Experiment Eleven: Dark Secrets Behind the Discovery of a Wonder Drug

Contents

Title Page

Dedication

Epigraph

PART I: THE DISCOVERY

1. Zones of Antagonism

2. The Apprentice and His Master

3. The Good Earth

4. The Sponsor

5. A Distinguished Visitor

6. The Race to Publish

7. A Conflict of Interest

PART II: THE RIFT

8. The Lilac Gardens

9. The Parable of the Sick Chicken

10. Mold in Their Pockets

11. Dr. Schatz Goes to Albany

12. The Five-Hundred-Dollar Check

13. A Patent That Shaped the World

PART III: THE CHALLENGE

14. The Letter

15. Choose a Lawyer

16. The Road to Court

17. Under Oath

18. The Settlement

PART IV: THE PRIZE

19. The Road to Stockholm

20. A Dog Yapping at the Heels of a Great World Figure

21. The Drug Harvest

22. The Master’s Memoir

23. The Copied Notebooks

PART V: THE RESTORATION

24. Wilderness Years

25. The English Scientist

26. A Medal

Afterword

Acknowledgments

Notes

A Note on the Author

By the Same Author

Copyright

To the researchers in science

who did the hard work, and never

reaped the glory.

Complete honesty is of course imperative in scientific work.

—W. I. B. Beveridge, The Art of Scientific

Investigation, 1957

PART I • The Discovery

1 • Zones of Antagonism

EVERY DAY AT DAWN IN THE summer of 1943, a young graduate student could be seen striding briskly across the peaceful campus of the College of Agriculture. He was short, wiry, and handsome, his sharp features focused intensely on his important mission. Even his clothes seemed an afterthought, a wrinkled white shirt and loose gray pants, worn and reworn like those of any devoted researcher surviving on a meager stipend and the excitement of his work. He came from the direction of the Plant Pathology greenhouse, where students were breeding new varieties for President Franklin Roosevelt’s Victory Gardens. He hurried past the dairy, with its herd of experimental Holsteins, past the poultry house, where Rhode Island Reds competed with white Leghorns for egg-laying prowess, and finally arrived at the Georgian-style Administration Building, which celebrated the proud colonial history of Rutgers University.

Albert Schatz, the harried student, was the first to arrive each day at the Department of Soil Microbiology. He let himself into the empty building and descended quickly into the basement laboratory. He pulled on his long white lab coat made of heavy cotton, worn haphazardly like his clothes and with a tear down one side. Then he began work on his experiments, searching for new antibiotics among the microbes he had found in the farmyard soil.

On that morning of August 23, he sat at his workbench and opened his notebook. On page 32, in his meticulous cursive, he entered the date and the title of his new experiment, Exp. 11 Antagonistic Actinomycetes. Then underneath, with the precision of a ledger clerk, he wrote, Control soils Nos. 2, 7A, 18A, leaf compost, straw compost and stable manure plated out on egg albumin agar. Transfer made from colonies of actinomycetes selected at random ... by casual macroscopic observation. And he added, for accuracy, Some actinomycetes obtained from plates of swabs of chickens’ throats ... from Miss Doris Jones.

It was the fourth summer of the world war and, although the New Jersey college farm was thousands of miles from the front lines, almost everything, even the plants in the greenhouse and the microbes in the soil, had some link to the war effort. Schatz had come to the college because he wanted to be a farmer, but now, aged twenty-three and at the start of his doctorate career, he found himself engaged in a special war-driven mission. Instead of hunting for microbes that could break down soil to make it more fertile, Schatz was part of a scientific race to find microbes capable of producing new and more powerful antibiotics. His Experiment 11 was a routine test, one of hundreds being made by other graduate students working on this nationwide project, but it would be much more than that.

By 1943, Eleven U.S. drug companies were producing penicillin, the first antibiotic, discovered by Alexander Fleming in 1928. The first vials of penicillin were being rushed to the front to treat common infections from battle wounds. But in this war, a new threat had emerged: biological weapons. Allied intelligence reported that Germany and Japan would not hesitate to use bombs and shells filled with deadly germs like anthrax, cholera, typhoid, and even the plague. Penicillin had no effect on such diseases.

