The developing chick excretes mostly ammonia for the first four days, when the total excretion is so small and the egg so large in comparison to the tiny embryo that dangerous concentrations are not reached. Then for the next nine days, nitrogen wastes are mostly in the form of urea, there still being a reasonable amount of water to keep the urea concentration low enough. Finally, during the last eleven days when things are getting tight, the wastes are mostly in the form of uric acid.

  Turtles seem to be betwixt and between. Their egg-laying is done in closer contact with seas or rivers and they apparently produce both urea and uric acid.

  Again a duplication of inventions. Certain invertebrates have also invaded the land (some even earlier than ever the vertebrates did). The insects and land-snails, for instance, also invented the uric acid dodge, quite independently.

  I have already mentioned the fact that from biochemical considerations we can say that vertebrates first developed in fresh water. It is also possible to speculate from other biochemical considerations about the ancestry of the vertebrates.

  It seems, you see, that there is an important compound in our muscles which is intimately connected with the mechanism whereby muscles contract and relax. It is called creatine phosphate and we will abbreviate it as CP. Now here’s an interesting thing: CP is found in vertebrate muscle of all sorts, but it is not found in invertebrate muscle.

  Invertebrate muscle contains instead a similar compound with similar functions, called arginine phosphate, which we can abbreviate as AP.

  Now the problem is: at what point in evolution was CP invented as a substitute for AP? Since all vertebrates have CP, it was probably invented at some point before the vertebrate developed (unless the different groups of vertebrates each invented it independently, which seems unlikely).

  Well, the vertebrates (which are characterized by bony skeletons) are part of a larger group of animals called the chordata. The less advanced animals in this group haven’t reached the point where they have bones, but instead have inner stiffenings of some softer material. The indispensable minimum that makes an animal a member of the chordata is the presence of a cartilaginous rod called a notochord inside the body at some time in life.

  There are three groups of these primitive chordates. The most advanced type is amphioxus, which is fish-shaped (with fins missing and a fringed hole where a mouth and jaws should be). It has a notochord running the length of its body all the days of its life. Its muscles have CP, just as your muscles do.

  The most primitive of these primitives are the tunicates, which show a small scrap of notochord in their larval form. As adults, they lose it altogether and are so invertebrate in appearance that they were originally classified as molluscs. The tunicates have AP in their muscles, just as invertebrates do.

  The intermediate group of the three includes the balanoglossus, a worm-like creature. It doesn’t have a fully developed notochord, but it does have a scrap of it that hangs on into adult life.

  Well, to end the suspense, balanoglossus muscle has both AP and CP.

  Can CP be traced further back?

  The answer is yes. The larvae of balanoglossus resemble the larvae of certain echinoderms (a group of animals that includes the familiar starfish) so much that before the adult form of the balanoglossus was discovered, the larvae were classified as echinoderms.

  What about the echinoderms, then? These are divided into a number of groups, of which the majority, including the starfish, contain AP in their muscles just as other invertebrates do. However, there is one group, the brittle stars (which resemble starfish except that the ‘arms’ are longer and more flexible, and emerge from a globular little ‘body’) with muscles that contain CP, as do those of vertebrates. The final group, the sea-urchins (with spiny bodies shaped like discs that are round above and fiat below) contain both CP and AP.

  CP can’t be traced any further back, so far. It would seem then that at some time in the past, some creature (of which the sea-urchin is the most direct descendant) invented CP.

  So if you should ever see a sea-urchin, be respectful. Of all the invertebrates from amebae to insects and from worms to octopi, it is possibly your closest relative.

  CHAPTER TEN—THE SOUND OF PANTING

  Back in September of 1950, Dr. William C. Boyd, Professor of Immunochemistry at Boston University School of Medicine—where I work—having just come back from several months in Egypt, and feeling full of spirit, lured me to one side and suggested that we write a textbook on biochemistry for medical students. This struck me as a terrific idea. Dr. Boyd had already written textbooks on blood-grouping, on immunology and on anthropology, so there was no doubt in my mind that he could supply the experience. As for myself I felt I could supply the enthusiasm. We then rung in Dr. Burnham S. Walker, who is the head of our department of biochemistry and who has an encyclopedic knowledge of the subject. He went along not only with the notion but also with alacrity.

  There followed a hectic interval in which we laid our plans, corralled a publisher and had a lot of fun. But there came a time when all the preliminaries were over and we came face to face with a typewriter and a clean sheet of paper.

  It took us a year and a half before the first edition was done and additional years to produce new editions. The title of the book is Biochemistry and Human Metabolism (Williams and Wilkins) and the third edition appeared in the autumn of 1957. As all this went on I learned a lot about textbooks.

  A textbook, after all, is an orderly presentation of what is known in a given branch of science and is intended to be used for the instruction of students. Note the word ‘orderly’. It implies that a textbook must begin at the beginning, proceed through the various stages of the middle, and end at the end. Unfortunately, unless the science concerned is a deductive one such as mathematics or logic, this neat procedure is hampered by the fact that there is no beginning, no middle and no end.

