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| From: Church & State: Articles |
| Date: January, 2021 |
| By: John Martin |
What is Life? |
In 1940 De Valera invited Erwin Schrodinger to head the Dublin Institute of Advanced Studies. The Taoiseach was even prepared to accommodate the great scientist’s unconventional domestic arrangements so as to secure his residency in Ireland. This does not accord with the present-day image of De Valera as being narrow and illiberal. But his initiative did not go unnoticed by an institution that pretends to be “liberalâ€. The Irish Times noted that, in a lecture entitled “Science and Humanismâ€, Schrodinger suggested that there was no logical basis for the belief of a first cause or divine creator. Also, the Celtic scholar, T.F. O’Rahilly, outlined his theory that there were two different Christian missionaries to Ireland—Palladius and Patrick—who had been confused historically as one figure, St Patrick. It might be thought that this was an interesting intellectual development in the life of the country. But the 'paper of record' would have none of it. It deployed its court jester, Myles na gCopaleen (Brian O’Nolan), to sneer. He commented that— "the fruit of this Institute, therefore, has been an effort to show that 'there are two Saint Patricks and no God’. There was a risk, he alleged, that the Institute would ‘make us the laughing stock of the world’…" (note 1). But the ruminations of The Irish Times did not disturb the Institute unduly. It had more pressing matters to attend to. In February 1943 Schrodinger gave a ground-breaking series of lectures. The following year the Institute published a book based on those lectures entitled: “What is Life?†Schrodinger wanted to know what life was made of and how it worked. He realised that this was not an easy question to answer, but suggested that it could be solved if scientists from diverse disciplines could work together. He noted that even the most distinguished scientists had very limited knowledge of developments outside their own area. With that in mind the winner of the Nobel prize for physics in 1933 felt it necessary to apologise in advance for his foray into this new unfamiliar subject which became known as molecular biology. But what could a physicist like Schrodinger contribute? At the beginning of the book he suggests that some of the tenets of Physics and particularly quantum theory—with which he will always be associated—may not be applicable to the new science. He observed that, when dealing with small numbers of atoms, there is disorder or “entropyâ€. Furthermore: “Only in the co-operation of an enormously large number of atoms do statistical laws begin to operate and control the behaviour of these assemblies with an accuracy increasing as the number of atoms involved increases.†But: “How can we, from the point of view of statistical physics, reconcile the facts that the gene structure seems to involve only a comparatively small number of atoms (of the order of 1000 and possibly much less), and that nevertheless it displays a most regular and lawful activity—with a durability of permanence that borders on the miraculousâ€. So, the laws of physics don’t appear to apply to living organisms. A small number of atoms in the chromosomes of a living organism can produce order and direct its growth. However, as Schrodinger examined the subject more closely, he noted that quantum theory may after all be relevant to living organisms. Change, variation and growth can occur through quantum leaps, it is not necessarily continuous. Gregor Mendel noted that heriditary units were discrete. In mathematical terms they could be thought of as whole numbers, rather than fractions. As well as acknowledging the contribution of Gregor Mendel, Schrodinger discussed the work of the German Scientist Max Delbruck. While experiments on viruses and bacteria have confirmed Darwin’s theory of evolution by natural selection, Delbruck was able to prove that, contrary to Darwin’s theory, random variations did not produce change in a species. It was necessary for a mutation, which might be in two or three out of tens of thousands of the species. This accorded with Schrodinger’s quantum theory. Transitions from one state to another often involved a “quantum jumpâ€. Furthermore: “... a number of atomic nuclei, including their body guards of electrons, when they find themselves close to each other, forming a ‘system’, are unable by their nature to adopt any arbitrary configuration we might think of. Their very nature leaves them only a very numerous but discrete series of ‘states’ to choose from.