior. I thought, this is what brings it all together. That was Bernie Agranoff, who had come back then to the NIH to present his now classic findings on learning and memory consolidation in goldfish. (Now, Jerry Lehrer, Wayne Albers, and Bernie Agranoff, by some strange coincidence, are sitting right together in the same row. I don't know how it happened. But there they are.)

In 1968, I took a position at the Mount Sinai Hospital. Mount Sinai Hospital had been around a long time, pretty active in research and teaching, but they did not have a Medical School till 1968. I was very privileged to be on the faculty of their first entering class. I was in the Department of Neurology, where M.B. Bender was Chairman and in the Department of Psychology where Irving Schwartz was chairman. We had to organize a neuroscience curriculum for this first entering class of 1968. Those were the days of the great campus unrest. These students were not to be set aside lightly. In any event, we had to organize an integrated neuroscience curriculum.

It was the time of integration-interdepartmental, integration and relevance. When I got there to work they asked me, "What do you do?" I answered, "Well, I just came out of the Laboratory of Neurochemistry at the NINDB……….." Their reply was, "Okay, you are a neurochemist. Now you organize a curriculum of neurochemistry to be integrated with neurology, physiology, anatomy, and pharmacology." So I said, "Well, wait a moment. What's this?" Then I remembered that Wayne Albers and Roscoe Brady had been giving a course in Neurochemistry at the NIH at that time and I reasoned, "Okay. They know neurochemistry." So, I went to Wayne and asked, "What do we teach in a curriculum in neurochemistry?" He said, "Well, I know what I teach. "But what do we teach around the country? What do we do for a medical school curriculum?" Wayne said, "Well, I don't know, let's go find out."

We decided to do a survey. We agreed that this has got to be a course in research and in teaching at medical school, graduate school and faculty levels. This course would not be just high school and collegiate schematic diagramming. This course had to be the "real stuff." We decided to find people who were doing the investigation and who were doing the teaching. Both. We wanted to ensure that we could build a comprehensive, didactic text with a skeleton on which new information and concepts could be added as research progressed. Wayne and I put together a list of people and sent out a survey to those involved in research and in teaching neurochemistry at their universities; and asked what did they teach? We collected a lot of responses and course curricula from these people. Then we needed another clinician who was also a neurochemist type to be brought in and we sought Robert Katzman who was then the chairman of the Department of Neurology at Albert Einstein College of Medicine to enter the picture. There were other people, whose names I'll mention later, who were at Albert Einstein in those days, in neurology and neuroscience; with considerable integration going on. I think that that was one of the departments around the country in which biochemistry, neurology and pathology were most integrated.

Robert Katzman, Wayne Albers and I surveyed these people and basically asked, "Who should like to come to a neurochemistry curriculum conference? We put together a proposal to the NIH asking for a grant to support a conference for this curriculum discussion. NIH provided the money. We held the conference at the Greystone Conference Center in Riverdale, New York, June 19, 20 1969. *(The list of participants and the curriculum are appended). At the conference, we invited Bernie Agranoff to be the fourth member of this organizing group. There were 30 people at the neurochemistry curriculum conference.

We organized the agenda by taking all the suggestions that people had made as to topics they would teach. We collated the topics and arranged them in what we thought would be a rational approach to studying the molecular basis for nervous system function. Wayne's wisdom in science was critical to this outline. We grouped the topics in sections, and arranged the conference participants into small groups such that each group had people with complimentary interests related to a particular topic. Some of the people at that original conference are actually still alive and those present in this room right now are: Kunihiko Suzuki, Bernie Agranoff, Jerry Lehrer, Wayne Albers and Bill Norton. I think that it's really a privilege for us in the ASN today that some of the people present at that original conference on neurochemistry curriculum 30 years ago are here, still present, in this room, participating in neurochemistry research and teaching. Later on, other people wrote chapters for subsequent editions of this book and I see some are present in the room: Lloyd Horrocks, Richard Quarles, and most recently, our ASN president, Nicholas Bazan. Our latest, 6th edition, has 70 contributors. All of these and other contributors to the intervening editions were critical to the continued evolution of the text as a contemporary curriculum.

