Columbia Management

Vaccines: Medicine’s Greatest Lifesaver

4th Quarter 2011

I recently read several books on the history of vaccines. As one of the authors put it, “Of all of the benefits of medical science, vaccination is at or near the summit.”¹

Deadly Diseases

“Bring out your dead!” cries a wretched man pulling a cart of bodies in Monty Python and the Holy Grail. Set in the middle ages, the movie makes fun of the impact of communicable disease at that time. In reality, such diseases were no laughing matter. Once mankind transitioned from isolated bands of nomadic hunter-gatherers to more densely populated groups of farmers, epidemic diseases began to ravage civilization.

Remarkable progress has been made as fatal, communicable disease has now become rare in the developed world. Clearly, improved sanitation and nutrition have helped, but much of the credit goes to the development of vaccines.

The First Vaccine

Dating back to at least the time of the Pharaohs, waves of smallpox epidemics ravaged mankind. In populations previously subject to the disease, mortality rates for those infected could be more than 30% and, for other populations, much more.² North American Indians had little immunity to the disease. Their population decreased 99% between Columbus’s voyage in 1492 and the year 1800, and smallpox was the largest killer.³

People observed that the disease was communicable and one who survived a smallpox infection became immune to the next epidemic of the disease. In ancient China and more recently in Asia and Africa, a crude form of vaccination called variolation developed whereby fluid from a smallpox pustule or parts of smallpox scabs were scraped into the skin of a healthy person. In most cases, immunity would build up before the disease reached a vital organ and the individual would survive.

In 1790, Lady Montague, the wife of the British ambassador to the Ottoman Empire, introduced variolation to Britain. The process was far riskier than vaccines today; most people suffered severe side effects and up to about 3% of those treated died as a result.⁴ But these were much better odds than for those infected with smallpox.

Edward Jenner, a pharmacist in England, learned that milkmaids were immune to smallpox because they often suffered blisters from cowpox, a related disease. In 1796, Jenner began experimenting with variolating using fluid from a milkmaid’s cowpox blisters, rather than smallpox sores. When his subjects were later variolated with smallpox fluid, no reaction occurred, indicating that they were immune from smallpox. Immunization using cowpox fluids rose rapidly and protected millions of people.⁵

A cowpox-derived vaccine for smallpox continued to be used well into the 20th century, including use by six million New Yorkers who were inoculated during a smallpox scare in 1947. Smallpox was eradicated from nature; the last case occurred in India in 1975.⁶ Smallpox immunizations ended when health authorities judged the risk of side effects from the vaccine exceeded the risk of the disease returning.

The Golden Age of Vaccines

Beginning in the 1860s, tremendous scientific advances were made. Robert Koch’s laboratory in Germany identified bacteria as the source of many diseases and proved that bacteria grown in a lab could cause disease.⁷ Koch’s lab created some vaccines, including those for diphtheria and tetanus.

In France, Louis Pasteur stunned the world by developing the first rabies vaccine in 1885; until then rabies infections resulted in horrible deaths. His mantra was to “isolate, attenuate and vaccinate” the pathogen causing a disease.⁸ He attenuated a germ by having it reproduce in petri dishes or animal cells where it would evolve in order to optimize in its new environment. Once it evolved to the point it would no longer thrive in and harm humans, it was injected into humans with the hope that the subject would build immunity to full power germs. The Goldilocks’ trick, of course, was to make the attenuated germ weak enough so as not to cause harm, but strong enough to create immunity.

While scientific understanding of disease increased rapidly, it was primitive compared to modern times. Diagnostic tools were poor. Bacteria could be seen by optical microscopes, but viruses were unseen until the development of the electron microscope in the 1930s. Viruses were inferred to exist as a result of an 1898 experiment by Danish professor Martinus Beijerinck, who filtered bacteria out through unglazed porcelain containers, but observed remaining, and much smaller, disease-causing elements. Scientists learned how to grow viruses in laboratories only in the late 1940s.⁹

Early vaccines were dangerous and unreliable by today’s standards, though far less dangerous than the underlying diseases they prevented. Vaccines did not stop the great influenza epidemic of 1918-1919. Of a worldwide population of one billion, an estimated 500 million were infected and more than 50 million people died.¹⁰ This virus was unusual in that it had high mortality among young, healthy people.

