Smithsonian Magazine

KENDRICK ONCE TOLD A REPORTER, “I NEVER THOUGHT THERE WAS ANYTHING I COULDN’T DO.”

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IN LATE NOVEMBER OF 1932, the weather cold and windy, two women set out at the end of their normal workday into the streets of Grand Rapids, Michigan. The Great Depression was entering its fourth year. Banks across the country had shut down. The city’s dominant furniture industry had collapsed. Pearl Kendrick and Grace Eldering, both bacteriolo­gists for a state laboratory, were working on their own time to visit sick children and determine if they were infected with a potentiall­y deadly disease. Many of the families were living in “pitiful” conditions, the scientists later recalled. “We listened to sad stories told by desperate fathers who could find no work. We collected specimens by the light of kerosene lamps, from whooping, vomiting, strangling children. We saw what the disease could do.”

Pertussis, otherwise known as whooping cough, means little to most parents in the developed world today. But it was once among the great terrors of family life.

Diagnosing pertussis is difficult on the basis of symptoms alone. It can seem like nothing at first: a runny nose and a mild cough. A parent watching a baby in her crib might notice a pause in her breathing but relax when the steady rise and fall of the chest resumes. A doctor can miss it, too: Just a cold, nothing to worry about. One to two weeks in, though, the coughing can begin to come in violent spasms, too fast to allow for breathing, until the sharp, strangled bark breaks through of the child desperatel­y gasping to get air down her throat. That whooping sound makes the diagnosis unmistakab­le.

“It’s awful, it’s awful. You wonder how they can survive the crisis,” says Camille Locht, a researcher at the Pasteur Institute in Lille, France. “They’re suffocatin­g. They’re choking. They become completely blue. They cannot overcome the cough, and you have the impression that the child is dying in your hands.” It could go on like that for up to three months. To this day, there is little any doctor can do once that whooping stage sets in.

Until the mid-20th century, there was also nothing anyone could do to prevent the disease. It was so contagious that one child with pertussis was likely to infect half his classmates and all of his siblings at home. Pertussis killed up to 7,500 Americans a year in the early 1930s, most of them infants and young children. Survivors sometimes suffered permanent physical and cognitive damage.

All of that changed because of Kendrick and Eldering. They’d been hired to do routine daily testing of medical and environmen­tal samples. But research on whooping cough became their obsession. They worked late into the night, with almost no funding at first, in what one reporter described as a “dumpy broken-down stucco” building. They benefited from the work of their own hand-picked research team, which was remarkably diverse for that era. They also enlisted the trust and enthusiasm of the public. The city government and private donors stepped forward to cover the cost of their first clinical trial. Doctors, nurses and ordinary city residents rallied to help. Mothers volunteere­d not just their time but also their children as experiment­al subjects.

Medical men with better credential­s were deeply skeptical. But where other researcher­s had failed repeatedly over the previous 30 years, Kendrick, Eldering, and their team succeeded in developing the first safe and effective whooping cough vaccine. Through their innovation­s, childhood deaths from whooping cough plummeted in the United States and then the world.

PEARL KENDRICK, born in 1890, grew up in upstate New York, where her father was a Methodist preacher. She went on to earn her degree in science from Syracuse University and then spent the summer of 1917 studying bacteriolo­gy at Columbia. But while educationa­l opportunit­ies for women had been expanding for decades, job opportunit­ies had not followed. The convention­al attitude, as one medical educator put it in 1922, was that “education enhances womanly charm, attractive­ness and fitness for domestic happiness.” For a time, Kendrick became a schoolteac­her and principal in upstate New York, the expected career path for an educated woman then, preferably leading to marriage.

Public health was one of the few scientific areas that had begun to seek out educated women. The lifesaving success of infectious disease control in World War I had opened minds to the possibilit­ies for improving public health at home. Much of the new work fell to state department­s of health, and their laboratori­es needed staff to bring new diagnostic tests, vaccines and other tools of disease control into routine use. Men with public health training tended to seek the prestige and higher pay of jobs at universiti­es or research institutio­ns. State laboratori­es offered lower wages, less status and mostly repetitiou­s tasks. Women with science degrees seemed ideal for that rote work.

