by Sam Kean
Similarly deadly to small wriggling cells, if a bit more quackish, is vanadium, element twenty-three, which also has a curious side effect in males: vanadium is the best spermicide ever devised. Most spermicides dissolve the fatty membrane that surrounds sperm cells, spilling their guts all over. Unfortunately, all cells have fatty membranes, so spermicides often irritate the lining of the vagina and make women susceptible to yeast infections. Not fun. Vanadium eschews any messy dissolving and simply cracks the crankshaft on the sperm’s tails. The tails then snap off, leaving the sperm whirling like one-oared rowboats.*
Vanadium hasn’t appeared on the market as a spermicide because—and this is a truism throughout medicine—knowing that an element or a drug has desirable effects in test tubes is much different from knowing how to harness those effects and create a safe medicine that humans can consume. For all its potency, vanadium is still a dubious element for the body to metabolize. Among other things, it mysteriously raises and lowers blood glucose levels. That’s why, despite its mild toxicity, vanadium water from (as some sites claim) the vanadium-rich springs of Mt. Fuji is sold online as a cure for diabetes.
Other elements have made the transition into effective medicines, like the hitherto useless gadolinium, a potential cancer assassin. Gadolinium’s value springs from its abundance of unpaired electrons. Despite the willingness of electrons to bond with other atoms, within their own atoms, they stay maximally far apart. Remember that electrons live in shells, and shells further break down into bunks called orbitals, each of which can accommodate two electrons. Curiously, electrons fill orbitals like patrons find seats on a bus: each electron sits by itself in an orbital until another electron is absolutely forced to double up.* When electrons do condescend to double up, they are picky. They always sit next to somebody with the opposite “spin,” a property related to an electron’s magnetic field. Linking electrons, spin, and magnets may seem weird, but all spinning charged particles have permanent magnetic fields, like tiny earths. When an electron buddies up with another electron with a contrary spin, their magnetic fields cancel out.
Gadolinium, which sits in the middle of the rare earth row, has the maximum number of electrons sitting by themselves. Having so many unpaired, noncanceling electrons allows gadolinium to be magnetized more strongly than any other element—a nice feature for magnetic resonance imaging (MRI). MRI machines work by slightly magnetizing body tissue with powerful magnets and then flipping the magnets off. When the field releases, the tissue relaxes, reorients itself randomly, and becomes invisible to a magnetic field. Highly magnetic bits like gadolinium take longer to relax, and the MRI machine picks up on that difference. So by affixing gadolinium to tumor-targeting agents—chemicals that seek out and bind only to tumors—doctors can pick tumors out on an MRI scan more easily. Gadolinium basically cranks up the contrast between tumors and normal flesh, and depending on the machine, the tumor will either stand out like a white island in a sea of grayish tissue or appear as an inky cloud in a bright white sky.
Even better, gadolinium might do more than just diagnose tumors. It might also provide doctors with a way to kill those tumors with intense radiation. Gadolinium’s array of unpaired electrons allows it to absorb scads of neutrons, which normal body tissue cannot absorb well. Absorbing neutrons turns gadolinium radioactive, and when it goes nuclear, it shreds the tissue around it. Normally, triggering a nano-nuke inside the body is bad, but if doctors can induce tumors to absorb gadolinium, it’s sort of an enemy of an enemy thing. As a bonus, gadolinium also inhibits proteins that repair DNA, so the tumor cells cannot rebuild their tattered chromosomes. As anyone who has ever had cancer can attest, a focused gadolinium attack would be a tremendous improvement over chemotherapy and normal cancer radiation, both of which kill cancer cells by scorching everything around them, too. Whereas those techniques are more like firebombs, gadolinium could someday allow oncologists to make surgical strikes without surgery.*
This is not to say that element sixty-four is a wonder drug. Atoms have a way of drifting inside the body, and like any element the body doesn’t use regularly, gadolinium has side effects. It causes kidney problems in some patients who cannot flush it out of their systems, and others report that it causes their muscles to stiffen up like early stages of rigor mortis and their skin to harden like a hide, making breathing difficult in some cases. From the looks of it, there’s a healthy Internet industry of people claiming that gadolinium (usually taken for an MRI) has ruined their health.