At that original conference, the objective was to construct an outline of a syllabus that everybody could take back with them and then fine tune and put into an order that could actually be used for teaching. We organized it as a three-day conference in this very beautiful conference center, a mansion on an estate in Riverdale, New York. We had a Xerox machine or some kind of a copying machine in the basement and we had a typewriter - imagine, a typewriter - and we hired a person to type. This person happened to be my sister-in-law, Elfi Hendell, who would sit there at the typewriter and type and make copies all day. The small groups would have their meetings during the day on their particular subjects - we had the agenda in a logical sequence. The idea was that the syllabus or outline that each group would produce, would immediately go down to the basement to be typed up, reproduced and then re-distributed to all the groups as they were working during the day. Thus, each group could see what the other groups were putting into their topics. We wanted to coordinate topics and we knew that certain material would overlap, but we didn't want to have too much overlap. There were the problems that certain material was needed as a basis for all subjects and certain topics were basic to other subjects, which would lead to some overlap. We wanted each group to know what the other groups were doing. At the end of each day and of the entire 3-day conference, we would have a plenary session in which all of this material would be discussed. The object was that everybody would go home with a syllabus that they could work on at home and we would then make those into professional-looking chapters later.

Well, we proceeded in this way but we got far behind. We got such a backlog of stuff to type. My poor sister-in-law was down there typing all day and running the copying machine. But at the end of the three days, we only had half of the stuff put together and then we worked on the rest of it after the people left. We sent out whatever outlines had been produced. Afterwards, we were to discuss what to do with them.

Now, it's interesting to mention some of the discussion points made at this conference in 1969. There was the big question… "How much basic biochemistry should be included in this book?" Some people said only those parts that were relevant to the particular neurochemical subject and some people thought that we shouldn't have any basic biochemistry, such as intermediary metabolism, because that's something everyone was expected to know. After all, we couldn't include everything! Some people thought we should just have bibliographies of references to basic biochemistry. That conflict, by the way, still exists today: How much basic biochemistry should we include in each chapter and how much can we expect these incoming students to know?

There was one idea, that the book should be designed for the people who give the course, so that they would have the references and concepts on which to build their own course. Instructors could choose sections from different parts of the book to tailor their own courses. We knew we couldn't design a course that would be good for everyone. We wanted it to be such that people would freely communicate with each other as to their information, opinions, omissions, and errors. And this, by the way is translated to what is now being proposed by Wayne Albers and others as a forum on the Internet, in which people can add their comments that are relevant to chapters. Such a forum could help in planning future editions.

There was a major discussion as to whether neurochemistry should be neurobiology, whether neurochemistry should be a separate course, or whether it should be integrated into the medical school curriculum or strictly into graduate school. And there was discussion of what word should be used. Should it be called neurochemistry, molecular neurobiology, or molecular neurology? The term molecular neurobiology was suggested by John O'Brien.

There was some concern about being speculative in such a book (--by the way, I'm reading from minutes that were recorded and transcribed in 1969--) Eli Robbins pointed out that we need a careful distinction between reasonably well-founded facts and mere speculation. Eugene Roberts pointed out an illustration of this: the rather widespread and uncritical acceptance of the role of RNA as a memory molecule. Eli Robbins cited the current acceptance of the relationship of the biogenic amines to psychiatric illness as another unproven fact. Today, we might say an historical analysis of the evolution of these concepts, relevant investigation and current status would be quite instructive.

At the end of the conference, a very important decision was made. We discussed what to do with all the Xeroxed, typewritten pages of outlines that the committees were putting together. The conference group agreed that an editorial committee consisting of Wayne Albers, Robert Katzman, Bernie Agranoff and myself should have the authority to make a decision on the basis of the outlines, as to whether a syllabus should be developed and what form the publication should take.

The subject of disposition of royalties was discussed. The participants favored the assignment of such funds to the American Society for Neurochemistry with the stipulation by the editorial committee as to the use of these funds for educational purposes, for the perpetuation of the syllabus and, if sufficient, as a travel fund. It was agreed that this should be discussed by the ASN Education Committee, of which Bernie Agranoff was the chairman at that time. You all probably know Bernie Agranoff's ideas about gastronomy and neurochemistry. This concept has been a pervading influence. A motion was made and carried to the effect that the editorial committee is authorized to work out the details of any disposition of funds with the ASN. Bob Katzman proposed that the priority for the use of such funds should be given to continuation and revision of the syllabus.

Now, what are the results of all this planning and implementation: Six editions of Basic Neurochemistry.

The first three editions were published by Little, Brown and Co. Numbers one and two were paperbacks with unjustified margins, printed on rather inexpensive paper. The third edition also published by Little, Brown and Co. was a hardcover book with two columns per page and justified margins. The publishers were beginning to have a little more confidence in this text.

