As, if the gout should seize the head,
Doctors pronounce the patient dead;
But if they can, by all their arts,
Eject it to the extremist parts,
They give the sick man joy, and praise
The gout that will prolong his days.
Bec’s Birthday, Jonathan Swift
In 1904, Havelock Ellis proposed a uric acid cycle of British genius. This was an expansion of ideas he had presented in the July 1901 issue of Popular Science Monthly.
The gouty type of British genius, when uric acid is circulating in his blood, Ellis declared, is gloomy and introspective. His mind is abnormally overclouded. But after the uric acid is deposited in his joints, thus giving him gout, he becomes clear headed and vigorous, in an emphatically masculine way.
The ideas are laid fully bare in the 1910 Evolution of Modesty, and appear again in the chapter on periodicity, in the 1933 Psychology of Sex.
There is a poetry to this story. It has a rhythm to it. Ellis says the rhythm is cosmic.
By cosmic, Havelock Ellis means that the earth wobbles about its axis, in a periodic way, bringing about the seasons. And that the seasons bring about fluxuations of uric acid in the blood. The seasonal fluxuations in uric acid correspond with the spring dancings around the Maypole at the high point, and the fall harvest festivals at the low. Dr. Alexander Haig is cited as authority for the fact.
Statistics taken from the maternity hospitals show the results of these seasonal uric acid fluxuations, the high point and the low, nine months later. Conceptions increase for both.
The theory is supported by the seasonal statistics on nocturnal seminal emissions. It is supported by the seasonal statistics on the checking out of fiction by young adults, at the free lending library at Birmingham.
The rhythmic fluxuations in uric acid are like the storms of May and October. They are like the sexual act.
(Queen Victoria had died in January 1901. It is possible that she died in order to spare herself this knowledge of biochemistry.)
So much is explained by the rhythmic cyclings of uric acid, the climaxes and the crashes in the blood. Your average British genius is basically on the point of madness of one type or another, unless he is lucky enough to have the uric acid settle out in his toe.
Alternatively, Queen Victoria might have died, in January 1901, to spare herself the insult of the February 1901 Popular Science Monthly, and the first of the British genius articles by Havelock Ellis.
The introductory article contains ideas about a principle of selection, by which persons of relatively less distinguished ability might be eliminated. Under the principle, the hereditary royalty would be eliminated all together.
Ellis only means to explain why he had not included, say, Victoria, Empress of India, in a study of British achievement. But the language sure sounds like a combination of eugenics and regicide at the same time.
In 1904, Dr. Alexander Haig published his epitome on uric acid. Uric acid explains so much. Most of what we call “disease” is really uric acid food poisoning. The book contains a strong advocacy for the empirical and experimental approach on matters of health, an account of how he had solved his headaches, and recommendations on frequency of masturbation.
Haig’s cycle of uric acid and mood goes in contrary motion to what Ellis proposed: high blood levels of uric acid are associated with the overstimulated high points, not the gloomy and introspective lows.
In 1905, Dr. Lewellys F. Barker published a counter-epitome to Haig. Uric acid has not one epitome — a height or perfection of what might be done with the subject — but two.
Barker represented the medical establishment. He was head of the A.M.A. His philosophy of science was not so much experimentalist or empirical, as that the experiments should not be conducted by quacks and cranks. His primary take on the medical importance of uric acid was that there should not be so many cures for its various purported ills being sold in advertisements at the backs of magazines.
Barker sharply pointed to the failure to replicate Haig’s finding that the feeding of uric acid to a human would result in a quick excretion of uric acid. Everyone but Haig found that this would result in an excretion of urea, in accord with the 1850s elucidation of the likely degradation path.
Starting in 1908, though, there was a general sense of embarrassment in the medical establishment. Dr. Alexander Haig, on uric acid and its path straight through humans, had been correct. New research from Germany backed him up.