†These ideas are not unlike Marx’s principles of dialectical materialism, where the quantum jump is analogous to a qualitative or revolutionary change. Also, the fact that there is a “discrete series of states to choose from†means that the number of choices is finite. This enables the change to be codified or programmed: something that would not be possible if the choices were on a continuum with an infinite number of possibilities. Schrodinger thought the chromosome structures were: “...law-code and executive power—or, to use another simile, they are architect’s plan and builder’s craft—in one†So, in summary, the task that Schrodinger had set for his fellow scientists was to decipher the code of life. Unfortunately, the Soviet Union ruled itself out of the race. Under the direction of Trofim Lysenko it rejected Mendelian genetics, which was the starting point for any investigation of the code of life. This resulted in some communists in the west leaving their party. One such person was the distinguished French scientist, Jacques Monod. Interestingly, he didn’t blame it on Stalin. He thought it was all down to the influence of Rousseau on socialism. The idea that man was good and society was bad seemed to contradict the emerging scientific evidence that what defines man as a species, and different men as individuals, is very largely biological rather than social. By contrast, in the same year as Schrodinger’s book was published, there was a scientific breakthrough. But, as has often been the case in this field, the significance was not appreciated until many years later. In 1944 the American scientists Oswald Avery, Maclyn McCarty and Colin MacLeod revisited a famous experiment performed by the British scientist Frederick Griffith in 1928. In the original experiment Griffith injected a benign strain of bacteria into mice. The mice survived. He then injected a lethal strain of the bacteria into the mice. Not surprisingly they all died. Then he killed the lethal strain of bacteria by heating it up. When he injected this dead bacteria into some more mice they survived. In the final part of his experiment he mixed the dead (formerly lethal) bacteria with the live benign bacteria. After injecting the mice with this mixture the mice died. Some material substance in the dead bacteria had 'transformed' the formerly benign bacteria into a lethal strain. But what? Griffith didn’t know. In 1944 Avery et al succeeded in splitting up the dead bacteria into its component parts. They could therefore identify which part was causing the transformation. It was found that when deoxyribonucleic acid (better known as DNA) from the dead bacteria was added to the benign bacteria it killed the mice. No other part of the dead bacteria did this. So, it appeared that DNA was the repository of the code that determined the character of a living organism. But the scientific community did not believe the results. They thought that the DNA must have been contaminated. Also, the lead scientist, Oswald Avery, was himself very tentative about his own experiment. No one believed that DNA could carry the code. It was thought that it was a 'stupid' molecule whose only function within the chromosome was structural. It wasn’t until 1952 that the issue was resolved. Alfred Hershey and Martha Chase, in a very different experiment using bacteriophage (viruses that attack bacteria), finally convinced the scientific community of the importance of DNA. This provided a new focus for Schrodinger’s question. Scientific resources were redirected towards understanding DNA. Horace Judson in his classic work, The Eighth Day Of Creation, describes the race to define the structure of DNA very well. The story is quite amusing because the reader can see highly intelligent scientists oblivious to the pitfalls that Schrodinger had anticipated. Some scientists that were highly knowledgeable in one area were ignorant of the basics in another area relevant to the question. Other scientists who had designed ingenious experiments were unable to interpret the results. In at least one case researchers in one part of a building were unaware of results obtained in another part of a building that would have cleared an impasse . . . and so on. The winners of the race were the American scientist, James Watson, and the British scientist, Francis Crick, working from Cambridge University. There is some doubt as to whether they deserved the accolade. They didn’t conduct any experiments of their own, but relied on the research of others. A key event on the road to discovering the structure of DNA was a visit to Cambridge from the Austrian scientist, Erwin Chargaff. Chargaff knew that all living things had four chemicals: Adenine, Thymine, Guanine and Cytosine. The proportion of these chemicals varied from species to species but there “appeared†to be a one to one relationship between Adenine and Thymine, as well between Guanine and Cytosine, in all species from the e-coli to the elephant. Unbelievably, before he made his visit, Crick and Watson didn’t seem to be aware of this. Chargaff’s account of this momentous meeting with two of the most celebrated scientists of the twentieth century is highly entertaining: “I seemed to have missed the shiver of recognition of a historical moment; a change in the rhythm of the heartbeats of biology... The impression: one (Crick), thirty five years old; the looks of a fading racing tout, something out of Hogarth (“The Rake’s Progressâ€); Cruikshank, Daumier; an incessant falsetto, with occasional nuggets glittering in the turbid stream of prattle. The other (Watson), quite undeveloped at twenty-three, a grin, more sly than sheepish; saying little, nothing of consequence... I told them all I knew. If they had heard before about the pairing rule, they concealed it. But as they did not seem to know much about anything, I was not unduly surprised†(note 2). And: “They impressed me by their extreme ignorance. Watson made that clear! I never met two men who knew so little—and aspired to so much. They were going about it in a roguish, jocular manner, very bright young people who didn’t know much. …It struck me as a typically British intellectual atmosphere, little work and lots of talk... Watson is now an able, effective administrator of science. In that respect he represents the American entrepreneurial type very well. Crick is something else—brighter than Watson, but he talks a lot, and so he talks a lot nonsense.