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John Enders

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John Enders - Measles and Polio Vaccines:
Measles: Before the availability of the live vaccine, an estimated 6–8 million children died of measles annually throughout the world. That number has since been reduced to less than 1 million. In the United States the incidence of measles has been reduced to less than 100 cases annually, and virtually all these cases can be traced to importation of the measles virus from abroad. Today there are many other countries in the Western Hemisphere where indigenous transmission of measles no longer occurs. To determine the number of lives saved, I took the estimated annual deaths in the prevaccine era and distributed the percent reduction across 21 years for the period of 1977 to 2008.

Polio: Using mostly CDC and WHO reports I determined two estimates of lives saved by the polio vaccine between the years of 1960 and 2008 for the entire Westernized World. These both resulted in very close final tallies so I felt fairly confident they were among the best estimates I could make with the information available.  I then used these data to extrapolate to the rest of the world. Although India accounts for about +70 percent of all reported cases (and some regions within Africa, especially Nigeria are also high), eradication efforts really only began there full scale in the past 15 years with strong results in the late 90s and early 2000s, so it was difficult to put a number on the rest of the world.  However, I took a percentage for the world from 2000-2008 when the efforts of global eradication became more fully realized.
--Amy R. Pearce, PhD

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John Enders, MD
(February 10, 1897 - September 8, 1985)
Born in the United States
Year of Discovery: 1949, 1958

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Virologist is Virulent to Viruses!

John Enders (1897 - 1985) was a virologist who, along with key researchers Thomas Weller and Frederick Robbins, pioneered techniques for studying viruses in the laboratory that revolutionized virology, leading directly to the development of vaccines against many serious diseases. At the late age of 50, he started a laboratory at Children's Hospital in Boston, after World War II. There, his team was the first to produce enough poliovirus in test tubes to be studied effectively. This work led to the vaccines developed by Jonas Salk and Albert Sabin that eradicated polio from the U.S. Although Salk and Sabin were the much more famous scientists, it was Enders' team who was awarded the Nobel Prize for Medicine or Physiology in 1954 for its work on culturing the poliovirus. After this, Enders made his greatest accomplishment when he led another team that created the measles vaccine, a vaccine that has saved well over 100 million lives.

Enders never rushed through life. He was a flight instructor in World War I when biplanes were made of canvas and had two wings. He graduated from Yale, and then tried his hand at business. Unhappy, he quit and returned to school at Harvard to get a graduate degree in English. Still passionless, he decided to get a doctorate in philology, the study of language in literature. But it wasn't fulfilling either. He wrote a friend, "I mouth the strange syllables of ten forgotten languages, letting my spirits fall, my youth pass. If this mood lasts, I shall by Heaven, throw it all to the four winds and go forth into the world like Faust, even if I have to bear his penalty." His life changed when he accompanied a friend to a lab. There, he was fascinated by the experiments and met a professor, Hans Zinsser, who would become his mentor.


His life changed when he accompanied a friend to a lab. There, he was fascinated by the experiments and met a professor, Hans Zinsser, who would become his mentor. Enders described Zinsser as, "A man of superlative energy. Literature, politics, history, and science-all he discussed with spontaneity and without self-consciousness. Everything was illuminated by an apt allusion drawn from the most diverse sources, or by a witty tale. Voltaire seemed just around the corner, and Laurence Sterne upon the stair. . . . Under such influences, the laboratory became much more than a place just to work and teach; it became a way of life."

At the age of thirty, Enders entered the doctoral program in bacteriology at Harvard. After getting his doctorate he still didn't rise quickly rise in the academic world. Instead, he worked in Zinsser's lab until Zinsser died. Soon thereafter World War II altered academic research and then Enders' wife died. Picking up the pieces in 1945, he was offered a chance to run his own lab at Boston's Children's Hospital.

There, Enders and his colleagues sparked a revolution in the field of virology with the development of their tissue culture techniques. Viruses had been grown in tissue cultures prior to Enders, but only sporadicallynot consistently  and with difficulty. Most researchers used live animals as the medium in which to grow viruses and, as a result, very little progress was made in virology.

Enders' team devised methods that allowed virologists to grow a limitless supply of many viruses in numerous tissues. They also demonstrated the value of looking for cell damage due to the invasion of the viruses. They built a toolbox of techniques to handle viruses in test tubes, drastically shortening the time required for experiments, and allowing for the testing of virtually endless ideas. Soon, their methods were used in laboratories all over the world, leading to numerous major discoveries.

When Enders began his work only 13 human disease-causing viruses had been isolated. By 1961, 58 more human viral pathogens had been cultured, plus another 300 viruses that infect animals. Finally, Enders' team demonstrated all the techniques necessary for each step in the creation of viral vaccines. Only 3 vaccines were available to children when Enders began his work. Today there are 12 more recommended childhood vaccines. Many procedures from the Enders' laboratory are still in use in laboratories around the world today.

Enders is also remembered for his personal charm and keen interest in all knowledge. He maintained close professional relationships with his associates, and mentored and furthered the careers of many fellow scientists. His spirit of personal and scientific collaboration fostered the important discoveries that saved millions of lives and improved the health of billions of people, especially children, across the world.

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Bookcoverjacket

Table of Contents

Introduction
Key Insight
Key Experiment or Research: Polio
Key Contribuors: Polio
Key Experiment or Research: Measles
Key Contributors: Measles
Quotes by John Enders
Quotes About Enders
Anecdotes
Excerpt from Scientists Greater than Einstein
Similar Scientists
Fun Trivia
The Science Behind the Discovery
Enders' Research: Polio
Enders' Research: Measles
Personal Information
Science Discovery Timeline
Recommended Books About the Science
Books by John Enders
Books About Enders
Awards
Major Academic Papers
Curriculum Vitae
Links to Science and Related Information on the Subject
Sources
The Rise of the March of Dimes, Joel Shurkin

 



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Enders got a Late Start
Enders Never Quit
Creator of the Measles Vaccine
Enders' Revolutionary Work
Enders Revolutionized Virology
Virus Facts




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Key Insight

The key insight that revolutionized virology was learning how to grow viruses in test tubes for long lengths of time. In 1940, Enders ran an experiment with his student, Thomas Weller, that used a roller tube apparatus to keep a cowpox virus alive for nine weeks, an unheard of accomplishment.

Roller tube tissue cultures had been perfected by George Gey in 1933, and Enders had been one of the first to use them with viruses. Rather than growing animal tissue in flasks, researchers using roller tubes plant tissue cells in plasma clots on the sides of test tubes. Viruses can then be inoculated into this tissue. A nutritious fluid consisting of inorganic salts, serum from animals or humans, and an extract from embryonic tissue is supplied to keep the tissue alive. The capped test tubes are then kept almost horizontal and heated in an incubator to 37 degrees Centigrade (99°F.), which is the temperature of the human body. The test tube is slowly turned at a rate of eight to ten times an hour, exposing the tissue to both the liquid nutrient and air. The goal is to more accurately mimic conditions inside the human body, where tissue is exposed to an active environment of nutrients and waste product removal, rather than the static environment of a motionless test tube or flask.
A big advantage of using the roller tube technique comes when viewing the cultures under a microscope. Tissue from flasks has to be chopped, and then prepared as slides for the microscope, while the outgrowth of cells into the plasma clot of a roller tube can be repeatedly examined in the living state, as the cells grow and the virus replicates.

The war interrupted such research but, when Enders had his lab up and running, Thomas Weller, recalling that experiment, used a technique that had some of the characteristics of a roller tube to keep a mumps virus alive for a long period of time. The team next kept poliovirus alive. The techniques the team built to keep viruses alive in test tubes completely changed virology, by allowing viruses to be experimented upon endlessly.

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Key Experiments or Research: Polio Virus

Polio was the most feared disease in America from the 1920s through the 1950s. Polio came like clockwork when the weather warmed, and left with the first chill. Usually, the epidemic was mild and most of the victims, largely children, recovered without permanent damage. Every few years, however, it struck with particular viciousness. In 1916, New York City tallied 9,300 cases, with 2,200 children dying. Half the survivors were paralyzed. In this setting, an accurate idea of how polio reproduced in human tissue was crucial to advancing knowledge about it, so a vaccine or cure could be produced. Karl Landsteiner published the basic facts about polio in 1909. It is a virus, and monkeys were the experimental animals of choice, since it also infects them. There was - and still is - no cure.
Little progress was made until Enders' team cultured polio in the laboratory almost forty years later. Enders' team also perfected all the methods to make a vaccine. However, Enders did not attempt to make a vaccine because he had a small laboratory and Jonas Salk and many others had large laboratories devoted to making a polio vaccine. Salk used some of Enders techniques to make his chemically killed vaccine and credited Enders, saying, "Dr. Enders pitched a very long forward pass, and I happened to be in the right place to receive it." Also using Enders' teams' techniques was Albert Sabin, who made an attenuated polio vaccine that ended up being used throughout most of the world.

 



Key Contributors: Polio Virus

The Team
Explore other scientists who furthered this lifesaving advance.
Lifesavers: Polio Vaccine
Thomas Weller
Came up with several breakthrough ideas in the development of tissue cell culture techniques for viruses.
Frederick Robbins
Worked with Enders on developing tissue cell culture techniques for viruses.
Jonas Salk
Developed the first vaccine to fight against the epidemic killer polio virus, using tissue cell culture techniques pioneered by Enders.
Thomas Francis Jr
Influenza and polio vaccine - taught Jonas Salk critical vaccine development technique.
Albert Sabin
Developed the "live" polio vaccine, given on a sugar cube, used throughout the world.



