Pub Medic:
Impress your mates at the pub
with your startling repertoire
of esoteric medical knowledge.

Egos, trials and nobel prizes

In light of the recent polio vaccination campaign in Africa, Christian Schopflin takes a look at the origins of the vaccine

We come across the two vaccines Sabin and Salk during our paediatric firms. But other than lending their names to the poliomyelitis section in textbooks, Albert Sabin and Jonas Salk are otherwise unknown.

Polio was never a big killer, but the evil of this disease was its ability to disappear and reappear every summer and autumn. It predominately affected children, hence the name "infantile paralysis," and although seldom fatal, the condition often caused paralysis and disability.

In 1908, Karl Landsteiner first explained polio's mysterious pattern of occurrence. By feeding monkeys tissue from the spinal cord of people with polio Landsteiner was able to show that polio occurred in nervous tissue and spread via the oral route.¹ Polio was soon shown to be a viral disease. In 1935, after earlier failing experiments, scientists had little doubt that a vaccine was the only real hope.

Doctors Albert Sabin and Jonas Salk were key figures in the research. Sabin used a live attenuated vaccine, a method pioneered by Edward Jenner in 1798. Salk decided to achieve immunity through exposure to the killed virus. Sabin received support from the scientific community, as it was felt that a live attenuated vaccine taken orally would mimic the natural route of transmission showed by Landsteiner.

Sources of the virus were scarce, however. In 1936, Sabin explained that the virus could only be cultured in live nervous tissue²: the virus was grown only in laboratory monkeys--an elaborate, expensive, and ethically delicate method.

Researchers also discovered multiple strains of the virus that needed to be classified. Sabin and Salk both worked on this project and, therefore, met often--but they did not get on. Sabin called Salk a "kitchen scientist," and added that "Salk never had an original idea in his life."³

By 1948, John Enders, had successfully cultured the poliovirus on human non-nervous tissue, undermining Sabin. Enders got the Nobel prize in 1954; Sabin was left empty handed.⁴

Now, with plenty of viruses, research advanced rapidly. By 1952, both vaccines had been found sufficiently active to raise antibody concentrations.^{5 6} In the next year, Salk announced that his vaccine was ready. Sabin's weakened form, however, still needed modifications.

The number of people affected by polio grew from 25 000 in 1946 to 57 000 in 1952 and 3000 deaths reported, the United States had become desperate and President Eisenhower needed to respond. So in 1954 America embarked on the largest randomised controlled trial in medical history.⁷

In all, 200 745 children were inoculated, 210 229 received a placebo and 1180000 served as unvaccinated controls. Unfortunately, tragedies overshadowed the trial. Faulty batches of the vaccine resulted in 200 actual cases, of which 150 resulted in paralysis and 11 died. However, by 1955 there was no doubt that the vaccine was a success. At a conference on 12 April 1955, the world was informed that a way had been found to defeat poliomyelitis.⁸

Salk, during a radio interview, was unfortunately overcome by a surge of self centredness and failed to share any credit for this great advance in medicine. He made no mention of Landsteiner, Enders, or all the other contributors. While the public celebrated Salk as a hero, the scientific community abandoned him and he was never officially recognised.

Five years later, Sabin's vaccine was finally ready too. It had been successfully tested in the Soviet Union, was easier to administer, resistant to heat, and, most importantly, it was cheaper.⁹ For these reasons Sabin's vaccine became the accepted standard across the world in 1961. In 1995-6, 400 million children were immunised against polio, predominately using the Sabin vaccine. The World Health Organization reported less than 4000 cases a year worldwide.¹⁰

Unfortunately, a small number of reports describe the occurrence of polio in children who received the Sabin vaccine.¹¹ Vaccine associated paralytic poliomyelitis occurs at a rate of one case for every million doses.¹² WHO estimated that about 500 such cases occurred last year.¹³ So why are we still using the vaccine?

