by Sam Kean
Everything was humming along nicely until Pauling requested that a graduate student check his calculations. The student did and was soon tying himself in knots trying to see where he was wrong and Pauling was right. Eventually, he pointed out to Pauling that it just didn’t seem like the phosphate molecules fit, for an elementary reason. Despite the emphasis in chemistry classes on neutral atoms, sophisticated chemists don’t think of elements that way. In nature, especially in biology, many elements exist only as ions, charged atoms. Indeed, according to laws Pauling had helped work out, the phosphorus atoms in DNA would always have a negative charge and would therefore repel each other. He couldn’t pack three phosphate strands into DNA’s core without blowing the damn thing apart.
The graduate student explained this, and Pauling, being Pauling, politely ignored him. It’s not clear why Pauling bothered to have someone check him if he wasn’t going to listen, but Pauling’s reason for ignoring the student is clear. He wanted scientific priority—he wanted every other DNA idea to be considered a knockoff of his. So contra his usual meticulousness, he assumed the anatomical details of the molecule would work themselves out, and he rushed his phosphorus-in, triple-stranded model into print in early 1953.
Meanwhile, across the Atlantic, two gawky graduate students at Cambridge University pored over advance copies of Pauling’s paper. Linus Pauling’s son, Peter, worked in the same lab as James Watson and Francis Crick* and had provided the paper as a courtesy. The unknown students desperately wanted to solve DNA to make their careers. And what they read in Pauling’s paper flabbergasted them: they had built the same model a year before—and had dismissed it, embarrassed, when a colleague had shown what a shoddy piece of work their triple helix was.
During that dressing-down, however, the colleague, Rosalind Franklin, had betrayed a secret. Franklin specialized in X-ray crystallography, which shows the shapes of molecules. Earlier that year, she had examined wet DNA from squid sperm and calculated that DNA was double-stranded. Pauling, while studying in Germany, had studied crystallography, too, and probably would have solved DNA instantly if he’d seen Franklin’s good data. (His data for dried-out DNA was also from X-ray crystallography.) However, as an outspoken liberal, Pauling had had his passport revoked by McCarthyites in the U.S. State Department, and he couldn’t travel to England in 1952 for an important conference, where he might have heard of Franklin’s work. And unlike Franklin, Watson and Crick never shared data with rivals. Instead, they took Franklin’s abuse, swallowed their pride, and started working with her ideas. Not long afterward, Watson and Crick saw all their earlier errors reproduced in Pauling’s paper.
Shaking off their disbelief, they rushed to their adviser, William Bragg. Bragg had won a Nobel Prize decades before but lately had become bitter about losing out on key discoveries—such as the shape of the alpha-helix—to Pauling, his flamboyant and (as one historian had it) “acerbic and publicity-seeking” rival. Bragg had banned Watson and Crick from working on DNA after their triple-stranded embarrassment. But when they showed him Pauling’s boners and admitted they’d continued to work in secret, Bragg saw a chance to beat Pauling yet. He ordered them back to DNA.
First thing, Crick wrote a cagey letter to Pauling asking how that phosphorus core stayed intact—considering Pauling’s theories said it was impossible and all. This distracted Pauling with futile calculations. Even while Peter Pauling alerted him that the two students were closing in, Pauling insisted his three-stranded model would prove correct, that he almost had it. Knowing that Pauling was stubborn but not stupid and would see his errors soon, Watson and Crick scrambled for ideas. They never ran experiments themselves, just brilliantly interpreted other people’s data. And in 1953, they finally wrested the missing clue from another scientist.
That man told them that the four nucleic acids in DNA (abbreviated A, C, T, and G) always show up in paired proportions. That is, if a DNA sample is 36 percent A, it will always be 36 percent T as well. Always. The same with C and G. From this, Watson and Crick realized that A and T, and C and G, must pair up inside DNA. (Ironically, that scientist had told Pauling the same thing years before on a sea cruise. Pauling, annoyed at his vacation being interrupted by a loudmouth colleague, had blown him off.) What’s more, miracle of miracles, those two pairs of nucleic acids fit together snugly, like puzzle pieces. This explained why DNA is packed so tightly together, a tightness that invalidated Pauling’s main reason for turning the phosphorus inward. So while Pauling struggled with his model, Watson and Crick turned theirs inside out, so the negative phosphorus ions wouldn’t touch. This gave them a sort of twisted ladder—the famed double helix. Everything checked out brilliantly, and before Pauling recovered,* they published this model in the April 25, 1953, issue of Nature.