Key Experiments or Research: Measles Virus

Measles usually strikes in waves of two to four years and is astonishingly communicable-even the slightest contact will pass it on. It remains incurable to this day, although secondary infections can be treated with antibiotics. Measles was a common childhood disease in America into the 1960s, with almost every child becoming sick from it. Although not a big killer in America, thanks to our country's good nutrition and medical care, worldwide it was devastating. The World Health Organization estimates that when Enders began his work, 106 million people got measles each year, and more than 6 million - mostly children - died.

Enders formed a new team after his success with polio and worked through most of the 1950's on a measles vaccine. In 1960 he handed the vaccine off to Maurice Hilleman at the pharmaceutical company, Merck. There the vaccine was perfected. It came into widespread use in 1963 and, now being used all over the world, the number of measles deaths today is down to less than 345,000 a year.

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Key Contributors: Measles

The Team
Explore other scientists who furthered this lifesaving advance.
Lifesavers: Measles Vaccine
Samuel Katz
Worked transferring measles virus from hen's eggs into chick embryo cell cultures, & vaccine tests w/monkeys, children.
Thomas Peebles
Worked on isolating the measles virus.
Kevin McCarthy
Worked on inoculating monkeys with a passaged virus.
Milan Milovanovic
Worked on passaging the measles virus through human cells.
Anna Mitus
Worked on passaging the measles virus through human cells.
Ann Holloway
Was Enders' "most able technician and associate" in the search for a measles vaccine.
Maurice Hilleman
Reformulated Enders' vaccine, making it commercially available worldwide.



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Quotes By John Enders

"I mouth the strange syllables of ten forgotten languages, letting my spirits fall, my youth pass. If this mood lasts, I shall by Heaven, throw it all to the four winds and go forth into the world like Faust, even if I have to bear his penalty."
-On his early work in philology, the study of language as used in literature, in a letter to a friend

"This antipodal revolution of my studies has been of large value in helping me to obtain that Pisgah sight of things and people that perhaps is the ultimate aim of my apparently inconsistent, faltering and obscure action." -On his changing his PhD to science, referencing Pisgah, the mountain which Moses ascended to see the Promised Land

"In these experiments the tissue culture method was employed with uncertain results. But the conviction was gained that it represented a basic tool for the study of viruses of which the possible applications were almost unlimited."
-Enders discussing his research in the 1930s

"From time to time we had considered the mounting evidence...in favor of the possibility that these agents (of polio) might not be strict neurotropes.... Such ideas were in our minds when the decision was taken to use a mixture of human embryonic skin and muscle tissue in suspended cell cultures in the hope that the virus of varicella might multiply in the cells of its natural host.... while close at hand in the storage cabinet was the Lansing strain of poliomyelitis virus. Thereupon it suddenly occurred to us that everything had been prepared almost without conscious effort on our part for a new attempt to cultivate the agent in extraneural tissue."
-Nobel Prize Speech

"At this point it seems appropriate to remark that the discovery of the antibiotics has, as in so many other areas, worked a revolution in the field of tissue culture. Through the use of these substances it is now not only possible to apply tissue cultures to the routine isolation of viruses from materials heavily contaminated with microorganisms, but it has become feasible to use them under conditions and in numbers which in the past would have been quite unthinkable. Here then we have another example of how one discovery leads to many others often of quite a different nature."
-Nobel Prize, discussing the importance of antibiotics in their own research

"From these observations we concluded that, as with other viral agents, the virulence of poliomyelitis virus is not a fixed attribute but on the contrary may readily be altered under appropriate conditions."
-Nobel Prize Speech, explaining in understated words that a vaccine was possible!



Quotes About John Enders

"The superficial Enders guise was that of a round-shouldered, overburdened, sometimes meek, pedantic scientist - a caricature he deliberately fostered and exploited effectively as a shield against the unwelcome intrusion of assignments to distracting committees or administrative chores. In fact, he was a strong, competitive, thoroughly contemporary, artful academician who conserved his energies for those challenges he judged worthy."
-Samuel Katz, who worked with Enders during the research on measles and knew him well.

"The achievement of Enders, Weller, and Robbins was the starting point not only of modern polio-virology, but it launched the revolution rightly called molecular virology."
-Hans J. Eggers, MD

"He favored doing small-scale experiments and reviewing the results of each as they came out to define another simple question and plan the next experiment to answer it."
-David Tyrrell, virologist

"The door was always open to visitors from throughout the world. Few scientists left such a visit unaccompanied by carefully packaged boxes containing samples of virus, cells, sera, reagents, or other ingredients, to ensure the ready progress of their own experiments back at home. The data in laboratory notebooks were shared with visitors who sought specific information on experiments recently completed or still underway.... His philosophy was that the more people working on a problem, the sooner a solution would be found."
-Samuel Katz

"Dr. Enders pitched a very long forward pass, and I happened to be in the right place to receive it."
-Jonas Salk

Enders was "firmly convinced that the size or magnificence of laboratory surroundings and equipment had little relationship to productivity or success - if anything an inverse relationship."
-Samuel Katz


"His relations with the staff were such that they were able, and indeed encouraged, to produce suggestions for the next experiment or a new idea to solve a problem. This would be discussed from all angles and quite often the chief would put forward a different idea, but in such a way that the trainee was glad to take it up rather than feeling resentfully that he had been forced to abandon his own idea and accept that of ‘the Boss.'"
-David Tyrrell, virologist

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Anecdotes


Enders' Teaching Style

After receiving his doctorate in bacteriology from Harvard, Enders became an instructor and laboratory scientist at Harvard. As a teacher, he was noted for his personal magnetism in small-group and one-on-one settings, including in the lab, but seemed less suited to giving lectures. "Delivery was another matter," said a later colleague, Samuel Katz. "After adjusting the microphone around his neck and checking that it was live, he would extract a large handkerchief from his vest pocket and blow his nose with significant amplification by the sound system. We were never certain whether that was a nervous habit or meant deliberately to arouse the students' attention or laughter, but it usually did both. He extracted a large gold pocket watch from another compartment of his vest and placed it on the lectern to assure punctuality in his presentation. The lecture was articulate, but dry, and rarely overwhelmed the audience. His own disciples sat squirming in the back row seats hoping the students would perceive the gems they were receiving. After the lecture, we joined him for the short walk back to the laboratory in the old Carnegie Building of Children's Hospital, assuring him of how fine his presentation had been, even though both he and we suspected that few of the students appreciated what had been offered."

Formative Years

A frequent visitor to Enders' family home when he was a child wore a white suit. It was Samuel Clemens, better known as Mark Twain.

He matriculated to Yale University, but interrupted his education to enlist in the Naval Reserve to serve in World War I. There he learned to pilot the fragile, rickety bi-planes of the time. Air flight was only fifteen years old, and these daring pilots sat in cold, open cockpits. Enders was not sent to combat, but became a flight instructor in Pensacola, Florida. If he had any notions of being a daredevil himself, his experiences flying completely cured him. He decided he had used up all his luck in the air, and forever after was extremely reluctant to fly.

Enders lived with medical students in Mrs. Patch's comfortable boarding house. There he met an animated Australian, Hugh Ward, whose daily description of his doctoral work in microbiology piqued Enders' interest. "We soon became friends," Enders wrote, "and thus I fell into the habit of going to the laboratory with him in the evening and watching him work. I became increasingly fascinated by the subject-which manifestly gave him so much pleasure and about which he talked with such enthusiasm."

Ward also introduced him to Hans Zinsser, a charismatic professor whom Enders described as, "A man of superlative energy. Literature, politics, history, and science-all he discussed with spontaneity and without self-consciousness. Everything was illuminated by an apt allusion drawn from the most diverse sources, or by a witty tale. Voltaire seemed just around the corner, and Laurence Sterne upon the stair. . . . Under such influences, the laboratory became much more than a place just to work and teach; it became a way of life."

The early 1940s greatly upset Enders' idyllic lab life. In September of 1940 Hans Zinsser died, not only costing Enders his cherished mentor, but also burdening him with the lab's bureaucratic administrative duties, which were definitely not his forte. Then, World War II began, resulting in most of the young doctoral candidates leaving for military service, thus ending many lines of research. Tragedy struck again in 1943, when Enders' wife, Sarah, suddenly died from acute myocarditis, an inflammation of the heart.

In the Lab

After the war, Enders was asked to establish a research laboratory on infectious diseases at Boston Children's Hospital, which was located just across the street from Harvard Medical School, and had various ties to Harvard. Today, that may sound like an odd place to do research, but in the 1940s it was ideal. Researchers were drawn to pediatrics, because children were both the battleground and the living laboratories of infectious microorganisms like polio and measles.

A technician in the lab, Alice Northrop (later to marry Frederick Robbins) says, "We all liked each other and admired Dr. Enders, whom we called ‘the Boss.' Because Dr. Enders did not wish to eat at the hospital, which Tom Weller always did, the rest of us had lunch at the big table in the large lab adjacent to Dr. Enders' office. Jeanette, Carol, and I made the lunch, being careful not to have anything containing egg as Dr. Enders was allergic to eggs. ‘Does it have egg in it, Alice?' he would say in a worried voice. Dr. Enders had unusually broad interests and enjoyed discussions in the lab at lunch about all sorts of things as well as work: politics, literature, the arts, even exciting sailing adventures." Enders' sly sense of humor often came out, whereupon he would give a half-grin and his eyes would twinkle.

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John Enders with His Microscope and Slides

Enders kept several novelty hats on a shelf in his office, some of which he had collected and others which had been given to him. When exciting experiments were to be examined, he would put one on.