Vaccines continued to progress. During World War II, all 11 million U.S. soldiers were vaccinated for typhoid, tetanus, smallpox, cholera and plague. Vaccines, coupled with antibiotics, drastically improved their health. Disease deaths outnumbered battle deaths by 13:1 in the Spanish American War, matched them in World War I and were outnumbered by 1:85 in World War II.¹¹

Maurice Hilleman’s Mission

Maurice Hilleman had a role in creating more vaccines than anyone else in history, some three dozen. As noted by Arthur Allen, author of Vaccine, The Controversial Story of Medicine’s Greatest Lifesaver, “…his products undoubtedly saved more lives than those of any other individual in the past half-century.”¹²

Hilleman grew up in Montana and earned a Ph.D. in microbiology at the University of Chicago, where he discovered that chlamydia is a tiny bacteria rather than a virus. He then stunned his mentors by departing academia to work in industry. At Squibb, he developed a vaccine against Japanese B encephalitis to protect American Pacific troops during World War II. In 1948, he joined the Walter Reed Army Medical Center, then a hub of vaccine development.

In 1957, Hilleman moved to Merck, where he continued to develop vaccines well past his official retirement in 1984. He had a tremendous work ethic, often working seven days a week and expecting the same from his staff. He and his team were on a mission to rid the world of disease. They developed eight of 14 now common vaccines for measles, mumps, hepatitis A and B, chickenpox, meningitis, pneumonia and Hib (hemophilus influenza, which harms infants and young children).¹³ One of his accomplishments was the combination MMR (measles, mumps and rubella) vaccine.

Hilleman discovered that the influenza virus is particularly difficult to deal with due to frequent minor drifts in its surface, which each year makes the last year’s vaccine obsolete. Periodically, the virus shifts its surface characteristics substantially, becoming much more virulent. Hilleman inferred that a shift occurred in Hong Kong in 1957 and, by having Merck produce 40 million doses of vaccine, saved thousands of lives in America. Potential future shifts keep virologists up at night.

Hilleman helped develop the first two anti-cancer vaccines. One vaccine prevents hepatitis B, the third most common known cause of cancer in the world (after sunlight and smoking).¹⁴ It was the first vaccine utilizing recombinant technology and the first made by a single protein. His innovations helped create a vaccine to prevent HPV (human papillomavirus), the cause of cervical cancer. Hilleman had high integrity, as he refused to risk changes in manufacturing processes in order to enhance yields and profits.¹⁵ He died in 2005 at age 85.

Vaccine Scares

Two notable scares set back progress on vaccine usage.

In 1982, a TV station in Washington D.C. aired “Vaccine Roulette,” a story highlighting risks of the DTP (diphtheria, tetanus and pertussis) vaccine. It showed reactions well known to physicians, including cases of seizures, high fevers and fainting. In a case of ambush journalism, it edited doctors’ comments out of context and failed to mention that none of the victims portrayed suffered permanent damage. Other media quoted the story further out of context, claiming permanent damage. The media also failed to mention the consequences of contracting the underlying diseases.¹⁶

In 1998, the British medical journal The Lancet published a paper alleging a link between the MMR vaccine and autism.¹⁷ It claimed that, in some cases, the vaccine caused the measles virus to lodge in the intestines and create leakage, allowing opioid peptides to escape and penetrate the brain, causing autism. The paper was under fire by scientists immediately. The opioid causation theory had already been widely discredited, the findings of measles in intestines could not be duplicated by other scientists and there was no comparison between autism rates of children who got the vaccine and those who did not. A review by 37 experts found that the theories were “biologically implausible,” and the conclusions essentially worthless.¹⁸

Fourteen separate groups of investigators did statistical studies that also refuted the link.¹⁹ One notable study covered 530,000 children in Denmark from 1991-1998, comparing vaccinated and unvaccinated children. It showed “strong evidence against the hypothesis that MMR vaccination causes autism.”²⁰ By 2004, 10 of the original 12 authors of The Lancet article withdrew their support of the paper.²¹ The Lancet formally retracted the paper in 2010 and, that same year, the primary author of the paper had his U.K. medical license revoked.