As a matter of fact, the Internet is an interesting place to scout out general claims for obscure medicinal elements. With virtually every element that’s not a toxic metal (and even occasionally with those), you can find some alternative medicine site selling it as a supplement.* Probably not coincidentally, you’ll also find personal-injury firms on the Internet willing to sue somebody for exposure to nearly every element. So far, the health gurus seem to have spread their message farther and wider than the lawyers, and elemental medicines (e.g., the zinc in lozenges) continue to grow more popular, especially those that have roots as folk remedies. For a century, people gradually replaced folk remedies with prescription drugs, but declining confidence in Western medicine has led some people to self-administer “drugs” such as silver once more.*
Again, there is an ostensible scientific basis for using silver, since it has the same self-sterilizing effects as copper. The difference between silver and copper is that silver, if ingested, colors the skin blue. Permanently. And it’s actually worse than that sounds. Calling silvered skin “blue” is easy shorthand. But there’s the fun electric blue in people’s imaginations when they hear this, and then there’s the ghastly gray zombie-Smurf blue people actually turn.
Thankfully, this condition, called argyria, isn’t fatal and causes no internal damage. A man in the early 1900s even made a living as “the Blue Man” in a freak show after overdosing on silver nitrate to cure his syphilis. (It didn’t work.) In our own times, a survivalist and fierce Libertarian from Montana, the doughty and doughy Stan Jones, ran for the U.S. Senate in 2002 and 2006 despite being startlingly blue. To his credit, Jones had as much fun with himself as the media did. When asked what he told children and adults who pointed at him on the street, he deadpanned, “I just tell them I’m practicing my Halloween costume.”
Jones also gladly explained how he contracted argyria. Having his ear to the tin can about conspiracy theories, Jones became obsessed in 1995 with the Y2K computer crash, and especially with the potential lack of antibiotics in the coming apocalypse. His immune system, he decided, had better get ready. So he began to distill a heavy-metal moonshine in his backyard by dipping silver wires attached to 9-volt batteries into tubs of water—a method not even hard-core silver evangelists recommend, since electric currents that strong dissolve far too many silver ions in the bath. Jones drank his stash faithfully for four and a half years, right until Y2K fizzled out in January 2000.
Despite that dud, and despite being gawked at during his serial Senate campaigns, Jones remains unrepentant. He certainly wasn’t running for office to wake up the Food and Drug Administration, which in good libertarian fashion intervenes with elemental cures only when they cause acute harm or make promises they cannot possibly keep. A year after losing the 2002 election, Jones told a national magazine, “It’s my fault that I overdosed [on silver], but I still believe it’s the best antibiotic in the world…. If there were a biological attack on America or if I came down with any type of disease, I’d immediately take it again. Being alive is more important than turning purple.”
Stan Jones’s advice notwithstanding, the best modern medicines are not isolated elements but complex compounds. Nevertheless, in the history of modern drugs, a few unexpected elements have played an outsized role. This history largely concerns lesser-known heroic scientists such as Gerhard Domagk, but it starts with Louis Pasteur and a peculiar discovery he made about a property of biomolecules called handedness, which gets at the ver
y essence of living matter.
Odds are you’re right-handed, but really you’re not. You’re left-handed. Every amino acid in every protein in your body has a left-handed twist to it. In fact, virtually every protein in every life form that has ever existed is exclusively left-handed. If astrobiologists ever find a microbe on a meteor or moon of Jupiter, almost the first thing they’ll test is the handedness of its proteins. If the proteins are left-handed, the microbe is possibly earthly contamination. If they’re right-handed, it’s certainly alien life.
Pasteur noticed this handedness because he began his career studying modest fragments of life as a chemist. In 1849, at age twenty-six, he was asked by a winery to investigate tartaric acid, a harmless waste product of wine production. Grape seeds and yeast carcasses decompose into tartaric acid and collect as crystals in the dregs of wine kegs. Yeast-born tartaric acid also has a curious property. Dissolve it in water and shine a vertical slit of light through the solution, and the beam will twist clockwise away from the vertical. It’s like rotating a dial. Industrial, human-made tartaric acid does nothing like that. A vertical beam emerges true and upright. Pasteur wanted to figure out why.