One day, peering into the microscope, Enders saw a poliovirus-infected cell explode. "Cytopathogenicity," he exclaimed, inventing a word. The word, truncated to cytopathic, later became common in virology.

Enders and his colleagues knew well they were dealing with a dangerous pathogen in polio, and had already developed safety procedures for handling viral specimens. Weller didn't even want his wife, Kay, to visit the lab. To be extra cautious, they put two monkeys they had autopsied at the animal building into heavy bags, lugged them back to the lab, and put them into the autoclave. Cooking the monkeys in it would kill any virus that remained alive so they could be disposed. The whole floor stank.

During this time, the Enders' team was writing papers and giving frequent presentations of its findings, so many researchers would visit. Jonas Salk was one. Katz says, "The door was always open to visitors from throughout the world. Few scientists left such a visit unaccompanied by carefully packaged boxes containing samples of virus, cells, sera, reagents, or other ingredients, to ensure the ready progress of their own experiments back at home. The data in laboratory notebooks were shared with visitors who sought specific information on experiments recently completed or still underway.... His philosophy was that the more people working on a problem, the sooner a solution would be found."

Fame or Lack Thereof

Working on measles they had great difficulty getting the virus to grow in chick eggs, a necessary step to any vaccine. Month after month these attempts proved unsuccessful, so time after time Enders and his team left the lab without making progress. Enders had the habit of taking a taxi home from the lab and got to know many of the drivers. As one of his beliefs in life was treating everyone equally, he showed them all respect. Katz says, "In twelve years of close daily association, I can recall only one person for whom he could not find some redeeming feature, and that man was indeed a rogue." One evening, on the trip home, the taxi driver asked Enders, "How is the progress of your research?" Enders couldn't pretend it was progressing well. The driver encouraged him to keep at it, "Perhaps you will discover something wonderful, like Dr. Salk."

Death Bed

On a September evening at their water front home in Connecticut, in 1985, Enders was reading T.S. Eliot aloud to his wife, Carolyn. He finished and went to bed, then quietly died. He was eighty-eight. At his memorial service his friend, the Bishop F.C. Laurence, said, "John Enders never lost his sense of wonder - wonder at the great mystery that exists and surrounds all of God's creation. This awareness is what gave him his wide vision and open mindedness, his continued interest in all things new, his ability to listen, his humility in the presence of this great mystery, and his never-ending search for the truth." His widow said that John briefly revealed his heart when he told her, concerning how creation ran, "There must be a mind behind it all."

Enders' Laboratory Was Like a Family

The Enders' laboratory began as a group of diverse researchers, but grew, literally, into a family. Shortly after Frederick Robbins joined the lab he fell in love with a laboratory technician, Alice Northrop. Soon they married. Enders followed suit, marrying Carolyn Keane, another laboratory worker, in 1951. Robbins writes that Carolyn's, "cheerful disposition, facility in social intercourse, and great energy proved to be of enormous support." Fred Robbins thought so much of Enders that he suggested to Alice that they name their second daughter after him. She agreed, and the name Louise Enders Robbins was entered upon the birth certificate.
A well-regarded tradition in the laboratory was the family Christmas party. Enders donned a crimson smoking jacket and plied his guests with drinks. Katz recalls, "One delightful tradition involved the drawing of names from a hat, a few weeks before the holiday, for the giving of Christmas presents. More attention was focused on the requisite poem which accompanied the gift, and which was read aloud at the time of presentation, than on the gift itself. Some of the efforts were indeed remarkable, but none matched those which Enders himself composed, and it was a true joy to be the recipient of his poem and gift. The evening ended with the Chief at the piano and his guests gathered round him, his "family" singing Christmas Carols."

Alice Robbins - remembrances email from March 7, 2008

"Dr. Enders had unusually broad interests and enjoyed discussions in the lab at lunch about all sorts of things as well as work: politics, literature, the arts, even exciting sailing adventures. The laboratory space was small, only four rooms--two labs, Dr. Enders' office, and a glassware washing room. Because Dr. Enders did not wish to eat at the hospital, which Tom Weller always did, the rest of us (Jeanette Levens, Carol Keane, Fred and I) had lunch at the big table in the large lab adjacent to Dr. Enders' office. Jeanette, Carol, and I made the lunch, being careful not to have anything containing egg as Dr. Enders was allergic to eggs. "Does it have egg in it, Alice?" he would say in a worried voice. Those lunch times and the conversations were fascinating and quite the highlight of the day for me.

It was a close-knit group because when Dr. Enders set up the lab, he wanted to have people around him that he knew. Besides Jeanette, his long-time technician, and Tom and Fred, whom he had known since they were medical students, he hired Carolyn Keane (always known as Carol) to be his secretary and me to be Tom's technician. He had known both of us at the Bacteriology Department at the medical school. We all liked each other and admired Dr. Enders, whom we called the Boss. Dr. Enders liked to know about our activities but he didn't really like my going off skiing on weekends. He used to see me off with the comment (jokingly) "If you break something, just be sure to break your leg and not your arm."

Dr. Enders had a relaxed manner, and coming in in the morning later than the rest of us, after having been served tea at home by his old family retainer, Bridget, who padded around in tennis shoes and called him "the master," he would often say, "I've been thinking this morning, Fred," and then describe an idea for an experiment. With his imaginative mind, charm, inquisitiveness, and soft-spoken manner, Dr. Enders, in his old well-loved tweed jackets, created an atmosphere in the lab which made it a very special place, memories of which we treasure."

Samuel Katz from email dated March 4, 2008

"Working with Enders (not for him) explains his uniquely wonderful role as a mentor for us. He deliberately enrolled only 4 or 5 fellows at a time in order to have sufficient interactions with them. He was a renaissance scholar, interested in all knowledge, not just medical science. He sought research productivity for its benefits to all mankind, not for personal recognition. He was generous of his time, knowledge and friendship, but penurious of public funds (the only NIH grantee to return funds to them at the end of a fiscal year). He never held press conferences, but our research results were published in carefully worded manuscripts in journals with critical editorial review. We gave virus, cells, sera to any legitimate investigator who visited to observe our research, because his philosophy was that the more people working on a problem, the sooner a solution would be found. I could go on and on. Obviously he was my father-figure as well as my mentor!"


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Excerpt from Scientists Greater Than Einstein: The Biggest Life Savers of the Twentieth Century

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Enders and Weller were allocated four rooms on the second floor of the Carnegie Building, a three-story building next to Harvard's coal-fired power plant. First it needed a thorough cleaning - oily soot had come through the loose window frames and coated the fixtures. Two rooms were turned into labs, one room was the glass washroom, and the final room was Enders' office. On the wall he hung pictures of Edward Jenner and Louis Pasteur, and would later add pictures of researchers who worked in the lab, each with a story Enders loved to tell. Animals were kept a block away in another building. Enders and Weller furnished the lab with the standard equipment, such as an autoclave to sterilize equipment and chemical hoods to work under, along with some more novel items. Embryonated hens' eggs had recently been introduced as media in which to grow viruses, so they purchased an egg incubator and visualizing lights to shine into the eggs. Turning the eggs was a daily chore, including on weekends, but one that had a side benefit. Not all of any batch of eggs were fertile, so the young researchers received a few free eggs from time to time to take home.

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John Enders

Developed the polio vaccine

Enders revolutionized virology, even though he began his work in this area after the age of fifty.

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Norman Borlaug

Father of the Green Revolution

Borlaug's disease-resistant wheat feeds millions.

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Frederick Banting

The discoverer of insulin

Frederick Banting discovered lifesaving insulin.

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Fun Facts/Trivia

What is an "eradicable" disease? "Eradicable" means there is a possibility that the disease can be completely eliminated from the world. For a disease to be considered eradicable, it must meet three conditions: humans must be the only host for the disease; it must be possible to diagnose the disease effectively; and, a reliable intervention must exist. Because of work on the final condition led by the Enders laboratory, both polio and measles are considered to be eradicable, according to the World Health Organization.

Measles is the most communicable disease in the world, so there are still 20 million cases a year worldwide.

The Enders team won the Nobel Prize in the same year (1954) that Linus Pauling won for chemistry and Ernest Hemingway for literature.

Today there are fewer than 2,000 cases of polio per year worldwide, all occurring in 4 countries where polio is still endemic - Nigeria, India, Pakistan, and Afghanistan.

Before a measles vaccine was available, more than 9 out of 10 children caught measles in the United States, totaling more than 2 million per year. In 2004, there were 37 cases of measles in the United States (all believed to be imported).

When Enders began his work, more than 6 million people died from measles each year. In 2006, the worldwide number was 345,000.

Currently, the government recommends 15 childhood vaccines, including polio and measles, plus rotavirus (a cause of diarrhea), diphtheria, tetanus, pertussis (whooping cough), HiB (a cause of various bacterial diseases) , pneumococcal (pneumonia), hepatitis A & B, meningococcal (meningitis) and influenza in some cases. When John Enders started his work on polio, only three of these vaccines existed.

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The Science Behind the Discovery

Basic Science Primer: Problems in Virus Research

Viruses

Viruses are very different from bacteria, the other type of agent that causes most disease. They are so tiny that they were not even seen until the advent of the electron microscope in the 1930's, when Enders was beginning his research. Made up of genetic material -- either DNA or RNA strands -- and encapsulated in a protective protein shell, viruses thrive in bacteria, fungi, plant, and animal cells, co-opting the cells' genetic machinery to acquire energy to reproduce. It is arguable whether they are even life forms, but they definitely have a large impact in humans. When they parasitically infect our bodies, they cause many diseases, including the common cold, flu, hepatitis, herpes, HIV, SARS, and Ebola, just to name a few.


