by Arthur Allen
One could say that Weigl dithered on the next step, which was human testing of the vaccine. More charitably, one could say that he was conscious of his lack of a medical degree and metabolically inclined to great deliberation. Whatever the case, Weigl never conducted a clinical trial of his vaccine, and until 1930 did not even vaccinate his staff. Weigl’s hesitation on this step is striking and contrasts sharply with the histories of more ambitious or fame-hungry investigators who pushed for human testing in order to establish themselves as scientific leaders. The first human experiment with the Weigl vaccine was published not in Lwów but in Tunisia, where the Pasteur Institute had taken a great interest in the vaccine.
The labs in Lwów and Tunis had developed a strong bond, mediated through the scientist Hélène Sparrow, a Russian-born, half-Polish, half-British scientist who fled to Warsaw in 1920 and spent the next 13 years working on public health and vaccination campaigns under Ludwik Hirszfeld at the National Institute of Hygiene. She also spent time in Paris, in Mexico, and in Weigl’s laboratory, before joining the Pasteur Institute in Tunis, where she introduced Charles Nicolle to Weigl’s louse-inoculating techniques. In 1928, Nicolle and Sparrow vaccinated four children, ages three to seven, with vaccine that Weigl had provided them during a visit to his institute. Several months to a year later, the children were injected with live typhus germs from an infected guinea pig brain. While certainly unethical by modern standards, this experiment had behind it a kind of logic. Typhus and some other pathogens, particularly viruses, are rarely fatal to children, in whom they produce less serious disease. The trial was a success in that the children remained well. The Pasteur Institute subsequently vaccinated all of its typhus specialists with the Weigl vaccine.
Shortly afterward, Weigl’s earliest collaborator, the lab technician Michał Martynowicz, decided to take things into his own hands in Lwów. Weigl had organized the laboratory so that only staff who had previously suffered typhus, and thus were presumably immune, could feed typhus-infected lice or work on other lab problems involving live typhus germs. Martynowicz, who had suffered a bout during World War I in Serbia, fed infected lice, while his wife, Rozalia, fed healthy ones. Without Weigl’s permission, Martynowicz vaccinated his wife repeatedly, and she then began feeding cages of typhus lice. “When I learned of this experiment I stopped it immediately,” Weigl wrote, “but by that time she had already been bitten hundreds of times.” Rozalia, to everyone’s satisfaction, did not become ill. She was permitted to continue feeding the lice. And gradually, Weigl was pushed to allow the vaccine to transition from an experimental phase to public use.
Weigl, Sparrow, and the Nobelist Charles Nicolle, Lwów, 1938. (Courtesy of National Museum, Przemyl. Photograph of original by S. Kosiedowski.)
By the late 1920s, Weigl’s lab had become a mecca for serious typhus researchers. The endless supply of typhus germs he could offer visiting scientists was well worth the eight-hour train ride from Warsaw or the two-day trip from Vienna. And come they did—French researchers from the Pasteur Institute, Germans from the Koch Institute in Berlin and the Institute for Naval and Tropical Diseases in Hamburg, Americans from Columbia and Harvard, Russians and Romanians, Britons, Czechs, and Danes. One of the visitors was Hilda Sikora, a self-taught, Madagascar-born parasitologist who had been trained by Rocha Lima in Hamburg. Sikora was a talented artist who drew extremely detailed anatomical sketches of lice and continued to work with them even after developing a severe asthmatic reaction. She observed every habit and preference of the tiny vermin with an attentiveness that tottered perversely on the border of love. (She was not alone in her passion: Zinsser once wrote, “One cannot carry pill boxes full of these little creatures under one’s sock for weeks at a time without developing what we may call, without exaggeration, an affectionate sympathy; especially if one has taken advantage of them for scientific purposes and finds each morning a corpse or two, with others obviously suffering—crawling languidly, without appetite, and hardly able to right themselves when placed on their backs.”) Sikora’s personality was perhaps fitting for this arcane field; she was single and ran a cat shelter in her home and sometimes came to the office with a pet snake, which would pop out of her lab coat pocket as she spoke with colleagues, testing the air with its forked tongue. Yet she knew as much about typhus as anyone in the field. The Nazis at the Hamburg institute fired her in 1943 because of her independent attitudes, and she spent the rest of her life as a painter in Vienna.
