Morange, Michel. 1998. A History of Molecular Biology. Translated by Matthew Cobb. Harvard University Press, Cambridge, Massachusetts, ISBN 0-674-39855-6, 336 pp., $39.95.
I really enjoy this book! It is the kind of book that every biologist should read and then display on their book shelf. As for me, I grew up with the names that appear in the past 50 years described by Morange. I first met the names of the famous contributors to molecular biology in the books and journals of our university libraries and in course textbooks. In some cases, my graduate school "Professors" would make it possible for me to meet a "name" that I had come to know. After a seminar. At a professional meeting. At a luncheon. At a home as one of the invited students. As I advanced in graduate school, I reached a level of "knowing" about the research published by the "names" in the overlapping fields of biochemistry, plant physiology, genetics, cell biology, and plant pathology that enabled me to ask "good" questions to which I knew at least half of the answer and could carry on a conversation about "his" work. ideas, and concepts. I write "his" because most of these "names" were men. It was always a pleasure to be a listener in a group of scientists and graduate students from other universities who gathered around a "history maker" after a symposium presentation at a professional meeting. Small groups would form; like mini-seminars. Some of the graduate students I met in those groups became famous leaders in their own areas of work. I can not recall a faculty member in such groups who did not do research. I became one of the "producers" during the past 40 years. I "know" this is a great book.
I participated in seminars (two or, sometimes, three per quarter; every quarter while in graduate school) and there was "trained" to enter the discussions; to be broad in scope. What I was doing was what my major professor expected of me: to be able to perform at a "high level" that one could recall as "an adventure." The joy of being "up" on the literature -- being literate in molecular biology -- being "up" on the understanding of a "valuable" contribution by "history makers" while reading the latest issue of a journal, and then running to the laboratory to share the new information -- from hand-copied notes --with others. That was exciting.
I had gained a special kind of "self-confidence" that was to last to the present time. I passed my pre-lims in four areas: Plant Physiology, Biochemistry, Plant Pathology, and Botany. The name and significance of the name rolled off my tongue as though both were landmarks in my home town. I "knew the history" and in my way contributed to it year after year. Some say it is not possible to do that now. I do not agree. We have a few of the new "great names" appearing in every new issue of a journal that hits the "current" shelf in the library reading room. The best molecular biologists on our campus are the best biology teachers. They are "hot." They are on their way to becoming "great." They constantly updated biology classes (from gene therapy, the human genome project, the creation of new animals and plants by genetic engineering, the cloning of mammals, and the understanding of molecular phylogeny, the origin of life, the pathways to cellular death, etc.) as though they have a CD-Rom of A History of Molecular Biology running in their brain when they lecture. They inspire the beginning students.
The history of molecular biology is written in the languages of biochemistry, cell biology, biophysical chemistry, statistics, and computer science. Although I learned the term "molecular biology" from Sidney W. Fox in 1954, as a student in his biochemistry class on intermediary metabolism, Morange credits Warren Weaver of the Rockefeller Foundation for coining the phrase in 1934. To me, Emil Fisher was a molecular biologist. The great names in carbohydrate chemistry, protein chemistry, lipid chemistry, and nucleic acid chemistry were those of molecular biologists. Stent's book on bacterial viruses was molecular biology. The Golden Age of electron microscopy in the 1950s pitted the unknown particles and membranes against Albert Claude, George Palade, and Christian de Duve. They were molecular biologists. I met de Duve and George Palade in the 70s. I was happy to meet Melvin Calvin and Francis Crick in the 50s and I thought they were molecular biologists. The term molecular biology means other things today.
I used Ernest DuPraw's book, Cell and Molecular Biology, the books by E. De Robertis and his son, like Cell and Molecular Biology; those by Kleinsmith and Kish, by S. L. Wolfe, and others. Those were great journeys. Using these textbooks in the advanced undergraduate classes should have been accompanied by the use of books like Plants, Genes, and Agriculture by M. Chrispeels and D. Sadava for introduction to botany. This wasn't possible then and doesn't seem possible even now. The "classicists" teaching those courses say such books are too tough for freshman botanists. Maybe we need two tracks for preparing professionals in phytobiology. That was evident even in the 50s.
The tools for this new field appeared in the 20 years following World War II. The big picture came into view in the early 1970s. In the past decade, wow!, and it has continued. Genetic engineering pushed the need for changing our biological concepts. Where did the cell come from? The gene? The intron? Gene expression? What is evolution? We need to teach the paradigm in which we live: the molecular paradigm. "PCR" is a symbol of this new biology. Why wait so long to teach it to undergraduates? This history of molecular biology is awesome.
Morange's book, is easy to understand (for me), logical in its order, clear in its definitions, and complete, yet balanced. Biochemistry is emphasized. Some of the key contributors are "sketched." Each chapter presents a theme that seems to stand alone. The reduction of biology to physics, mechanics, and chemistry underlies the histories of the biological disciplines. The key events? The development of the fields of biochemistry and genetics. Now we can move to understand birth, metabolism, growth, development, embryology, cellular abnormalities (diseases) and death at the molecular level. Without a word, computer science entered into this merged field in our new biology. Theoretical models of folding proteins, active and inactive, are in the hands of the young physiologist turned molecular. How long will it be before molecular biologists understand that Sidney W. Fox and his associates have synthesized cellular life? Who could have discovered the origin of life by reductionist methods? (Shades of the 16th through 19th century.) The "best" theory doesn't always lead to the correct answer. Who teaches the importance of experimental constraints?