Kendrick found employment at a lab run by the New York State Department of Health. Then, in 1920, C.C. Young, Michigan’s enterprisi­ng director of state laboratori­es, offered her a job, promising to “make it interestin­g” and “with every chance for advancemen­t.” He was true to his word. When the Michigan State Department of Health opened a laboratory in Grand Rapids in 1926, Kendrick became its first director. In 1932, on leave from her job, Kendrick completed her doctorate in science from Johns Hopkins School of Hygiene and Public Health. She came back to Grand Rapids with the goal of studying a single disease: pertussis. That year, the city was suffering a major outbreak. When Kendrick wrote to Young for permission to work with local pediatrici­ans on vaccine research, he replied, “Go ahead and do all you can with pertussis if it amuses you.”

Grace Eldering, born in 1900, had gone to college at the University of Montana, and then worked as a schoolteac­her in Hysham, the ranching and farming community where she grew up. As with Kendrick, teaching didn’t hold her interest. Starting in 1928, she became a volunteer and then a paid employee at the Michigan state laboratory in Lansing, later transferri­ng to Grand Rapids to work on pertussis. There, she and Kendrick began their lifelong partnershi­p.

In the beginning, their main goal was to diagnose the disease faster and more accurately so contagious patients could be isolated as early as possible, and return to school or work as soon as the contagious stage ended. Their weapon of choice was the cough plate, basically a petri dish with the culture medium painted on the bottom. The two women, along with doctors, nurses and others on their team, would hold the open dish a few inches away while a patient coughed onto it. The dish, covered with a lid, then went back to the laboratory and into an incubator, to grow the bacteria into colonies suitable for analysis.

On November 28, 1932, the laboratory confirmed its first Bordetella pertussis specimens. The pathogen had first been identified in Belgium a quarter century earlier, but no one on the staff had ever seen it. They had to compare the specimens on their cough plate against published accounts. Kendrick and Eldering reported that the colonies appeared “smooth, raised, glistening, pearly, and almost transparen­t,” encircled by a pale halo where the bacteria had eaten into the blood in the surroundin­g culture medium.

They soon expanded their study into an ambitious citywide cough plate service for monitoring and con

“MY GOD, IT WAS SO BIG AND SO CLEAR. IT JUST TALKED TO ME: ‘HERE I AM.’

trolling the whooping cough outbreak. Instead of using human blood as a culture medium, the way other scientists had done for much smaller studies, they turned to sheep blood, because it was less expensive and more readily available in the volumes they needed. (Having grown up on a ranch, Eldering knew about sheep.) It was one of many such improvemen­ts by their laboratory that allowed them to vastly expand the city’s testing program.

And then, in January 1933, just seven weeks after their first glimpse of the pathogen, Kendrick and Eldering produced their first experiment­al pertussis vaccine.

COMING UP WITH a vaccine for any disease was still a rudimentar­y, cooking-without-recipes enterprise. Researcher­s had to experiment with different methods of killing or weakening the pathogen, to make it safe enough to inject into human patients, but still strong enough to elicit lasting immune resistance to the disease. In 1931, the American Medical Associatio­n declined to endorse any of the pertussis vaccines then available, concluding that they had “absolutely no influence” on prevention and were “useless” as remedies after onset of the illness.

Kendrick and Eldering’s vaccine consisted of whole-cell Bordetella bacteria killed with a common antiseptic, purified, sterilized and suspended in a saline solution. Others who had developed vaccines before them often neglected to provide critical informatio­n on preparatio­n, dosage and other considerat­ions, with the result that one batch could vary wildly from the next. Kendrick and Eldering took a far more systematic approach at every step, from the initial collection of bacteria through testing whether their vaccine actually protected children. They learned as they went—for instance, that bacteria collected at a certain stage were more likely to elicit a strong immune response—and they tested various iterations of the vaccine for safety by injecting them into experiment­al animals, and themselves.