Weigl’s reluctance to test his vaccine on people may have stemmed from the series of terrible accidents that occurred in his laboratory. Over a decade, the lab saw at least 10 typhus outbreaks, including one that claimed the life of Edmund Weil of Prague, co-inventor of the Weil-Felix diagnostic test. Weil had come to Lwów, in search of typhus germs, in May 1922. He dreamed of creating a typhus vaccine and thought he might do this by keeping R. prowazekii alive in small mammals. While inoculating a rabbit at Weigl’s side, Weil accidentally splashed his eye with an emulsion of louse intestines. Disregarding the accident, he finished his work and returned home, but fell sick and died two weeks later. Weigl’s son Wiktor also got typhus, while playing in the laboratory. Yet rather than keeping researchers away, the risk of typhus seems to have attracted them. “The Weigl laboratory was surrounded with an aura of secrets and anxiety, partly because the work there was dangerous,” said Władysław Wolff, who joined the lab in 1928. “A young person was attracted to that—because it was dangerous, and because of the strange things people were doing there. It was romantic, an adventure.”
Around this same time, Rajchman and Hirszfeld at the Hygiene Institute began to press Weigl to release supplies of his vaccine for cleanup efforts against typhus in Poland. Some 300 Polish doctors died fighting typhus between 1915 and 1929, and it was not easy to enroll unprotected medical staff in these campaigns. There is no record of communications between Weigl and the health authorities regarding this matter, but the Weigl lab began to increase production, to about 30 doses per day by the end of 1930, and to more than 100 per day a few years later. In 1931 and 1932, Polish authorities vaccinated a total of 2,794 people, mostly medical staff and others who came into close contact with typhus patients. Only one case of typhus was reported in the vaccinated group, with the exception of a few instances in which typhus had been incubating in patients prior to vaccination. The campaign lacked scientific rigor: vaccines were distributed on the basis of perceived need, and no effort was made to randomize the results or provide placebo to staff in dangerous areas. Yet the anecdotal evidence offered a powerful suggestion that the vaccine worked. And the news of its success began to trickle out of Lwów and into the wider world.
In the summer of 1931, in a clearing near the family’s house at Ilemnia, young Wiktor Weigl looked up from his mud pies and saw a curious figure—a tall man in flowing dark robes and a ridiculously wide-brimmed black hat. The visitor, crossing the stream toward the house in the company of two local mountain men, was Josef Rutten, a Belgian priest resident in China. He had been trying to track down Weigl for a year. Rutten led the Scheut missionaries, who worked in some of the poorest villages of Mongolia and northern China, barren areas, freezing cold in the winter, where lice were plentiful and typhus rife. Since 1908, Rutten explained to Weigl, the disease had killed 84 of his priests—nearly half. The mission was spread across vast, desolate areas, and there was no way to avoid lice infestations. Could Weigl help him? Weigl immediately provided 600 doses of the vaccine to Rutten, who returned to Beijing and called together his 200 priests for three rounds of vaccination over a month. During the next several years, the only member of the Scheut order to die of typhus had not been present for the vaccinations. Elated by the vaccine’s efficacy, Rutten sent Zhang Hanmin, a student from the microbiology department at Fu Jen Catholic University, to Lwów, where he spent several months learning Weigl’s technique before returning to establish a louse-vaccine production facility in China.
Vaccination and delousing ca
mpaigns were also organized in various typhus-endemic regions of Poland, in particular south of Lwów. Piotr Radło, a Hygiene Institute officer, Weigl confidante, and district physician in the town of Jaworow, traveled frequently with public health scientists to the isolated mountain towns. In the 1930s, they fought outbreaks of the disease around two small Carpathian towns, to prevent it from spreading to Skole, a prosperous summer resort, and to nearby ski areas. By 1938, about 68,000 Poles had been vaccinated; by March 1940, the number had increased to 160,000. Among the vaccinated there were only 30 recorded cases of typhus, and no deaths. Weigl’s vaccine contributed to a dramatic decrease in typhus in Poland, though most of the decline was probably due to other public health measures like louse control. Overall, the number of cases sank from 44,000 in 1919 to 8,500 in 1922 and to 400 in 1929. There were never more than 1,000 per year from 1930 until the beginning of the war.
