[Narrator:] This is the virus, a tiny organism less than one millionth of an inch in diameter, magnified here thousands of times by the electron microscope. This, the disease caused by the virus. One which has plagued man since recorded history. This, the scientist, Dr. John Enders of Harvard, whose work made possible an effective vaccine which can prevent the disease. This, the place where the vaccine is tested and produced for use throughout the world. West Point, Pennsylvania. And this, the vaccine itself, the end product of medicine's long match with measles. [Music] [Mission: Measles, The Story of a Vaccine] [Presented as a public service by Merck Sharp & Dohme, Division of Merck & Co., Inc.] [Narrator:] Many parents think of measles as just a common nuisance, which makes their children feel miserable and keeps them out of school for a while. But physicians today know that measles is more than a nuisance. It can bring on bacterial infections, can cause fatal pneumonia, and in some cases encephalitis, inflammation of the brain. Each case needs good medical care. It is not so much because of the usual rash and fever symptoms of measles that the doctor says he'll check back in a day or so, but rather to be sure the young patient is not developing serious complications. Electroencephalograms indicate that half the patients with natural measles show some brain involvement during the disease. After the disease has passed, most patients, such as this boy being tested in Philadelphia's Children's Hospital, show a return to a normal brain wave pattern, a distinct contrast to the abnormal pattern recorded during the disease. Still, in those patients who showed the abnormal encephalogram during their illness, the possibility of future emotional instability, or mental deficiency, or even mental retardation, cannot be ruled out. Fortunately, only about one measles patient in a thousand develops encephalitis. As of this time, measles is by far our most serious epidemic childhood disease. [Bar graph of reported measles cases] Although nearly half a million cases are reported each year, the actual number is probably closer to four million. In 1961, after the polio vaccines had reduced the deaths from that disease to 90, that same year, 434 measles deaths were reported. [Bar graph of deaths from measles versus polio] In the less developed countries of the world, the toll taken by measles is much greater. In Nigeria it is estimated that one out of four babies contracting measles dies from it. The tragic toll of measles is also told in a neighboring republic, Upper Volta, where in one village an epidemic killed 113 out of 115 children who got the disease. Across the ocean in Chile, measles accounts for half of all childhood deaths from acute communicable diseases each year. Thus now, as it has for centuries past, measles takes its toll of human life. It was a Persian physician named Rhazes who gave the first classical description of measles ten centuries ago. He and other Arabian physicians first suggested that measles is a distinct and separate disease. It had often been considered a form of the pox. But these early doctors described and treated the symptoms of the disease, not the cause. There were many remedies but no prevention. The cause remained a mystery. Then, in the eighteenth century, the light began to dawn on some of the causes of infectious disease. Jenner of England, Pasteur of France, Koch of Germany founded the science of bacteriology. With improved microscopes came the microbe hunters. They identified bacteria, grew them, and experimented with them in their laboratories. Their search pointed the way to discovery of another disease agent, a millimicrobe, the virus, and to the development of a new medical research specialty, virology. At hospitals and research centers today, virology is a major and growing scientific discipline. And in a laboratory attached to Children's Hospital in Boston, is one of the nation's most respected virologists, Harvard scientist and Nobel Prize winner Dr. John Enders. In 1953, a few years after Dr. Enders' work paved the way for the polio vaccines, he and his team turned their attention to measles. The first objective: to find and to grow the measles virus. Blood samples taken by Dr. Thomas Peebles from children with natural measles were injected into cultures of human kidney cells and incubated. With techniques like these being carried out today by Dr. Samuel Katz, tissue cultures brought from the incubator are checked for any changes in the cells. Obtaining even one successful growth of pure virulent measles virus is one of the most difficult laboratory achievements. Finally, in 1954, one culture obtained from an 11-year old measles patient named David Edmonston begins to show remarkable changes in cell structure. These might be caused by the measles virus. Dr. Enders is called in to observe it. To prove that it is the measles virus, they decide to inject it, as Dr. Katz