He determined that it had nothing to do with the chemistry of the two types of tartaric acid. They behaved identically in reactions, and the elemental composition of both was the same. Only when he examined the crystals with a magnifying glass did he notice any difference. The tartaric acid crystals from yeast all twisted in one direction, like tiny, severed left-handed fists. The industrial tartaric acid twisted both ways, a mixture of left- and right-handed fists. Intrigued, Pasteur began the unimaginably tedious job of separating the salt-sized grains into a lefty pile and a righty pile with tweezers. He then dissolved each pile in water and tested more beams of light. Just as he suspected, the yeastlike crystals rotated light clockwise, while the mirror-image crystals rotated light counterclockwise, and exactly the same number of degrees.
Pasteur mentioned these results to his mentor, Jean Baptiste Biot, who had first discovered that some compounds could twist light. The old man demanded that Pasteur show him—then nearly broke down, he was so deeply moved at the elegance of the experiment. In essence, Pasteur had shown that there are two identical but mirror-image types of tartaric acid. More important, Pasteur later expanded this idea to show that life has a strong bias for molecules of only one handedness, or “chirality.”*
Pasteur later admitted he’d been a little lucky with this brilliant work. Tartaric acid, unlike most molecules, is easy to see as chiral. In addition, although no one could have anticipated a link between chirality and rotating light, Pasteur had Biot to guide him through the optical rotation experiments. Most serendipitously, the weather cooperated. When preparing the man-made tartaric acid, Pasteur had cooled it on a windowsill. The acid separates into left- and right-handed crystals only below 79°F, and had it been warmer that season, he never would have discovered handedness. Still, Pasteur knew that luck explained just part of his success. As he himself declared, “Chance favors only the prepared mind.”
Pasteur was skilled enough for this “luck” to persist throughout his life. Though not the first to do so, he performed an ingenious experiment on meat broth in sterile flasks and proved definitively that air contains no “vitalizing element,” no spirit that can summon life from dead matter. Life is built solely, if mysteriously, from the elements on the periodic table. Pasteur also developed pasteurization, a process that heats milk to kill infectious diseases; and, most famously at the time, he saved a young boy’s life with his rabies vaccine. For the latter deed, he became a national hero, and he parlayed that fame into the clout he needed to open an eponymous institute outside Paris to further his revolutionary germ theory of disease.
Not quite coincidentally, it was at the Pasteur Institute in the 1930s that a few vengeful, vindictive scientists figured out how the first laboratory-made pharmaceuticals worked—and in doing so hung yet another millstone around the neck of Pasteur’s intellectual descendant, the great microbiologist of his era, Gerhard Domagk.
In early December 1935, Domagk’s daughter Hildegard tripped down the staircase of the family home in Wuppertal, Germany, while holding a sewing needle. The needle punctured her hand, eyelet first, and snapped off inside her. A doctor extracted the shard, but days later Hildegard was languishing, suffering from a high fever and a brutal streptococcal infection all up and down her arm. As she grew worse, Domagk himself languished and suffered, because death was a frighteningly common outcome for such infections. Once the bacteria began multiplying, no known drug could check their greed.
Except there was one drug—or, rather, one possible drug. It was really a red industrial dye that Domagk had been quietly testing in his lab. On December 20, 1932, he had injected a litter of mice with ten times the lethal dose of streptococcal bacteria. He had done the same with another litter. He’d also injected the second litter with that industrial dye, prontosil, ninety minutes later. On Christmas Eve, Domagk, until that day an insignificant chemist, stole back into his lab to peek. Every mouse in the second litter was alive. Every mouse in the first had died.
That wasn’t the only fact confronting Domagk as he kept vigil over Hildegard. Prontosil—a ringed organic molecule that, a little unusually, contains a sulfur atom—had unpredictable properties. Germans at the time believed, a little oddly, that dyes killed germs by turning the germs’ vital organs the wrong color. But prontosil, though lethal to microbes inside mice, had no effect on bacteria in test tubes. They swam around happily in the red wash. No one knew why, and because of that ignorance, numerous European doctors had attacked German “chemotherapy,” dismissing it as inferior to surgery in treating infection. Even Domagk didn’t quite believe in his drug. Between the mouse experiment in 1932 and Hildegard’s accident, tentative clinical trials in humans had gone well, but with occasional serious side effects (not to mention that it caused people to flush bright red, like lobsters). Although he was willing to risk the possible deaths of patients in clinical trials for the greater good, risking his daughter was another matter.