Uricase — an enzyme breaking down uric acid — seemed to be a late evolutionary development, they now thought. It had been acquired only by the mammals, but was not present in humans. Birds, reptiles, and in fact all life outside the mammals lacked it. From a sense of caution, the findings were carefully replicated. But they were still not correct.
By 1929, the new methods from Germany, which had discredited the earlier methods, were discredited themselves. And a mistake deriving from a mistake in the still newer methods, which hadn’t been discredited yet, now led Joseph Needham astray.
A paper had said that birds had active uricase, but only for a time in the shell. Needham made an epic poetry to explain this result, about uric acid and the rise of creatures from the sea.
Aquatic creatures have uricase, and excrete urea and ammonia. The reptiles, no longer needing it, had left their uricase behind when they crawled out of the sea. Mammals had gotten their uricase back, because they are formed in an artificial sea within. And chick embryos count as sea creatures, but only for a short time, because they are recapitulating to the state of a previous ancestor at that point.
This might be poetry concerning uric acid. But it is not very true.
Havelock Ellis was ahead of his time about homosexuality. His ideas about the effects of uric acid in the blood were a bit overwrought, and his racialist and eugenic ideas badly wrong.
Alexander Haig was wrong about uric acid being the cause of most every chronic disease imaginable. He was right about humans lacking the ability to break it down in the blood.
Lewellys Barker was right that you should not be buying medical cures from advertisements in the backs of magazines. He was wrong that humans, fed uric acid, would excrete urea like a bat.
Joseph Needham was wrong about chick embryos being able to break down uric acid, and thus his elaborate story to explain it. Ideas about chemical embryology, however, a synthesis of molecular and developmental biology, were in some ways ahead of their time.
We are beginning to know something of its significance, though far less, it must be admitted, than many people imagine.
Truth and Poetry Concerning Uric Acid, Lewellys F. Barker
Uric acid is a purine, which is a particular double ring structure with four nitrogens. It is a breakdown product of both adenine and guanine, the two purine nucleotides. We are in a neighborhood of significant biochemistry here.
Uricase is found in nearly all organisms. It oxidizes uric acid to 5-hydroxyisourate, which is unstable and quickly degrades to allantoin. From allantoin, a form of urea, there are two more catalyzed steps to urea itself.
Humans lack the ability to oxidize uric acid, however. All the apes do. The ability is also lacking in birds (if they exist), some reptiles (they do not), and some new world monkeys.
Our gene for the uricase protein is a pseudogene. It is there, but completely wrecked. Uricase activity has been generally declining in the primates, across some 50 million years. With much reduced strength of uricase activity in the great ape-gibbon last common ancestor, different nonsense mutations were fixed, making the gene into a pseudogene in both lines. In the great apes, with the pseudogene entirely free of selective constraint, further nonsense mutations piled up.
High levels of uric acid can cause gout, a painful inflammatory arthritis, when needles of uric acid crystallize out in joints and soft tissues. Relations to cardiovascular disease, obesity, and diabetes are being investigated. It also, though, functions as an anti-oxidant. We are in a neighborhood of significant disease here as well.
In 1962, James Neel said that diabetes, the high frequency of a harmful disease with a strong genetic component, presents an enigma to the population geneticist. He proposed the thrifty gene hypothesis to explain it. A predisposition to diabetes might have been anciently advantageous, but detrimental in the modern world. Loss of uricase is sometimes discussed in thrifty gene terms, for the proposed connection to obesity.
The combination of fast gene sequencing, statistical techniques for inferring ancestral genes, and fast gene synthesis now allows the recreation of ancestral proteins. The story given above, of how humans came to lose their uricase, comes from the use of this technique.
We are in the neighborhood of some significant evolutionary theory.
In 1955, Egon Orowan took a shot at the big time in evolutionary biology. His letter to Nature was titled “the Origin of Man”. This is a decidedly presumptuous title on a presumptuous subject, for the first publication of a metallurgist and physicist on biology.
