PUBLIC HEALTH THEN AND NOW Passive Immunization Against Poliomyelitis The Hammon Gamma Globulin Field Trials, 1951–1953 | Charles R. Rinaldo Jr, PhD POLIOMYELITIS, OR POLIO, IS Western Europe in the late 19th particularly William McDowall Poliomyelitis has gone from being a modern saga. The poliovirus century. In the summer of 1916, Hammon, also of the University one of the worst scourges of the 20th has likely been in the human North America underwent a hor- of Pittsburgh. Here I present a century to nearing eradication in the population for thousands of rifying polio epidemic reportedly historical review of Hammon’s 21st. This success is well known to years. However, before the late claiming more than 7000 lives in development of passive immu- be attributable to the Salk inacti- 18 00s, paralytic disease attribut- 20 states.1 The peak of the US nization in the prevention of vated and Sabin attenuated polio- able to poliovirus was sporadic epidemic occurred in 1952: al- poliomyelitis, which was one of virus vaccines. and endemic, not epidemic. As most 57000 cases, more than the key advances leading to the However, before introduction of an enterovirus, it is predomi- 21 000 of them paralytic. Similar Salk vaccine.2–5 these vaccines, William McDowall nantly spread via the fecal–oral epidemic trends were occurring Hammon of the University of Pitts- route and is stable in the envi- all over the Western world. HAMMON’S BASIS FOR POLIO PREVENTION BY burgh Graduate School of Public Health ronment. Thus, conditions of Clearly there was a desperate poor sanitation and crowding need for a way to prevent polio- PASSIVE IMMUNIZATION led the first major breakthrough in common before the 20th century myelitis, preferably through a prevention of the disease by using pas- led to widespread infection at vaccine such as that developed Pittsburgh was the Steel City sive immunization in one of the earli- early ages. Improved hygienic for childhood whooping cough in 1949, covered with smoke est double-blind, placebo-controlled standards opened the portal for (pertussis) and diphtheria early in and soot, with a postwar, civic clinical trials. This study provided the poliovirus to cause more serious the 20th century. Thus, the best push to rid the city of its dirty first evidence that antibodies to polio- disease in an epidemic form. scientific and medical minds of image. It was “a city on the rise,” virus could prevent the disease in hu- Children lost their passive mater- the 1930s, 1940s, and 1950s fo- according to the Pittsburgh Press. mans. (Am J Public Health. 2005;95: nal antibody as they aged, leav- cused on polio. We all know of At the University of Pittsburgh in 790–799. doi:10.2105/AJPH.2004. ing them vulnerable to infection Jonas Salk of the University of the city’s historic Oakland sec- 040790) and, for reasons still unclear, to Pittsburgh and Albert Sabin of tion, there was an unremarkable the more severe, paralytic mani- the University of Cincinnati for School of Medicine and a brand festations of polio. their polio vaccines. However, new Graduate School of Public Annual, seasonal polio epi- many other prominent figures Health, both endowed by demics first became common- were involved in the develop- wealthy Pittsburgh families, the place in the United States and ment of the poliovirus vaccine, Scaifes and Mellons. The first 790 | Public Health Then and Now | Peer Reviewed | Rinaldo American Journal of Public Health | May 2005, Vol 95, No. 5 PUBLIC HEALTH THEN AND NOW dean of the Graduate School of nor.9 This private organization data, although from poorly con- Public Health was Thomas Par- depended on public donations. trolled human trials conducted in ran, a world-renowned physician Its well-known publicity theme the 1920s and 1930s, suggesting and former US surgeon general. was small contributions, or the that paralysis could be prevented He recruited the cream of public “March of Dimes,” which became by passive administration of health leaders to head 6 new de- the organization’s formal name whole blood or convalescent partments. Among these individ- in 1979. NFIP funded the re- serum.4 There was also evidence uals was the eminent 45-year-old search that eventually led to the that mass immunization with William Hammon, tapped to prevention of polio. plasma could prevent the spread chair the Department of Epide- Hammon laid out his future ap- of measles virus.11 Hammon miology and Microbiology. Ham- proach to preventing poliomyelitis based much of his reasoning that mon was born in Ohio in 1904, in an address delivered at the an- antibody was protective against and his family settled in Con- nual meeting of the American polio on his postwar research in neautville, 60 miles (96 km) Academy of Pediatrics in Novem- Guam.10 He noted that the last north of Pittsburgh, so this ap- ber 1949.10 It revealed the reported polio outbreak in Guam pointment meant a return to his strengths and flaws in his reason- was in 1899. An outbreak in roots. Salk later professed his ing, based on his scientific ortho- 1948 was restricted to Ameri- strong desire