Apart from the practical and economic issues, there is also a good scientific reason. The attenuated virus replicates on mucosal surfaces, thereby providing IgA mediated immunity in the gastrointestinal tract. As the killed vaccine only generates IgG mediated immunity this provides good protection in the bloodstream, but the mucosal surfaces remain vulnerable to viral colonisation. Although this pool of pathogens is harmless to the vaccinated individual, it poses a threat to these who are not vaccinated. In theory, the only way to overcome this problem is either to vaccinate every individual in a population or to eradicate the virus. In reality the solution lies somewhere in between.¹⁴

Excellent recent progress towards the global elimination of polio coupled with high vaccination uptake world wide has finally led the Joint Committee on Vaccination and Immunisation, to the recommendation that in England the risk of developing vaccine associated paralytic poliomyelitis after immunisation with the Sabin vaccine now outweighs the risk of wild poliomyelitis developing in an unvaccinated individual. In response to this the UK Department of Health has announced the reintroduction of the Salk vaccine to the childhood immunisation programme.¹²

Since 27 September 2004, all children immunised against poliomyelitis get the Salk vaccine. The vaccine is part of a new "5 in 1" diphtheria, tetanus, acellular pertussis, inactive polio, haemophilus influenzae vaccine available from local general practitioners free of charge.¹²

So, once Salk, then Sabin, now Salk again--who knows what the future will bring. What we do know is that this era has brought the largest randomised controlled trial in history, one Nobel prize, and two effective vaccines.

Christian Schopflin, medical student, St George's Medical School, London
Email: ms004743@sghms.ac.uk

I thank Robert Arnott, Joe Collier, and Michael Farthing for their kinf help and advice.

studentBMJ 2004;12:393-436 November ISSN 0966-6494

1. Seavey N, Gilden J, Smith S, Wagner P. A paralyzing fear: the triumph over polio in America. New York: TV Books, 1998: 164.
2. Sabin AB, Olitsky PK. Cultivation of poliomyelitis virus in vitro in human embryonic nervous tissue. Proc Soc Exp Biol Med 1936;34:357-9.
3. Sheed W, Salk J. Time 1999 Mar 29;135(12):168-70.
4. Enders JF, Weller TH, Robbins FC. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 1949;109:85-7.
5. Casals J, Olitsky PK, Sabin AB. Development, persistence, and significance of type 2, poliomyelitis complement-fixing antibody in man. J Exp Med 1952;96:35-53.
6. Youngner JS, Ward EN, Salk JE. Studies on poliomyelitis viruses in cultures of monkey testicular tissue. II: Differences among strains in tissue culture infectivity with preliminary data on the quantitative estimation of virus and antibody. Am J Hyg 1952;55:301-22.
7. The Salk vaccine trials. http://wps.aw.com/wps/media/objects/14/15269/projects/ch12_salk (accessed 30 Sep 2004).
8. Zacharias P. Conquering the dreaded crippler, polio. Detroit News 1999 May 9: 44.
9. 9. Agol VI, Drozdov SG. Russian contribution to OPV. Biologicals 1993;21:321-5.
10. Progress toward global eradication of poliomyelitis, 1996. MMWR Morb Mortal Wkly Rep 1997;46:579-84.
11. Querfurth H, Swanson PD. Vaccine-associated paralytic poliomyelitis. Regional case series and review. Arch Neurol 1990;47:541-4.
12. Department of Health. New vaccinations for the childhood immunisation programme. London: DoH, 2004. (PL CPHO (2004)3.)
13. World Health Organization. Report of the interim meeting of the Technical Consultative Group (TCG) on the global eradication of poliomyelitis, Geneva, 13-14 November 2002. Geneva: WHO, 2003. (WHO/V&B/03.04.)
14. Herremans TM, Reimerink JH, Buisman AM, Kimman TG, Koopmans MP. Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus. J Immunol 1999;162:5011-8.

   

           

Responses published this month Articles Responses EDUCATION Egos, trials, and nobel prizes       Christian Schopflin (November 2004) Awad Al-Beshray (November 13, 2004) Read this response EDUCATION Egos, trials, and nobel prizes       Christian Schopflin (November 2004) Awad Al-Beshray (November 13, 2004)       2nd year medical student, Al-Qasseem medical school mati@iom.edu.np It's apparently that having knowledge of medicine literature is extremely important for understanding how the new trends of management of diseases and the prevention of many ominous diseases had unfolded and discovered by the hard working scientists like Salk and Sabin. It also gives you knowledge of pathology of diseases and their proper way of prevention. For example, knowing how a Dutch physician had challanged the dogma that rice is the approperiate resolution of poverity that countries under coloniolization were having, leads you to know a list of diseases that occur because of vitamins deficiency. Thanks for the effort and the well written essay