Lets get to Biology 315-2 Origin of life. On page 11, we read that Pasteur had describe fermentation as a sign of life (in the 1850s) and in 1897, Edward Buchner succeeded in demonstrating sugar fermentation in vivo! Was this the first evidence that life could be acellular? No. I don't think so. Though metabolism could be studied thereafter in cell free preparations, there was no cheer for cell free life. That life was cellular was understood in and supported since the 1830s. Why does NASA not like the word "cell," -- as in the origin of cellular life?
The colloid theory dominated the first two decades of the 1900s but even Oparin never got a colloid to the state that it could be called "living." Life required large molecules in a large structure called the cell membrane. It took quite a while to "see" a membrane (electron microscopy in the 1950s) let alone describe it as a fluid mosaic system (1970s). The "macromolecule" (coined by Hermann Staudinger, 1922; page 12) theory replaced the colloid theory. Emil Fisher's lock and key (1890) metaphor leads to talk of specificity. It was Sidney Fox who told me about the meeting between his friend Linus Pauling and the immunologist, Karl Landsteiner. Stereomacromolecular chemistry followed with strong and weak chemical bonds -- now in the biologist's vocabulary. Stereospecificity was supported. Later, the induced fit hypothesis came into view through Monod (1965, page 160). Are thermal proteins self-chaparoned to form protocells? The amphiphilic (duel solubility -- polar-nonpolar -- properties; or, amphipathic) thermal proteins make good wall-membranes for protocells and metaprotocells. That they become better when mixed with lipids has been demonstrated.
As for genetics, the Mendelian laws of heredity were rediscovered (1903) and Thomas Hunt Morgan described what we call the chromosome theory (1910s). Some years later, Dr. Morgan directed the Ph.D. studies of Sidney W. Fox. Statistics was invented. One of the statisticians was J. B. S. Haldane (well known to us who study the history of the "origin" of life). The writings of Theodosius Dobzhansky, who formulated the new view of Darwinian evolution (page 20) were paraphrased by S. W. Fox: molecular variations (mutations) undergo molecular selection. Dobzhansky continued: "Unlike Darwin's view, this theory rejects the inheritance of acquired characters. It implies that genotype does not depend on phenotype." In the case of protocells, the genotypes evolve from thermal proteins (thermal proteomes) through oligo/polypeptides (proteomes) into small RNAs (RNAomes of progenotes) and finally to small DNAs (DNAomes of the cenancestor from which prokaryotes emerged). I will summarize this at the Illinois State Academy of Science Annual Meeting on this campus April 10, 1999 (see the Transactions of the Illinois State Academy of Science Supplement 90: 61 Abstract).
This ends Chapter one, The Roots Of the New Science. What will we find for our class in the remaining pages? Chapter 2 is The One Gene - One Enzyme Hypothesis. (We need that for understanding Horowitz in the 1940s : see your Biology 315 Textbook.) The Birth of Molecular Biology (PART I) continues: The Nature of the Gene; The "Phage" Group; The Birth of Bacterial Genetics; The Crystallization of the Tobacco Mosaic Virus; The Role of Physicists; The Influence of the Rockefeller Foundation; A new World View; and The Role of Physics.
Part II is The Development of Molecular Biology. The chapters are: The Discovery of the Double Helix; Deciphering the Genetic Code; The Discovery of Messenger RNA; and The French School.
PART III is The Expansion of Molecular Biology. The chapter titles are: Normal Science; Genetic Engineering; Split Genes and Splicing; A Molecular Biology; The Discovery of Oncogenes; From DNA Polymerase to the Amplification of DNA; and, Molecular Biology in the Life Sciences. Definitions are appended as are notes.
An important part of the history of origin of life is wrapped in the concept of protein synthesis as understood between 1940 and 1955. During that period, Sidney W. Fox became interested in the amino acid sequences in proteins and developed methods for determining these. Frederick Sanger used these procedures and determined the amino acid sequence of insulin. BINGO! Nobel Prize for the first complete amino acid sequence in a protein. Fox was very disappointed that his methods were to be part of that honor. But he persisted . He asked whether it was it possible to synthesize a protein in the laboratory directly from amino acids.
Protein synthesis presented a major theoretical problem (page 126). Many proposed that each protein in a living cell was synthesized by a multi-enzyme complex. But where did these complexes come from? The idea of one protein - one multi-enzyme complex did not agree with the proposal of Beadle and Tatum (one gene - one enzyme). There was no need for nucleic acids in the proposal! How to get around the gene control for the first proteins? Many, like Linus Pauling, believed that the genes were proteins! That got around the problem. There were data showing high correlations between increased RNA content in the cytoplasm and increased protein synthesis. Well, The DNA story in 1953 by Watson and Crick put an end to the ideas about proteins as genes and the explanation of the types of RNA did the rest. But, the question, of how did these macromolecules arise --- the beginning of cellular life --- , remained. In 1957, Francis Crick and Leslie Orgel (now a leader in the study of the origin of life) struggled to develop an explanation of the "reading frame" on DNA. This is well reviewed by Morange. Others solved that problem.