Once the MMR-autism link was largely discredited, vaccine opponents claimed a link between mercury in vaccines and autism. Minute amounts of ethyl mercury were utilized in vaccines, usually less than the more toxic methyl mercury infants get exposed to from the environment. Combined, in some cases, the dosage did exceed government guidelines, so the mercury was removed. Studies showed that reported rates of autism continued to climb once mercury was removed from vaccines.²² “In spite of all the concern…there has not been a single case of proven mercury toxicity from vaccines…,” writes Kurt Link, author of The Vaccine Controversy: The History, Use, and Safety of Vaccinations.²³

Unfortunately, many people appear to rely on one-sided scares and opinions expressed in talk shows and by celebrity activists, rather than on scientific evidence. Immunization rates around the world have fluctuated with publicity, funding for inoculations, public policy and legal requirements. Where immunizations have dropped, outbreaks have occurred. A diphtheria epidemic hit the former Soviet Union in 1993, causing 4,000 deaths.²⁴ In Japan, where pertussis immunizations fell from 80% in 1974 to 10% in 1976, a 1979 epidemic of that disease resulted in 13,000 infections and 41 deaths.²⁵ In the United States, where pockets of low immunization rates exist, outbreaks occur. Some of the Chicago suburbs are currently experiencing a whooping cough outbreak.²⁶

Perspectives on Risks

There have been mistakes in vaccine development, production and use that have resulted in injuries and deaths. However, those numbers pale in comparison to the injuries and deaths caused by the underlying diseases that are being conquered by vaccines. While rare vaccine side effects continue to exist, drugs and vaccines come with disclosures of the known side effects and risks, however unlikely. Diseases don’t.

Many people believe some vaccine-preventable diseases to be fairly benign and some are, in most cases. Yet measles is one of the most contagious viruses and has killed more children than any other disease in history.²⁷ It hospitalized 48,000 Americans yearly in the 1960s and killed 400 during a 1964 epidemic.²⁸

Chickenpox is perceived to be a mild disease and it usually is. Acquiring chickenpox creates lifetime immunity to the disease (though susceptibility to shingles) so some question the usefulness of the vaccine. However, Paul Offit, author of Vaccinated, One Man’s Quest to Defeat the World’s Deadliest Diseases, points out that chickenpox creates risk of encephalitis, hepatitis, pneumonia and Group A streptococci, the “flesh-eating bacteria.” He notes that, before the vaccine, some 10,000 people a year were hospitalized and 100 died annually in the United States due to the disease or related illnesses.²⁹

German measles (rubella) was considered a benign illness featuring a rash and a low fever until Australian ophthalmologist Sir Norman McAllister Gregg discovered a link to birth defects. When striking a mother in her first trimester, rubella causes fetal anomalies in 90% of pregnancies. In 1964-65, prior to the rubella vaccine, the last major epidemic in the United States caused thousands of birth defects.³⁰ Hilleman’s MMR vaccine was approved in 1971 and the number dropped to seven U.S. cases in 1983.³¹

Whooping cough (pertussis) is a horrible disease for babies and small children. Babies have died because of outbreaks when vaccination rates declined as a result of scares. The underlying vaccine has changed since the “Vaccine Roulette” television program, to an acellular version with fewer side effects.³² That is why the combination vaccine is now called DTaP rather than DTP.