The Challenge of Studying Viruses

The exceedingly small size of viruses (hundreds or thousands of viruses can exist inside a single human cell) makes them devilishly difficult to study. At the time Enders began to take an interest in them, most viruses could only be grown in vivo (Latin for "in the living"), which meant in living animals. Animal experiments are expensive, slow, and awkward - not to mention, they often require the sacrificing of live animals when a scientist wants to observe the effect of a particular trial.

Scientists needed techniques for studying viruses in vitro (in test tubes), which presented several challenges. First, a given virus will only grow in certain cells from certain animals. Second, the cells must be healthy when infected with a virus, and a test tube is not a naturally healthy setting for a living cell. Third, the cells must remain healthy throughout the experiment, which means they must be provided with nutritious food.

Fourth, the cells must remain uncontaminated but, in a test tube, bacteria, other viruses, and fungi can easily contaminate and kill cells. Finally, if a virus can be induced to multiply, it often kills the very cells into which it has been cultured, releasing viruses into the liquid remnants. The only way to maintain those viruses is to transfer them to a tissue culture of new cells - called a subculture. All of this has to be repeated over and over again. In the 1940s, growing viruses in test tubes in sufficient quantity to experiment with was a major barrier to virology research.


The Problems Posed by Polio

Polio received lots of public attention, both because it affected children and because the future President - Franklin Delano Roosevelt - was diagnosed with it in 1921. FDR was an adult when he was diagnosed and, since he came from a wealthy family, was able to turn many resources toward polio research, eventually founding the National Foundation for Infantile Paralysis. The Foundation became the largest voluntary health organization in the country and a model for modern private charities. Almost every authority on the disease in America eventually either worked directly for the Foundation, or was funded by it.

Before the establishment of the National Foundation for Infantile Paralysis, the Rockefeller Institute for Medical Research funded most medical research. Founded in 1901 by John D. Rockefeller, the Rockefeller Institute produced impressive research. The institute's first director, whose tenure lasted more than three decades, was Simon Flexner. Unfortunately, researchers under Flexner made several mistaken conclusions concerning polio, one of which led to a misconception that, propagated by Flexner, held back polio research for over a decade. Flexner's researchers proved that that polio was neurotropic, meaning it multiplied in nerve tissue, which Flexner mistakenly interpreted as meaning that polio multiplied only in nerve tissue.

This idea, that the poliovirus could be grown only in nerve tissue, fit into the common beliefs of the time. The creation of a vaccine would require both a way to multiply the poliovirus dramatically, which was very difficult to do in nerve cells, and an accurate paradigm, or model of how the virus worked. The laboratory of John Enders played a crucial role in meeting these two needs for the field of virology.

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Enders' Research - Polio

Growth of Poliovirus in a Flask

Enders ran a collaborative laboratory. Samuel Katz, who worked with him on the measles vaccine, said, "Every day Enders took time to make the rounds of the laboratory benches to talk with each fellow and ask, ‘What's new?' That two-word question was a wonderfully effective stimulus to enhanced laboratory productivity because a fresh answer to the inquiry earned extra personal time with the Chief to discuss one's observations."

With such a free flow of ideas, early in 1948 Thomas Weller set about trying to isolate the varicella virus, the cause of chicken pox and shingles, using embryonated hens' eggs. He failed. As a next experiment he decided to use the varicella virus. Enders had worked a lot with the mumps virus, so suggested that he try it next instead. Weller's idea was to build upon the experiment he had performed with Enders when he had been a student back in 1940. The experiment allowed them to keep cowpox virus alive for nine weeks using a roller tube apparatus in a flask, which was revolutionary. The war had interrupted their work, but now he set about attempting to grow viruses in a flask by modifying the Maitland technique, whereby tissue is placed in a flask along with a nutrient solution, then inoculated with a virus. He inoculated chicken eggs' amniotic membranes (the fluid sac that surrounds and protects the embryo) with the mumps virus, and placed it in a flask with a nutrient solution of balanced salt solution and ox serum ultrafiltrate. After a short time, the fluid containing the virus was drawn off and put into another flask with fresh tissue - making a subculture. Weller's idea was to modify this technique by leaving the tissue in the flask and replacing the nutrient fluid every 4 days. This allowed the tissue to remain alive for a longer period of time, giving the virus more time to grow in each cell. The experiment worked. The tissue did not quickly die, and the mumps virus continued to multiply and grow. Enders suggested they do the same experiment using an influenza virus. They isolated it as well, and found they could keep tissue growing for 30 days or longer.

Next, Weller prepared to use this technique to try to isolate the chicken pox virus, as he had originally intended. Since the varicella virus was only known to grow in human cells, he prepared cultures of skin and muscle tissue from aborted human embryonic tissue, minced them, and placed them into flasks. He inoculated four of them with cultures of throat washings from a child who had chicken pox. Another four flasks were not inoculated - they would act as controls to compare the results of the first four. He had enough skin and muscle culture left for four more flasks.

The lab had cultures of the Lansing strain of the polio virus and Weller put it in the four remaining flasks. He recalls, "It was almost as an afterthought: I was focusing on growing the varicella virus, not the poliovirus." He was disappointed - there was no evidence that the chicken pox virus was growing in the flasks. However, he took fluids of the cultures he had inoculated with poliovirus, and injected them into the brains of five mice. Within one week, one mouse became paralyzed and died. As the days passed, 3 more mice died.

Never before had there been evidence that poliovirus could be grown in non-nerve cells. In their Nobel lecture, the Enders team said, "...Thereupon it suddenly occurred to us that everything had been prepared almost without conscious effort on our part for a new attempt to cultivate the agent in extraneural tissue."
Further experiments showed they could grow the other two known types of polio, the Brunhilde and Leon strains, in the same manner. Enders and his colleagues demonstrated that the virus would grow in human embryonic tissues from the intestine, liver, kidney, adrenal, brain, heart, spleen, and lung. The Flexner polio paradigm was completely overturned.

Cytopathic Effect and Other Ways of Monitoring Viruses

Enders' previous work with the mumps virus had shown that fluids infected with the virus visibly affected red blood cells, which could be observed under a microscope. This provided an important lab test that could be used to tell if a fluid was really infected by the mumps virus. If he and his colleagues could find a similar test for the polio virus, showing that it infected and harmed tissue cells, it would be much easier than autopsying monkeys after inoculating them.

One day, peering into the microscope, Enders saw a poliovirus-infected cell explode. "Cytopathogenicity," he exclaimed, inventing a word. The word, truncated to cytopathic, later became common in virology. He and his team could observe the effect of the poliovirus on the cultured tissue cells 16 to 32 days after being inoculated.

Next, they found a chemical marker for the growth of the virus in infected tissue by adding phenol red, a dye. The poliovirus affected the cells' metabolism so that infected cells produced less acid than those not infected. In uninfected control cells, the dye changed color to yellow as the cells acidified. In infected cells, it remained red. Thus they had a ready test for the presence of polio in human tissues. The researchers also discovered a positive correlation between the acidity of the cultures inoculated with poliovirus and the amount of time since inoculation. Such precision allowed them to measure the infectivity of the virus as well as determine the minimum dose needed to infect various types of tissue.

The team eventually shortened their ability to recognize the virus to eight days and developed a test tube assay to determine the types of poliovirus and their respective antibodies in human or animal blood serum. These techniques would all become common testing techniques in virology, although not all viruses produce visible changes under the microscope, nor do they produce the same chemical changes as poliovirus.

The Roller Tube Apparatus

Roller tube tissue cultures had been perfected by George Gey in 1933 and Enders was one of the first to use them with viruses. Rather than growing animal tissue in flasks, researchers using roller tubes planted tissue on the sides of test tubes. The test tube is slowly rotated to mimic conditions inside the human body, where tissue is exposed to an active environment of nutrients and waste product removal, rather than the static environment of a motionless test tube or flask.

A big advantage of using the roller tube technique comes when viewing the cultures under a microscope. Tissue from flasks has to be prepared as slides for the microscope, whereas the outgrowth of cells in a roller tube can be repeatedly examined in the living state as the cells grow and the virus replicates.

A handy carpenter made the Enders researchers a roller tube apparatus with a round wooden holder of about 100 test tubes. When they used the roller tubes, they found that the virus grew more rapidly and to higher titres (concentrations) than in the suspended cultures in the flasks. This cut the time necessary to observe the growing virus to four days.

Identifying Poliovirus Infection in Animals and Humans Using Antibiotics in Culture - Leaving Monkeys at Play

Until the Enders laboratory found their new technique, scientists who wanted to isolate and type polio virus cultures could only do so by injecting the virus directly into the brains of living monkeys, letting the virus infect the brain tissue, killing the monkeys, and testing samples for virus. In the end, more than 100,000 monkeys were sacrificed in the development of an as-yet only dreamed-of polio vaccine. Enders and his team found a way to spare future monkeys by successfully isolating poliovirus from the monkeys' feces.

Frederick Robbins performed much of this research, adding penicillin and streptomycin - two newly discovered antibiotics - to the feces samples to kill off bacteria. Tissue cultures, inoculated with the purified samples, quickly showed the telltale signs of polio infection. They found that they could often isolate and type virus from feces within 48 hours in humans as well. Experiments demonstrated that many children carry viruses similar to polio, often with no symptoms. Within two years, the team had isolated and typed 13 strains of poliovirus. They also discovered the first of a whole group of viruses that became known as ECHO viruses (enteric cytopathic human orphan viruses), which are cousins to polio.