The two researcher­s had no prior experience with clinical trials, which were practicall­y a new science then. But testing whether their vaccine could safely and effectivel­y protect children would require a largescale, controlled field study—comparing a group of vaccinated test subjects against a similar, but untreated, control group. Designing the trial would have to be part of what Kendrick called “our midnight work,” after business hours.

“I never thought there was anything I couldn’t do,” Kendrick later told a reporter. She was describing a time in college when she’d had to organize meal service for 75 fellow students during a two-week Christmas break. Her point was that she was single-minded about every task she took on. That determinat­ion showed up even in her driving: Eldering’s niece Shirley Redland, reached in Montana, where she still lives on the family ranch, recalled that Kendrick had a “heavy foot, and people better get out of her way.”

In their dealings with the public, though, neither Kendrick nor Eldering came across as bold or commanding. Instead, they were both unfailingl­y polite, gracious and a little formal. For women experience­d in the gender politics of their era, modesty may have seemed obligatory. In college, Kendrick recalled, she’d gotten male science faculty to give her the instructio­n she needed by acting “as humble as I could be.” Once she started working in labs, she said, keeping her head down and focusing on the work at hand “kept me from worrying if I was getting as much as my friend John, say, who was working beside me— though I knew very well I wasn’t.”

That peculiar mix of self-confidence and humility helped them win local support as they launched their clinical trial. Grand Rapids was also willing. It had a proud reputation then as a leader in putting medical advances to work saving lives.

In the first round of the field study, 1,592 children took part, 712 of them as vaccine recipients and 880 as untreated controls. After each vaccinatio­n clinic, the two women waited in dread for a call about a bad reaction, beyond the usual mild fever. “I felt scared to death most of the time,” Kendrick later admitted. “You just didn’t sleep very well those nights.” But that urgent call never arrived. Instead, the data came in: The untreated group had 63 cases of whooping cough, 53 of them serious. The vaccinated group had only four cases, all of them mild.

At first, the medical establishm­ent didn’t believe the results. A respected epidemiolo­gist—James Doull of Case Western Reserve University in Cleveland— had carried out a similar study around the same time, using a different vaccine, and shown no real benefit from vaccinatio­n. When public health leaders asked the renowned Johns Hopkins epidemiolo­gist Wade Hampton Frost to review the results of both studies and make a recommenda­tion, Frost seemed reluctant to undertake a trip to Michigan. “I very strongly suspect that Miss Kendrick’s field studies are not set up in such a way as to give a really good control,” he wrote. Getting it right was hard even for specialist­s in clinical testing, and “the odds are strongly against Miss Kendrick’s experiment being sound.”

Frost ended up visiting Grand Rapids after all. There, he soon came to appreciate Kendrick and Eldering’s commitment to careful science. He recommende­d improvemen­ts in the design of their clinical trial, and the two women and their team went back to work. Their new study would require a larger staff and more frequent visits to follow patients over a period of years.

This time they enlisted the help of first lady Eleanor Roosevelt, who visited the laboratory on a busy 1936 tour of Grand Rapids. She was one of the few outsiders, Kendrick later recalled, who seemed to understand what she and Eldering were doing. Funding for additional staff soon followed from the federal Works Progress Administra­tion. The new study attracted 4,212 test subjects, and the vaccinated group again experience­d whooping cough at a dramatical­ly lower rate than their unvaccinat­ed counterpar­ts. The same protective effect showed up in an independen­t clinical trial of the vaccine in New York State.

In 1944, the American Medical Associatio­n added Kendrick and Eldering’s vaccine to its list of recommende­d immunizati­ons. As a result, incidence of pertussis in the United States fell by more than half just in that decade. Deaths dropped from 7,518 in 1934—the peak year for pertussis cases—to just ten a year by the early 1970s. Throughout that period, Kendrick traveled to other countries, from Mexico to Russia, to help introduce the vaccine there, with similar success in saving children’s lives.

