The Double Helix

Biologist James Dewey Watson, co-discoverer of the double helix structure of DNA (with Francis Crick) and co-winner of the 1962 Nobel Prize for Physiology or Medicine, was born on this day in 1928 in Chicago, Illinois.

Watson grew up in an intellectually curious household and was enough of a brainpower show-off as a youngster to be featured on the Quiz Kids NBC radio show. He studied zoology at Chicago but formed an obsession with genetics, overcoming his fear of organic chemistry long enough to get his doctorate at Indiana University in 1950 under Hermann Muller studying bacteriophages -- viruses which multiply inside bacteria. He went to Copenhagen on a fellowship, and in 1951 attended a lecture in Naples by Maurice Wilkins in which Wilkins described his use of X-ray crystallography in studying DNA.

Armed with his insights on bacteriophages and, from Wilkins, the revelation that genes could crystallize, Watson joined the Cavendish Lab at Cambridge, where he met physicist Francis Crick. Watson was just 23 and Crick was 35, but Watson quickly earned Crick's respect as an uncompromising investigator with skills which complemented his own. Working together, they anonymously entered the feverish international race to discover the structure of DNA which captivated famous scientists such as Linus Pauling. As Crick and Watson built cardboard models of the DNA molecule, it was Watson who first articulated the similarity between the structure of two base pairs of nucleotides within DNA -- the adenine-thymine pair which was held together by two hydrogen bonds, and the guanine-cytosine pair also held together by hydrogen bonds.

Building upon that insight, Crick and Watson developed a model of the structure of DNA which suggested the means of replication which would be an essential process within chromosomal heredity, and they published their model in Nature (Apr. 1953).

Shortly thereafter, Watson left Cambridge for the California Institute of Technology, and later Harvard. In 1965 he published what became the standard work on molecular biology, The Molecular Biology of the Gene, and 3 years later wrote a best-selling memoir of his role in discovering the structure of DNA, The Double Helix. (The story was the basis for a TV movie, in which Jeff Goldblum starred as Watson.)

After running the Cold Spring Harbor Lab on Long Island, where his group discovered ras, the "oncogene" that causes cancer, Watson became the head of the Office of Human Genome Research at the National Institutes of Health, leading the effort to chart all 50-100,000 genes within the human genome. After a stormy tenure there, he resigned in 1992 and was succeeded by Francis Collins.

Giliani the Prosector

Alessandra Giliani died on this day in 1326 at the age of 19.

A student at the University of Bologna, Giliani became an assistant to Mondino dei Luzzi, a leading anatomist, serving as the first woman prosector, or preparer of dissections for anatomical study. She developed a method of draining blood from the corpse and replacing it with quick-hardening colored fluids, thus allowing scientists to see the smallest blood vessels with ease. She may be said to have been the lynchpin of Mondino's success, for he seems to have disappeared from the stage of history after her death.

When Alessandra died (her cause of death is not known), it is said that her boyfriend Otto Agenius (also one of Mondino's assistants) died a short time later from grief.

The Nobel Committee Doesn't Get to Say Who's Best

Physiologist Charles Best was born on this day in 1899 in West Pembroke, Maine.

A former sergeant in the Canadian tank corps during World War I and a University of Toronto grad who paid for his education by playing minor league baseball, Charles Best joined Frederick Banting in John J.R. MacLeod's Toronto physiology lab in 1922. Banting was also a Canadian war veteran: he had joined the Canadian Army medical corps right after medical school and was awarded the Military Cross for gallantry in action in World War I. After the War, Banting began studying the pancreas -- particularly the already-discovered connection between pancreatic activity and diabetes mellitus. At MacLeod's lab, Banting experimented with a new method he had devised of attempting to isolate the pancreatic hormone that regulates blood sugar. Best became his chief assistant.

MacLeod was skeptical; but while MacLeod was away on vacation, Banting and Best closed the pancreatic ducts of dogs and mined the islets of Langerhans for an extraction which was free of other pancreatic substances. They then used the substance on diabetic dogs and observed the reduction of their blood sugar. When MacLeod returned, he brought in his chemist James Collip to purify the extractions for human use. Banting, Best and Collip received a patent for the resulting hormone, named insulin by MacLeod, and licensed it for production by Eli Lilley & Co.

