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CONQUERING POLIO AND ONE ANOTHER: TALES ABOUT THE VACCINES AND THEIR DEVELOPERS

Katz, Michael MD

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Dr. Katz is Senior Vice President for Research and Global Programs at the March of Dimes Birth Defects Foundation and Carpentier Professor Emeritus of Pediatrics, and Professor Emeritus of Public Health at Columbia University.

CONQUERING POLIO AND ONE ANOTHER: TALES ABOUT THE VACCINES AND THEIR DEVELOPERS

Polio: An American Story By David Oshinsky • 342 Pages • Oxford University Press 2005

Splendid Solution: Jonas Salk and the Conquest of Polio By Jeffrey Kluger • 384 Pages • G.P. Putnam's Sons 2005

By Michael Katz, MD

The year 2005 marks an important anniversary. Fifty years ago, the Salk vaccine against poliomyelitis was declared “safe, effective, and potent” in the famous announcement by Thomas Francis, whose message was heard around the world. For those who have grown up without the fear of poliomyelitis, it may be difficult to imagine the intense drama that surrounded this declaration. For others whose memories of this fear may have faded, this anniversary serves as an anamnestic booster shot.

Today we are on the verge of eliminating poliomyelitis from the world. This will be a major achievement, matched thus far only by the elimination of smallpox. A history of the events that allowed us to reach this point must still await an objective scholar and I, for one, hope that it will be written from a non-partisan point of view. The story is exciting and dramatic. It encompasses ingenuity, serendipity, and plain good luck. Its dramatis personae are complex, often unfair to one another, but obviously, consumed by their desire to prevent polio.

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POLIO GROWN IN TISSUE CULTURE

The story begins in earnest with the discovery by John Enders and his two postdoctoral fellows Frederick Robins and Thomas Weller that polio virus could be grown in tissue culture. This finding offered an opportunity to generate large enough quantities of the virus to attempt to develop a vaccine. No other step in what would become a long process was as important and it was recognized by its awarding of the Nobel Prize in Physiology or Medicine to the three investigators.

Using tissue culture as the substrate, three virologists, Herald Cox, Hilary Koprowski, and Albert Sabin began a race to develop a vaccine. Still ahead of them was their need to determine how many types of the poliovirus there were and the accomplishment of attenuation that would render the virus non-pathogenic while it retained its infectivity and antigenicity.

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JONAS SALK: A KILLED POLIO VACCINE

Jonas Salk had a different view. Basing his arguments on his successful work with Francis during World War II on the influenza vaccine, he declared his intention to make a killed polio vaccine. The advantage of this approach was that he could produce enough poliovirus and kill it by the well-established method of adding formaldehyde to the harvested pathogen. This inert material could then be injected into susceptible people and evoke an antibody response, which would be sufficient to neutralize wild poliovirus.

The three virologists attempting the attenuation were adamantly opposed to Salk's efforts. Sabin was highly critical, as well as disdainful. He did not believe that killed vaccine could be effective, but he also dismissed Salk's efforts as “kitchen science.”

The science establishment of which Cox, Koprowski, and Sabin were members showed little respect for Salk, considering him an upstart. The three were more tolerant of one another, but not enough to form a meaningful collaboration. Cox eventually abandoned his efforts, Koprowski continued and was the first to swallow the live vaccine and to test it in others; Sabin's ultimate victory was based on his gigantic trial of the vaccine in the Soviet Union.

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BASIL O'CONNOR: A DYNAMIC FORCE

A key partner in these efforts was the National Foundation for Infantile Paralysis (NFIP). Established in 1938 on the initiative of a famous polio victim, Franklin Delano Roosevelt, this organization mobilized the whole country to make contributions – some as small as a Dime – hence the then informal name “March of Dimes.” Basil O'Connor, Roosevelt's attorney and law firm colleague, became its president. He was a dynamic force, who led the Foundation through this crucial period.

Roosevelt and O'Connor relied heavily on the scientific advice of Thomas Rivers, a virologist at the Rockefeller Institute. It is substantially to Rivers' credit that the two leaders were committed to the support of scientific research relevant to polio and that prevention of the disease, rather than treatment of those afflicted, was their pivotal goal. O'Connor committed most of the support to Salk, although Sabin received at least a million dollars from the Foundation for his research.