demonstrates here, into the only animal that will contract the disease--monkeys. Monkeys which have never been exposed to measles. In a few days, when the monkey develops measles, they know they have isolated and grown the Edmonston strain of the measles virus. Now they discuss the longest, and in many ways the most difficult, task of all--how to attenuate or weaken the virus so that it will produce antibodies and thus provide immunity without transmitting the disease itself. It's a little like walking on a tightrope. The virus is grown first in one tissue culture, then in another. Human kidney tissues, human amnion, egg amnion, chick embryo. It is transferred. It is incubated. Always carefully watched and safeguarded against bacterial infection at every stage. As the weeks pass, the virus makes 72 passages in all before Dr. Enders decides it's ready for the next tests with experimental animals. Two groups of monkeys are used. One group is given the attenuated virus as a vaccine. The other group is not vaccinated. Later, both groups are given the full-strength measles virus. In a few weeks the results are evident. The monkeys that were not vaccinated developed measles. The ones like this one that were given the experimental vaccine show no signs of measles, but they have developed protective antibodies. Dr. Enders and Dr. Katz now know that they have developed for the first time a vaccine which will provide safe protection against measles. It only remains to test the attenuated live virus vaccine with humans. Starting first with children at a state school, Dr. Katz then inoculates volunteers who come to his lab at the hospital. The results are most encouraging and spark interest throughout the world of virology. One who saw the importance of moving forward with this breakthrough was Dr. Maurice Hilleman, Director of Virus and Cell Biology at the Merck Sharp and Dohme Research Laboratories in West Point, Pennsylvania. With cultures of attenuated virus from Dr. Enders' lab, Dr. Hilleman, Dr. Eugene Buynak, and colleagues undertake development of larger experimental quantities. At the same time, Dr. Hilleman draws up the design of the next critical step--broadscale clinical testing. Collaborating with Dr. Hilleman is a group at Children's Hospital, Philadelphia, headed by Dr. Joseph Stokes, nationally known pediatrician and medical scientist. Here with him, Doctors Robert E. Weibel, J. Ronald Halenda, and Charles M. Riley map out a plan for field trials in southeastern Pennsylvania. More than fifteen hundred children and their parents cooperate. One group of children receives the live vaccine by injection. The trial also studies how gamma globulin given in the other arm modifies reactions to the vaccine. Another set of children for comparison receives injections that do not contain the live vaccine. A blood sample taken from each child before vaccination tells which children have not previously had the disease. These samples are analyzed in the research laboratory. Another sample taken four weeks later shows whether the child has developed antibodies to the vaccine. Then over the next year or so, a close check is kept to see if any of the children contract the real disease. The results fulfill all expectations. The vaccinated children are protected. None of them get measles when exposed to it. From New York University, Dr. Saul Krugman reports similar findings, as does Dr. Fred MCCrumb at the University of Maryland. The trials spread across the country. The vaccine is tested in 18 states from the eastern seaboard to California. As the data from all these field trials accumulate, answers to earlier questions emerge. The live measles vaccine is producing a high level of immunity, safely, consistently, and the immunity appears to be long-lasting. Answers are also emerging on the problems of large-scale production and quality control, as manufacture gets underway in the biological laboratories at West Point, Pennsylvania. The less-developed countries in Africa watch this progress with great interest. Helping them launch studies of the vaccine are first, the U.S. Armed Forces Epidemiological Board, and later the World Health Organization and U.S Public Health Service. It was to the National Institutes of Health in 1962 that an urgent request came from one of these African nations. Upper Volta, satisfied with preliminary testing, asks for a massive vaccination effort. "Help us protect our children before measles strikes again." Begun in time, it could save thousands of lives. The response is immediate. To help train local teams and study the immunization of this population, the Public Health Service sends a medical team from its Division of Biologic Standards. Vehicles are supplied by the Agency for International Development. The vaccine is contributed by Merck Sharp and Dohme. The drum speaks to the people. "Come to the village, the doctors are here with the medicine. It can protect your children." And the people do