The fourth and fifth editions of Basic Neurochemistry were published by Raven Press and we enjoyed the enthusiastic support of their editors, Graham Lees and Jasna Markova. We introduced topical outlines for the chapters in the fourth edition and, in the fifth edition, color and art. Bernie Agranoff is to be credited with organizing the artistic contributions for this book. In the sixth edition, published by Lippincott-Raven, we employed additional art and color, and produced a CD disc. (Figure 2.)

The CD includes one of the other initial requests made at the original conference in 1969, namely, to bring in clinical presentations that would be connected to the biochemistry, although the means for this was then presumably written text. The CD has in it videotapes of patients with movement disorders, related to the basal ganglia chapter. The CD also has videotapes of the movement of particles in axoplasmic transport with the musical accompaniment of a banjo that Roscoe Brady provided and animated cartoons illustrating enzymatic and molecular signaling. One of the major concerns in the curriculum conference was to be able to update the references frequently to keep the book current with the anticipated evolution in neuroscience. Our CD has outlinkage to Pub Med through the Internet. You can't get more current than that!

That's the story of Basic Neurochemistry. In the future it probably will go more into electronic publishing with more of the revising and editing being performed on-line.

Comments by Bernard W. Agranoff:

I'll make a brief comment about the book, to say how much I've enjoyed working with George and Wayne. Wayne's encyclopedic knowledge of neurochemistry qualify him to be a living treasure. George provided us not only with scientific rigor, but also kept us and our chapter authors on schedule. It was a lot of work, sometimes aggravating and sometimes enjoyable. I think you will agree that with each edition we not only updated the facts, but improved the overall quality and continuity of the multi-authored book.

I remember in particular one dramatic crisis. We had just finished editing the entire manuscript for the third edition. All of the editorial information was on a single copy of the manuscript, which could not be photocopied because little blue slips with handwritten corrections were attached to each of the pages. Our precious cargo was shipped to the publisher in Boston. The package was checked in at the publishers loading dock, and then disappeared. When it became apparent that it had not merely been misplaced but was gone forever, we editors spent three days and nights in a New York hotel, re-editing the entire book. Needless to say, for the fourth edition we had a new publisher ! Fortunately we owned the copyright, so this was not a problem.

In closing, I have a story about the editing of Basic Neurochemistry. After our editing of each chapter, the manuscript went to copy editors and from there to galleys. With the fifth edition, we had a copy editor who thought he knew better than we editors and re-introduced errors we had edited out. This is graphically summarized by the three-part Figure:


George Siegel edits Basic Neurochemistry, 5th edition.

As you can see, George finds an error in the manuscript in June, is pleased to see it corrected in the page proofs in July, only to find that it has re-appeared in the galleys in August.

Now the true story behind this three picture figure:
It comes from a lunch George and I had in Montpellier in connection with the ISN meeting in 1993. I had showed George a book of hidden 3-D drawings that pop out when you stare at them, and George was trying to make it work. I was sitting across the table from him and took these pictures. My thanks to George for permitting me to share this with you. Thank you.

Reply by George J. Siegel

That is pretty funny, Bernie. I didn't know you were going to do that. I wish to mention several other names that ought to be remembered in connection with Basic Neurochemistry. One of them is Helene Jordan Wadell who was the Editor for Rockefeller University Press. When we started working on this with Little, Brown and Co. and with their then acquisitions editor, Lin Richter, we really needed somebody to help us with the syntax and style for readability. Little, Brown, persuaded by Lin Richter, provided a small grant that we could use. Bernie knew Helene Jordan. Helene was willing to work on this project really for the same reason all of us were doing this - for the love of neuroscience and education. She worked on every chapter right along with us. I can't calculate how many hours were involved. By her own efforts, she stimulated us and kept us enthused and optimistic that it would succeed. Helene worked on the second and third editions as well. During the fourth edition, she developed a brain tumor. Helene through her dedication was very much responsible for helping us to get started. In the fourth and fifth editions, Perry Molinoff worked with us as an editor helping to develop neuropharmacology. In the current 6th edition, Stephen Fisher and Michael Uhler joined us as editors helping to develop intracellular signaling and molecular neurobiology in the text. In this current edition, working with Lippincott, Williams and Wilkins (who bought Raven and Little, Brown), Ann Sydor, the development editor at Lippincott, has been very helpful in keeping our production well orchestrated with a consistent and readable style. Since 1969, I have been fortunate and privileged to have the supportive working relationships and the intellectual and scientific wisdom of many people, but most notably of Wayne Albers and Bernie Agranoff in all of this continuing project.

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