The researchers best suited to the task of finding new antibiotics were not at medical schools, but at the agricultural colleges. Aggies like Albert Schatz were quite familiar with microbes from the soil that were capable of producing a chemical toxin that killed off the harmful bacteria that might be used in biological weapons. Each time they grew these microbes in a petri dish, they saw the telltale clear zones, or zones of antagonism, as they were known, killing fields measured in millimeters where one microbe battled another for space or food. If they dropped penicillin into a petri dish of typhoid bacteria or cholera or the plague, no clear zones would develop. For this job, a stronger antibiotic was needed, the kind that Albert Schatz was hoping to find.

The basement laboratory where Schatz worked was primitive and sparsely equipped, grim even by the utilitarian standards of the times. But to this determined young man it was a hideaway, a place where he could work uninterrupted. And he had volunteered for this isolation. His ambitious Ph.D. had two parts: One was to find antibiotics against cholera and typhoid; a second was to find a cure for the deadliest of all infectious diseases, tuberculosis. Over the previous two centuries, two billion people had died from tuberculosis, caused by a slow-growing, pickle-shaped microbe, Mycobacterium tuberculosis. It was highly contagious, spreading easily from a victim’s sneeze or spit. Known as the Great White Plague, TB cut down rich and poor alike, although in the Industrial Revolution it spread more easily in the crowded slums and factories. In wartime it spread quickly in bombed-out cities and crowded refugee camps. There was no effective cure. Doctors had tried everything from prolonged rest to fortify the body’s resistance, to drastic collapsed-lung surgery, to a range of alchemies and the new so-called sulfa drugs discovered by German researchers from industrial dyes. Albert Schatz’s professor, Dr. Selman Waksman, had warned of the risks. Waksman insisted that when Schatz handled the deadly TB microbe, he must work alone in the basement and never bring the germ to the labs on the third floor.

In recent days, Schatz’s laboratory had taken on the appearance of an ancient dispensary. In one corner an aging autoclave, a kind of pressure cooker used for sterilizing glassware, hissed away. Conical glass flasks contained rich dark brews of meat extract similar to gravy, a concoction Schatz used to feed his microbes. On his bench were rows of petri dishes with microbe food in agar, the jellied extract of algae that microbiologists use for growing their molds. The microbes Schatz was cultivating came from the multicolored and somewhat mysterious group known as the actinomycetes, or ray fungi. These are strange, thread-like creatures that first appeared more than four hundred million years ago. They have wispy hyphae like the tentacles of a jellyfish, half bacteria and half fungus, a sort of evolutionary link between the two. They were favorites of Dr. Waksman, and common in the farmyard soil, and they had already shown promise in producing antibiotics. They form strikingly beautiful colonies of blues, reds, and grayish greens, and in the soil they are responsible for the pleasant odor of earth after a light rain.

Albert knew where to look for them. His favorite hunting grounds included the compost heaps of moldering leaves and twigs outside Plant Pathology, and the college stables, where he filled pots of fresh horse manure. The richest for his experiments, he knew, was the freshest—less than twelve hours old. Each gram of soil or compost Schatz collected was teeming with millions of different microbes, but always some actinomycetes. He diluted the soil with tap water and let drops of the mixture fall onto petri dishes containing microbial food in the jellied agar. Then he incubated the dishes and watched the actinomycetes grow. Within a few days, he had good colonies of mold in his petri dishes. Some of them were surrounded by the telltale clear zones, indicating that they might be antibiotic producers. He chose his likely candidates for their robust look and their widest zones of antagonism, like a gardener spotting a sturdy shoot, or a farmer selecting a high-yielding crop for breeding. Then he tested them for their action against known disease-producing bacteria from the same group as the typhoid and cholera germs.

By mid-September, he had selected two strains of a species of a gray-green actinomycete named griseus, Latin for gray. One strain had come from heavily manured farmyard soil and he named it 18-16, for the sixteenth strain of the eighteenth soil sample. The other came from a colleague, Doris Jones, as he had noted in his lab notebook. He named her strain D-1, for Doris. Much quicker than he had dared to hope, Schatz had become convinced that he had discovered a new antibiotic, the first to be found in the Department of Soil Microbiology for several months, and everyone was excited, especially Dr. Waksman.