Meanwhile, MacLeod and Banting were awarded the Nobel Prize in 1923, but Banting was angry that MacLeod received any credit at all while Best received none, and threatened to refuse the prize. Instead Banting took the prize and divided it with Best, while MacLeod divided his with Collip, before taking his leave of Toronto and returning to Scotland permanently as professor of physiology at Aberdeen. Banting assumed the leadership of Toronto's Banting-Best research department in 1930, and focused his research on cancer and adrenal cortex function.

As leader of the Banting-Best department of medical research after Banting's death, Best went on to discover choline, a vitamin used in treating liver damage, and histaminase, an enzyme used in breaking down histamine, the hormone transmitter which produces the symptoms of allergy; to introduce the use of heparin as an anticoagulant; and to show that zinc could be used to prolong the activity of insulin.

The Fleming Myth

No one can underestimate the value of the antibiotic penicillin once it was unleashed on wartime infections in 1941: it has saved millions of lives, reducing the risk of infection associated with surgery and combating the mortal power of diseases such as pneumonia and meningitis. Alexander Fleming, its discoverer, was awarded the Nobel Prize for Medicine in 1945, and lauded as an instant celebrity, the world’s great genius.

In truth, Fleming was an adequate researcher with good common sense who had gained a solid reputation as a bacteriologist, publishing useful if ordinary journal articles on diseases such as acne and syphilis. In 1921 he studied his own nasal mucus and discovered that it contained lysozyme, an enzyme which ate bacteria without destroying living tissue. The only problem was that it did not seem to kill the bacteria associated with the post-nasal drip itself. Although the substance was later isolated by others and put to good use, Fleming himself let the matter sit.

In 1928, he was working with staphylococcus and noticed that some kind of mold (introduced accidentally while he was away on vacation) was killing off the bacteria in one of his laboratory petri dishes. The mold turned out to be something known as "penicillium," and was being grown for other research purposes on another floor in his building. Fleming named the antibacterial substance "penicillin," performed a few experiments using live animals and published an article on it, but failed to grasp the full importance of it.

In 1935, however, Howard Florey and Ernst Chain read Fleming’s article and for several years tested penicillin in their quest for an effective antibacterial agent. After confirming its power, they put it into mass production. Fleming, meanwhile, had been laboring away in obscurity when news of the great discovery hit the airwaves, and much to the surprise of Florey and Chain, paid a call on them in 1940 -- by which time Chain had assumed that Fleming was probably deceased. Chain did not hear from Fleming again until 2 years later, when Fleming wrote to him requesting some penicillin for a friend suffering from meningitis, along with instructions for the proper use of the antibiotic.

Enthusiastic reporters eventually seized on the story of the unknown, unpretentious Scot and, coupled with the mass adulation that the effectiveness of penicillin itself inspired, turned Fleming into a superstar. Florey and Chain shared in the Nobel Prize, but not in the celebrity. For his own part, Fleming was painfully aware of the exaggerated claims made for him in the press, and kept a scrapbook which he sardonically entitled "The Fleming Myth."

Sir Alexander Fleming, who was knighted in 1944, was born on this day in 1881 in Lochfield, Ayrshire, Scotland, and died on March 11, 1955.

The Secret of Life

Physicist and molecular biologist Francis Crick, co-discoverer of the double helix structure of DNA with James Dewey Watson (1953) and co-winner of the 1962 Nobel Prize for Physiology or Medicine, was born on this day in 1916 near Northampton, England.

The son of a shoe salesman, Francis Crick studied physics at University College London, and during World War II designed non-contact "magnetic" mines for the British navy. After the war, influenced by his own long-held atheism and by Schrodinger's What is Life?, Crick decided to immerse himself in the "living-nonliving borderline" of biology to study the basis of life, taking up the call of Linus Pauling, who just after the war had boasted about the prospective role of structural chemistry in understanding the biological microworld.

Crick went to Cambridge and eventually joined Max Perutz's X-ray crystallography lab which was then investigating the structure of proteins. Although it was thought that the genetic material in a cell was a protein and that a polymer, deoxyribonucleic acid (DNA), might be a factor in the manufacture of proteins, little insight had been gained into why this polymer was particularly suited to replication.