So how did Pauling react to the public humiliation of triple helixes and inverted phosphorus? And to losing out—to his rival Bragg’s lab, no less—on the great biological discovery of the century? With incredible dignity. The same dignity all of us should hope we could summon in a similar situation. Pauling admitted his mistakes, conceded defeat, and even promoted Watson and Crick by inviting them to a professional conference he organized in late 1953. Given his stature, Pauling could afford to be magnanimous; his early championing of the double helix proved he was.
The years after 1953 went much better for both Pauling and Segrè. In 1955, Segrè and yet another Berkeley scientist, Owen Chamberlain, discovered the antiproton. Antiprotons are the mirror image of regular protons: they have a negative charge, may travel backward in time, and, scarily, will annihilate any “real” matter, such as you or me, on contact. After the prediction in 1928 that antimatter exists, one type of antimatter, the antielectron (or positron) was quickly and easily discovered in 1932. Yet the antiproton proved to be the elusive technetium of the particle physics world. The fact that Segrè tracked it down after years of false starts and dubious claims is a testament to his persistence. That’s why, four years later, his gaffes forgotten, Segrè won the Nobel Prize in Physics.* Fittingly, he borrowed Edwin McMillan’s white vest for the ceremony.
After losing out on DNA, Pauling got a consolation prize: an overdue Nobel of his own, in Chemistry in 1954. Typically for him, Pauling then branched out into new fields. Frustrated by his chronic colds, he started experimenting on himself by taking megadoses of vitamins. For whatever reason, the doses seemed to cure him, and he excitedly told others. Eventually, his imprimatur as a Nobel Prize winner gave momentum to the nutritional supplement craze still going strong today, including the scientifically dubious notion (sorry!) that vitamin C can cure a cold. In addition, Pauling—who had refused to work on the Manhattan Project—became the world’s leading anti–nuclear weapons activist, marching in protests and penning books with titles such as No More War! He even won a second, surprise Nobel Prize in 1962, the Nobel Peace Prize, becoming the only person to win two unshared Nobels. He did, however, share the stage in Stockholm that year with two laureates in medicine or physiology: James Watson and Francis Crick.
9
Poisoner’s Corridor: “Ouch-Ouch”
Pauling learned the hardest way that the rules of biology are much more delicate than the rules of chemistry. You can nigh well abuse amino acids chemically and end up with the same bunch of agitated but intact molecules. The fragile and more complex proteins of a living creature will wilt under the same stress, be it heat, acid, or, worst of all, rogue elements. The most delinquent elements can exploit any number of vulnerabilities in living cells, often by masking themselves as life-giving minerals and micronutrients. And the stories of how ingeniously those elements undo life—the exploits of “poisoner’s corridor”—provide one of the darker subplots of the periodic table.
The lightest element in poisoner’s corridor is cadmium, which traces its notoriety to an ancient mine in central Japan. Miners began digging up precious metals from the Kamioka mines in AD 710. In the following centuries, the mountains of Kamioka yielded gold, lead
, silver, and copper as various shoguns and then business magnates vied for the land. But not until twelve hundred years after striking the first lode did miners begin processing cadmium, the metal that made the mines infamous and the cry “Itai-itai!” a byword in Japan for suffering.
The Russo-Japanese War of 1904–1905 and World War I a decade later greatly increased Japanese demand for metals, including zinc, to use in armor, airplanes, and ammunition. Cadmium appears below zinc on the periodic table, and the two metals mix indistinguishably in the earth’s crust. To purify the zinc mined in Kamioka, miners probably roasted it like coffee and percolated it with acid, removing the cadmium. Following the environmental regulations of the day, they then dumped the leftover cadmium sludge into streams or onto the ground, where it leeched into the water table.