Weakening the Poliovirus to Make a Vaccine - Attenuation as the Holy Grail

A vaccine is a preventative medicine that jumpstarts the immune system into producing antibodies to attack a specific disease, usually before the immunized person contracts the disease itself. A virus that is devastating to humans can be passed serially through various non-human tissues and end up vastly weakened - known in virology as attenuated - yet retain enough of its original protein coat signature that the antibodies produced by the human immune system to fight the attenuated virus in the vaccine will also fight the original virus. A virus has to be grown over and over again in different media until it mutates into the desired weaker form.This "playing with evolution", a method developed by Louis Pasteur in the 1870's from his work with chicken cholera, anthrax, and rabies, is time-consuming and arduous.

In the Enders laboratory, Thomas Weller worked on propagating and attenuating the poliovirus. He grew the Lansing virus through 23 passages (a passage occurring whenever he changed the tissues in which the virus was growing, aka subcultures) over 331 days. He grew the Brunhilde strain -- the dominant cause of polio in humans -- through 15 passages over a period of 267 days. Periodically, the researchers tested it. They found that the virulence (or strength of the virus) had declined after three passages. As the number of passages increased, the virus' virulence decreased well over 100,000-fold. The team's conclusion was spelled out in their Nobel Prize lecture: "From these observations we concluded that, as with other viral agents, the virulence of poliomyelitis virus is not a fixed attribute but on the contrary may readily be altered under appropriate conditions." In less understated words - a vaccine was possible!

Enders' team published their findings in 1949

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Vaccine Production was left to Jonas Salk and Albert Sabin

Interestingly, the Enders lab did not try to develop the polio vaccine itself, even though they had the knowledge and could have easily secured the funding. "Enders, in his thoughtful way," Robbins said, "felt that this was not the kind of work our laboratory was best suited for." So the team stepped back and passed the task to Jonas Salk and Albert Sabin, who already had big labs dedicated to vaccine development. Both had pretty much stalled before the breakthroughs in tissue culture made by Enders' team. Suddenly, with a way to obtain an endless supply of viruses, they made quick progress. Salk himself said, "Dr. Enders pitched a very long forward pass, and I happened to be in the right place to receive it."

In 1952, Salk developed a vaccine that contained chemically killed virus from all three types of polio. In what was then the largest public medical experiment in history, 200,000 children were injected with the Salk vaccine, and the vaccine proved almost 80 percent effective at preventing infection with polio. It came at a propitious time for, in 1952, polio again flared up. The Salk vaccine was licensed for use in 1955, and within the next decade, immunization made polio epidemics a thing of the past in most of the developed world.

In 1957, Albert Sabin developed a vaccine of weakened, or attenuated, virus, which he insisted was safer and more effective than the Salk killed vaccine, and which could be taken orally in delicious sugar cubes. Because it was oral, Sabin's vaccine had the additional advantage of causing the body to produce antibodies in the intestine as well as in the bloodstream. Therefore, unlike the killed vaccine, it prevented the intestines from serving as reservoirs for poliovirus. Nor did it require the booster shots that Salk's vaccine required. It was Sabin's live vaccine that became the standard vaccine used in the United States in 1961. Endorsed by the World Health Organization, it eventually was used throughout most of the world.

Over one million lives have been saved by the polio vaccine.


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Enders' Research - Measles

Pediatrician Louis Z. Cooper described it at that time: "Before a measles vaccine was available, more than nine out of ten children caught measles, half of them before they were five. Measles starts with a high fever, a runny nose, a cough, and a sore throat. After five days, a blotchy red rash develops. Usually the disease runs its course in another week, but sometimes there are complications. One measles patient in every six develops pneumonia or a serious ear infection. One in every thousand gets measles encephalitis, an inflammation of the brain that can cause paralysis, mental retardation, and even death. Far from being a harmless childhood disease, measles kills more children than any other acute infectious illness."

Measles had been a particularly difficult virus to work with because there was no good animal host on which to experiment. When Enders began researching measles in 1953, Asian monkeys were the only nonhuman species that had been found to be susceptible to the virus, and they sometimes became infected and sometimes did not. Without a reliable test animal, and the tissue culture technique still being relatively new, little progress had been made with the measles virus.

Enders sent Tom Peebles, a pediatric resident, out to draw blood and collect throat swabs from kids in Boston who had measles. Using roller tube techniques, they began trying to isolate and grow virus from their samples. They continued to grow the viruses in serial passages through these media. From four to ten days after they were inoculated, the tissues began to show the abnormal, cytopathic changes that indicated a virus had taken over the cells. The cells would develop multiple nuclei and become enlarged, then die. Over time, nearly all of the cells followed this path to destruction. They next combined human sera from twelve people who had had measles to the tissues to see if antibodies in their sera would inhibit the cytopathic process. It did. This meant they were dealing with the measles virus and that the human immune system reacted successfully to the virus. As early as 1954 the tissue culture techniques were producing great results.

Next, Enders and his colleagues inoculated monkeys with the virus they had grown after 1, 2, and 23 serial tissue passages. Just as previous researchers had found, the results varied - some monkeys showed symptoms and others did not. To try to solve this riddle, they examined their next set of experimental monkeys before running any trials on them, and found that 22 of 24 monkeys from three different laboratories already had measles antibodies in their blood. They didn't know how the laboratory monkeys had become contaminated with measles antibodies, but that did explain the variable results. It also allowed monkeys to be used as reliable test animals - once the contaminated ones were weeded out.

Growing Measles Virus in Chick Cells

The Enders lab tried to grow the measles virus in tissues other than humans, such as pig, cattle or chick cells. In order to make a vaccine it was important to find a non-primate tissue in which to grow the virus. Otherwise, there was a high risk of contamination by other agents that would be pathogenic to humans. For several years they were completely stymied. In the team's third year of working with measles, they observed an interesting phenomenon. After passaging the Edmonston strain 23 times through human kidney cells, then 14 times through human amnion cells, they noticed that some cells did not undergo the typical cytopathic change. Instead of enlarging and blowing up when infected, some cells became star- or spindle-shaped. As the researchers continued to passage the virus, these cells came to be the predominant manifestation of the virus.
The virus had obviously changed. Might it now grow in a chick cell? After passaging the virus 23 times through human kidney cells and then 28 times through human amnion cells, the researchers cultured it in chick embryo amnion cells, chosen in the hope they would be analogous to human amnion cells. Success! They could continue to passage the virus many more times through those cells and obtain the same cytopathic reaction as they had seen in human amnion cells. They next tried growing measles in other chick embryonic tissues, and that worked too. At long last, they had found a growth medium that might yield a viable vaccine.

Attenuation of Measles Virus

There is no definite recipe for growing a virus in foreign tissue or for developing a vaccine. Virologist Joel Warren noted, with a literary allusion John Enders would have relished, that it is not unlike the recipe found in Macbeth: "Round about the cauldron go, in the poison'd entrail throw...cool it with a baboon's blood, then the charm is firm and good."

One technique used in making a vaccine is to help evolution along by helping a virus multiply in various tissues until it weakens - called attenuation. In order to attenuate the measles virus, Enders and his team needed to put it through enough passages to weaken it so it would no longer infect humans, but still be strong enough to produce the viral antigens needed to create an immune reaction. The lab developed two potential recipes. The best was from the Edmonston strain of measles virus. It was produced after an additional 6 passages through chick embryos and 14 passages in chick cell cultures. Tests on monkeys showed that the attenuated virus differed from the infectious virus in two necessary ways. The weakened virus could multiply and cause infection in chick-cell cultures, but neither multiplied nor caused symptoms in monkeys. Most important, monkeys produced measles antibodies 15 to 23 days after inoculation, which indicated that their immune systems would fight off the wild measles virus.

Measles Vaccine Development

Enders' team now had to establish that their attenuated virus would work as a vaccine in humans, so medical doctors began tests on small groups of children. Between December of 1958 and March of 1960, they ran six sets of tests on children. The vaccine gave the children a mild infection but nothing worse, and did not make them contagious. More importantly, it gave children immunity from full-fledged measles. They published their results in eight papers in the New England Journal of Medicine in July, 1960. At a conference in New York, the eminent virologist and bacteriologist Joseph Smadel stood up and said "John, you've done it again."

The one negative effect of the vaccine was that 30 percent of the children in the trials came down with a fever as a result of the shots. Joseph Stokes, a pediatrician at the Children's Hospital in Philadelphia, developed the practical solution of giving shots of human gamma globulin, containing measles antibodies in one arm, and the measles vaccine in the other, but this was not going to work on a world-wide scale. So, as he had done with polio, Enders made his attenuated strain available to others to refine his work.

Here the vaccine developer Maurice Hilleman stepped in, and applied the resources of the pharmaceutical company Merck, Sharp, and Dohme (now the giant corporation, Merck). Hilleman discovered that Enders' strain had become contaminated with a chicken leukemia virus, and he found a breeder in California who had developed a line of chickens that were immune to the virus. Illustrating once again the importance of the serial passage technique, Merck's team passed Ender's measles virus 24 times through primary human kidney cells and 28 times through human amniotic cells, as Enders had done, but then upped it to 12 times through embryonated hens' eggs, and 57 times through chick embryo cells. The end result of Hilleman's labor, after passing 35 quality control tests, was a commercial vaccine licensed for use in 1963.

Enders later wrote that his work on the measles vaccine was the most personally satisfying and socially significant. Over the following decades, the measles vaccine spread all over the world. By 2000, more than 80 percent of the world's children were receiving it. By 2006, the number of measles cases had fallen from 106 million in 1963, to 20 million, and the death rate from over 6 million to 345,000.

Over 113 million lives have been saved by the measles vaccine.