But no one could yet know whether his discovery would be useful as a medicine; if it was powerful enough to destroy typhoid and cholera it might also destroy human body cells. And it was only the first stage of Schatz’s project; he still had to see if his new antibiotic would be effective against the toughest germ that causes TB. Schatz checked and rechecked Experiment 11, running the same tests over and over again until he was sure that he had not made a mistake. Each effort was carefully recorded in his lab notebook.

By the middle of October, he had confirmed that 18-16 and D-1 were indeed behaving like good producers of a new antibiotic. On October 19 at two o’clock in the afternoon, he placed a culture of his Actinomyces griseus in a test tube and sealed it for posterity by heating the end over a Bunsen burner and twisting the glass shut. That weekend, he wrapped the tube in cotton wool, put it in his pocket, and caught the train from the Rutgers University town of New Brunswick to Newark, then the bus to Passaic, where his parents lived in a working-class section of the textile town on the Passaic River. There, he showed the test tube to his father, Julius, and his uncle Joe and presented it to his mother, Rachel. She had not finished grade school and had no real idea what the test tube represented. He told her that he had found a new medicine that might eventually fight the infectious diseases, maybe even tuberculosis, that she had seen too often destroying the lives of her friends and neighbors. That she could understand.

2 • The Apprentice and His Master

The schatz family came from the peasant class in the old Russia, and their entry into America is an immigrant story of the kind often told at the turn of the twentieth century. Albert’s grandfather, Shlomo (Sam) Schatz, was a butcher, and his grandmother’s family, the Tunicks, were known for their physical strength and much revered in the community for forming local vigilante committees to defend Jews during the pogroms. Sam himself was a strong man who once, legend has it, leaped on a bull that was running amok through the village and wrestled it to the ground. But Russia was a barren and hostile place, especially for Jews, and Sam left his village on the outskirts of Minsk in 1899 and immigrated to America, leaving his pregnant wife, Rose, and their five children with her father, Ephraim. He arrived at Ellis Island and moved in with a cousin on Manhattan’s Lower East Side. It took him five years, working as a house-painter, to save enough money to bring his family, including Albert’s father, Julius, to New York.

The family lived in a walkup, and soon after their arrival one child died of a weak heart. They moved into a Brooklyn tenement, and Sam and Rose had six more children, but the man who could wrestle a bull grew weak from heavy smoking and living in the putrid city air. When doctors told him he should leave for a life in the country, the Jewish community had just the answer.

Baron Maurice de Hirsch, a German-born Jewish banker, gave mortgages to immigrant Jews to enable them to build their own barns and homes. He also set up the small Woodbine Agricultural College in New Jersey to produce intelligent, practical farmers. With the help of Hirsch funds, Sam Schatz bought a dirt farm in Fitchville, Connecticut, joining other Jewish settlers in small communities across the state. On most of these farms the soil was poor, exhausted by Yankee farmers who had abandoned it to move west or, in some cases, for better jobs in the cities.

The Schatzes were the first Jewish family at Bird’s Eye View Farm, a stone house, two wooden barns, and a manure pit built on a rise known as Cannonball Hill. The family scratched a living from a dozen milk cows and some chickens. They sold vegetables in the spring, and in the summer they took in boarders from the city. While the urban renters lived in the farmhouse and enjoyed the great outdoors, the Schatz family lived in tents. Julius joined the U.S. Army in World War One, and after he returned, he was delivering vegetables by horse cart to nearby Norwich one day when he met a pretty, dark-haired young woman named Rachel Martin who worked in a bakery. They soon married. Her parents were Jewish immigrants from Poland who had come to America via Britain.

On February 2, 1920, Albert Schatz was born in a Norwich hospital. The family stayed on the farm until he was three, when they moved to Passaic, New Jersey, where Julius’s sister Rebecca and her husband, Abe, had a grocery store. They lived in a wooden three-story house with six apartments, three at the front and three at the back. Two girls were born, and the family moved back and forth from Passaic to the farm, wherever there was work. As soon as he was able, Albert helped out on the farm. He learned how to sharpen farm tools, milk cows, make butter and cheese, and drive the horse cart. When he was older, he shot groundhogs, mended his own clothes, and darned his socks. He attended the local one-room school-house, which had one teacher and twenty students, grades one through eight. The building was twenty by twenty-five feet and had two entrances, one for boys and one for girls. Albert wanted to be a farmer, like his father and grandfather.