In the illustration of some purines above, #8 is uric acid, and #7 is caffeine. I suspect that Orowan got the idea for his paper, which explains the origin of human intelligence, while sipping his morning coffee.
The Darwin–Mendel–De Vries theory of evolution provides a general framework for understanding, Orowan said, but it leaves open crucial questions of detail. The particular crucial question of detail at issue was, why do humans and the higher apes so strikingly exceed other animals in intellectual development? Did it come about as a gradualism, or as a saltation?
The paper got a response from J.B.S. Haldane, cofounder of the field of population genetics, printed in the next issue. I suspect that when Haldane read Orowan’s opening, he spurted out his afternoon tea.
From the naming of Mendel and Hugo De Vries, we can see that Orowan was a Mendelian-Mutationist. And from his identifying himself in this way, before posing a gradualism or saltation question, we can guess that he is going to say saltation.
The higher apes had become so smart in a mutational saltation, Egon Orowan proposed. We had suddenly lost our ability to oxidize uric acid, and it had thus suddenly coursed through our brains, like so much stimulating caffeine.
Unless you are of a school of thought that strongly downplays the creative role of mutation, it is an appealing but poetic tale.
Thesis: Species descend from other species by insensibly fine gradations, with change driven by natural selection (Darwin).
Antithesis: Darwinian notions of blended inheritance do not work (Jenkin). Some inheritance, at least, is particulate, and works according to mathematical rules (Mendel). The details of the mutation of a fruit fly eye, from red to white, demonstrate a particulate inheritance mechanism of genes located in specific sites on chromosomes (Morgan). Mutation can be a creative force in evolution.
Synthesis: Gradualist Darwinian natural selection and particulate Mendelian inheritance can be mathematically reconciled (Fisher). Evolution should be conceived of as natural selection operating on a population, by shifting the gene frequencies of true breeding types. The creative role of mutation should be strongly downplayed.
We might not be hearing the Hegel in it, when we encounter the phrase “Modern Synthesis” today.
In the 1932 book Causes of Evolution, a key text of the Modern Synthesis, J.B.S. Haldane had cited the ability of most monkeys to break down uric acid, and the absence of the ability in humans and apes, as evidence of the close relation of apes and humans.
Of late years several new branches of comparative biology have been of value in working out relationships. For example, the majority of mammals are capable of oxidising uric acid to a more soluble substance, allantoin. Man is not; hence he is liable to gout. Most of the monkeys can oxidise uric acid. Our inability is shared by the tailless apes such as the gorilla and the chimpanzee. This fact certainly adds to the improbability of the view held in some quarters that man and the tailless apes sprang separately from tailed stock.
The Causes of Evolution, J.B.S. Haldane
He had taken up the battle for neo-Darwinism, against mutationism, Lamarckism, orthogenics, and such.
But I venture to hope that certain arguments in the body of the book (in particular that which purports to prove that mutation, Lamarckian transformation, and so on, cannot prevail against natural selection of even moderate intensity) will not be rejected unless a fallacy is discovered in the mathematical reasoning on which they rest.
He had stated that if he were to look for saltational change, however, he would be most inclined to look for it in the origin of human mental activity.
It is conceivable, though to my mind unlikely, that there was a sharp break at some point in human evolution at which a new type of mental activity suddenly became possible. But there is a vastly greater probability of finding evidence of such a discontinuity in individual than in racial history. I do not think the likelihood very great, but if I believed in such radical changes, that is where I should be inclined to look for them.
And as a minor aside, he had given as an example of a subtle adaptation, Joseph Needham’s recent epic poem concerning uric acid, creatures crawling out of the sea, and the temporary ability of the chicken in its egg.
Later on we find subtler adaptations, for example, … the relation shown by Needham (1929) between the nitrogenous end-products of animal metabolism and the capacity of the embryo for getting rid of them.
The book is not an argument for the existence of evolution. It is an argument about the cause of it. In 1932, not all evolutionists would have believed in the sufficiency or primacy of natural selection as the driver of evolutionary change.
