Nazi expulsion of scientists.
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photo courtesy of nobelprize.org |
“How fortunate for brain science throughout the world that England, Australia, New Zealand and the United States opened their doors to the remarkable scholars of the synapse cast out by Austria and Germany [at the start of World War II], including Loewi, Feldberg, Kuffler, and Katz. I am reminded of a story told about Sigmund Freud when he arrived in England and was shown the beautiful house on the outskirts of London that he was to live in. On seeing the tranquility and civility that his forced emigration had brought to him, he was moved to whisper with typical Viennese irony, ‘Heil Hitler!’” P. 102
Thinking vs. working.
“The argument with [Kandel’s wife] Denise about spending more time with her and [Kandel’s son] Paul did cause me to pause and think. As a consequence I learned from this argument the obvious lesson that hard thinking, especially if it leads to even one useful idea, is much more valuable than simply running more experiments. I was later reminded of a comment made about Jim Watson by Max Perutz, the Viennese-born British structural biologist: ‘Jim never made the mistake of confusing hard work with hard thinking.’” P. 162.
Maturation as a scientist.
Kandel spent 1962 and 1963 working in the Paris laboratory of Ladislav Tuac learning to work with the sea slug Aplysia. At the end of this experience “without quite knowing it, I had found my voice, much as a writer must feel after having written a number of satisfactory stories. . . . I had many moments of disappointment . . . but I always found that by reading the literature and showing up at my lab looking at the data as they emerged day by day and discussing them with my students and postdoctoral fellows, I would gain a notion of what to do next.
“As I had done when selecting Aplysia to study, I learned to trust my instincts, to unconsciously follow my nose. Maturation as a scientist involves many components, but a key one for me was the development of taste, much as it is in the enjoyment of art, music, food, or wine. One needs to learn what problems are important. I sensed myself developing taste, distinguishing what was interesting from what was not—and among the things that were interesting, I also learned what was doable.” Pp. 172-173.
Practical use of research.
“After a season of working on Aplysia, I was reminded of a story Bernard Katz had told me about the great physiologist A. V. Hill, his mentor at University College, London. On Hill’s first visit to the United States, in 1924, shortly after having won the Nobel Prize at age thirty-six for his work on the mechanism of muscular contraction, he gave a talk on the subject at a scientific meeting. At the end of the talk, an elderly gentleman rose and asked him about the practical use of his research.
“Hill pondered for a moment as to whether he should enumerate the many instances in which great benefits for mankind have arisen from experiments undertaken purely to satisfy intellectual curiosity. Rather than take this path, however, he simply turned to the man and said with a smile, ‘To tell the truth, sir, we don’t do it because it’s useful, we do it because it’s amusing.’” P. 172.
From cell to organism.
“I had no direct evidence that, in a behaving animal, actual learning leads to changes in the effectiveness of synapses. I needed to move beyond modeling learning in individual cells of an isolated ganglion to studying instances of learning and memory in the neural circuit of a behavior in the intact, behaving animal.
“I therefore set two goals for the next several years. First, I would develop a detailed catalog of the behavioral repertoire of Aplysia and determine which behaviors could be modified by learning. Second, I would select for research one behavior capable of being modified by learning and use it to explore how learning occurs and how memories are stored in the neural circuitry of that behavior.” P. 187.
Theoretical biology.
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“What is the use of such general ideas [as the central dogma]? Obviously they are speculative and so may turn out to be wrong. Nevertheless, they help to organize more positive and explicit hypotheses. If well formulated, they can act as a guide through a tangled jumble of theories. Without such a guide, any theory seems possible. With it, many hypotheses fall away and one sees more clearly which ones to concentrate on. If such an approach still leaves one lost in the jungle, one tries again with a new dogma, to see if that fares any better. Fortunately in molecular biology the first one selected turned out to be correct.
“I believe this is one of the most useful functions a theorist can perform in biology. In all cases it is virtually impossible for a theorist, by thought alone, to arrive at the correct solution to a set of biological problems. Because they have evolved by natural selection, the mechanisms involved are usually too accidental and too intricate. The best a theorist can hope to do is suggesting what directions to avoid. If one has little hope of arriving, unaided, at the correct theory, then it is more useful to suggest which class of theories are unlikely to be true, using some general argument about what is known of the nature of the system.” Pp. 109-110.
Biological models.
“I cannot help thinking that so many ‘models’ of the brain that are inflicted on us are mainly produced because their authors love playing computers and writing computer programs and are simply carried away when a program produces a pretty result. They hardly seem to care whether the brain actually uses the devices incorporated in their ‘model.’