As Weigl’s fame grew, lab administration and the entertainment of visiting dignitaries chewed up more and more of his time, which he did not appreciate. When he got a chance, he’d skip town and head for the Carpathians to join his boys. “When he came to our field lab he became himself again,” recalled one of his assistants. “They’d call him from Lwów, saying he had an important visitor, but he preferred to stay with us and look through our microscopes, and in the afternoons we’d go fishing and he’d tell us anecdotes from his life, the happy and jovial professor. When his train left the station in Slawsko, he’d wave out the window a long time.” A grainy film that Radło produced in the early 1930s shows the Lwów physicians and technicians driving a Red Cross panel truck over mountain roads to mud-and-thatch dwellings where women washed clothes by beating them on rocks in the river, and families harvested wheat with scythes. The sight of a motor vehicle was rare enough to bring whole villages out to have a look. The public health men set up delousing tents and fumigated houses with hydrogen cyanide while vaccinating peasant leaders and caregivers. Some of the people in the region were religious Jews; many others were Hutsuls—an isolated highland people who spoke their own dialect of Ukrainian. Entire villages surrendered their clothes and entered large white field tents, naked, while their clothes were disinfected in large steam kettles. Young boys happily bathed in cauldrons of hot water provided by the fieldworkers. If there were no roads to the afflicted towns, the doctors brought their gear on horseback over rough and muddy trails.
The fieldwork gave Weigl’s team new insights into the survival of typhus in nonepidemic periods. They noted that when a Hutsul man died, his clothes were kept in the family attic. Louse feces in these clothes, it turned out, could still infect a guinea pig several months after their wearer had died. Lice lived comfortably in the folds of the peasants’ gaily colored sheepskins, protected by the ill repute in which their wearers held bathing. In many rural parts of Poland, peasants put on their jackets in the fall, fastened them with wire, and took them off in the spring. The hygiene teams found that, vaccination aside, the best way to combat typhus was to encourage village elders to buy a few extra shirts and nightgowns, and to wash them regularly throughout the winter.
As the vaccine passed from an experimental to a manufacturing phase, Weigl’s staff in the early 1930s grew to about a dozen scientists with an equal number of technicians and assistants, and more and more louse feeders. The expansion of the Weigl lab and the growing demand for his vaccine required technical innovation. To raise millions of healthy lice, one needed improved systems to breed, infect, and harvest the lice. In the system devised by Weigl and his staff, larvae hatched in temperature-controlled cabinets were put in matchbox-size cages to feed on human blood twice a day for about 10 days. The next step was to inject a diluted, typhus-contaminated slurry of louse guts into the rectums of the healthy lice. Initially, Weigl injected each louse by hand, placing it on a slide or a paper card and injecting a pipette attached to a piece of tubing taped over the end of a syringe. Gradually, he mechanized the technique, attaching the pipettes to a hydraulic, foot pedal–controlled pump that squirted a microdroplet of the emulsion into the louse rectum once the pipette had been moved into place. A device known as the Weigl clamp held as many as 50 lice at a time immobile, with their rear ends presented for injection.
Putting lice into a Weigl clamp. (Courtesy of Emil-von-Behring-Bibliothek, Philipps-Universität Marburg.)
After the artificially infected lice had fed on blood again for about five days, they swelled and turned ruby red. This signified that the growing bacterial population in the cells lining the louse intestines had caused them to leak or even burst, which rendered the creatures incapable of digesting the fresh blood they fed upon. At this point, the cages were removed and the lice taken to the preparatorzy (dissectors), who used a small lancet to remove the blood-filled intestines, which were crushed and homogenized in a mortar, centrifuged to remove cellular debris, and diluted in saline solution with enough phenol to kill the bacteria. The dead bacteria could no longer infect a person, but the intact proteins in the dead bugs stimulated a person’s immune system to protect against typhus.
