Blogs / The Loom

As a science writer, I often find it sobering to read scientific history. Science works slowly, even though we wish it would work in nanosecond breakthroughs.

In 1913, for example, a Russian scientist named Nikolai Anichkov ran an experiment in which he had egg yolks fed to rabbits. On this cholesterol-heavy diet the rabbits developed atherosclerosis. The more cholesterol the rabbits ate, the bigger the deposits on their blood vessels became. It was a tremendous discovery, considered by some one of the greatest in medical history.

But it did not lead overnight to a treatment for heart disease. In fact, it did not even lead, on its own, to a clear understanding of how cholesterol ends up in the blood vessels. Instead, it focused the attention of later scientists on the question of cholesterol. It took many years for scientists to figure out the steps by which enzymes produce cholesterol molecules. Then scientists began searching for drugs that might interfere with those enzymes.

In 1971, six decades after Anichkov ran his egg-yolk experiments, Akira Endo of Tokyo Noko University and his colleagues, decided to see if microbes made natural cholesterol-fighting compounds (free pdf). They reasoned that such a compound would be a potent weapon against microbial competitors, since cholesterol and related molecules are essential for building cells. In 1973 they found a fungus that blocks a key enzyme in the cholesterol pathway. It took more than another decade before drugs based on Endo’s explorations, known as statins, reached the market. Today drugs like Lipitor are prescribed to millions of people.

If a journalist wrote an article on Anchikov’s intial research, the most accurate headline would have been something like: “RUSSIAN SCIENTIST DISCOVERS LINK BETWEEN MOLECULE AND HEART DISEASE. WILL LEAD TO POWERFUL NEW MEDICINE IN EIGHTY YEARS.”

Of course, it would be a rare journalist who would be able to see eighty years in the future like that. And headlines about events readers won’t be alive to see can seem awfully remote. Anchikov’s discovery did not change the lives of the people who could have read about it at the time. Their grandchildren, yes.

I’ve been thinking about Anchikov recently, after having read a letter to the New England Journal of Medicine. It’s by Joel Hirschhorn of Harvard, on the subject of genomes.

A decade ago a complete sequence of the human genome was still a dream, although a dream close to becoming real. In a typical article from 1999, a reporter wrote that “scientists hope to treat diseases in much the same way that software engineers fix faulty computer programs, by isolating flaws in the code.” Once we could read the entire human genome, the article promised, nothing would be the same: “By identifying the genetic roots of illnesses like cancer and heart disease, some experts say, the science of the genome, or genomics, may make it possible for a child born today to live to 150–or, some say, much longer.”

What a difference a decade makes. Scientists have been finding many genetic markers for common diseases like heart disease and diabetes, but they’re not pointing the way to obvious treatments. The falling cost of DNA is letting scientists sequence genomes left and right–not just people’s genomes, but the genomes of their cancer cells and their microbes. And for now, scientists are drowning in data rather than plucking out new cures.

Hirschhorn wants the growing number of skeptics to keep history in mind. In his NEJM letter he writes,

New biologic insights do not guarantee a rapid translation into clinical practice; the latter will require great effort by basic, translational, and clinical researchers. The difficulty in translation is not unique to genetic discoveries: nearly a century and three Nobel Prizes separate the determination of the chemical composition of cholesterol from the development of statins. Each discovery of a biologically relevant locus is a potential first step in a translational journey, and some journeys will be shorter than others. With a more complete collection of relevant genes and pathways, we can hope to shorten the interval between biologic knowledge and improved patient care. 

In the next issue of Newsweek, I consider the near-term and the long-term future of genomes. My essay is called “The Gene Puzzle.” Check it out.

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My mother, on whom I depend for all my New Jersey history, passed on a delightful tale of George Washington, Tom Paine, and their passion for chemistry experiments. In early November 1783, Tom Paine paid a visit to George Washington in Rockingham, New Jersey, where Washington was waiting for news of the end of the revolutionary war.  One night Paine and Washington got to talking with two colonels about the will-o-the-wisp, the fiery globe that people sometimes claimed to see floating over marshes.

They came up with two plausible hypotheses. The colonels thought that they were produced from some kind of matter in the marches, such as turpentine. Washington and Paine thought it was a gas.

So the next night, they got in a scow with some soliders and set out on the Millstone River to conduct an experiment. The soliders poked poles into the mud, and Washington and Paine held torches close. They saw bubbles rise, and then a flash of light broke out across the water. Washington and Paine were right. The gas would turn out to be methane, produced by the microbes in the mud.

