The Unsung Heroes Who Ended a Deadly Plague

ENHANCING “WOMANLY CHARM”

(Continued from page one)

Pearl Kendrick (1890-1980), 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.  Educational opportunities for women had been expanding for decades.  But job opportunities did not necessarily follow.  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. 

Left, 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. Center and right, a culture and an artist’s rendering of Bordetella pertussis, the pathogen that causes whooping cough. The bacteria spread through airborne droplets and colonize cells in the lungs. They have only one known host species: humans. (Photos: Grand Rapids History Center, Grand Rapids Public Library; Dr. Camille Locht Institut de Lille; Sarah Bailey Cutchin / CDC)

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 gravitated to the prestige and higher pay of jobs in universities or research institutions.  State laboratories, offering lower wages, less status, and mostly repetitious work, needed women.

Kendrick spent the summer of 1917 studying bacteriology at Columbia University. She worked briefly as a laboratory assistant in New York.  Then C.C. Young, Michigan’s enterprising director of state laboratories, recruited her, promising to “make it interesting” and “with every chance for advancement.” He was true to his word. When the 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 determined to study a single disease.  That year the city was suffering a major whooping cough outbreak. When Kendrick asked Young for permission to work on the disease after the laboratory closed for the day, he replied, “Go ahead and do all you can with pertussis, if it amuses you.”

Grace Eldering (Photo: GRPL)

Eldering (1900-1988), had graduated from the University of Montana, and then worked as a schoolteacher, in Hysham, the ranching and farming community where she grew up.  It did not hold her interest. Instead, 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 became lifelong partners, at work and at home.

In the beginning, the main goal of their research was to diagnose pertussis faster and more accurately, so contagious patients could be isolated as early as possible, and safely returned to school or work when the contagious stage ended.  Their weapon of choice was the cough plate, basically a petri dish with the culture medium painted on the bottom.  Doctors, nurses—and Kendrick and Eldering, too, after working hours–held up the open dish a few inches away while the patient coughed into it. The dish, covered with a lid, then went into an incubator, to grow the bacteria into colonies suitable for analysis.

On November 28, 1932, Kendrick and Eldering identified their first Bordetella pertussis specimen. The bacterium that causes whooping cough had been known since Belgian researchers first described it in 1906. But no one in the laboratory had seen it before.  They had to compare the ones on their cough plate against published accounts. The bacterial colonies, they reported, “appear smooth, raised, glistening, pearly, and almost transparent,” encircled by a pale halo where the bacteria had eaten into the blood in the culture medium.

Kendrick and Eldering devised a series of small improvements to grow bacterial colonies quickly and in quantity. Instead of using human blood in the culture medium, as 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. They soon expanded their study into an ambitious city-wide cough plate service for monitoring and controlling whooping cough.

COOKING WITHOUT RECIPES

Developing a vaccine for any disease was still a rudimentary, cooking-without-recipes enterprise.  It meant experimenting with a long list of variables leading to a killed or weakened pathogen that was safe enough to inject into human patients, and yet strong enough to elicit lasting immune resistance to the disease.  Adverse effects, from sore arms to anaphylactic shock, were common. But people were willing to accept the risks because they still had vivid experience of how much deadlier it was to experience the actual disease.  In 1931, however, the American Medical Association declined to endorse any of the pertussis vaccines then in use, concluding that they had “absolutely no influence” on prevention and were “useless” as remedies after onset of the disease.

Then, in January, 1933, just seven weeks after their first glimpse of the pathogen, Kendrick and Eldering produced their first experimental pertussis vaccine.  It consisted of whole-cell Bordetella bacteria killed with a common antiseptic, purified, sterilized, and suspended in a saline solution. Others who had developed similar 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 collecting the bacteria to delivering the vaccine. They learned as they went—for instance, that bacteria collected at a certain stage in the illness were more likely to elicit a strong immune response–and they tested various versions of the vaccine for safety by injecting them into experimental animals, and themselves. 