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Personal Information

Early Life

John Enders was born on February 10, 1897, into a family of high achievers. His grandfather walked from town to town selling insurance, eventually becoming president of the Aetna Insurance Company. His father was president of Hartford National Bank. A frequent family visitor during Enders' childhood wore a spotless white suit and was better known by his pseudonym - Mark Twain. In school, Enders had trouble with math and physics, and later said that during those years he "preferred in the main certain of the so-called humanities - Latin, French, German, and English literature, although biological subjects always proved highly attractive."

He matriculated at Yale University, but interrupted his education to enlist in the Naval Reserve to serve in World War I. There he learned to pilot the fragile, rickety bi-planes of the time. Enders was not sent to combat, but became a flight instructor in Pensacola, Florida. If he had any notions of being a daredevil himself, his flying experiences completely cured him. He decided he had used up all his luck in the air, and forever after was extremely reluctant to fly.

Education: A Late Start in Science

After graduating from Yale, Enders set out to uphold the family tradition of business. He brokered real estate for a while, but had trouble seeing the value of convincing someone to buy something they already wanted. After four uninspired years in business, Enders quit and went back to school.

Choosing Harvard, he received a masters degree in English, then decided to pursue a doctorate in philology, the study of language used in literature. He couldn't get excited about it either, writing a friend, "I mouth the strange syllables of ten forgotten languages, letting my spirits fall, my youth pass. If this mood lasts, I shall by Heaven, throw it all to the four winds and go forth into the world like Faust, even if I have to bear his penalty." While lost in purpose, Enders' life was far from miserable. He lived with some medical students in Mrs. Patch's comfortable boarding house. There he met an animated Australian, Hugh Ward, whose daily description of his doctoral work in microbiology piqued Enders' interest. "We soon became friends," Enders wrote, "and thus I fell into the habit of going to the laboratory with him in the evening and watching him work. I became increasingly fascinated by the subject-which manifestly gave him so much pleasure and about which he talked with such enthusiasm." Ward also introduced him to Hans Zinsser, a charismatic professor.

Together, Ward and Zinsser transformed Enders' life, convincing him that his intellect was best suited to science. So, in 1927, at the age of 30, considered late even in his day, Enders made a 180 degree turn in his studies and entered the doctoral program in bacteriology at Harvard. It was rare to earn a doctorate under Zinsser, a demanding taskmaster, but Enders earned his in 1930, with a thesis on anaphylactic shock caused by carbohydrates extracted from tubercular bacteria.

Family

In 1927, Enders married Sarah Frances Bennett. They had a son, John Ostrom Enders II, and daughter, Sarah. Tragically, his wife died in 1943 of acute myocarditis, an inflammation of the heart. In 1951 Enders married Carolyn Keane and gained a stepson, William Edmund Keane. They resided in Boston, Massachusetts and kept a summer home on Long Island sound.

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Career Path

After earning his doctorate in 1930, Enders became an instructor and worked in the Harvard laboratories under Hans Zinsser. Enders showed little of the academic ambition typical of PhD's in their thirties. It was five years before he became an assistant professor, and another seven years before he became an associate professor. It took him thirteen years before he employed a personal technician. Research, as opposed to advancing his career, was his main interest.

When, in 1937, Harvard's experimental kittens came down with feline distemper, Enders and a young epidemiologist, William Hammon, began a careful study of the disease. They found it was caused by a virus, and worked on developing a vaccine. This and other studies turned Enders' interest toward viruses, where he made his first major breakthrough - "the development of serologic techniques for the detection of antibodies to the mumps virus."

After World War II, Enders was asked to establish a research laboratory on infectious diseases at Boston Children's Hospital, which was located just across the street from Harvard Medical School, and had various ties to Harvard. In 1940, Enders had worked with Thomas Weller, a young medical student, on an experiment that had revolutionary implications. Using a roller tube apparatus they had kept cowpox virus (vaccinia) growing for nine weeks. Previous viral life span in tissue culture had usually been measured in hours or days, not weeks. Now that Weller was back from military duty, Enders brought him on to be the assistant director and to take care of administrative duties.

Enders and Weller were allocated four rooms on the second floor of the Carnegie Building, a three-story building next to Harvard's coal-fired power plant. Two rooms were turned into labs, one room was the glass washroom, and the final room was Enders' office. Animals were kept a block away in another building. Enders and Weller furnished the lab with the standard equipment, such as an autoclave to sterilize equipment and chemical hoods, along with some more novel items. Embryonated hens' eggs had recently been introduced as media in which to grow viruses, so they purchased an egg incubator and visualizing lights to shine into the eggs. Early in 1948, they added Frederick Robbins, Weller's college roommate to the team.

The aim of the lab, which many thought futile, was to study numerous viruses in tissue cultures. Enders had already worked with viruses such as herpes simplex, influenza, measles, and mumps, and wanted the new lab to expand such research. There were numerous experiments going on at any one time.

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John Enders' Life: A Timeline

1896 - Born in West Hartford, Connecticut
1917 - World War I Naval Reserves flight instructor in Pensacola, Florida
1920 - Yale Graduate, B.A.
1921-1925 - Real Estate Broker
1925-1927 - Harvard MA, English
1927 - 1930 - Harvard PhD, Bacteriology
1930-1940 - Laboratory assistant in Hans Zinsser's lab, Harvard
1937 - With William Hammon, investigated distemper and worked on distemper vaccine
1939 - Developed serologic techniques for the detection of antibodies to the mumps virus
1940 - Revolutionary experiment that allowed viruses to grow in cell cultures for nine weeks
1943 - Wife Sarah died
1947 - Began laboratory at Boston's Children's Hospital with Thomas Weller
1948 - Frederick Robbins joined lab
1949 - Published revolutionary article on how to grow the poliovirus
1951 - Married Carolyn Keane
1952 - Jonas Salk developed the killed polio vaccine
1953 - Enders began research on measles
1954 - Enders, Weller and Robbins win the Nobel Prize for their work on polio
1956 - Became a full professor at Harvard
1957 - Albert Sabin developed the attenuated polio vaccine
1958 - Began testing a measles vaccine
1963 - Measles vaccine, improved by Maurice Hilleman at Merck, produced commercially
1985 - Died on September 8, at home, in Waterford, Connecticut, age 88

 

 



Scientific Discovery Timeline

 



Recommended Books about the Science of Polio and Measles

 



Books by John Enders

 



Books about Enders

Woodward, Billy, Shurkin, Joel and Gordon, Debra. Scientists Greater than Einstein: The Biggest Lifesavers of the Twentith Century. Linden Publishing, 2009.



Awards

1954 - Nobel Prize for Medicine: Enders, with Thomas Wells and Frederick Robbins, received the prize "for discovery of the ability of poliomyelitis to grow in cultures of various types of tissues."
1954 Lasker Award
1959 Time Man of the Year
1963 Presidential Medal of Freedom


 

Major Academic Papers

 



Curriculum Vitae

 



Links

National Academies Press Biographical Memoirs
http://www.nap.edu/openbook.php?record_id=6061&page=47
Short History of Vaccines
http://americanhistory.si.edu/polio/virusvaccine/history3.htm
Nobel Prize Biography
http://nobelprize.org/nobel_prizes/medicine/laureates/1954/enders-bio.html
World Health Organization Measles Fact Sheet
http://www.who.int/mediacentre/factsheets/fs286/en/
NNDB biographical notes
http://www.nndb.com/people/630/000129243/



Sources/References

Enders, JF, Weller, TH, Robbins, FC. 1949. Cultivation of the Lansing Strain of Poliomyelitis Virus in Cultures of Various Human Embryonic Tissues. Science. 109:85-87.

Allen, A. 2007. Vaccine - The Controversial Story of Medicine's Greatest Lifesaver. New York: W.W. Norton, Co.

Bendiner, E. 1982. Enders, Wellers, and Robbins: ‘The Trio that Fished in Troubled Waters'. Hospital Practice. Jan 17 (1):163-197.

Chase, Allan. 1982. Magic Shots. New York: William Morrow & Co., Inc.

Driscoll, Jr., E.J., 1985. John Enders. Boston Globe Obituaries. September 10.

Eggars, H.J. 1999. Milestones in early poliomyelitis research (1840-1949). Journal of Virology 73(6):4533-4535.

Enders, J. 1925. A note on Johnson's staple of news. Modern Language Notes 40(7).

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The Rise of the March of Dimes
By Joel Shurkin

Poliomyelitis is a strange disease, one that seems to run counter to what we think we know of pestilence. Many infectious diseases are particularly endemic among the poor, in conditions of polluted water and contaminated food. Clean up the environment and you usually can stem an epidemic or prevent a recurrence. Think of cholera, bubonic plague, and typhoid. Polio, or at least the terrifying epidemic that spread fear and panic throughout America in the first half of the 20th, was a disease actually made far more terrible by cleanliness; it was a disease that struck most severely the children of the middle and upper classes who did not swim in dirty rivers or eat spoiled food or live in neighborhoods ridden with rats. Perhaps it was this fact that made the need for a vaccine so urgent: Nothing moves society faster than the middle class in passion.