O'Connor and other members of the NFIP played key roles in assuring that the trial of the Salk vaccine was conducted on a large enough population of susceptible children for a convincing statistical analysis of the result. Called “the biggest public health experiment ever,” Francis conducted this trial with a scientific elegance and precision, and it remains one of his most important professional achievements.

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BOTH VACCINE APPROACHES WERE BENEFICIAL

Although the Salk vaccine was approved for general use in 1955 and it would take another six years before Sabin's oral live attenuated polio vaccine would be approved, in the end, both concepts won. The Salk vaccine, which was developed sooner, helped ensure the health of many people who would have contracted polio during the interval before Sabin's became available for general use.

The later vaccine, using the live virus, assured the elimination of the disease. Because it was easily administered, it generated intestinal antibodies, and led to herd immunity. In this sense, it triumphed over the Salk vaccine, but it carried the risk that a rare mutated vaccine virus caused paralytic polio. For this reason, the Salk vaccine is now the sole agent used in universal vaccination in the US and many European countries. However, it has not been feasible to use it in countries with less integrated public health services, because it requires three injections.

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TWO BEHIND-THE-SCENES ACCOUNTS

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Two new books recount the story of the NFIP and the development of vaccines the Foundation supported – Polio, An American Story, by David M. Oshinsky and Splendid Solution, Jonas Salk and the Conquest of Polio, by Jeffrey Kluger. Both stories emphasize the role played by Salk, but both attempt to flesh out the picture by discussing the background and the corollary aspects of these efforts.

The Oshinsky book is by far the better one. The author, a historian, offers a clear account of the events that culminated in the development of both vaccines. Oshinsky's focus is the Salk vaccine and the role that the NFIP and its principals played in it. He portrays all of the participants, major and minor, with fairness and accuracy and does not camouflage any of their warts.

Throughout, the book radiates both understanding and fairness. Particularly noteworthy is Oshinsky's account of the Salk vaccine trial and all of the plans and arguments that preceded it. The book's epilogue brings the reader up to date about the fates that befell all of the protagonists after the major battles receded into the past.

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KLUGER BOOK: NUMEROUS INACCURACIES

Where the Oshinsky book succeeds admirably, the book by Kluger largely fails. Its account is more superficial, often betraying a lack of understanding of the principles that underlay the development of the polio vaccine. Its personal vignettes are more numerous and detailed than in the other book, but – at least to this reader – they are often tedious and, quite frankly, boring.

None of this would matter significantly if it were not for the numerous inaccuracies and distinct errors that are found throughout the text. Some reflect just ordinary inattention to specific details, but others reveal the author's apparent failure to understand the biology of vaccines.

These errors include a reference to Harry Weaver, the then-Director of Research at the NFIP (page 92) as one who lacked serious scientific credentials, but who is later described (page 195) as a scientist. Julius Youngner, Salk's associate, is described (page 115) as “…a twenty-eight-year-old M.D.” Dr. Youngner's degree is ScD. Hilary Koprowski is identified as affiliated with “Rockefeller University” – which was still an institute at that time – whereas his two affiliations were first Lederle and later the Wistar Institute, which he directed. A careful copy editor should have corrected these minor specks and they are only trivial irritants.

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ERRORS IN SCIENTIFIC INFORMATION

More important are the unfortunate errors in the scientific information. On pages 170 and 277, the author implies that the Salk vaccine would be injected intravenously. On page 164 he states that the polio “virus would…multiply in the stomach,” whereas it multiplies in the small intestine. On page 218, he attributes the following quotation to Sabin: “The ultimate goal for the control of poliomyelitis is immunization with a living, virulent virus.” Whatever Sabin actually said, he obviously did not advocate deliberately infecting children with the virulent virus. One could go on, because there are many other errors of this type, but there is no need. When one reads the book, one inevitably wonders about what other unrecognized errors there are that may mar the text. This is why I cannot recommend this book to any audience.

The book by Oshinsky, on the other hand will please the lay and the scientific reader – the former, by providing an understandable explanation about the nature of this vaccine and both, by offering a fascinating glimpse at the history of this successful effort. The subject covered could make an exceptional theatrical drama. Are there any playwrights who will step up to the challenge?

©2005 American Academy of Neurology

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