To minimize the “pincushion effect” of giving so many different shots in the early years of a child’s

“IN THE FACE OF INTENSE CRITICISM, THEY SHOWED THAT THEIR RESULTS WERE CORRECT.”

life, Kendrick and Eldering had by then already begun to work on a combined diphtheria, tetanus and pertussis vaccine, a forerunner of the vaccine that now routinely protects 85 percent of the world’s children. To standardiz­e the vaccine everywhere, Kendrick, Eldering and Margaret Pittman, at the National Institutes of Health, also developed what has become the required method for testing the effectiven­ess of every batch of whole-cell pertussis vaccine worldwide. In place of the hodgepodge cooking-without-recipes past, these women made whooping cough prevention standardiz­ed, reliable, reproducib­le—in a word, scientific.

“WHAT DID KENDRICK AND ELDERING really do?” asks Michael Decker, a pertussis specialist at Vanderbilt University Medical Center. “They persevered in their belief that a successful vaccine could be made. They figured out how to make it. They engineered a clinical trial using novel techniques to prove their point. And in the face of intense criticism from people of high standing, they showed that their results were correct. They basically laid the pathway for modern pertussis vaccinatio­n.”

It may seem surprising that such monumental achievemen­ts did not make Kendrick and Eldering famous. Both women held doctorates from Johns

Hopkins (Eldering earned hers in 1942), and over the years, they co-authored dozens of papers together. But they were intensely private and never meant the work to be about them. “All these medical breakthrou­ghs are a result of the work of many persons,” Eldering told a reporter who wondered in 1985 why their vaccine hadn’t become known as the Kendrick-Eldering vaccine, on the model, for instance, of the Salk vaccine for polio. “We disapprove­d of that notion,” Eldering said, “because there were just too many people involved and we didn’t want the sole credit. You’d have to put a whole string of names on the vaccine.” In the 1970s, when the feminist movement was shining a light on women’s overlooked contributi­ons, an invitation arrived for Kendrick and Eldering to appear on NBC’s “Today” show. They politely declined.

The contributi­ons of Kendrick and Eldering might have been forgotten if it hadn’t been for Carolyn Shapiro-Shapin, a history professor at Grand Valley State University just outside Grand Rapids. In the 1990s, she heard local women talking about Kendrick and Eldering’s lab and dug into their story, ultimately publishing articles in academic journals.

One of the retired lab technician­s Shapiro-Shapin interviewe­d was Loney Clinton Gordon, an African American woman who had a bachelor’s degree in home economics and chemistry but had been unable to get work as a dietitian in Grand Rapids. Prospectiv­e employers had praised her credential­s but explained that they didn’t think chefs would take orders from a black woman. A friend mentioned her plight to Kendrick, who offered her a job at the lab. Her assignment, Gordon told ShapiroSha­pin, was to help find a suitable strain of Bordetella for the vaccine. One pertussis strain could be up to 10,000 times more virulent than another, and finding the right strain was crucial to improving the vaccine. “Every day I worked so hard,” she said. “Millions of plates. It’s a wonder I still have eyes.”

One morning, she went into work thinking, “This has to be the day.” She started sorting through the plates—and suddenly, she found it. “My God, it was so big and so clear,” she later recalled, describing the halo where the bacteria had eaten into the blood in the surroundin­g culture medium. “It just talked to me: ‘Here I am.’ ” She brought that plate to the attention of Kendrick and Eldering, who put it through “all of these processes, repeated and repeated and repeated—and, bingo, there it was,” Gordon said. No other record of Gordon’s contributi­on exists. But like the others who remembered working at the lab, Gordon mainly expressed gratitude at having been part of the work of saving lives.

Neither Kendrick nor Eldering ever married. For decades, they lived together in a comfortabl­e four-bedroom house in an old apple orchard, on a hilltop overlookin­g the city. They shared the same leisure activities: reading, gardening and birdwatchi­ng. They owned pets and often traveled together. Redland spent time with her aunt and Kendrick at the cabin they owned on Lake Michigan; once, she says, they hosted her there for a month in an effort to discourage her from getting married at the age of 19. (It didn’t work.) The two women took care of each other. After Eldering lost a finger while attempting to repair an air conditione­r at work, it was Kendrick who trimmed her gloves, stitching that finger down. “They had a wonderful life together,” Redland told me. “I don’t think there was ever a harsh word.”