Vaccination of a large population required mind-boggling amounts of lice nourished on the blood of patient human feeders. Weigl estimated in 1924 that each infected louse intestine contained 10 to 100 million bacteria, and that each individual required the neutralized contents of about 5 billion of these germs to be fully immunized. The first vaccination series Weigl designed contained the ingredients of 350 louse intestines, split into three shots spaced over two- to three-week intervals. The total was reduced to 175 intestines after a few years, and by 1935 Weigl recommended a total of 90 intestines per three doses. The vaccine could be preserved in a refrigerator for three years; immunity lasted at least a year after the third vaccination.
The need for lice feeders was enormous as demand for vaccine grew. By the end of 1933, there were 50 people feeding lice at least once a day in the lab. Many were staff members, others hired to perform this very exotic form of blood donation. It was one of the creepiest jobs one could imagine, but Weigl and his staff were rather matter-of-fact about it. An associate provided the following job description: “Lice feeders must be chosen with care. We recommend the choice of mature men, with calm temperaments and skin that is healthy and smooth. They must have no predisposition to skin conditions such as eczema or uticarias. They must be capable of great patience and self-control—in order to resist the desire to scratch. They must be well behaved and assiduous about cleanliness. Their workplace must have a shower that they make regular use of.” Adam Finkel, a hematologist working in the Weigl lab, noted in a 1933 publication that 100 lice—about enough to make a three-dose vaccine series—typically sucked up to 40 milligrams of blood in 15 minutes; they had to feed twice a day for eight days before they were ready to harvest. A typical louse feeder nourished 30,000 lice at a time, meaning that the blood of one person feeding lice for a little over a week could provide vaccine for 300 people. Longtime feeders often developed allergic reactions that forced them to stop feeding. They also had to be careful about their own nutrition. Feeding 30,000 lice twice a day resulted in the loss of about 720 grams (a pound and a half) of blood in one month.
A louse feeder. (Courtesy of National Museum of Health and Medicine.)
If the work was perilous, the mood was often playful. Weigl was curious about the private lives of his young employees, and enjoyed occasionally visiting art studios and bars with them. He allowed his staff to make amateur films in the institute. One shows a “Louse Theater” production put on by the epidemiologist Piotr Radło, featuring such titles as “Heroic Expeditions of the Horsemen of Death” and “Work Is No Dishonor.” Weigl was an idiosyncratic boss. Writing was torture and a waste of time as far as he was concerned. His lack of interest angered assistants, because it reduced the number of publications they could put on their résumés. His style was to allow junior scientists to develop their own questions and experimental designs. He approved of independence, but when unimpressed by a p
erson or idea, did not hide his displeasure.
Whatever Weigl was doing involved a certain degree of obsessive perfectionism. He always had the latest mechanical devices—though he never owned a car—and often made small improvements on them. For instance, he insisted that pots be set on a medium flame for most efficient heating, and that phosphorescent matches be struck at a certain angle in order to have the best chance of lighting. In his laboratory, Weigl designed microscope lens adjustment knobs adopted by the German companies Reichert and Zeiss. He neither requested nor received royalties. Weigl’s employees learned not to approach him while he was walking in the Botanical Garden, where he elaborated his thought. He usually addressed them with a familiar “you,” or “my child,” or dziecinko, roughly translatable as “kiddo.” If he used the formal pan (Mr.), it meant something was wrong, or important.
Deeply immersed in work, Weigl often seemed oblivious to his surroundings. On one occasion, goes a story that circulated in the lab, Weigl was staying at the Bristol Hotel in Warsaw and after a meeting at the health ministry asked the taxi driver to take him to the best restaurant in town, which turned out to be in the Bristol itself. After lunch he forgot where he was staying, but the waiters called around until they found him reserved at the Bristol. By then, however, Weigl had forgotten where he was, so he left the restaurant, got into a taxi, and asked the puzzled driver to take him to the Bristol.