In this dilemma, Domagk found himself in the same situation that Pasteur had fifty years before, when a young mother had brought her son, so mangled by a rabid dog he could barely walk, to Pasteur in France. Pasteur treated the boy with a rabies vaccine tested only on animals, and the boy lived.* Pasteur wasn’t a licensed doctor, and he administered the vaccine despite the threat of criminal prosecution if it failed. If Domagk failed, he would have the additional burden of having killed a family member. Yet as Hildegard sank further, he likely could not rid his memory of the two cages of mice that Christmas Eve, one teeming with busy rodents, the other still. When Hildegard’s doctor announced he would have to amputate her arm, Domagk laid aside his caution. Violating pretty much every research protocol you could draw up, he sneaked some doses of the experimental drug from his lab and began injecting her with the blood-colored serum.
At first Hildegard worsened. Her fever alternately spiked and crashed over the next couple of weeks. Suddenly, exactly three years after her father’s mouse experiment, Hildegard stabilized. She would live, with both arms intact.
Though euphoric, Domagk held back mentioning his clandestine experiment to his colleagues, so as not to bias the clinical trials. But his colleagues didn’t need to hear about Hildegard to know that Domagk had found a blockbuster—the first genuine antibacterial drug. It’s hard to overstate what a revelation this drug was. The world in Domagk’s day was modern in many ways. People had quick cross-continental transportation via trains and quick international communication via the telegraph; what they didn’t have was much hope of surviving even common infections. With prontosil, plagues that had ravaged human beings since history began seemed conquerable and might even be eradicated. The only remaining question was how prontosil worked.
Not to break my authorial distance, but the following explanation must be chaperoned with an apology. After expounding on the util
ity of the octet rule, I hate telling you that there are exceptions and that prontosil succeeds as a drug largely because it violates this rule. Specifically, if surrounded by stronger-willed elements, sulfur will farm out all six of its outer-shell electrons and expand its octet into a dozenet. In prontosil’s case, the sulfur shares one electron with a benzene ring of carbon atoms, one with a short nitrogen chain, and two each with two greedy oxygen atoms. That’s six bonds with twelve electrons, a lot to juggle. And no element but sulfur could pull it off. Sulfur lies in the periodic table’s third row, so it’s large enough to take on more than eight electrons and bring all those important parts together; yet it’s only in the third row and therefore small enough to let everything fit around it in the proper three-dimensional arrangement.
Domagk, primarily a bacteriologist, was ignorant of all that chemistry, and he eventually decided to publish his results so other scientists could help him figure out how prontosil works. But there were tricky business issues to consider. The chemical cartel Domagk worked for, I. G. Farbenindustrie (IGF, the company that later manufactured Fritz Haber’s Zyklon B), already sold prontosil as a dye, but it filed for a patent extension on prontosil as a medicine immediately after Christmas in 1932. And with clinical proof that the drug worked well in humans, IGF was fervid about maintaining its intellectual property rights. When Domagk pushed to publish his results, the company forced him to hold back until the medicinal patent on prontosil came through, a delay that earned Domagk and IGF criticism, since people died while lawyers quibbled. Then IGF made Domagk publish in an obscure, German-only periodical, to prevent other firms from finding out about prontosil.
Despite the precaution, and despite prontosil’s revolutionary promise, the drug flopped when it hit the market. Foreign doctors continued to harangue about it and many simply didn’t believe it could work. Not until the drug saved the life of Franklin Delano Roosevelt Jr., who was struck by a severe strep throat in 1936, and earned a headline in the New York Times did prontosil and its lone sulfur atom win any respect. Suddenly, Domagk might as well have been an alchemist for all the money IGF stood to make, and any ignorance about how prontosil worked seemed trifling. Who cared when sales figures jumped fivefold in 1936, then fivefold more the next year.
