Chapter 25
“Al Hit Paydirt!”
June–October 1943
Twenty miles from Sea View, on a bright and warm June day, Dr. Selman Waksman, the soil microbiologist from Rutgers, entered the Pennsylvania Hotel in midtown Manhattan. Making his way through the lobby, he took the elevator to a high floor, where he entered a meeting room. Stepping inside, he greeted the small group of men from the Trudeau Sanatorium’s Saranac Laboratory, the National Tuberculosis Association (NTA), several university labs, and Merck Pharmaceuticals, who had come together to discuss TB drugs, or lack thereof.
It was a laid-back meeting, with a quiet mood, infused with the same dour pessimism surrounding so many other meetings about tuberculosis and medications and a cure. Prontosil and penicillin and most of the sulfa drugs had been cast aside, considered useless against TB. A new group of drugs, sulfones, being tested at the famous Mayo Clinic in Rochester, Minnesota, were also proving no good; they had too many side effects.
How about the digestive enzymes of earthworms? asked Dr. William White from the NTA. Waksman straightened his back, thinking it was an impractical idea, on the verge of being comical. But as he listened, it became clear that he was an outlier. Merck and the NTA were taking White’s suggestions about earthworms seriously.
Waksman interrupted. While earthworms could produce an enzyme capable of digesting the TB bacteria, he said, in humans “any enzyme system powerful enough to bring this about would certainly digest the human organs as well.”
The response vexed White, a veteran doctor who’d spent his career thinking about tuberculosis. Waksman was not a physician or a chemist; the Russian doctor was a soil microbiologist whose area of expertise was protozoa and fungi, not chest cavities and the pathology of disease.
White challenged him: “How do you propose to go about this problem?”
Waksman thought for a minute.
“The antibiotics will do it . . . They will kill the bacterium not by digesting it,” he said, “but by interfering with its metabolism and its growth, without injuring the host.” Eyes shifted and brows raised. Antibiotics, everyone believed, were useless against the microbe.
What was Waksman talking about? Was the soil expert hiding something?
Some years earlier, Waksman had a chance encounter with Dr. Alexander Fleming, the Scottish physician who discovered penicillin. During the meeting, Fleming had remarked how the future of medicine lay in antibiotics culled from organic substances—mold and microorganisms—not synthetic substances like sulfa. Waksman was captivated by Fleming’s idea of a new generation of drugs born of the earth rather than in a lab.
After their conversation, Waksman returned to Rutgers and that long-forgotten study, the one proving that something in manured soil killed tuberculosis, the same one he’d said was “very interesting but it was leading nowhere,” began to make sense: if Fleming could create penicillin from mold, then maybe he could fashion an effective TB antibiotic from something in the soil.
With these thoughts, he committed to search the vast underground network of microbes and protozoa, fungi and nematodes, to find the organism capable of killing tuberculosis. But there was one problem: the disease terrified him. His solution: hire a graduate student.
Weeks later, Albert Schatz appeared at Waksman’s door. Young with an old-Hollywood kind of handsome, the dark-haired twenty-three-year-old had recently returned from the war, where he’d served as a bacteriologist in the US Air Force Medical Corps. He was reed thin, penniless, and desperate to finish his PhD.
Waksman knew Schatz from his prewar undergraduate days at Rutgers and was happy to offer him a position as his assistant researching antibiotics for a stipend of forty dollars a month. It was a paltry amount, the lowest of all the graduate students, but in exchange for chores, Waksman said Schatz could live in a small side room in the plant pathology greenhouse. It was an enchanting place where students played with seeds, growing hydroponic plants that blossomed into different varieties for FDR’s victory gardens.
Then Waksman let Schatz in on his secret: in the soil lived a microbe or set of microbes that cured tuberculosis. Schatz’s job was to find it.
When Schatz was a boy, tuberculosis had wheedled itself into his life. Growing up poor on his grandparents’ farm in rural Connecticut, Schatz saw classmates and neighbors “lose weight and waste away.” He recalled how “none of them could go to a sanatorium, so they remained home, coughing and infecting others,” until eventually they died.