†“...if in our day such pygmies throw such giant shadows, it only shows how late in the day it has become`' (note 3). All very well! But Crick and Watson won the prize. Perhaps there is something to be said for talking! And they were not the only ones who had forgotten about the Chargaff pairs. The American double Nobel prize winner, Linus Pauling, also neglected to consider them and, as a consequence, his proposed structure for the DNA molecule collapsed in ignominy. The problem was that Chargaff, like Avery before him, was too tentative. He didn’t actually say that the relationship was one to one, but thought they were approximately one to one. In the history of science it would be difficult to find anyone more diffident than the Augustinian friar, Gregor Mendel. He was of such a nervous disposition that he was incapable of sitting a science exam. And yet, unlike the urbane and sophisticated Chargaff, he was capable of making that final inductive leap and develop the necessary implications. In Mendel’s experiments he “knew†that the ratio was three: not “approximately†three. In the case of Chargaff, it was left to Watson and Crick to make that final inductive leap for him. The ratio was one, not approximately one. Perhaps that was the source of the anger, or maybe the Austrian recognised that the intellectual centre of science had moved from Central Europe to the Anglo Saxon world—a long process which began with the emigration of the best scientific minds to America and the UK in the 1930s. Chargaff himself was working for an American university. What became known as the Chargaff rule was the final piece in the jigsaw. In 1953 Crick and Watson unveiled the “double helical†structure of the DNA molecule. In plain man’s terms a double helix is a twisted or spiral ladder. The scientific community was amazed at how simple the structure was. The outer rails of the ladder consist of a regular pattern of phosphates and sugars. The rungs or what scientists call “bases†consist of the four chemicals Chargaff identified: Adenine, Thymine, Guanine and Cytosine. Adenine always matches with Thymine and Guanine always matches with Cytosine. The sequence of bases gives the specificity or character of genes. That is all there is to Mendel’s “hereditary factorâ€. But, of course, even a simple life form like Covid 19 has about 30,000 bases. Legend has it that, following their discovery, Francis Crick announced at a cocktail party that he had discovered the “secret of lifeâ€: it is 20 angstroms wide; there are 3.4 angstroms between the bases and 34 angstroms between each turn (1 angstrom equals one ten billionths of a metre). Well, if Schrodinger had been present at the party, he would have said: “My dear Francis. You have done very well but you have not quite won the pretty girl. All you have done is describe the structure. You don’t know how DNA relates to the rest of the chromosome and you have not at all discovered the code!†But it must be admitted that knowing the structure gave clues to the outstanding questions. Very soon afterwards scientists figured out how DNA replicated itself. The twisted ladder first straightened itself out and then spilt vertically in two. Each section is used as a template to form a new section to make the DNA molecule whole again; always obeying Chargaff’s rule. But from then on progress seemed to stall. Francis Crick with the status he garnered from establishing the structure of DNA became an unofficial chairman of a scientific club dedicated to finding the code. It is interesting to note the approach adopted by this group. It took an attitude of scepticism towards all experimental data unless it fitted into a coherent theory. Its reasoning was that measurements at a molecular level could not be relied upon. This seemed to be at variance with the scientific method. A second element to their approach was what became known as the “central dogmaâ€. This was the view that DNA creates Ribonucleic acid (RNA), which in turn creates the proteins which are the agents of the life processes. The members of the club cheerfully admitted that the evidence for this was quite flimsy, which was why they called it a dogma. Their justification for it was that, since they were operating in a vast desert, they needed something to hold on to in order to direct their research which, even if it was a mirage, was better than nothing. In the early period a lot of the effort of the group was directed towards finding the code. When nature is considered as a whole there are very few variables which can nevertheless be arranged into an infinite number of combinations. For example, there are only 94 natural elements. And even these can be reduced to three items: protons, electrons and neutrons. So, while there appears to be a qualitative difference between copper and gold, the difference is in fact quantitative. Copper has 29 protons (and electrons) while gold has 79 protons. As regards