While no vaccine is 100% effective, the fact remains that if the vast majority of people are vaccinated, a disease cannot infect enough victims to spread. Link writes, “In the prevaccine era, every family lost a child or knew of one so lost due to vaccine-preventable diseases. Today in the USA, the death of a child is an unexpected tragedy; in the past it was an expected sorrow.”³³ American life expectancies increased 30 years during the 20th century, largely due to vaccines.³⁴

Charles P. McQuaid
President and Chief Investment Officer
Columbia Wanger Asset Management, LLC

The information and data provided in this analysis are derived from sources that we deem to be reliable and accurate. These views are not guarantees of future performance and involve certain risks, uncertainties and assumptions that are difficult to predict so actual outcomes and results may differ significantly from the views expressed. The views/opinions expressed in “Squirrel Chatter II” are those of the author and not of the Columbia Acorn Trust Board, are subject to change at any time based upon economic, market or other conditions, may differ from views expressed by other Columbia Management associates and the respective parties disclaim any responsibility to update such views. These views may not be relied on as investment advice and, because investment decisions for a Columbia Acorn Fund are based on numerous factors, may not be relied on as an indication of trading intent on behalf of any particular Columbia Acorn Fund.

¹ Link, M.D., Kurt, The Vaccine Controversy, The History, Use, And Safety of Vaccinations, (Westport, Connecticut, Praeger Publishers 2005) p. 38.

² Mnookin, Seth, The Panic Virus, A True Story of Medicine, Science, and Fear, (New York, New York, Simon & Schuster 2011) p. 30.

³ Offit, M.D., Paul A., Vaccinated, One Man’s Quest to Defeat the World’s Deadliest Diseases, (New York, New York, HarperCollins Publishers 2007) pg. 32.

⁴ Link, M.D., Kurt, op. cit., p. 12.

⁵ Allen, Arthur, Vaccine, The Controversial Story of Medicines Greatest Lifesaver, (New York, New York, W. W. Norton & Company 2007) p. 49-50.

⁶ Ibid., p. 115, 303.

⁷ Offit, M.D., Paul A., op. cit., p. 144.

⁸ Allen, Arthur, op. cit., p. 65, 121.

⁹ Offit, M.D., Paul A., op. cit., p. 37, 41-42.

¹⁰ Ibid., p. 2-3.

¹¹ Allen, Arthur, op. cit., p. 119, 159.

¹² Ibid., p. 221.

¹³ Link, M.D., Kurt, op. cit., p. 101.

¹⁴ Offit, M.D., Paul A., op. cit., p. 115.

¹⁵ Ibid., p. 130, 156.

¹⁶ Allen, Arthur, op. cit., p. 251-256.

¹⁷ Wakefield, Andrew J., et al., “Ileal-lymphoid-nodular Hyperplasia, Non-Specific Colitis, and Pervasive Developmental Disorders in Children,” The Lancet 351, Issue 9103 (1998), p. 637-41.

¹⁸ Mnookin, Seth, op. cit., p. 106-107, 114.

¹⁹ Offit, M.D., Paul A., op. cit., p. 167.

²⁰ Mnookin, Seth, op. cit., p. 163.

²¹ Murch, Simon H., et al., “Retraction of an Interpretation,” The Lancet 363, Issue 9411 (2004), p. 750.

²² Mnookin, Seth, op. cit., p. 167.

²³ Link, M.D., Kurt, op. cit., p. 21.

²⁴ Ibid., p. 57.

²⁵ Mnookin, Seth, op. cit., p. 277.

²⁶ Synett, Lawerence, “Whooping Cough Strikes Collar Counties,” Chicago Tribune, December 6, 2011.

²⁷ Mnookin, Seth, op. cit., p. 19.

²⁸ Allen, Arthur, op. cit., p. 217.

²⁹ Offit, M.D., Paul A., op. cit., p. 102.

³⁰ Link, M.D., Kurt, op. cit., p. 82-84.

³¹ Allen, Arthur, op. cit., p. 240.

³² Ibid., p. 352, 286.

³³ Link, M.D., Kurt, op. cit., p. 163.

³⁴ Offit, M.D., Paul A., op. cit., p. xiv.

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