come, bringing their children, bringing their hopes and fears. At each village, the jet inoculator used is carefully explained. Then begins the long hard job of giving the lifesaving vaccine to the children. As soon as one village has been protected, the team must move onto the next. Everywhere, they are greeted by huge crowds. The vaccine must be kept refrigerated to protect it from the intense African heat. At each new location the inoculator is cleaned and checked. The lines seem endless. But all the children must get the vaccine. Village after village, the people come by the thousands. The team works around the clock. At last the work is done. By March 1963, 700,000 children in Upper Volta receive live-virus measles vaccine. Many thousands of lives may have been saved. That same month, the Department of Health, Education, and Welfare licenses the vaccine for general use in the United States. The Surgeon General of the United States Public Health Service, Dr. Luther Terry, has this to say. [Dr. Terry:] Over the past several years, measles vaccines have been successfully tested both in this country and abroad. This painstaking evaluation was made possible by the cooperative effort of scientists, both in and out of government, by physicians, by the drug industry, and by thousands of unselfish and courageous parents who have permitted their children to participate in the field trials. The Secretary of Health, Education, and Welfare has now licensed the vaccines for general use. As increasing numbers of children are vaccinated, we will be well on the way to eradicating a disease that down through the centuries has killed millions of children and left others impaired mentally and physically. All of those who have contributed in any way to this cause for better health can be proud of a great achievement. [Narrator:] Within 48 hours of official government licensing, supplies of the vaccine are ready for shipment to doctors throughout the country. Today, production of the vaccine is in full swing, protected at each step by the elaborate manufacturing controls established by industry, together with the federal government. Production of the live virus vaccine begins with fertile chicken eggs. To assure absolute purity, the eggs are taken from select disease-free chickens kept in strict sanitary isolation. The eggs are opened and the embryos are carefully removed. They are minced and washed, then further broken down by a chemical substance that reduces the tissue to individual cells. It is only in living cells that the virus can grow. To keep these cells alive and growing, a special nutrient is prepared. A precise number of cells is counted and introduced into each bottle. Then the measles virus is introduced. Eighty percent of the culture bottles are infected. The other 20 percent are used as controls. They provide a way to check against any possible impurities in the cells. The cells attach themselves to the walls, and in the infected bottles the virus grows in the cells. Now begins a three-week period in which the nutrient is periodically replaced. The cells are rinsed and the growth is carefully watched. The fluid now taken from the culture bottles contains a high concentration of measles virus. The individual harvests are pooled together. Also, a stabilizer is added and samples are removed for testing. Finally, the entire pool of vaccine is filtered. This at last is the pure live virus vaccine. It is frozen at minus 75 degrees to await results of final testing. It takes 137 days to produce the vaccine. Ninety-six of these are devoted to meticulous quality control testing. More than 35 separate tests are performed to ensure potency, safety, and other measures of quality control. For each person involved in the actual production of the vaccine, eight people devote their time to testing and control. Finally, the vaccine which has passed all of the tests is thawed and transferred to individual bottles. These are then freeze-dried, capped, and sealed. The end result is a single-dose vial of the live, attenuated-virus measles vaccine. But the real story of a vaccine is told in the fears and smiles of a little girl who today is given greater protection than ever before against the infectious diseases of childhood. There remain other viruses to be isolated, other vaccines to come, but they will. And like this little girl, millions of children over the world will have an even safer and healthier life. [Music] [This film was made with the gracious cooperation of Dr. John F. Enders and colleagues at Children's Hospital, Boston... Dr. Joseph Stokes, Jr. and colleagues at the Children's Hospital, Philadelphia...and the U.S. Public Health Service.] [A Potomac Films Production, Executive Producer....Nicholas C. Read, Producer........Joseph Fiorelli] [Script..........Tom Carroll, Jr., Editing........Joseph M. Foley, World Relief Map courtesy of Aero Service Corporation, Historic Stills......The Bettmann Archive, Inc.] [The End]