There will be a reenactment of that presidential hands-on science in celebration of its 225th anniversary on November 5 at dusk on the Millstone River, Rocky Hill, NJ at the junction of Routes 518 and 603. You can watch from the north side of the Rt. 518 Bridge as it crosses the Millstone River.

Before 1833 there were no scientists.

It was in that year that William Whewell, a British philosopher, geologist, and all-around bright bulb, coined the word scientist. His mentor, the poet Samuel Coleridge, thought the English language needed a term for someone who studied the natural world but who did not inhabit the lofty heights of philosophy (like Coleridge).

There are plenty of people who lived before 1833 that most of us would call scientists–Isaac Newton, Antoine Lavoisier, Edmund Halley, Carol Linnaeus to name just a few. But the word would have been meaningless to them. The closest term they might use was “natural philosopher.” Their work and ideas were still deeply rooted in medieval ways of thinking about the world, and about the work they did.

Science did not emerge suddenly in a sudden onslaught of Modern Reason crushing Old Ignorance. Its rise was much slower and much more interesting. One of the most important parts of science as we know it is a way for people to share their observations and experiments. Today peer-reviewed journals are at the core of the scientific process. But until the seventeenth century, nothing like them existed. Natural philosophers generally were more interested in what the ancient Greeks and Romans had to say about medicine, physics, and biology, than what they might observe for themselves. In 1665, a group of natural philosophers in England got together and decided to publish what is arguably the first scientific journal: the Philosophical Transactions of the Royal Society of London.

It’s still going strong today, putting out a lot of important papers. And for the next couple months, the Royal Society is making the entire archive–all the way back to 1665–available for free.

In a press release, the Royal Society pointed to some particularly neat papers, such as Ben Franklin’s 1752 description of flying a kite in a thunderstorm. But I immediately looked up a much older paper about lightning from 1666, entitled “A relation of an accident by thunder and lightning, at Oxford.”

I first came across this paper a couple years ago while working on my book Soul Made Flesh. In the book, I describe how scientists natural philosophers discovered how the brain works in the 1600s. I focus mainly on Thomas Willis, widely considered the first neurologist. Willis did astonishing work, recognizing some of the fundamental features of the brain–that the flesh of the brain itself was the seat of thought, for example, rather than the spaces around it, known as ventricles. Willis published the first accurate pictures of the brain, in the first book about the brain. He argued that melancholy, epilepsy, and nightmares were all chemical disturbances in the brain. He even coined the word neurology.

For all that, however, Willis was still floundering in the dark. He had no idea of how the brain communicated with the rest of the body. He laid out an elaborate theory about how particles (”spirits”) moved around in the brain and then traveled down the nerves. But he had no actual evidence for this idea. And he knew nothing about electricity.

The communication recounts how Willis and his colleagues dissected a man killed by lightning. The bolt had thrown its victim, an Oxford scholar, out of the boat he had been rowing. When the scholar’s body was brought back to town, Thomas Willis came to see it along with his assistant Richard Lower and the mathematician John Wallis, who later wrote the . They picked up the man’s hat and put their fists through the hole the lightning had torn. His doublet had been ripped open and his buttons knocked off. Willis and his friends found spots and streaks across the torso where the skin seemed to be seared and hard, “like Leather burnt with the fire,” Wallis later wrote to the Royal Society.

The following night Willis and company returned, along with a crowd of onlookers, to cut the man open. “The whole Body was, by night, very much swell’d,” Wallis wrote. The stench that rose from the body was unbearable, but they soldiered on because such an opportunity might not come again in their lives. “There appear’d no sign of contusion,” Wallis wrote, “the brain full and in good order; the nerves whole and sound, the vessels of the brain pretty full of blood.” They opened the man’s chest and found that the burns did not reach below the skin. “The Lungs and Heart appear’d all well, and well-colour’d without any disorder,” Wallis wrote. The heavens had struck the man dead, and yet the natural philosophers could find nothing changed inside the body.

It would take Benjamin Franklin and other eighteenth century scientists to begin working out the nature of electricity, and to recognize its role in the nervous system. But I still like to picture Willis puzzling over a cadaver, not realizing that the man had been killed by the same thing that made thought possible.

Here are some other landmark papers you can find in the archives…get them while you can.