In the air force, he’d struggled with a similar helplessness. In those field hospitals on the fringes of tiny European towns, Schatz saw hundreds of soldiers, not much older than himself, being carried in on stretchers with shrapnel dug deep into their bones and organs. They came with limbs and bodies grotesquely swollen from wounds and infections and disease: cholera, pneumonia, sepsis, typhoid, and tuberculosis. He worked hard trying to save them, using the only two available antibiotics: sulfa and penicillin. Sometimes the drugs worked, especially with pneumonia or flesh wounds, but they were useless for the more stubborn bacteria. And so, at night after his shift, he sat with the dying, comforting them just as Edna and Missouria were doing half a world away. In the soldiers’ faces, he saw the anarchy of war; in their bodies, the chaos of disease; and in their last breaths, the terror of falling into a place without dimension and time.
During those vigils, he had vowed to do something to fight bacterial infections, and despite the low stipend, Waksman’s offer appealed to him personally and intuitively. A “mystical sixth sense,” he said, guided many of his decisions. And that feeling was now telling him that “he would find something.”
Yes, he would do it.
But, Waksman explained, there was one stipulation: Schatz was never to come up to his third-floor lab with the TB bacteria. Ever.
For almost a decade, Waksman had been teasing through the soil, screening various groups of microbes to determine if any were powerful enough to inhibit the growth of different bacteria. Of the many minuscule soil microbes he found, one group had caught his attention, actinomycetes, or “ray fungi.” They were curious-looking creatures that reached back four million years. A hybrid of bacteria and fungus, they were notable for their signature feature: long hyphae that branched out like the tentacles of a jellyfish and produced enzymes that could decompose dead animals and remake nutrients for plants to grow. They were versatile, easy to grow, and found everywhere—in soil, fresh water, sea water, and compost. And they gave the earth that unique after-the-rain smell.
Waksman loved them.
Some years ago, he had isolated a strain of actinomycetes that appeared to have antibiotic properties against the bacteria responsible for typhoid, plague, cholera, and salmonella. But hopes for it died when it kept killing the test mice. Although the drug would never be used in humans, it had caught the attention of Merck. Executives from the pharmaceutical giant reached out to Waksman and offered him a partnership. In exchange for funding, they asked him to search out potential antibiotics. If something came to fruition, Merck would help him research it and give him a percentage of any royalties.
In early summer, Schatz began his great dig into the recesses of the earth to find the strain of actinomycetes that might yield an antibiotic strong enough to fight tuberculosis. Every day, Schatz rose before dawn, pulled on the same worn gray trousers and crumpled white shirt, and strode across campus. He walked with determination, passing the dairy barn where the Holstein cows grazed and the poultry house with its assortment of hens, to search the soil.
He looked under logs, around the bases of trees, under leaves, beside wild mushrooms, and in the discarded petri dishes of colleagues. But his favorite places to dig were the mounds of decomposing compost outside the plant pathology building and in the college stables, full of fresh horse manure; the best soil, Schatz felt, was less than twelve hours old. It was rich, soft, and vibrant. And it stunk.
One mid-August morning when Schatz returned from his foraging, his close friend Doris Jones, a graduate student studying the effects of microorganisms and antibiotic substances on fowl viruses, handed him a used petri dish. It was streaked with a swab from a healthy chicken’s throat. Schatz thanked her and took the dish to his lab, a run-down room where fantastic configurations of apparatuses rose from the wooden tables bringing to life the inner workings of his mind.
Taking Jones’s sample, he diluted it, then dropped it onto several petri dishes lined with nutrient agar. He repeated the process with a separate batch of soil he’d collected from the stables that morning, and then placed both in an incubator.
A week or so later, he removed them, and a universe of powdery microbial colonies in stunning shades of muted yellow, red, brown, and grayish green covered each plate. Some were surrounded by “clear zones,” areas indicating that the soil microbes had successfully warded off the respective bacteria. They might make a solid antibiotic. Schatz studied each colony, and with nothing more than a hunch, that “mystical sixth sense,” and what his wife called “Albert’s eagle eye,” he selected those that looked like germ killers.