living beings, we have already seen that, within the DNA molecule, there are only four chemicals that give specificity or determine the character of the living organism. One of the members of Francis Crick’s club, the Russian physicist George Gamow, noticed that there are only twenty amino acids which are the building blocks of proteins in living organisms. This reduced the coding to a very simple mathematical problem. If there are only four variables (Adenine, Thymine, Guanine and Cytosine) that select one out of twenty amino acids, how big must the code be? Well the code cannot be just one character long because with four variables there would be only four possible combinations. If the code had two characters, there would be sixteen possible combinations (4x4) which would still not be enough. So Gamow speculated that the code must consist of three characters which could have sixty four combinations (4 x 4 x 4)—more than enough for the twenty amino acids. This code of three characters was called a “codonâ€. And that was about it. It became a little embarrassing. Every year Francis Crick would stand up in front of prestigious scientific conferences only to express his frustration at the lack of progress being made. When a breakthrough eventually was made, it came from outside the club. At a Conference in Moscow in 1961 an American scientist, Marshall Nirenberg, collaborating with a German scientist Johann Matthae, announced that they had managed to create synthetic RNA and were using it to decipher the DNA code. By the mid 1960s all the code had been deciphered. It turned out that George Gamow was right all along about the codons. There are indeed sixty four codes, consisting of three characters. Three of the codes signify a stop sign or end of program; the remainder represent an individual amino acid. But, since there are more codes than amino acids, the same amino acid can have more than one code. And it also emerged that the “central dogma†was substantially correct. In broad brush strokes the DNA splits into two strands. The RNA uses a strand of the DNA as a template to produce code. The RNA—consisting of a single strand of code—enters a structure containing ribosomes. When this apparatus interprets the code, it not only knows what polypeptide chain or protein it is required to produce but also where in the organism that protein is to be dispatched. The secret of life had been revealed. It was a bit late for Erwin Schrodinger who died in 1961, but it could be said that all the questions that he had asked in his 1944 book have been answered. Of course, the question “what is life†is not just a scientific question; it is also a philosophical one. The present writer doesn’t propose to delve into this aspect. But it is interesting to record what some of the scientists thought they were doing. Francis Crick defined molecular biology as the “borderline between living and dead thingsâ€. When Max Delbruck won his Nobel prize in 1969 he was delighted to learn that Samuel Beckett had won the prize for literature. Perhaps he thought they were at the same game—stripping life back to its essentials. Delbruck was looking forward to meeting his hero at the ceremony. But in a case of life imitating art the scientist was left waiting. The writer failed to show up! Here and there, as the spectre of genetic engineering loomed, doubts began to creep in. Maurice Wilkins, who shared the Nobel prize with Watson and Crick in 1962, liked to quote the Austrian writer Robert Musil: “…knowledge is an attitude, a passion. Actually an illicit attitude. For the compulsion to know is a mania: it produces a character out of balance. It is not at all true that the scientist goes after truth. It goes after him. It is something he suffers from.†And, of course Chargaff remained sceptical: “I am against the over-explanation of science, because I think it impedes the flow of scientific imagination and associations. My main objection to molecular biology is that by its claim to be able to explain everything, it actually impedes the flow of free scientific explanation. But there is not a scientist I have met who would share my opinion†(note 3). Finally, and to return to the beginning of this article, it need hardly be said that Erwin Schrodinger was not a “laughing stockâ€. Au contraire! There can hardly be a scientist in the field of molecular biology who had not read “What is Life?â€. James Watson often said that the book had a “decisive†influence on him. The physicist Maurice Wilkins said the book made him “interested in putting physics to work on the complexities of living processesâ€. Francis Crick thought the book “suggested that biological problems could be thought about, in physical terms—and thus it gave the impression that exciting things in this field were not far offâ€. There is no doubt that, during his time in Dublin, Schrodinger made a substantial contribution to molecular biology which is a science whose ramifications continue to extend and whose implications for humanity have yet to be determined. Note 1 P130, The Irish Times: A History, Mark O’Brien, Four Courts Press, 2008). Note 2 P633, The Eighth Day of Creation, Horace Freeland Judson, Cold Spring Harbour Laboratory Press, 2013. Note 3 P120, The Eighth Day of Creation, Horace Freeland Judson, Cold Spring Harbour Laboratory Press, 2013. |