Additionally, it was an uncommon disease before the 20th century. It was with us, but not with enough frequency to draw much attention. Polio is an intestinal viral infection, spread from person to person without an animal host. The disease lives in fecal waste and is transferred by unwashed hands or objects or contamination. It goes almost immediately through the gastrointestinal tract where it breeds in the small intestine. That's when the first symptoms appear: headache, fever, nausea, fatigue and a stiff neck. Most of the time, that's all that happens and the patient recovers after a few days. Once in about 100 cases, however, the virus invades the central nervous system, destroying motor neurons, the fibers that make muscles contract. This is what leads to paralysis. Death occurs when the muscles of the diaphragm are paralyzed, making it impossible for the victim to breathe. Again, however, this is not the common result of the infection; most people recover and move on.
The disease has many names, the most famous, "infantile paralysis" is for its most noted victims, young children. Technically, it was known as poliomyelitis, a combination of polio (Greek for gray) and myelos (marrow) and itis (inflammation). Headline writers, always interested in saving space, shortened it to "polio" after World War 2.

Paintings from ancient Egypt show people with withered limbs that look exactly like the limbs of polio victims, one as old as 1500 B.C. Both Hippocrates and Galen described something that reads like polio, but whatever they were describing was relatively rare. The Emperor Claudius, who had a withered leg, might have been a victim. Other cases have been reported in the Middle Ages, but again, it appeared to be an uncommon affliction. More detailed descriptions were recorded in the 17th and 18th centuries. Sir Walter Scott, also might have been another victim. {Oshinsky, 2005, Polio: An American Story} The German, Jacob von Heine, first described the disease in 1840. {Kluger, 2004, Splendid Solution: Jonas Salk and the Conquest of Polio} Cases remained of little note until the mid-19th century, when doctors started to report cases in Western Europe and the United States. The only thing the cases had in common was that the victims were usually young, and all the cases were reported in the summer. Outbreaks were isolated from one another, which physicians noted, was in itself, odd.

The first epidemic in the United States was near Rutland, Vermont, the summer of 1894, 123 cases all recorded by a country doctor, Charles Caverly. Most of the victims were male, and 84 percent was under the age of six. Caverly noted that it wasn't particularly contagious (one case in a family, often although that would change somewhat in later years), and that most victims recovered without any permanent damage. There was, he surmised, a mild form of the disease that was more common than the disastrous form. He also guessed that chilling the body or overexertion played a role in susceptibility to polio, which might account for the number of boys getting sick.

Another epidemic hit Sweden in 1905, and a Stockholm pediatrician, Ivar Wickman, found that even people who had mild cases were carriers and could spread the contagion. In 1908, Karl Landsteiner, who appears elsewhere in the book, isolated the poliovirus by taking fluid from the spine of a boy who died of polio and injecting it into the brains of two rhesus monkeys. The monkeys quickly got polio. Most of the research was continued in Europe; America did not have a tradition of medical research in the first half of the 20th century until John J. Rockefeller, under attack for his business practices, formed the Rockefeller Institute in New York City, at last partly to deflect attention from his legal troubles. His first director was a member of one of the most distinguished brother acts in American science, Simon Flexner, elder sibling of Abraham Flexner. (Abraham issued the 1910 report that revolutionized American medical education. He later founded the Institute for Advanced Study in Princeton, Einstein's home.) Simon's reputation was unassailable (he had already isolated the dysentery bacillus) which was unfortunate here because he soon made a mistake that would cost decades in the attempt to find a polio vaccine and no one bothered to catch it.

Flexner was highly successful at Rockefeller from the first, discovering a treatment for meningitis before the discovery of antibiotics. By this time, polio had become more common in America. In 1907, New York City counted 2,000 cases. Other states reported cases in the following years, including another epidemic in Vermont for Caverly to worry about. Epidemiologists were puzzled because the only thing they had in common was the young age of the victims and the season, summer. Even more puzzling, it was hitting the middle class, not slum children. Flexner devoted his research time to studying polio.

First, he verified the cause as a filterable virus. Good. That meant it could be studied in lab animals, particularly monkeys. (A great many monkeys eventually would die in this cause, more than 100,000.) Then he turned to find how the virus entered the victim. He fed rhesus monkeys fecal matter containing the virus and nothing happened. Then he swabbed their nasal passages with the virus and they came down with the disease. Bad. Flexner concluded, logically, that's how people got it: they inhaled it. Unfortunately, it meant the virus probably did not enter the blood stream on its way to the nervous system. That was really bad news because vaccines fight viruses in the blood stream and if the poliovirus attacked the nervous system without ever entering the blood stream, vaccines would be difficult if not impossible to produce. The best idea he could come up with was to stuff some chemical agent in the nose that might block the virus. With that conclusion, he announced in 1910 he could prevent polio. He could not.
His error led to a cascade of errors that set back research into a vaccine for 40 years. For instance, in the course of his experiments, Flexner produced a strain of virus, MV, which was neurotropic and could multiply only in nerve tissue. Two men working for him, Albert Sabin and Paul Olitsky demonstrated this in 1935: you could only grow the virus in nerve tissue. Because Flexner was Flexner, most polio researchers used his strain in their research. Flexner also concluded there was only one type. Wrong again.

Flexner used the wrong monkeys. Rhesus monkeys can't catch polio orally. No one knows why. Other monkeys, however, can and had he used another species he would have not have made his mistake. Other scientists accepted this conclusion. Poliovirus enters the body (human or primate) through the mouth and does enter the blood stream.(In fairness, Flexner's reign at Rockefeller produced some of America's best scientists and research. The polio research was the nadir of an otherwise illustrious and admirable career.)

The Shadow of Summer

Essentially, polio was largely unnoticed at the turn of the 20th century. However, with the discovery of pasteurized milk, which virtually eliminated tuberculosis, polio became the primary disabling disease. {Children's Hospital of Boston, 2005, Polio Vaccine: The Story Behind the Story} When it struck, terror followed, and if you had children, the terror was completely understandable. Readers over the age of 60 remember it well because it lurked in the dark shadows of their nightmares when they were children, unlike anything parents face now. Parents examined their children weekly during the summer, pumping their legs to look for the telltale weakness, touching their foreheads to check their temperature. It became a part of life in the American summer.

There was--and still is--no cure.

Polio came like clockwork when the weather warmed and left when the first chill came. The hotter the weather, the worse the pestilence. Most of the time the epidemic was mild, and most of the victims, largely children, recovered without permanent damage. Then, every few years, it struck with particular viciousness. Take the summer of 1916.

Whole blocks could be quarantined. The Board of Health used subterfuge to spot victims. It set up milk stations around the city, inviting women to come and get fresh, unspoiled milk for their children (this was before efficient refrigeration). When the children and their mothers showed up, the nurses watched to see which looked ill. Children seen as suspect were whisked away to quarantine in ominous black automobiles. Once the mothers figured that out, they stopped coming to the milk stations and police began to monitor playgrounds. Doctors would examine any child deemed suspicious, and sometimes accompanied by a social worker, would visit a home. Sometimes, if the doctor decided that the child was being quarantined sufficiently, the family was allowed to stay together, if not, the child was taken by force off to a hospital, often over the physical resistance of a hysterical mother. In particularly bad epidemics, special hospitals were constructed to house the youngsters.
By July 1st, 1916, 350 cases had been reported, the worst epidemic ever in New York. An astonishing 75 had died. Brooklyn was hardest hit--the epidemic had erupted first in a section known as Pigtown. When the disease first appeared, the authorities did the logical thing. Hundreds of trash collectors showed up to clean the streets of Pigtown--cleanliness, after all, had helped stem disease like cholera and typhoid. Rats had spread the Black Death in Europe. The efforts certainly improved the neighborhood, but did nothing to mitigate the epidemic. {Oshinsky, 2005, Polio: An American Story} Panic raced through the city. Rumors flew that cats spread the disease and in a few weeks, 70,000 cats were killed. That didn't work either. By the second week in July, 1,000 cases were reported and people began fleeing the city. Children needed a certificate attesting to being polio-free before they were allowed to leave, and many towns in the surrounding area banned New York City children from entering, certificate or not. Polio spread.

Peculiarities abounded. Staten Island, the least urban of the city's five boroughs, and probably the cleanest, had the worst outbreak. Rural areas in New Jersey and Connecticut suffered at least as much as the city. Cultural explanations--the disease was the result of unclean habits, probably brought in by the burgeoning immigrant population-did not work here.

When the epidemic ended nationally, 27,000 cases had been reported nationally, 6,000 of them fatal. New York tallied 9,300 cases; 2,200 children died. Half the survivors were paralyzed. One child who escaped the disease that summer in New York was the two-year-old Jonas Salk.

Gradually, the size and intensity of the epidemics grew as the century moved on--unaccountably. Why were the victims' ages getting older? Why was there a rhythm to the outbreaks? There was a rhythm. In New York City, the disease began to come in five-year waves. It would strike the city's children one summer and then almost disappear for the next four, only to roar back even more intensely the fifth summer. You could almost feel it coming. Everything about the disease was puzzling.

At the risk of anthropomorphizing, the virus struck the wrong person in 1921.

The Iron Lung

In August of that year, Franklin Delano Roosevelt was 39-years-old, in the peak of health and reveling in a body that seemed to glow with activity. He loved to swim. He enjoyed nothing more than physically romping with his children. That hot summer, he was at the family home on Campobello Island, part of the Province of New Brunswick, Canada, but right off the Maine coast. He had just spent some time at a Boy Scout Jamboree held at his family estate at Hyde Park, and he was photographed marching with a group of Boy Scouts, the last picture of him walking extent. {Oshinsky, 2005, Polio: An American Story} Roosevelt was under enormous psychological stress. He had just finished an unsuccessful campaign for Vice President of the United States and was under political pressure for a scandal that had occurred a few years earlier when he was at the Navy Department.

He arrived on Campobello on August 7 to join his family, who had been there for a month. The next day was typically active. First, he went sailing. Noticing a brush fire on his way back, he spent several hours helping put it out. Then the children challenged him to a race, running and then swimming in the frigid waters of the Bay of Fundy and then running back. He loved it. When he was done, he sat around in a wet bathing suit reading newspapers and catching up on correspondence, a happy man.