Today no one would think of dumping cadmium like that. It’s become too valuable as a coating for batteries and computer parts, to prevent corrosion. It also has a long history of use in pigments, tanning agents, and solders. In the twentieth century, people even used shiny cadmium plating to line trendy drinking cups. But the main reason no one would dump cadmium today is that it has rather horrifying medical connotations. Manufacturers pulled it from the trendy tankards because hundreds of people fell ill every year when acidic fruit juice, like lemonade, leached the cadmium from the vessel walls. And when rescue workers at Ground Zero after the September 11, 2001, terrorist attacks developed respiratory diseases, some doctors immediately suspected cadmium, among other substances, since the collapse of the World Trade Center towers had vaporized thousands of electronic devices. That assumption was incorrect, but it’s telling how reflexively health officials fingered element forty-eight.
Sadly, that conclusion was a reflex because of what happened a century ago near the Kamioka mines. As early as 1912, doctors there noticed local rice farmers being felled by awful new diseases. The farmers came in doubled over with joint and deep bone pain, especially the women, who accounted for forty-nine of every fifty cases. Their kidneys often failed, too, and their bones softened and snapped from the pressure of everyday tasks. One doctor broke a girl’s wrist while taking her pulse. The mystery disease exploded in the 1930s and 1940s as militarism overran Japan. Demand for zinc kept the ores and sludge pouring down the mountains, and although the local prefecture (the Japanese equivalent of a state) was removed from actual combat, few areas suffered as much during World War II as those around the Kamioka mines. As the disease crept from village to village, it became known as itai-itai, or “ouch-ouch,” disease, after the cries of pain that escaped victims.
Only after the war, in 1946, did a local doctor, Noboru Hagino, begin studying itai-itai disease. He first suspected malnutrition as the cause. This theory proved untenable by itself, so he switched his focus to the mines, whose high-tech, Western excavation methods contrasted with the farmers’ primitive paddies. With a public health professor’s help, Hagino produced an epidemiological map plotting cases of itai-itai. He also made a hydrological map showing where the Jinzu River—which ran through the mines and irrigated the farmers’ fields miles away—deposited its runoff. Laid over the top of each other, the two maps look almost identical. After testing local crops, Hagino realized that the rice was a cadmium sponge.
Painstaking work soon revealed the pathology of cadmium. Zinc is an essential mineral, and just as cadmium mixes with zinc in the ground, it interferes with zinc in the body by replacing it. Cadmium also sometimes evicts sulfur and calcium, which explains why it affected people’s bones. Unfortunately, cadmium is a clumsy element and can’t perform the same biological roles as the others. Even more unfortunately, once cadmium slips into the body, it cannot be flushed out. The malnutrition Hagino suspected at first also played a role. The local diet depended heavily on rice, which lacks essential nutrients, so the farmers’ bodies were starved of certain minerals. Cadmium mimicked those minerals well enough that the farmers’ cells, in dietary desperation, began to weave it into their organs at even higher rates than they otherwise would have.
Hagino went public with his results in 1961. Predictably and perhaps understandably, the mining company legally responsible, Mitsui Mining and Smelting, denied all wrongdoing (it had only bought the company that had done the damage). To its shame, Mitsui also campaigned to discredit Hagino. When a local medical committee formed to investigate itai-itai, Mitsui made sure that the committee excluded Hagino, the world expert on the disease. Hagino ran an end around by working on newfound cases of itai-itai in Nagasaki, which only bolstered his claims. Eventually, the conscience-stricken local committee, despite being stacked against Hagino, admitted that cadmium might cause the disease. Upon appeal of this wishy-washy ruling, a national government health committee, overwhelmed by Hagino’s evidence, ruled that cadmium absolutely causes itai-itai. By 1972, the mining company began paying restitution to 178 survivors, who collectively sought more than 2.3 billion yen annually. Thirteen years later, the horror of element forty-eight still retained such a hold on Japan that when filmmakers needed to kill off Godzilla in the then-latest sequel, The Return of Godzilla, the Japanese military in the film deployed cadmium-tipped missiles. Considering that an H-bomb had given Godzilla life, that’s a pretty dim view of this element.
Still, itai-itai disease was not an isolated incident in Japan last century. Three other times in the 1900s (twice with mercury, once with sulfur dioxide and nitrogen dioxide), Japanese villagers found themselves victims of mass industrial poisonings. These cases are known as the Big Four Pollution Diseases of Japan. In addition, thousands more suffered from radiation poisoning when the United States dropped a uranium and a plutonium bomb on the island in 1945. But the atomic bombs and three of the Big Four were preceded by the long-silent holocaust near Kamioka. Except it wasn’t so silent for the people there. “Itai-itai.”