  An inductive science such as biochemistry consists, essentially, of a vast agglomeration of data out of which a number of thinkers have abstracted certain tentative conclusions. It resembles a three-dimensional lacework all knotted together. To expound any portion of biochemistry properly, a certain knowledge of other areas of the science must be assumed. It is, therefore, the task of the writer to decide what one-dimensional order of presentation is least confusing. What subjects can he discuss in the earlier chapters with the best chance of being understood despite the absence of information contained in the later chapters? How often must an author stop to explain at a given point and how often can he get away with a simple reference to a page halfway up the book, or even with a curt ‘See Appendix’? (I, by the way, was a devotee of the ‘stop and explain’ method and I was consequently periodically crushed by the democratic procedure of being out-voted two to one.)

  Note also that a textbook is intended to instruct students. This cannot be done by lulling them gently to sleep or by confusing them with a display of incomprehensible brilliance. As far as is consistent with a respect for the facts and for accurate exposition, one must not scorn to write entertainingly. In short, there is the question of style.

  This raises the point that three collaborators have three different styles. True! Fortunately, by dint of revising each other’s work and then beating out the results in triple conference, a reasonably uniform style was achieved with elimination of extremes. Dr. Walker, for instance, whose natural style is extremely condensed, was forced to include occasional conjunctions and to allow the existence of a few subordinate clauses. I, on the other hand, found that my more passionate outbursts of lyricism were ruthlessly pruned. Many was the gallant rearguard fight by one or another of us in an attempt to insert a comma or delete it; many the anguished search through the Unabridged in defense of a maligned word.

  However, back to my definition of textbook. It is an orderly presentation of what is known: The implication is that it deals with what is known up to the very moment of writing.

  That’s easy, isn’t it?

  And how does one find out what is known?

  First of all, there are other textbooks, and one naturally turns to them for another man’s panoramic view of a field. But there are limitations to the textbook.

  For instance, textbooks must be selective, rather than inclusive, as that is the only chance of staying below ten thousand pages. This means that the author of the textbook you read has already winnowed the facts and his winnowing may not be your notion of winnowing at all. Secondly, every textbook writer imposes his own interpretation on the data, either by actually stating his interpretation, or by implying it through his choice of what facts to place in the book.

  (Occasionally, we three co-authors didn’t agree on interpretations among ourselves. For instance, there are two major theories concerning the cause of cancer. One is the ‘mutation theory’ and one is the ‘virus theory’. I’m a mutation fan and Dr. Boyd is a virus supporter. Since I had the cancer chapter in my charge in editions one and two, I pitched mutation into a page or two of eloquent prose and dismissed viruses in a cool, unimpassioned paragraph. Such arguments! Scarcely a lunch hour passed in which Dr. Boyd didn’t advance determinedly to the fight, armed with a new article on the virus theory. He has managed to win me over somewhat and in the next edition of the book, I think he will be in charge of the cancer chapter.)

  Probing more deeply than the textbook, we come to the monograph. The monograph is no attempt at instructing beginners at all. It is a presentation of all the available facts—within human limitations—for the benefit of the expert in the field. The subject of the monograph is, of necessity, narrower—and usually much narrower—than the subject of the textbook.

  The one-man monograph is vanishing. That is the result, in part, of the growing ocean of known fact and the consequent narrowing of focus of the human mind. The ‘universal genius’ is gone forever. Nowadays, it is almost impossible to find a man who considers himself qualified to write all about some small subdivision of biochemistry, which is itself a subdivision of biology and chemistry, which are themselves subdivisions of the field of the physical sciences which are themselves subdivisions——

  Take an example. Recently an extensive monograph on proteins has been coming out. It is in four volumes—total pages, 2,526; total price $54.00. It is edited by two men, but it contains a series of articles to which a total of thirty-one authors have contributed, one of them being Dr. Boyd, incidentally. Each chapter is a ‘review article’ concerning some subdivision of the biochemistry of proteins.

  Scientists are very grateful for review articles. They summarize the ‘literature’ (I’ll explain what that means in a little while) in one finely-focused facet of the science.

  Whole systems of volumes are devoted to nothing but review articles. For instance, every year for the last twenty-odd, a book called Annual Reviews of Biochemistry has come out. It is divided into chapters, each dealing with a subdivision of biochemistry and each written by an appropriate expert. Each chapter summarizes the work that has been done in that subdivision over the past year as concisely as possible. Despite the fact that the book is concise almost to the point of obscurity, it ends by being a good-sized volume.

  Then there are periodicals like Chemical Reviews and Physiological Reviews, which don’t try to cover the whole field every issue. They appear at monthly intervals with selected reviews on this subject or that. The July, 1954 issue of Physiological Reviews, for instance, has eight reviews, including a twenty-five-page article on the single substance, serotonin, a compound of importance in the workings of the brain which was first identified in 1949. The August, 1954 issue of Chemical Reviews contains four review articles, including twenty-four pages on the micro-heterogeneity of proteins (a subject bearing on my discourse in Chapter 3).

  Annual volumes are also put out containing review articles on more restricted subject matter. For instance Advances in Enzymology was first put out in 1940 and has been appearing annually since. It contains review articles dealing only with enzymes and related subjects. This sort of specialized review volume proved so useful and desirable that other subdivisions of biochemistry demanded similar service.