“A good model in biology, then, should not only address the problem in hand but if at all possible should serve to unite evidence from several different approaches so that various sorts of tests can be made of it. This may not always be possible to do straight away – the theory of natural selection could not immediately be tested at the cellular and molecular level – but a theory will always command more attention if it is supported by unexpected evidence, particularly of a different kind.” P. 115
One ribosome, one protein.
“It was uncertain at that time whether any protein synthesis took place in the nucleus of the cell (where most of the DNA was), but everything suggested that the majority of it took place in the cytoplasm. In some way the sequence information in the nuclear DNA had to be made available outside the nucleus, in the cytoplasm. The obvious idea, which predated the DNA model, was that this messenger was RNA. . . .
“It was known that cells very active in protein synthesis had more RNA in their cytoplasm than cells that were less active. By the late 1950’s it had been shown that most of their RNA was in small particles, now named ribosomes, that consisted of RNA molecules plus a mixture of proteins. What more natural than to assume each ribosome synthesized just one protein and that its RNA was the postulated messenger RNA? We assumed that each active gene produced a (single-stranded) RNA copy of itself, that this was packaged in the nucleus with a set of proteins to help it do its job and then exported to the cytoplasm where it directed the syntheses of the particular polypeptide chain coded for by this RNA. Pp. 116-117.
Collecting ants in South Australia with entomologist Caryl Haskins in 1955.
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Photo courtesy of Alabama Center for the Book |
“Carl set out at once to collect colonies of bulldog ants, his favorite insects. This was no casual undertaking. The workers, measuring up to three centimeters in length, possess large bulging eyes with excellent vision, long saw-toothed mandibles, and painful stings. They are among the most belligerent insects in the world. Imagine a crater nest one or two meters across, with an opening in the center several centimeters wide, from which come and go dozens of surly red-and-black-ants the size of hornets. Disturb them in the slightest and they charge you fearlessly. A few will follow your retreat for as much as ten meters from the nest. These ants, in short, are not the furtive picnic and kitchen raiders of America.” Pp. 177-178.
Hypothesis and observation.
“I felt gratified—indeed, exuberant—that I had discovered what appeared to be a broad ecological pattern from my undisciplined collections and journal. But this was the way it is supposed to be. Nature first, then theory. Or, better, Nature and theory closely intertwined while you throw all your intellectual capital at the subject. Love the organisms for themselves first, the strain for general explanations, and, with good fortune, discoveries will flow. If they don’t, the love and pleasure will have been enough.” P. 191.
Young James Watson.
“When he was a young man, 1950s and 1960s, I found him the most unpleasant human being I had ever met. . . . He arrived with a conviction that biology must be transformed into a science directed at molecules and cells and rewritten in the language of physics and chemistry. . . . At department meetings Watson radiated contempt in all directions. He shunned ordinary courtesy and polite conversation, evidently in the belief that they would only encourage the traditionalists to stay around. His bad manners were tolerated because of the greatness of the discovery he had made. . . . Watson, having risen to historic fame at an early age, became the Caligula of biology. He was given license to say anything that came to his mind and expect to be taken seriously. And unfortunately, he did so, with a casual and brutal offhandedness. . . .” Pp. 218-219.
“At least there was no guile in the man. Watson evidently felt, at one level, that he was working for the good of science, and a blunt tool was needed. Have to crack eggs to make an omelet, and so forth. What he dreamed at a deeper level I never knew. I am only sure that had his discovery been of lesser magnitude he would have been treated at Harvard as one more gifted eccentric, and much of his honesty would have been publicly dismissed as poor judgment.” Pp. 222-223.
Systematics and molecular biology.
“The passage of thirty years has done much to close the divide between molecular and evolutionary biology. As I write, systematists, the solitary experts on groups of organisms, have unfortunately been eliminated from academic departments by the encroachment of the new fields. That is the worst single damage caused by the molecular revolution. Ecologists, pushed to the margin for years, have begun a resurgence through the widespread recognition of the global environment crisis. Molecular biologists, as they promised, have taken up evolutionary studies, making important contributions whenever they can find systematists to tell them the names of organisms.” Pp. 230-231.
Names and knowing.
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“I learned very early the difference between knowing the name of something and knowing something.” P. 15.
Teaching and thinking.
“I don’t believe I can really do without teaching. The reason is, I have to have something so that when I don’t have any ideas and I’m not getting anywhere I can say to myself, ‘At least I’m living; at least I’m doing something; I’m making some contribution’—it’s just psychological. . . .
“In any thinking process there are moments when everything is going good and you’ve got wonderful ideas. Teaching is an interruption, and so it’s the greatest pain in the neck in the world. And then there are the longer periods of time when not much is coming to you. You’re not getting any ideas, and if you’re doing nothing at all, it drives you nuts. You’ can’t even say, ‘Well, at least I’m teaching my class.’