Nowadays a certain number of believers in evolution do not regard natural selection as a cause of it.
By 1955, when Haldane spit out his tea at the appearance in Nature of a Mendelian-Mutationist speculation, coming from a department of mechanical engineering, under the title “Origin of Man,” this would not have been nearly so true.
Haldane’s counter-speculation was published in the next issue. It was the same poem concerning uric acid as Orowan’s, except rewritten to a slower pace. A gradualist Mendelian-Selectionist mechanism for the self-caffeinated origin of our intelligence, was substituted for the saltational Mendelian-Mutationist one.
Four years later, in Science, an n = 817 study of army recruits found a small but significant correlation between serum uric acid levels and scores on an intelligence battery. The paper cites Orowan. It set off a wholesale quantity of new papers on the nearly fossilized idea of linking uric acid and intelligence or achievement.
In 1963, in JAMA, the journal of the American Medical Association, where Lewellys F. Barker had once written editorials warning against buying stuff concerning uric acid sold in magazines, James Dunn, George Brooks, and Judith Mausner wrote of a possible social class gradient in uric acid, with executives having higher levels than tradesmen.
In 1966, in JAMA, George Brooks and Ernst Mueller found serum uric acid levels correlated with the drive, achievement, and leadership of n = 51 professors at the University of Michigan. “The tendency to gout is a tendency to the executive suite”, they said.
By 1969, JAMA was apparently publishing editorials, under the title “Uric Acid and the Psyche," decrying the lack of testing of kindergartners for the level of uric acid coursing through their heads. This seems to be the peak delivery of fossilized bird guano coming from the American Medical Association, at least concerning uric acid.
Over at the British Medical Association, in a review of studies with n = 910, n = 321, and n = 1213, Roy Acheson saw no special relation between the uric acid level in a person’s blood, and their social class.
And in Nature, in 1970, Peter Proctor pointed out that a high level of uric acid also happens to course through the brains of Dalmatian dogs. But that it does not seem to have done anything special for their intelligence, drive, achievement, or leadership, or to have given them any particular tendency to the executive suite.
In 1865, Charles Darwin wrote to Joseph Hooker, saying that all the doctors thought he had a case of suppressed gout.
“What the devil is this suppressed gout?”, Hooker wrote back. “If it is suppressed how do they know it is gout? If it is apparent, why the devil do they call it suppressed?"”
Uric acid is a powerful anti-oxidant. In the 1970 paper in Nature, Peter Proctor had proposed that the uricase mutation replaces anti-oxidant activity lost when primates lost the ability to synthesize ascorbic acid.
In 1981, Bruce Ames and Richard Cathcart extended the idea to propose that the anti-oxidant effects of uric acid make humans live longer.
Dalmatian dogs happen to have high levels of uric acid coursing though their bodies, however. And it does not seem to have done anything special for their longevity.
In 1828, Friedrich Wöhler had accidentally synthesized urea. This was the beginning of organic chemistry. It is of perhaps even greater philosophical import than the time, in 1859, when Louis Pasteur had demonstrated that flies do not spontaneously generate, but must come from other flies.
Wöhler had shown that the chemicals of life can be created from chemicals of the ordinary sort, and that there is nothing special in them.
The two ideas are in some tension. Life now only comes from other life. But humans can create the chemical constituents of it.
Joseph Needham was a Christian Marxist Sinophile. J.B.S. Haldane an anti-Christian Marxist Indophile. Both were attempting an anti-reductionist molecular biology, a contradiction if there ever was one. They were trying to get at this tension.
In Needham’s 1931Chemical Embryology, a synthesis of holistic embryology and reductive biochemistry, the story concerning uric acid, the chick in the egg, and recapitulation theory is on page 1638 of volume III.
There is some irony to urea being the first synthesized organic chemical as well. As mentioned above, I believe, humans are somewhat exceptional in lacking the ability to produce urea organically, from uric acid. But they are entirely exceptional in having created it in a lab.