  A single publishing house now puts out Advances in Protein Chemistry, Advances in Carbohydrate Chemistry, Advances in Cancer Research, Advances in Genetics, Advances in Virus Research, Advances in Food Research, Advances in Agronomy, Vitamins and Hormones, Recent Progress in Hormone Research, International Review of Cytology, Progress in Biophysics and Biophysical Interactions, Progress in Organic Chemistry, The Alkaloids. Each appears once a year or so, and there are many others to keep these company.

  But all these, textbooks, monographs, reviews, are only secondary sources. Where do they get their information?

  Well, the primary source of knowledge is derived from all the work done in all the laboratories, libraries, offices and thinking places, of all the colleges, universities, research institutions, industrial establishments, hospitals and similar places by all the scientists, engineers, physicians and technicians.

  Whenever any of these has completed a series of experiments or arrived at a certain set of thoughts which seem to yield a small nugget of useful information which does not completely coincide with any of the other nuggets of useful information of which he is aware, it is his bounden duty to make known this nugget to the scientific world.

  This is done by writing a ‘paper’; that is, by preparing a description of his experiments and their results, preceded by a very brief summary of previous work in the field and succeeded by a cautious interpretation of the significance of his own work. The paper is then submitted for publication in a periodical devoted to such things. Such periodicals are referred to, in rather cavalier fashion, as ‘journals’ and the sum total of all the papers written is referred to, still more cavalierly, as the ‘literature’. (I told you we’d get around to that word.)

  There are literally thousands of journals printed. I’ll confine myself to journals of biochemistry and we’ll run through a couple, just to get the taste of things. The aristocrat of biochemical journals is the Journal of Biological Chemistry. It comes out once a month and the individual issues have been thickening with the years. When it first appeared some fifty years ago, the entire year’s output could be bound into a moderately sized volume. The year’s output is now bound into six somewhat larger volumes. The British analogue is the Biochemical Journal. which has fewer but larger pages.

  There is the Journal of the American Chemical Society. which specializes in physical chemistry and organic chemistry, although the biochemical papers it contains are first rate. It comes out twice a month now—the monthly issue became too unwieldy. The British analogue is the Journal of the Chemical Society.

  There is Science, which appears weekly and specializes in short papers covering the entire field of the sciences, with biochemistry well represented. The British analogue is Nature.

  We haven’t even scraped the surface, though. There are journals devoted to specific diseases, with titles like Cancer, Cancer Research, Diabetes and so on. There are journals devoted to particular parts of the body or particular aspects of its mechanism, like Blood, Circulation, Brain, Metabolism. There are journals put out by various scientific institutes or organizations, such as: Proceedings of the Society for Experimental Biology and Medicine, Proceedings of the National Academy of Sciences of the United States, Journal of the National Cancer Institute, Annals of the New York Academy of Science, Bulletin of the New York Academy of Medicine. There are journals devoted to certain branches of biochemistry or to allied subjects: Journal of Immunology, Journal of Bacteriology, Journal of Nutrition, Journal of Clinical Nutrition, Journal of Clinical Investigation, American Journal of Clinical Pathology, Journal of Clinical Endocrinology. (I’m just pulling them out of the air at random.) Various schools and hospitals put out journals devoted to their own work: There is the Quarterly Bulletin of Northwestern University Medical School, Yale Journal of Biology and Medicine, and many more.

  Furthermore, new journals are continually being brought into existence. Just this week, I received the announcement of a new journal, Virology, to come out approximately bimonthly and to be devoted to the various aspects of virus research.

  And then, you know, science is international. There are whole clusters of foreign-language journals. The Germans have Zeitschrift für Physiologische Chemie as their chief biochemical journal. The French have Comptes rendus des séances de la société de biologie et de ses filiales as theirs. The Russians, of course, have moved up in journal production in recent years, and if you want to see what the title of a Russian journal looks like—transliterated from the Cyrillic alphabet—try this on for size: Doklady Akademii Nauk Soyuza Sovetskikh Sotsialisticheskikh Respublik—which means ‘Proceedings of the Academy of Sciences of the Union of Soviet Socialist Republics’. There are Japanese journals, Swedish journals, Swiss journals, Dutch journals, Spanish and various Latin-American journals. There’s the Journal of the Pharmaceutical Association of Siam, Journal of the Philippine Medical Association, The Irish Journal of Medical Science and so on and so on and so on——

  (Special note: I am not making up a thing. Every journal listed in this article is a real, honest for true, genuine journal.)

  Now, then, the number of papers of biochemical interest which appear in these journals amounts to some twenty-five hundred each month. How does any biochemist keep up with them? Reading them all is out of the question. Yet unless we get acquainted somehow with all of them, how can we tell but what some extremely vital nugget of information is escaping us?

  (You think such escape isn’t possible? When Mendel discovered the basic laws of genetics, he duly published his results in the Proceedings of the Natural History Society of Brünn, where it lay quietly undisturbed and unnoticed for thirty-four years. Count ‘em. Thirty-four.)