“If you’re teaching a class, you can think about the elementary things that you know very well. These things are kind of fun and delightful. It doesn't’t do any harm to thin, them over again: Is there a better way to present them? Are there any new problems associated with them? Are there any new thoughts you can make about them? The elementary things are easy to think about; if you can’t think of a new thought, no/184/harm done—what you thought about it before is good enough for the class. If you do think of something new, you’re rather pleased that you have a new way of looking at it.
“The questions of the students are often the source of new research. They often ask profound questions that I’ve thought about at times and then given up on for a while. . . . The students may not be able to see the thing I want to answer, or the subtleties I want to think about, but they remind me of a problem by asking questions in the neighborhood of that problem. It’s not so easy to remind yourself of these things.” Pp. 183-184
Reasoning from specific examples.
“I can’t understand anything in general unless I’m carrying along in my mind a specific example and watching it go. Some people think in the beginning that I’m kind of slow and I don’t understand the problem because I ask a lot of these ‘dumb’ questions: ‘Is a cathode plus or minus? Is an anion this way, or that way?’
“But later, when the guy’s in the middle of a bunch of equations, he’ll say something and I’ll say, ‘Wait a minute! There’s an error. That can’t be right!’
“The guy looks at his equations, and sure enough, after a while, he finds the mistake and wonders, ‘How the hell did this guy, who hardly understood at the beginning, find that mistake in the mess of all these equations?’
He thinks I’m following the steps mathematically, but that’s not what I’m doing. I have the specific, physical example of what he’s try/258/ing to analyze, and I know from instinct and experience the properties of the thing. So when the equation says it should behave so-and-so, and I know that’s the wrong way around, I jump up and say, ‘Wait! There’s a mistake!’” Pp. 257-258.
Clarity.
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photo courtesy of nobelprize.org |
“What, I wonder, was the origin of the philosophically self-destructive belief that obscurity makes a prima-facie case for profundity?—the origin, I mean, of the comically fallacious syllogism that runs Profound reasoning is difficult to understand; this work is difficult to understand; therefore this work is profound.” P. 21.
“In all territories of thought which science or philosophy can lay claim to, . . . no one who has something original or important to say will willingly run the risk of being misunderstood; people who write obscurely are either unskilled in writing or up to mischief.” P. 52
Scientific thought.
“Scientific reasoning is an exploratory dialog that can always be resolved into two voices or two episodes of thought, imaginative and critical, which alternate and interact. In the imaginative episode we form an opinion, take a view, make an informed guess, which may explain the phenomena under investigation. The generative act is the formation of a hypothesis. . . . The process by which we come to formulate a hypothesis is not illogical but non-logical, that is, outside logic. But once we have formed an opinion we can expose it to criticism, usually by experimentation; this episode lies within and makes use of logic, for it is an empirical testing of the logical consequences of our beliefs.”
“Scientists are usually too proud or too shy to speak about creativity and ‘creative imagination’’; they feel it to be incompatible with their conception of themselves as ‘men of facts’ and rigorous inductive judgments. The role of creativity has always been acknowledged by inventors, because inventors are often simple unpretentious people who do not give themselves airs, whose education has not been dignified by courses on scientific method. Inventors speak unaffectedly about brainwaves and inspirations; and what, after all, is a mechanical invention if not a solid hypothesis, the literal embodiment of a belief or opinion of which mechanical working is the test?” P. 108
Breakthroughs.
“All scientists despise the ideology of ‘breakthroughs’—I mean the belief that science proceeds from one revelation to another, each one opening up a new world of understanding and advancing still farther a sharp line of demarcation between what is true and what is false. . . . Everyone actually engaged in scientific research knows that this way of looking at things is altogether misleading, and that the frontier between understanding and bewilderment is rather like the plasma membrane of a cell as it creeps over its substratum, a pushing forward here, a retraction there—an exploratory probing that will eventually move forward the whole body of the cell.” P. 192.
Administrative burdens.
“Service on committees and other extramural distractions should never be used as an excuse for not doing research, for that is the scientist’s first business. I know no good scientist who makes such excuses --- only bad ones. So great is the counter appeal of laboratory work that the burden of administrative duties upon a scientist is almost always overestimated. P. 56.
What does your daddy do?
“My father took the first steps towards earning a living by becoming the agent in Rio de Janeiro of a British firm manufacturing dental supplies. . . .The most comic moments of my youth and early manhood were when schoolfellows or fellow students at Oxford asked me what my father did and I was able to tell them “He sells false teeth in South America”. It was a joy to see the agonies of embarrassment into which this threw my interlocutors as they struggled to find words to put me at my ease and good-naturedly did their best to relieve me of the burden of shame which they took for granted must weigh upon my every waking moment.” P. 5