By late afternoon he began to feel unwell. Great chills swept his body. His muscles ached. He felt numbness. He went to bed, skipping dinner with the family. But the next morning, his left leg began to drag, he had a fever and he hurt. The family called a local doctor, who reported he had a virus, probably from over-exhaustion. The pain grew worse and the numbness was now spreading to his other leg. His skin became so sensitive the feel of his pajama bottoms was excruciating. A second doctor was called, a noted physician from Philadelphia who was vacationing in Bar Harbor. He said the paralysis probably came from a blood clot in his legs and it would go away. He left a bill for $600.

By now, Roosevelt was paralyzed from the waist down. The family finally called in an expert from Harvard and Boston Children's Hospital, Robert Lovett, who by coincidence had written the definitive textbook on polio. Lovett knew a case of polio when he saw one and he saw one in Roosevelt. He ordered Roosevelt to return to New York for rehabilitation as soon as he stabilized. The task of nursing FDR fell on his wife, Eleanor, including catheterizing him so he could urinate, administering painkillers and giving him enemas.

Roosevelt at first glance did not appear to be a likely victim. He was, after all almost 40 years old. But he was a walking target. He led a sheltered life of privilege, isolated from large crowds of children in a clean ordered world with less exposure to routine viruses and bacteria than most. Moreover, he had been unusually active that week, had spent time with a horde of Boy Scouts who probably were carrying a myriad of germs, was chilled and probably exhausted. He also was under considerable stress, which can diminish the power of the immune system.

Roosevelt returned to New York City in September, carefully shielded from the press. Treatment for polio had become well institutionalized. Boston Children's built two hospital buildings mainly to treat children with polio. The first floor of the Bader Building held a swimming pool, or therapeutic tank, as well as therapy rooms where paralyzed leg muscles were exercised. The buoyancy of the pool made it easier for the children to move. Pictures show them lying on cots suspended in the water with therapists in bathing suits massaging the muscles. The hospital had a gym with exercise rings to help "straighten out" their legs. The real tragedy sat in other rooms, hissing and thumping: the iron lung.

Children who could not breathe because of paralysis of their abdomen could only be kept alive in a respirator, technically known as a negative pressure ventilator. Most people called them "Iron lungs," although the name sounded more like a medieval torture chamber than a lifesaver. Invented at Harvard in the late 1920s, it actually was made of steel, a drum that sealed the body from the chest down, leaving the head and shoulders free. Pumps increased and decreased air pressure in the chamber. When the pressure in the drum fell below the level of the pressure in the lungs, the lungs expanded and sucked in air; when the pressure was greater outside the lungs, then the lungs are squeezed to exhale. Hospital wards were filled with them. Boston Children's even had a room-sized iron lung that could accommodate four children at one time.

Fear Itself

The doctors told FDR-accurately-that if he did not make significant progress in the first six months, he would not improve at all. He made very little. He never gave up, however, always looking for a treatment that would restore his legs, always ready to listen to a story about someone who had beaten the disease. He spent hours corresponding with other victims, strangers with whom he felt a kinship. So, when, in 1923, a friend from Harvard, George Foster Peabody, told him about a natural springs spa in Georgia that Peabody partly-owned, the Meriwether Inn at Warm Springs, he was an apt audience. Peabody mentioned a polio victim who had improved in the waters at the spa so much he could walk around without braces. The warm spring water, always 88 degrees, had a high mineral content (calcium and magnesium), which increased buoyancy, and made patients more comfortable. FDR traveled to the resort, 75 miles southwest of Atlanta, to check it out.

The place was a mess, dilapidated and unkempt, but the pool was open and FDR tried it. The warm water and the buoyancy were a comfort, and he thought he could detect just a touch of movement in one of his legs. Over Eleanor's objection, he bought the place, and turned it into a therapeutic resort for polio victims. FDR would spend much time there, eventually turning it into "the Little White House." (He died there in 1945.)

Another event in FDR's life is crucial to the story. One day, a few years after he became ill, FDR was visiting an office building in New York when he slipped out of the arms of his assistant in the lobby and fell. A lawyer in the lobby helped pull him up. That, according to legend, is how he met Basil O'Connor. They had lunch. The two men became friends and eventually, law partners in a firm called Roosevelt & O'Connor. One of the first things O'Connor did was to turn the spa into a nonprofit foundation for tax purposes-the Georgia Warm Springs Foundation.

FDR loved the place. Eleanor hated it. But soon, polio victims--several hundred a year--came from around the country to Warm Springs, partly because of the water, and partly simply to be around other people like themselves.

In 1928, the Democratic nominee for president, Al Smith, convinced FDR to run for governor of New York. He campaigned vigorously, although it was a logistical nightmare. He had a steel bar built into his car so he could stand with his braces locked. He walked a few feet to speaking podiums using canes and swinging his hips. "Too bad about this unfortunate sick man, isn't it?" He joked to his audience. He won. He ran for President three years later. The public, knowing a little about his disability, seemed not to care. By gentleman's agreement, the press corps declined to mention his disability. The Depression was tearing their lives apart and whether the new President wore leg braces was hardly relevant.

The time away from Warm Springs, however, made it necessary for him to find someone else to run the place and he turned to O'Connor, who was unhappy with the assignment. O'Connor hired Keith Morgan to do the day-to-day operation. Warm Springs was losing money. It could not charge patients the actual cost, so the shortfall had to be made up of contributions. Morgan hired a Jewish refugee, an innovator in the new field of public relations, Carl Byior, to drum up more financial support.

Byior decided to throw a party at the Waldorf-Astoria in honor of FDR's birthday as a fundraiser. Then he sent letters to every newspaper editor in the country suggesting they get their local civic leaders to do the same. FDR agreed to the use of his name. The money would go to the Warm Springs Foundation. The shameless motto was: "We Dance So Others Might Walk." Then Byior, traveling with the aviator Wiley Post, went around the country drumming up publicity. He was practically inventing modern public relations on the spot. Six thousand parties were held on January 6, 1934, in the teeth of the Depression, raising $1,016,443 for Warm Springs, an astounding sum. Most of the money was in small donations. In some ways, that was too much money; Warm Springs didn't that much, but the battle against polio did.

That next year, Hollywood got involved, with MGM sending its stars to Washington to glamorize the party. Byior quit in 1937 because of political differences with FDR, but the next year, the President announced the formation of the National Foundation for Infantile Paralysis, with Basil O'Connor in charge.

O'Connor is a uniquely American character. He was the son of a tinsmith and worked his way through college and law school playing the violin. He had absolutely nothing in common with the aristocratic Roosevelt. He was a terrific businessman, and when he helped pick FDR up off the lobby floor, he had accumulated a small fortune. He liked living well and elegantly. The first year of Roosevelt & O'Connor was lucrative for both men, and a lifelong friendship was sealed.

The National Foundation became the model for modern private charities, the largest voluntary health organization in history. O'Connor knew his job: to defeat polio, either by finding a cure or a vaccine to prevent the disease, he needed two things. First, he needed an effective organization. He created one, an organization unlike any that had existed before. Second, he had to scare the hell out of everyone about this disease: terror is the best motivator.

The comedian Eddie Cantor became the national spokesman and suggested people be asked to mail dimes to the White House, directly to FDR. O'Connor probably gulped hard, but Cantor was a friend of FDR so he passed the suggestion on to the White House. FDR bought it. Cantor also thought up the name, March of Dimes. He went on the radio to tout his plan, joined by the Lone Ranger, Jack Benny, Bing Crosby, Rudy Vallee and Edgar Bergen.
On an average day, the White House got 5000 letters. The day after the Cantor show, 30,000 showed up. The next day it went to 50,000 and on the third day, 150,000. When they cleared out the hallways and desktops, they counted 2,680,000 dimes.

O'Connor meanwhile built an army of volunteers, usually mothers, to solicit funds, and a cadre of talented office workers in New York, including a huge public relations department. He then convinced Hollywood studios to produce and show short films about polio in their theaters, and he had buckets passed through the crowd at theaters. Eventually, every movie theater in America had mothers marching up and down the aisles collecting money.

Only the Red Cross has ever collected more. The money was not wasted.

The National Foundation handled the finances for the treatment of most polio patients in America who needed help, even building instant hospitals in rural areas when the disease struck. No patient was turned away. Doctors learned to phone New York immediately on seeing their first case, and the foundation immediately sent expert help and funds. Every authority on the disease in America eventually either worked directly for the foundation, or was funded by it. More important to this story, the National Foundation was virtually the sole source of research funding for polio. Although the National Institutes of Health were organized in 1930, its budget was tiny. There was no well for large-scale medical research in America until Basil O'Connor and the foundation. Fortunately for all, the organization was superb; the people eminently competent, and the research thrust was right on target. Polio would not have been conquered without O'Connor and his March of Dimes.

After Roosevelt died and birthday parties seemed inappropriate, some volunteers in Arizona came up with an idea: door-to-door solicitation. It would not take long, and the giving was prearranged: Anyone willing to contribute would leave a porch light on in the daylight hours and volunteers would knock on those doors. So mothers marched through the newly burgeoning suburbs and the nicer parts of cities and replaced the collection cups at the theaters. The publicity was centered on another new concept, poster children, pictures of polio victims carefully selected to break your heart.

 
Comments (2)
2 Wednesday, 22 August 2012 13:54
frtgioiyg
not bad really
1 Wednesday, 29 September 2010 08:04
jackie
this was longg really interesting though :)

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