for this chairman- doxy, that would lead him and cans. He found that serum from ship, having been appointed to most others in the field to reject indigenous Guamanians had neu- the School of Medicine 2 years Salk’s views on an inactivated tralizing antibodies to poliovirus, earlier, and expressed his disap- pointment that Parran recruited Hammon instead.5,6 Hammon was married with 2 Hammon believed that gamma globulin obtained from children by the time he graduated pooled plasma with known neutralizing activity for 7 from medical school. He was an neurotropic strains of poliovirus held the best promise ordained Methodist minister who, “ for protecting against natural infection. after completing undergraduate work at Allegheny College in 1931, served as a missionary in the Belgian Congo. Upon return- polio vaccine. He stressed the use probably as a result of the natu- ” ing, he was admitted to Harvard of passive immunization to pre- ral infection with the virus that Medical School and joined the vent the infection temporarily dur- persisted on the island. laboratory of Hans Zinsser, the ing the polio season. Passive im- Hammon emphasized that the famous bacteriologist and epi- munization refers to injection of role of antibody in immunity to demiologist. He received his med- blood gamma globulins that trans- poliovirus was still uncertain. ical degree in 1936, a master’s fer specific antibodies to the virus, It was only 2 years earlier of public health degree in 1938, in contrast to active immunization, that Isabel Morgan and David and a doctor of philosophy de- in which an antigenic substance is Bodian of Johns Hopkins Uni- gree in 1939. He excelled under injected that induces specific anti- versity had shown that neutraliz- Zinsser’s guidance, developing the bodies to the virus. Hammon be- ing antibody protected against first vaccine for feline panleuko- lieved that gamma globulin ob- virus challenge in monkeys.12 penia in collaboration with John tained from pooled plasma with How long neutralizing antibod- Enders.8 In 1940, Hammon was known neutralizing activity for ies endured in the blood was recruited by the University of neurotropic strains of poliovirus still unknown. Morgan and California at Berkeley. held the best promise for protect- Bodian also showed that there About the time Hammon was ing against natural infection. were 3 poliovirus serotypes,13 a learning virology at Harvard, the Hammon did not necessarily number later confirmed by the National Foundation for Infantile hope to prevent infection with NFIP Virus Typing Committee, Paralysis (NFIP) was established this approach; the goal was to of which Hammon was a mem- by President Franklin Roosevelt, prevent the virus’s pathogenic ef- ber.14 This “problem of multiple a famous polio victim, and his fects on the nervous system. immunologic types”10(p700) was former law partner Basil O’Con- There were already tantalizing one of Hammon’s arguments May 2005, Vol 95, No. 5 | American Journal of Public Health Rinaldo | Peer Reviewed | Public Health Then and Now | 791 PUBLIC HEALTH THEN AND NOW against the use of active vaccina- vaccines, respectively.17 ,18 These antibodies to infectious agents, tion for polio prevention. vaccines proved ineffective, with particularly measles and polio. Another barrier was making the killed vaccine causing aller- Clinical trials had shown that commercial-scale virus prepara- gic reactions and the live vaccine gamma globulin was effective tions. Work on polio was greatly resulting in several cases of against measles virus,11 and Blox- hampered by the fact that the paralysis and death. It was som22 had reported a decrease in virus could not be grown effi- unclear how much poliovirus the expected number of paralytic ciently in tissue culture. Wild- “inactivation” would be enough polio cases in an uncontrolled type virus grew preferentially in to prevent its replication yet re- gamma globulin trial involving primates and had to be adapted tain immunogenicity. Even if a more than 800 cases in Texas in to nonprimate species through superior killed vaccine became 1949. Finally, much of the impe- passage in cells or animals. available, Hammon was adamant tus for Hammon’s gamma globu- Sabin and colleagues had tried that multiple, annual inoculations lin trials came from his collabora- unsuccessfully to grow the virus would be necessary to maintain tor, Joseph Stokes Jr, a renowned in different tissue types, being immunity. In support of this pediatrician at Children’s Hospi- able to replicate their monkey view, Morgan had shown that re- tal of Philadelphia. Stokes, an brain–passaged strain only in peated, large doses of formalin- early proponent of passive immu- nervous system tissue.15 They did inactivated virus induced only nization, had conducted human not realize that this strain had temporary immunity in mon- prophylaxis trials with whole adapted to the tissue, making it keys.19 It was apparent then, and blood for poliomyelitis in the less virulent for cells derived is now well established,20 that 193 0s 23 and, with the prominent from other tissues.