Meanwhile, in 1951, young Jim Watson, an American biochemist, arrived at Perutz's lab, and the two became fast friends and office-mates; apart from both having read Schrodinger, they shared a ruthless, somewhat arrogant sense of the same mission -- figuring out the relationship between the structure of DNA and its function in molecular genetics. Relying upon the experimental work of others (including the X-ray photographs of DNA taken by Rosalind Franklin in Maurice Wilkins' lab at University College London), Crick and Watson began to build models of the DNA molecule out of cardboard, wire and beads. On February 21, 1953, Watson noticed the complementary shape of adrene-thymine and guanine-cytosine, the base pairs of proteins underlying DNA, and together Crick and Watson worked out a picture of DNA as a ladder-like double helix, founded upon what was known through experiments, showing two chains of molecules linked by hydrogen bonds.

Watson says Crick went to the Eagle Pub at the end of the day and announced at the top of his lungs that he had discovered the secret of life; Crick's wife said he was always saying things like that, so she didn't pay him any particular attention. Crick and Watson published a short paper on their hypothesis in Nature (Apr. 1953), and in it noted, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
Watson left Cambridge shortly thereafter, but Crick stayed on at Cambridge to become a dominant force in molecular biology, predicting the discovery of transfer-RNA as a mechanism for the manufacture of proteins within a cell and postulating the "central dogma" in molecular genetics (since unraveled by the behavior of certain viruses, but still largely revered as a key principle), that genetic information could only pass one way -- from protein to RNA to DNA. In 1976, Crick moved to the Salk Institute for Biological Studies in La Jolla, California to study consciousness and the brain. In The Astonishing Hypothesis (1994), his materialist habits of mind revealed themselves again as he theorized an electrophysical basis of human consciousness. He died July 29, 2004 in San Diego, California.

The Origin of Darwin

"More than any other modern thinker -- even Freud and Marx -- this affable old-world naturalist from the minor Shropshire gentry has transformed the way we see ourselves on this planet." -- Desmond & Moore.

A mediocre student at Cambridge; a tentative young adult still in search of a career, somewhat of a disappointment to his prosperous, industrious family; and a devout creationist who occasionally suffered derision for his habit of quoting the Bible as unanswerable authority -- these facts seem to be at odds with the image of Charles Darwin, the most influential thinker of the 19th century, the scary, long-bearded radical who (as his critics, then and now, might say) reached down and plucked the Book of Genesis out of the ground by the roots and planted grasping science in its place.

Born on this day in 1809 in Shrewsbury, England, the grandson of two illustrious men of science and industry, naturalist Erasmus Darwin and pottery magnate Josiah Wedgwood -- the arc of this unpromising man's life, so difficult to calculate at age 22, was ultimately formed by inexhaustible curiosity about the natural environment and its deeper meanings than any desire for influence. As a youth he attended Samuel Butler's Shrewsbury School and did very poorly with the classical curriculum; entered Edinburgh University at age 16 to study medicine (to follow in the footsteps of his father), but couldn't bear to watch surgeries; and enrolled in Christ College, Cambridge at age 19 to study for the clergy, which he did listlessly.

All the while, however, Darwin enthusiastically indulged his interest in nature: at Shrewsbury, he spent much of his time collecting rocks and birds' eggs; at Edinburgh, he fell in with a taxidermist, as well as zoologist Robert Grant, who first exposed him to Lamarck's theory of heredity; and at Cambridge, he collected beetles and went on nature walks with botanist John Stevens Henslow.

Upon graduation, at Henslow's recommendation he was offered the chance to see the world before settling down in some quiet corner of England as a parish parson, and he signed on as an unpaid naturalist on the H.M.S. Beagle, which was set to survey the coast of Tierra del Fuego, Chile and Peru, and the South Sea Islands. His male-ingénue errand was to provide well-bred intellectual companionship to the ship's captain and to make a few notes about local flora and fauna; but the voyage transformed Darwin's image of himself.