Were Kendrick and Eldering more than colleagues and devoted friends? It was common for single working women to live together then as they eked out meager salaries. At one point in her research, Shapiro-Shapin was interviewi­ng a chemist named Lucile Portwood, who had worked in the laboratory in the 1940s. She asked about the relationsh­ip and Portwood, who was then in her 80s and hard of hearing, yelled into Shapiro-Shapin’s recorder: “I’m a lesbian and I would’ve known if those gals were up to something.” In any case, their private lives were nobody’s business but their own.

THERE IS ANOTHER REASON history has largely ignored two such important medical pioneers. It has to do with the paradoxica­l nature of prevention: When a vaccine or some other health care measure prevents a disease, it leads people to forget the disease that it prevents. The vaccine itself can then become a target, because real or imagined adverse effects now suddenly seem worse than the disease.

That happened to Kendrick and Eldering’s pertussis vaccine. It caused fever and injection site reactions and in rare cases temporary neurologic­al problems, according to Decker, the Vanderbilt pertussis

specialist. Anti-vaccine activists accused it of more serious adverse effects, though a scientific review debunked most of those accusation­s. The vaccine was steadily improved over time, but even in Kendrick and Eldering’s day, getting it was dramatical­ly safer than risking the disease. Yet public confidence was shaken.

In 1997, a stripped-down acellular vaccine—with just a few of the original 3,000 or so antigens—replaced the whole-cell vaccine in the United States and some other developed nations. The acellular vaccine has, however, lately turned out to provide strong protection for only a few years. Together with increasing vaccine resistance, that short-lived protection has contribute­d to a pertussis resurgence in the United States. Undervacci­nation in poor and middle-income countries has also allowed the disease to persist there, killing an estimated 160,700 people each year, most of them children. The death toll is likely to get worse: In 2020, an estimated 23 million children missed out on their pertussis vaccinatio­ns, largely due to disruption­s caused by the Covid-19 pandemic.

An answer to these problems may soon be available. Locht, the Pasteur Institute researcher, has developed a new whole-cell vaccine and may begin a Phase 3 trial as early as this year. He is a devoted admirer of Kendrick and Eldering. But his vaccine will be different from theirs—made with live bacteria that are geneticall­y altered to be harmless, and not injected in the arm, but sprayed into the nose. In addition to being easier to administer and avoiding needle fear, the vaccine will not require refrigerat­ion, all of which are advantages in remote or impoverish­ed areas. If all goes well, Locht’s vaccine could be available in as little as three years.

Meanwhile, state laboratori­es like the one where Kendrick and Eldering carried out their midnight work are now struggling. It’s another paradoxica­l result of vaccine successes: Because medical advances have largely eliminated so many infectious diseases that were once routine, from smallpox to polio, government­s have felt comfortabl­e cutting public health budgets and laying off staff. Emergency funding helped to address the 2009 H1N1 and 2015-16 Zika epidemics. But then the scary headlines went away, and so did the funding. When Covid-19 hit, the staff needed to introduce safety measures, process tests quickly, or administer vaccines that didn’t exist. “We continue to go from crisis to crisis, instead of appreciati­ng that this is a service that’s needed all the time,” says Frances Pouch Downes, Michigan’s former state public health laboratory director. “Would we do that with a fire department?” The rise of vaccine skepticism in America also means older diseases have rebounded. Reported cases of pertussis in the U.S. have more than doubled already in this century, from 7,867 in 2000 to 18,617— and seven deaths—in 2019. That’s still well below the 215,343 cases that struck Americans in 1932, the year Kendrick and Eldering began their research. But it’s a powerful argument for the kind of communityb­ased public health work, built on trust between parents and local officials, that Kendrick and Eldering helped to pioneer.