During the Great Depression the family lived mostly in Passaic. They joined other immigrants from Eastern Europe—Hungarians, Czechs, Poles, and Russians. Albert witnessed much poverty and sickness, people fighting for scraps on the garbage dumps and dying from infectious diseases, like pneumonia, diphtheria, and, of course, tuberculosis. It was a raw and sometimes violent period. One of the young boy’s lasting memories was of the bloody police charges that ended the fourteen-month-long Passaic textile workers’ strike involving fifteen thousand workers, in 1926–27. The police dispersed the strikers with horses and water cannons, and schools were often closed. Despite the disruptions, Albert managed to stay in classes and was a consistently promising student at Passaic High School.

Albert Schatz, age twelve, with his mother, sisters Sheila and Elaine, and his maternal grandmother on the Connecticut farm in 1932.

(Courtesy Vivian Schatz)

In his junior year, in 1936, when he was sixteen, he contributed three paragraphs to the school newspaper about his life’s ambition, to be a farmer. He did not seek wealth for I should not know what to do with it. He wanted to sweat by honest labor and to roam the open fields. He wanted to chop wood until his muscles ached. "I want to LIVE."

Aged eighteen, Albert won a scholarship to the Rutgers’ College of Agriculture, the first in his family ever to attend an institution of higher learning. In his second year, he was elected to Phi Beta Kappa, a rare achievement for an aggie. The head of the Department of Soil Microbiology, Dr. Waksman, was another Jewish immigrant of Russian descent. He was always on the lookout for bright young graduates, and was happy to accept Albert as a Ph.D. candidate.

SELMAN ABRAHAM WAKSMAN, the man behind the intense wartime hunt for antibiotics at Rutgers, was no ordinary soil scientist. Like the Schatz family, Waksman had arrived in America at the beginning of the twentieth century, but he came from a different social order and had achieved much in the New World.

He was born on July 8, 1888, according to the old Russian calendar, in the small market town of Novaya Priluka, in western Ukraine, two hundred miles from the regional capital of Kiev. He wrote in his memoir that it was "a mere dot in the boundless steppes," surrounded by chernozem, the fertile black earth on which wheat, rye, barley, and oats flourished, as long as the rains came. Without them, famine swept the land. The inhabitants of the small towns and villages of Western Ukraine were recently freed serfs who scratched a living from smallholdings, and Jewish artisans and tradesman who marketed the farm and forest products.

His life there was simple, but not uncomfortable. His father was the relatively well-off son of a coppersmith and had inherited property. His mother was the daughter of a successful businesswoman who ran a dry goods store, a "prominent merchant in the community." His mother had inherited the store, and together his parents were able to pay for Selman’s private tutors.

Immediately after marriage, his father had been drafted, like all able-bodied men, into the czar’s army for five years, leaving Selman’s mother to carry on her business and fend for herself. When his father had returned from service, Selman had been born, but his father showed little interest in being with his son, most of the time living twenty miles away in the nearest large city, Vinnitsa, where he had inherited property. Selman was brought up by his mother, several aunts and maiden cousins, and his maternal grandmother, who had eight daughters. Selman was the son of the youngest daughter. Inevitably, he was spoiled.

His mother taught him to read and sent him to the local heder (private school) and then to private tutors. She also made sure that he studied the Bible and the Talmud. The young Selman quickly learned Hebrew and Russian literature, history, and geography. And he was frequently picked as the one to read a chapter from the Bible or deliver the blessing on the initiate at a bar mitzvah.

Jews and Ukrainians lived side by side in Novaya Priluka. The Waksmans lived in the wealthier part of town. His mother gave birth to a daughter when Selman was seven, but the daughter died less than two years later of diphtheria.

In the Waksman household there was usually money left over to help a needy niece or nephew, or the less fortunate on the town’s poorer side. Encouraged by his mother, Selman gave free lessons in Hebrew and Russian, and later private lessons to the sons of the wealthier inhabitants and the richer peasants.

The first Russian uprising of 1904–05 did not affect little Novaya Priluka, but revolution was in the air. Selman’s friends were divided on the future. One believed that socialism was inevitable, and another, the Zionists, looked for salvation in a new homeland in Palestine. Selman was uncommitted, with divided sympathies—on the fringe of the two groups. Instinctively, he favored the revolutionaries, but he disliked the fierce arguments over the form of a future government, should a revolution be successful. He was more interested in pursuing a higher education, but the way was blocked because he was a Jew. He could not enter the gymnasium or go on to university without passing a special competitive exam.