He chose one colony from the chicken batch that his friend Doris Jones had given him. He named it D-1—“D” for Doris and “1” because they were the first actinomycetes he isolated from the agar plate. He planned to test D-1 beside another colony that came from the stables, which he named 18-16. Once each colony was isolated, he transferred it to fresh agar plates. In two weeks, a new pure colony would grow.
While he waited for D-1 and 18-16 to mature, he continued testing other soil samples, working long into the night, until his nails turned black and his hands smelled like earth and manure. Sometimes, overcome by exhaustion, he curled up on the floor and fell asleep. When he woke, he splashed water on his face and began again, despite the unfavorable odds.
“The failure rate [was] about 99.99 percent,” Jones said. But Schatz ignored percentages. His drive came from a prescient sense that he, Albert Schatz, would discover something effective.
Two weeks later, on October 19, 1943, Schatz walked into his lab. It was 2 p.m. when the skinny graduate student pulled out two petri dishes—the one labeled D-1 and the other 18-16—and looked at them. In front of him, appearing diagonally across the plate, were not one but two new strands of actinomycetes.
Their color was a pale grayish-green, and under a microscope they looked like a strand of rare pearls. But they weren’t just beautiful. When he tested them for antibiotic properties against a particular bacteria, each one showed wide clear zones, meaning both new strands stopped the growth of bacteria that was smeared on the petri dish. This was the first indication they might work as a drug.
In the words of Jones, “Al hit paydirt!”
Holding the two plates, Schatz walked down the long corridor, up to the third floor, and entered Waksman’s office. He put down plates D-1 and 18-16, with their clear zones. Waksman contemplated them, then instructed him to isolate them, find their food source, and begin more tests. Immediately.
In the cramped lab, Schatz worked round the clock trying to produce an antibiotic from the two new strands of D-1 and 18-16, which he was now calling Streptomyces griseus (S. griseus). Similar to all bacteria, S. griseus needed food to flourish, and Schatz discovered that D-1 and 18-16 grew best in a meat-extract mixture. To speed up the process, he ran “endless numbers of one liter Erlenmeyer flasks” containing beef broth.
Soon batches of fuzzy, grayish-looking colonies began sprouting on the surface of the beef broth, floating around like isolated storm clouds. Schatz, in a painstaking process, removed them, and to the best of his ability, filtered out the impurities. Then he began testing them on different diseases.
Daily, he dropped diluted strains of S. griseus onto agar plates brushed with typhoid, cholera, and other common germs. Out they came, again and again, flaunting the much-desired clear zones. Things kept getting better. Tests showed that S. griseus was effective against bacteria that evaded penicillin, like the deadly and stubborn Staphylococcus. Now certain that D-1 and 18-16 were acting like antibiotics, Waksman and Schatz were ready to begin in vivo tests on animals.
But Rutgers housed none of the conventional lab animals used by scientists for such tests—mice, monkeys, guinea pigs, or rabbits. The only available animals were horses and chickens and Holstein cows. All of them were too big and cumbersome for a drug trial.
Waksman had an idea: chicks. Unborn baby chicks from the poultry lab.
Infecting them fell to Doris Jones, a dreadful process requiring her to use a dental drill to pierce the egg, and with a tiny syringe drip fowl typhoid into the embryo of the unborn chicks. She hated the job and the way the egg felt in her palm. Its smoothness and warmth and weight reminded her of the growing baby tucked inside it, the one she would kill.
After poisoning all the embryos, she injected a small amount of Schatz’s potential antibiotic into half the eggs. The other half received nothing. Two days later, the untreated chicks died. But the ones given Schatz’s potential antibiotic began hatching. Jones squealed in delight at the sight of the wobbly, furry creatures. Her joy was short lived. Waksman wanted her to kill the newborns and autopsy their tiny bodies to confirm their internal organs were disease-free. Jones started crying.
With tears streaming down her face, she slipped the scissors through their necks, cut open their chests, and examined their organs. Two days later, she announced the baby chicks were typhoid-free.
Jubilant, Waksman returned to his office and called Merck, upholding the agreement to inform the company of any prospective drugs. He had one.
It was, he said, aptly called “streptomycin,” and it held “great promise.”