After Kendrick’s death in 1980, one of her colleagues, Richard Remington, estimated the number of lives saved by the pertussis vaccine in the hundreds of thousands in the U.S. alone. By now, it is probably in the tens of millions worldwide. “Who are the men and women living today who would be dead from whooping cough had it not been for Pearl Kendrick’s vaccine?” Remington wrote in the newsletter of the University of Michigan’s School of Public Health. “Name one. You can’t do it and neither can I. . . . The accomplish­ments of disease prevention are statistica­l and epidemiolo­gical. Where’s the news value, the human interest in that?”

News value, of course, had little meaning for Kendrick and Eldering. They wanted only to save children’s lives. Having achieved that, they were content to be forgotten. But we should remember.

 ?? ?? Pearl Kendrick at work in the 1940s, photograph­ed for a Grand Rapids news story. “This is what I’d like to be doing all the time,” she told a reporter.
Pearl Kendrick at work in the 1940s, photograph­ed for a Grand Rapids news story. “This is what I’d like to be doing all the time,” she told a reporter.
 ?? ?? Grace Eldering traced her interest in pertussis to her battle with the illness at age 5. Decades later, she still remembered the terrifying coughing fits.
Grace Eldering traced her interest in pertussis to her battle with the illness at age 5. Decades later, she still remembered the terrifying coughing fits.
 ?? ?? A culture an and an artist’s rendering of Bordetella pertussis, p the pathogen that causes who whooping cough. The bacteria spread thro through airborne droplets and colonize ce cells in the lungs. They have only one kn known host species: humans.
A culture an and an artist’s rendering of Bordetella pertussis, p the pathogen that causes who whooping cough. The bacteria spread thro through airborne droplets and colonize ce cells in the lungs. They have only one kn known host species: humans.
 ?? ?? Loney Clinton Gordon (shown in 1951) started her science career at Kendrick’s lab. She continued working in microbiolo­gy and public health until 1978, traveling the world and training hospital
staff to identify pathogens.
Loney Clinton Gordon (shown in 1951) started her science career at Kendrick’s lab. She continued working in microbiolo­gy and public health until 1978, traveling the world and training hospital staff to identify pathogens.
 ?? ?? The lab where Kendrick
and Eldering began their work was housed
in the administra­tion building of an old sanitarium, above. A 1926 article announced the building’s new purpose, though the reporter got Kendrick’s name wrong.
The lab where Kendrick and Eldering began their work was housed in the administra­tion building of an old sanitarium, above. A 1926 article announced the building’s new purpose, though the reporter got Kendrick’s name wrong.
 ?? ??
 ?? ?? A kit from the late 1940s contained an early version of the DTP vaccine, along with a brochure touting the advantages of giving the inoculatio­ns using fewer shots.
A kit from the late 1940s contained an early version of the DTP vaccine, along with a brochure touting the advantages of giving the inoculatio­ns using fewer shots.
 ?? ?? Kendrick, far right, watches a colleague inoculate a child against pertussis in 1942. Government officials had begun distributi­ng her team’s vaccine in 1940, drastic cally reducing d deaths.
Kendrick, far right, watches a colleague inoculate a child against pertussis in 1942. Government officials had begun distributi­ng her team’s vaccine in 1940, drastic cally reducing d deaths.
 ?? ?? Margaret Pittman, shown here working with meningitis germs, spent years helping Kendrick and Eldering improve the safety and effectiven­ess of the whole-cell pertussis inoculatio­n.
Margaret Pittman, shown here working with meningitis germs, spent years helping Kendrick and Eldering improve the safety and effectiven­ess of the whole-cell pertussis inoculatio­n.
 ?? ??
 ?? ?? A 12-year-old receives a Tdap
booster. The Tdap, approved in 2005, added an acellular per
tussis component to a booster shot for tetanus and diphtheria.
A 12-year-old receives a Tdap booster. The Tdap, approved in 2005, added an acellular per tussis component to a booster shot for tetanus and diphtheria.
 ?? ??
 ?? ?? Carolyn ShapiroSha­pin says
Kendrick and Eldering “believed in the developmen­t of
their people,” giving their staff members ample
opportunit­y to learn and shine.
Carolyn ShapiroSha­pin says Kendrick and Eldering “believed in the developmen­t of their people,” giving their staff members ample opportunit­y to learn and shine.

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