The Complementary Structure of Deoxyribonucleic Acid
F.H.C Crick and J.D Watson – 1954

On the Hoyle-Narlikar Theory of Gravitation
S. W. Hawking – 1965

An Account of an Experiment Made by Mr. Hook, of Preserving Animals Alive by Blowing through Their Lungs with Bellows
Robert Hooke – 1667

An Account of a Very Odd Monstrous Calf
Robert Boyle – 1665

Observables upon a Monstrous Head
Robert Boyle – 1666

Account of a very remarkable young musician (Mozart)
Daines Barrington – 1770

Alexander Fleming (Paper describing early stages of penicillin discoveries) – 1922

Arthur Eddington’s solar eclipse observations, confirming Einstein’s general theory of relativity (Phil Trans 1919)

John Noble Wilford has a long, interesting article in today’s New York Times on the rehabilitation of the alchemist. Once the icon of the bad old days before the scientific revolution, alchemy has been emerging in recent years as more of a proto-science. Indeed, a fair number of the heroes of the scientific revolution were dyed-in-the-wool alchemists. Robert Boyle, one of the founders of chemistry, wanted to reform alchemy, not destroy it. He chased after the philsopher’s stone for his whole life. Many of his papers were destroyed in the eighteenth century because they were loaded with discussions of alchemy–which by then had acquired its bad reputation. Boyle’s legacy had to be protected.

Wilford reported from a recent meeting of historians of chemistry in Philadelphia. From his report (as well as this one from the New York Sun and this one from Chemical and Engineering News), it seems as if the meeting neglected one of the most interesting sides of alchemy: its role in the history of bio-chemistry. Alchemists believed that the life was the greatest transmutation of all, and they believed that the philsopher’s stone would serve as the ultimate medicine. While a lot of alchemists dealt in Kevin-Trudeau-style hogwash, some did important work.

Jan Baptist van Helmont, a sixteenth-century Belgian alchemist, carried out a classic experiment on biological growth. He put a five pound willow sapling in a tube of 200 pounds of earth. For five years he gave the tree nothing but water, and then weighed both tree and earth. The tree had grown to 169 pounds, while the earth had lost a few ounces. “Hence one hundred and sixty-four pounds of wood, bark, and roots have come up from water alone,” he announced. Van Helmont believed that the willow was nothing more than transmuted water, given form by the willow’s inner soul.

I first came to appreciate the importance of alchemy in the rise of biochemistry while working on my book Soul Made Flesh, on the history of neurology. Thomas Willis, the first neurologist, started out as an alchemist, deeply influenced by Van Helmont. He came into contact with Robert Boyle through their shared interest in alchemy. And his first important work was a book that used alchemy to reinterpret physiology. Instead of the four humours, Willis saw body being made up of corpuscles of different sorts, borrowing concepts of Van Helmont and other alchemists. These corpuscles interacted with one another to produce changes, just as ferments made bread rise and grape juice turn to wine.

Willis later did groundbreaking work on the anatomy and function of the brain, which until his time had generally been considered a pretty useless organ. Willis envisioned the brain as an alembic, the distilling container of alchemy, in which some of the corpuscles of the blood were distilled into the animal spirits, which then flowed through the nerves. While some of Willis’s language and concepts are now hopelessly old-fashioned, he set the study of the brain–and thus the soul–on a new foundation.

The intersection of alchemy and biology is just further evidence that science does not advance by simply wiping the slate clean and starting completely from scratch. Some of the most dramatic revolutions were born within systems of thought that today seem hopelessly backwards. I wonder how twenty-ninth cenutry historians will look back at our own revolutions today. Who will be cast aside as the new alchemists?

It’s always great to hear senior scientists talk about the bad old days, when one computer could fill an entire room and no one could say what genes were made of. Eric Kandel of Columbia has been studying memory since the 1950s, and won the Nobel Prize in 2000 for his work. These days he’s observing genes switching on and off at the junctions between neurons. But when he started out, he had to content himself with sticking electrodes into crayfish (chosen for their fat neurons). To observe their neurons, scientists would hook up the electrodes to amplifiers and loudspeakers, and the crackle of nerves would fill the room. With hindsight, we can cluck at the primitiveness of it all. But for Kandel, it was a new world. He had wanted to find Freud’s ego and the rest in the brain, and quickly discovered that it was a futile task. But being able to hear a crayfish’s neurons was, to him, the ultimate psychoanalysis.

For more on Kandel, you can read my new profile. The article is in the New York Academy of Science’s webzine (as well as the hard-copy version). They’ve also got a link to a recent lecture Kandel gave at NYAS that was the spur for the article.