Scarily, cadmium is not even the worst poison among the elements. It sits above mercury, a neurotoxin. And to the right of mercury sit the most horrific mug shots on the periodic table—thallium, lead, and polonium—the nucleus of poisoner’s corridor.
This clustering is partly coincidence, but there are legitimate chemical and physical reasons for the high concentration of poisons in the southeast corner. One, paradoxically, is that none of these heavy metals is volatile. Raw sodium or potassium, if ingested, would explode upon contact with every cell inside you, since they react with water. But potassium and sodium are so reactive they never appear in their pure, dangerous form in nature. The poisoner’s corridor elements are subtler and can migrate deep inside the body before going off. What’s more, these elements (like many heavy metals) can give up different numbers of electrons depending on the circumstances. For example, whereas potassium always reacts as K+, thallium can be Tl+ or Tl+3. As a result, thallium can mimic many elements and wriggle into many different biochemical niches.
That’s why thallium, element eighty-one, is considered the deadliest element on the table. Animal cells have special ion channels to vacuum up potassium, and thallium rides into the body via those channels, often by skin osmosis. Once inside the body, thallium drops the pretense of being potassium and starts unstitching key amino acid bonds inside proteins and unraveling their elaborate folds, rendering them useless. And unlike cadmium, thallium doesn’t stick in the bones or kidneys, but roams like a molecular Mongol horde. Each atom can do an outsized amount of damage.
For these reasons, thallium is known as the poisoner’s poison, the element for people who derive an almost aesthetic pleasure from lacing food and drinks with toxins. In the 1960s, a notorious British lad named Graham Frederick Young, after reading sensationalized accounts of serial killers, began experimenting on his family by sprinkling thallium into their teacups and stew pots. He was soon sent to a mental institution but was later, unaccountably, released, at which point he poisoned seventy more people, including a succession of bosses. Only three died, since Young made sure to prolong their suffering with less-than-lethal doses.
> Young’s victims are hardly alone in history. Thallium has a gruesome record* of killing spies, orphans, and great-aunts with large estates. But rather than relive darker scenes, maybe it’s better to recall element eighty-one’s single foray into (admittedly morbid) comedy. During its Cuba-obsessed years, the Central Intelligence Agency hatched a plan to powder Fidel Castro’s socks with a sort of talcum powder tainted with thallium. The spies were especially tickled that the poison would cause all his hair, including his famous beard, to fall out, which they hoped would emasculate Castro in front of his comrades before killing him. There’s no record of why this plan was never attempted.
Another reason thallium, cadmium, and other related elements work so well as poisons is that they stick around for aeons. I don’t just mean they accumulate in the body, as cadmium does. Rather, like oxygen, these elements are likely to form stable, near-spherical nuclei that never go radioactive. Therefore, a fair amount of each still survives in the earth’s crust. For instance, the heaviest eternally stable element, lead, sits in box eighty-two, a magic number. And the heaviest almost-stable element, bismuth, is its neighbor, in box eighty-three.
Because bismuth plays a surprising role in poisoner’s corridor, this oddball element merits a closer look. Some quick bismuth facts: Though a whitish metal with a pinkish hue, bismuth burns with a blue flame and emits yellow fumes. Like cadmium and lead, bismuth has found widespread use in paints and dyes, and it often replaces “red lead” in the crackling fireworks known as dragon’s eggs. Also, of the nearly infinite number of possible chemicals you can make by combining elements on the periodic table, bismuth is one of the very few that expands when it freezes. We don’t appreciate how bizarre this is because of common ice, which floats on lakes while fish slide around below it. A theoretical lake of bismuth would behave the same way—but almost uniquely so on the periodic table, since solids virtually always pack themselves more tightly than liquids. What’s more, that bismuth ice would probably be gorgeous. Bismuth has become a favorite desktop ornament and decorative knickknack for mineralogists and element nuts because it can form rocks known as hopper crystals, which twist themselves into elaborate rainbow staircases. Newly frozen bismuth might look like Technicolor M. C. Escher drawings come to life.