They had no prior experience with clinical trials, which were practically a new science then.  But testing whether their vaccine protected children would require a large-scale, controlled field study– comparing a group of vaccinated test subjects against a similar, but untreated, control group.  The trial would have to be part of what Kendrick called “our midnight work,” after business hours.

Grand Rapids then was a leader in putting medical advances to work saving lives. The city government and private donors stepped forward with funding to cover the clinical trial’s cost of $1250 over the first two years. Doctors, nurses and ordinary city residents rallied to help. Mothers volunteered not just their time, but also their children’s well-being as experimental subjects.

After a vaccination clinic, the two researchers 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.  But that call seems never to have come. In the first round of the field study, 1600 children took part, 712 of them vaccinated, and 880 as untreated controls.  In the untreated group, there were 63 cases of whooping cough, all but 10 of them serious. Among the vaccinated children, only four cases occurred, all of them mild. 

SKEPTICAL MEN

The medical establishment didn’t believe it.  James Doull, an epidemiologist at Case Western University in Cleveland, had completed a similar study using a different vaccine, and shown no real benefit from vaccination. When public health leaders asked Johns Hopkins epidemiologist Wade Hampton Frost to review the conflicting results and make a recommendation, he seemed interested at first mainly in avoiding 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, despite himself.  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 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.  Funding for additional staff soon followed from the federal Works Progress Administration.  The new study attracted 4200 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 the disease in the United States fell by more than half just in that decade. Deaths dropped from 7518 in 1934, the peak year for pertussis, to just 10 a year by the early 1970s.  Kendrick regularly traveled to help introduce the vaccine to other countries, from Mexico to Russia, with similar success in saving children’s lives. 

To minimize the “pincushion effect” of so giving so many shots in the early years of a child’s life, Kendrick and Eldering worked 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, they 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.

UNDUE MODESTY

 “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.  But they were intensely private and never meant the work to be about them, according to Carolyn Shapiro-Shapin, a historian at Grand Valley State University, who began researching the two women in the 1990s.  Their vaccine was the product of “a whole community working together,” in her phrase, and they liked it that way.

Loney Clinton Gordon (shown in 1951) started her science career in Kendrick’s lab. She worked in public health until 1978, traveling the world and training hospital staff to identify pathogens. (Photo: GRPL)

One part of that community was an African-American woman named Loney Clinton Gordon.  She had come to Grand Rapids in the early 1940s seeking work at a local hospital as an experienced dietitian. It didn’t go well, she recalled in a 1998 interview with Shapiro-Shapin.  Prospective employers praised her credentials, but then added, “we just don’t think chefs would want to take orders from you.” Instead, at the suggestion of a friend, Kendrick phoned to offer a job.

Gordon was soon at work sorting through “piles of cultures” every morning.  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. Millions of plates. It’s a wonder I still have eyes.”  One day, she went in and “started looking, and all of a sudden here was a plate. My God, it was so big and so clear,” she recalled, describing the halo where the bacteria had eaten had eaten into the blood in the surrounding culture medium.  “It just talked to me. ‘Here I am.’” Gordon took that plate to Kendrick and Eldering, who put it through “all of these processes, repeated and repeated and repeated,” to see if it met their criteria for a better vaccine, “and, bingo, there it was.”   No other record of Gordon’s contribution exists.  But like others who remembered working in the lab, she mainly expressed gratitude at having been part of the work of saving lives.

“All these medical breakthroughs are a result of the work of many persons,” Eldering later told a reporter, who wondered why the vaccine hadn’t become known as the Kendrick-Eldering vaccine, on the model of the Salk vaccine for polio. “We disapproved of that notion 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.”  They also preferred to remain private. 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.  

For women experienced in the gender politics of their era, modesty may have seemed obligatory. In college, Kendrick once told a reporter, she had gotten male science faculty to take her seriously and provide the instruction she needed by acting “as humble as I could be.” Managing feelings and emotional displays in this fashion could easily become a career strategy.  When a student once asked, “Were you discriminated against?” as a woman in a male-dominated medical world, Kendrick answered, “If so, I didn’t recognize it.” Focusing on the work at hand, she explained, “kept me from worrying if I was getting [paid] as much as my friend John, say, who was working beside me–though I knew very well I wasn’t.” 