In 1908, he left with four friends for Odessa to be coached, at a price, for the crucial exam. He passed "with flying colors and returned home a hero now set to attend university in Odessa. But suddenly he suffered a terrible blow. In the summer of 1909, his mother died of an intestinal blockage. During the seven days of mourning, he read and reread the Bible, perhaps for the last time."

He returned to Odessa to find new political barriers. Candidates for the university had to have been born in Odessa or have spent the last twenty years there. Selman managed to bribe a government official to give him the necessary papers, but when his friends were refused admission, they all decided to leave Russia for good. He thought briefly of going to Switzerland, a destination favored by his father, but his cousins in Philadelphia, having heard of his mother’s death, urged him to join them.

In October 1910, Selman and a group of five young people from Novaya Priluka, three men and two women, left by train for Bremen, and thence for America. They landed in Philadelphia on November 2.

BY THE BEGINNING of the twentieth century more than three million Russians had immigrated to the United States. Waksman, now aged twenty-two, went to work on his cousin’s five-acre farm near Metuchen, New Jersey, thirty miles from New York City. He helped with the hens, learned how to make compost from stable manures, and planted vegetables in the spring for local markets. His cousin was a great teacher, and at the end of his first year Waksman published an article in the Rural New Yorker titled How I Raised a Flock of Chickens, for which he was paid his first ten dollars.

Selman Waksman as he was about to leave Russia in 1910. (Special Collections and University Archives, Rutgers University Libraries)

But his goal was college. He thought of becoming a doctor, and was accepted at Columbia University medical school. Another cousin, who was a dentist, offered to help with the fees, but Waksman did not want to be tied down by debt.

So he had to take what was available, and in those days the most accessible institutions were the land grant colleges. These were created by the Morrill Act of 1862, which gave states land grants to fund public agricultural and engineering colleges. One of the first such establishments was at Rutgers College, established originally as Queen’s College in 1766 and still a small institution at the turn of the twentieth century.

Rutgers was only eight miles from Metuchen, and Waksman’s farmer cousin suggested he should go and see Jacob Lipman, another Russian immigrant, who was then head of the Department of Bacteriology. By 1911, Lipman was an established figure in soil science, having made his reputation on studies of bacteria that make nitrogen available for crops.

Waksman was persuaded that a course in agriculture would satisfy his curiosity about the biochemistry of living organisms, plus he was awarded a full scholarship. Aged twenty-three, he found it hard, at first, to be among much younger boys of seventeen, who teased him for his clumsy English and dislike of sports. He also found the level of teaching poor. In his sophomore year, his chemistry professor was "an unimaginative bore, physics was a great disappointment," he found the courses on American and English literature uninteresting, and he disliked Shakespeare. The French teacher was enthusiastic, but he felt he already had enough knowledge of foreign languages. The only courses that earned his approval were zoology and botany.

At the end of his second year, he yearned for independence and moved into a room in an old house on the college farm, paying for his accommodation by working in the college greenhouse and helping out in the laboratory. He bought cracked eggs from the Poultry Department at eleven cents a dozen.

Another and more important reason for striking out on his own was the arrival in New York from Novaya Priluka of a young woman named Deborah Mitnick. The daughter of a prosperous grain merchant, she was the sister of Waksman’s best friend, Peisi, back in Ukraine, and after finishing grade school she had come to stay with her cousins, braving the voyage from Riga on her own in the middle of winter. She was good looking, bright, and energetic. In America, she quickly joined Peisi in New York—he had come to America with Waksman, in 1910. She worked in a sweatshop, became a member of the International Ladies’ Garment Workers’ Union, and took singing lessons. She was affectionately known as Bobili, Russian for young grandmother, a nickname given in the hope that she would reach a ripe old age. Waksman had been her tutor in Novaya Priluka, had always admired her, and planned to marry her.

In his studies, Waksman had at last found a subject that interested him: general bacteriology under Dr. Lipman. "I felt that I was finally under the tutelage of a master," he wrote. Waksman was the only student majoring in soil microbiology. For his senior thesis he listed the different groups of microbes—bacteria and fungi—but he was fascinated by the actinomycetes. He dug trenches on the college