But, in the late 1950s, Fox and his associates showed that heating a "correct" mixture of amino acids yielded protein-like macromolecules (later to be called thermal proteins) and that the amino acids in the primary structure of these thermal proteins were self-ordered. MOLECULAR DETERMINISM. A problem existed in the determination of the entire sequence because when synthesized at 180 C, some amino acids rearranged to form flavin- and pteridine-like compounds. Thus, only short pieces cut by enzymes could be sequenced. Probably today, three-dimensional NMR could solve this problem. Of greater significance, when the thermal proteins were moistened (in water or simulated sea water, etc.) spheres bounded by two layers formed (self-assembly; self-organized) formed and when carefully studied (over the following 40 years) the spheres were shown to exhibit all of the attributes of cellular life; i. e., they were protocells, the smallest units of protolife. Check the study guide (1997) for our course for this history. I had the great honor of showing Dr. Fox that dialysis removed important material that formed extra-protocellular networks and represented an external metabolic poly-cationic and poly-anionic matrix that could bind substrates and products, etc., necessary for life. When dried, these matrices were highly diagnostic for the contents (formed molecules; as "crystal" morphologies useful as a diagnostic atlas for thermal proteins and for their structural studies). Fox studied "washed" protocells. We studied the whole preparation.
The idea here is that the hypothesis that the is a kind of "acelular chemical life" is nice but data on protocellular life is better. So it was with the Crick and Orgel "reading frames:" put to their end by data. So let it be with the RNA world and DNA world that Crick, Orgel and others support today as explanations for the origin of acellular life
The nice thing about protocells (with wall-membranes) is that they were shown to be structural and mutizymic, simultaneously, capable of synthesizing oligo/polypeptides and oligo/polynucleotides. Jacob and Monod distinguished two kinds of information (page 159) in organisms: structural information that was necessary for the formation of cellular components and regulatory information that was responsible for metabolism, etc.( the things that living cell do). Thermal proteins have these traits simultaneously expressed by a structure-multizymic wall-membrane boundary. The matrix thermal proteins are believed to function as sites of metabolism, storage sites for ionic substrates and products, attachment molecules for protocellular aggregations (networks), and nutrient reserves for growth and reproduction.
In What Is Life?, Erwin Schrodinger described an attribute of life seldom mentioned by biologists: (page 76) "-- neguentropy --- the property of living beings that enables them to increase order at the cost of their surrounding environment --." His book was not aimed at encouraging new experiments nor intended to present new models about life.
In contrast to Schrodinger, my writing with Fox on thermal proteins and protocells are new theory. Domain Protolife, my new vision, was to encourage experimentation. We presented new, informed, macromolecules (thermal proteomes) in protocells and (proteomes) in metaprotocells (as well as in the matrices). Then, evolved RNAomes and DNAomes within metaprotocells (progenotes and cenancestor, respectively). When the central dogma became the way of retaining and expressing information(minimum of 256 DNA genes), prokaryotic life emerged. What is life? It is cellular codes and programs; the molecular information that enables metabolism, growth, differentiation, reproduction, response to stimuli, membrane potentials, membrane semi-permeabilities, energy transduction systems, and more. These are some of the attributes of (1) cellular life we know (Domains Archea, Bacteria, and Eucarya) and (2) protocellular life we are beginning to know (Domain Protolife). In my opinion, life is a highly determined cosmos activity that obeys physical/chemical laws and is best described by its container, contents, and the exhibited behaviors listed by cytologists. Some of the parts exhibit molecular "memories;" -- genetic memories. (Check out Schrodinger's beliefs on pages 77 and 78. Are we in agreement?) The deep, hidden order I and Sidney "saw" was that of the big bang, the evolving sub-atomic particles, physical evolution, chemical evolution, and biological evolution. Each transition (bridges of the gaps) is now known and the whole process is now described by a new word; cosmogenesis. I believe it is appropriate to use the Thermal Protein (Protolife) Theory for the origin and early evolution of cellular life to bridge between Oparin (chemical evolution) and Darwin (biological evolution).
Morange cautions us about the role of physics and physicists in the development of molecular biology. Biology has not been reduced to either physics or chemistry (page 100). "The most important contribution of the physicists was perhaps simply to have been convinced (with a certain dose of naivet‚) and to have convinced the biologists that the secret of life was not an eternal mystery, but was within reach." But, did the physical scientists alter the definition of life? For biologists (page 236), replicating a phage (Kornberg, 1967) in vitro: "-- is not the equivalent of creating life. Life does not lie in molecules; it is to be found in the complexity of the systems under study."
This review was prepared by Aristotel Pappelis (Professor, Department of Plant Biology, Southern Illinois University at Carbondale, Carbondale, IL 62901).