He did make copious notes about the geology (heavily influenced by Charles Lyell, whose Principles of Geology he read while sailing), the flora and the fauna, but he also rode with the gauchos across the Pampas; encountered an armed revolt in Montevideo; and waded upstream through thick-jungled river valleys, helping to tow the ship's reconnaissance boats. In the Galapagos Islands, he became particularly interested in the slight variations in bird and tortoise species which seemed peculiarly suited to their distinct habitats from island to island, and made observations of them which would form part of the argument for his theory of evolution 20 years later.

Upon returning to England in 1836, Darwin suddenly had a calling in life; he was quickly accepted into the British scientific fraternity and began to establish his scientific reputation with Journal of Researches into the Geology and Natural History of the Various Countries Visited by H.M.S. Beagle (1839), The Zoology of the Voyage of H.M.S. Beagle (1840) and The Structure and Distribution of Coral Reefs (1842), all accessible and vividly written works of traditional science.

As early as 1838, however, while reading Thomas Malthus, Darwin recalled the birds and tortoises of the Galapagos and conceived the idea of natural selection -- the process by which certain advantageous traits are conserved and multiplied through reproduction which enables the adaptation of an organism to its environment. Through natural selection, Darwin surmised, the evolution of organisms unfolds. He kept silent, however, realizing that the scientific community, let alone the world at large, was not ready to accept a theory of such earthbound determinism; in England and elsewhere during the early 19th century, the hand of God was said to be seen in the spontaneous creation of species variations, and Darwin's theory would be considered blasphemous.

He continued to collect evidence for the theory, however, and drafted some preliminary sketches of it which he shared with his friends, Lyell and the botanist Joseph Dalton Hooker. Despite their urging, he would not publish the theory, until in 1858 when he received a paper from an amateur naturalist, Alfred Russell Wallace, which proposed the same theory which Darwin had been working on for 20 years. After Darwin's precedence was proven, the 2 presented separate papers on the subject before the Linnaean Society, after which Darwin published his classic elaboration on natural selection, The Origin of Species (1859).

The book was an immediate best-seller, and most of the scientific community (with some notable exceptions, such as Louis Agassiz and Darwin's old mentor Henslow) accepted his view; but as Darwin had predicted the orthodox clergy saw the theory as completely inconsistent with Genesis and ridiculed him. Broader-minded clerics, then as now, saw the trace of evolution suggested by Darwin as bold evidence of God's continuing creative presence in the world. Darwin's friend, T.H. Huxley (later known as "Darwin's bulldog") took up the defense, notably chastising the Bishop of Oxford for his narrow-mindedness, saying that he would "rather be related to an ape than to a man of proven ability who used his brains to pervert the truth."

For his own part, Darwin returned to writing and solving the issues at the edge of his theory. In The Variations of Animals and Plants Under Domestication (1868), Darwin advanced the theory of "pangenesis" -- the notion that cells throughout the body contribute instructions to reproductive cells -- to explain the workings of heredity; the theory was later disproven as the work of Gregor Mendel and Thomas Hunt Morgan eventually came to light. His Descent of Man (1871) attempted to apply natural selection to moral and spiritual traits, stimulating the work already begun by sociologist Herbert Spencer and launching a host of imitators noodling on the psychological and political implications of evolutionary theory.

Still a controversial figure at the time of his death on April 19, 1882, 20 members of Parliament nonetheless immediately moved to request that he be buried in a place of honor at Westminster Abbey; his tomb is located just a few paces away from those of Isaac Newton and Michael Faraday. The theory of evolution has had a profound influence on numerous modern scientific disciplines, as well as popular knowledge and political philosophy, and if anything has gained momentum as microbiology and genetics have provided it with more complex underpinnings.

Miss Sherrington

Sir Charles Sherrington, physiologist and co-winner of the 1932 Nobel Prize for Physiology or Medicine (with Edgar Adrian) for his description of the human nervous system as an integrated, functioning unit, was born on this day in 1857 in Islington, London, England.

Sherrington received 134 nominations for the Nobel Prize, beginning in 1902. Better late than never. He also published a book of verse, The Assaying of Brabantius (1925), which caused one reviewer to hope that "Miss Sherrington" would publish more poetry in the future.