With Kendrick, though, the determination also showed through. “I never thought there was anything I couldn’t do,” she once told a reporter.  She was talking about a time in college when she had to organize meal service for 75 fellow students during a two-week Christmas break. The point was that she was single-minded about whatever she took on.  That determination also showed up outside of work. Shirley Redland, Eldering’s niece, recalls visiting the two women as a child and sitting in the back seat of the car, wide-eyed, when Kendrick was at the wheel: She had a “heavy foot, and people better get out of her way.”

From the 1930s on, Kendrick and Eldering shared a comfortable four-bedroom house in an old apple orchard, on a hilltop overlooking the city. It was common for single working women to live together then, to eke out systematically meagre salaries, and the arrangement seems not to have raised eyebrows in Grand Rapids.  They shared the same outside interests, in reading, gardening, and birdwatching.  They kept cats and dogs.  They owned a summer cabin on Lake Michigan, often traveled together, and clearly cared for each other. After Eldering lost a finger while attempting to repair an air conditioner at work, it was Kendrick who stitched down that finger on her gloves. “They had a wonderful life together,” Redland recalled. “I don’t think there was ever a harsh word.”

Were they more than devoted friends? At one point in her research, Shapiro-Shapin was interviewing a pediatrician named Lucile Portwood, who had worked in the laboratory in the 1940s.  She asked about the relationship, and Portwood, who was then 80 and near-deaf, “yelled into my tape recorder, ‘I’M A LESBIAN AND I WOULD HAVE KNOWN IF THOSE GALS WERE UP TO SOMETHING.’”  In any case, Kendrick and Eldering would have considered it nobody’s business but their own.

THE VACCINATION PARADOX

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 healthcare measure largely eliminates a disease from people’s lives, the vaccine itself can become a target, because real or imagined adverse effects may now seem worse than the forgotten disease.  That happened to Kendrick and Eldering’s whole-cell pertussis vaccine in the 1970s. It caused fever and injection site reactions, and in rare cases temporary neurological problems.  Anti-vaxxers also accused it of more serious adverse effects, though a scientific review debunked most of these accusations.  The vaccine was steadily improved over time,  and was always infinitely safer than risking the disease.  But public confidence in it was shaken.

A stripped-down “acellular” vaccine—basically just three or four of the original 3000 or so antigens—soon replaced the whole-cell vaccine in the United States and some other developed nations.  The acellular vaccine has, however, recently turned out to provide strong protection for only a few years.  Together with increasing vaccine resistance, that shorter period of effectiveness has contributed to a whooping cough resurgence in the United States.  Under-vaccination in poorer countries has also allowed whooping cough to persist there, killing an estimated 160,000 people each year, mostly 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.  Pasteur Institute molecular biologist Camille Locht, a devoted admirer of Kendrick and Eldering, has developed a new whole-cell vaccine.  It will of course be different from theirs—made with live bacteria that are genetically altered to render them harmless, and not injected in the arm, but sprayed into the nose. In addition to being easier to administer and avoiding needle fear, it will not require refrigeration, all advantages in remote and impoverished areas. If all goes well, it could become available by 2025.

Meanwhile, the current descendant of Kendrick and Eldering’s vaccine continues to save children’s lives in countries around the world.  After Kendrick’s death in 1980, a colleague estimated the number of lives saved by the vaccine in the hundreds of thousands in the United States alone. It is probably in the tens of millions by now 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?” her colleague wondered, in a memorial note. “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 accomplished that, they were content to be forgotten.  But we should remember.

Kendrick, far right, watches a colleague inoculate a child against pertussis in 1942. Government officials had begun distributing her team’s vaccine in 1940, saving thousands of lives every year. (Photo: GRPL)