Vaccines are one of mankind’s greatest innovations in biotechnology and have saved millions of lives by protecting us against infectious diseases. Today, every child on earth can be vaccinated with a series of vaccines that prevent death at an early age. Before vaccines, infant mortality due to infections was extremely common. Vaccines against the measles, mumps, rubella and varicella (chicken pox) viruses, as well as against diphtheria, tetanus and pertussis among others, are now routinely given to children.


Measles is a highly contagious viral infection that is transmitted by airborne droplets. The infection results in a severe rash throughout the body, a telltale sign of the disease. Seven to eight million children died every year of the measles infection until the vaccine was developed in 1963; the number is now down to a few hundred.

We take protection against measles for granted. The World Health Organization (WHO) has declared it to be next in line to be eradicated from the world, after smallpox and polio. It is rare to see a patient with measles, let alone die of it. It was not so in the past.

The story of vaccines started with an experiment done by Nature and observed by humans. Peter Panum, a Danish physiologist and pathologist, was sent by the government to study a measles outbreak in the Faroe Islands of Denmark, which lie between Iceland and Scotland.

Panum wrote in great detail about his five-month sojourn on the islands, where people kept their stoves burning in the cold summer temperatures. His paper, which is considered a medical classic, states that “people developed the measles rash approximately fourteen days after exposure to the infective matter, and that surviving the infection resulted in lifelong immunity against the disease.”

Humans, and yes only humans not animals, get infected in the lungs with the measles virus by breathing. It is one of the most transmittable diseases, several times more so than HIV and Ebola. It enters the lining of the lung, starts dividing and then spreads to the lymph nodes.

If the virus manages to get to the brain, it causes severe permanent damage to the nervous system. A battle between the virus and immune system ensues. For most healthy people, the immune system wins. For about 10 to 25 per cent of the population (depending on age, region and other factors), the virus is lethal. The immune system is not able to contain it and patients die of secondary infections such as pneumonia. It takes about fourteen days for the virus to be cleared by the immune system.

This fact was noted by Peter Panum in 1846 when neither was the virus known nor was it understood that the immune system was responsible for its clearance. The patient at this stage of the infection is highly contagious. The virus enters the respiratory system through the nose. Sick patients transmit the virus through nasal secretions or sneezing, where each droplet contains thousands of virus particles. And so the disease spreads.

Each patient can infect about seven to fourteen individuals. Relatively, a patient suffering from the Ebola virus (which caused outbreaks in 1976, 2014-16, 2018-20 and most recently from 7 February-3 May 2021) can infect only two individuals.

Back to the story in the Faroe Islands in the summer of 1846. Peter Panum noticed that while measles was a childhood disease, it attacked the entire population of the island. He wrote in his historic paper about the daughter of a farmer named J Hansen, who was also a churchwarden. She infected nine other members of the household.

Because of his keen observations, Peter Panum deduced that once one person in a household was infected, others would follow suit. The most interesting fact that emerged from his important medical observations was that despite the virulence, inhabitants of the Faroe Islands who had had the measles sixty-five years earlier escaped infection.

This report was the first that suggested the possibility of prevention of infections by vaccinations, even before it was known how measles was transmitted. In fact, it would take approximately another hundred years for the measles virus to be discovered. Thomas C Peebles (1921-2010), along with John Franklin Enders, isolated the virus from an eleven-year-old boy, David Edmonston, in Boston, in 1954.

Enders, who won the Nobel Prize in Physiology or Medicine in 1954 for isolating the polio virus, is considered the father of modern vaccines. In another part of the world, the American microbiologist Maurice Hilleman and his colleagues at Merck in West Point, Philadelphia, developed the vaccine to prevent measles in 1963 from a measles virus isolated from his daughter, Jeryl-Lynn.

Both Edmonston and Jeryl-Lynn are names of strains of measles viruses. The principle of the vaccine was to give a “non-infectious virus” as a vaccine, which would in turn activate the immune system to make antibodies, which in turn would block the measles virus from infecting the lungs. We take this mechanism of action of the vaccine for granted.

Maurice Hilleman and many of his peers developed several vaccines, such as those against rubella and mumps, which have prevented millions of deaths. But the development of vaccines is not a financially lucrative business. The cost of development is in the hundreds of millions of dollars. Also, there is a very high requirement of efficacy and safety.

Thus, the unrealistic expectations of a vaccine are that it should be 100 per cent efficacious (ie, the vaccine should work for everyone), there should be no side effects and it should be free. An impossible task in drug development. Despite these massive challenges, there is a desperate need to vaccinate billions of people against a variety of diseases so that they do not die.

We must therefore ask, why is it so expensive to develop a vaccine? Why are the expectations of a vaccine so high? Let us look at the story of the vaccine against rotavirus infection as an example.

The pharmaceutical company Wyeth LLC was being held accountable for the death and severe adverse events caused by the administration of the rotavirus vaccine to twenty-eight children. The case presented evidence for and against the cause of death by the vaccine to be associated with a rare intestinal condition, called intussusception, which is a telescoping of the intestine, resulting in blockage.

In February 2011, the court ruled in favour of Wyeth LLC, and in doing so limiting the liability of civil claims. The case was seen as a victory for vaccine manufacturing companies. As is the case in many landmark verdicts, the case was neither a resounding loss nor victory for society at large.

Until recently, more than five hundred thousand children in the world died of diarrhoeal diseases every year. There are many organisms that infect the gut and cause severe disease, especially in children. Salmonella and E coli are the most common. Among viruses, one of the most virulent is rotavirus. It is highly contagious and causes severe disease, including diarrhoea, which results in dehydration and ultimately death.

Most children in the US and European countries who are infected with rotavirus and are seriously ill are hospitalised and treated. In countries where the healthcare system is poor, many children die. Until 1998 there was no vaccine to prevent rotavirus infection. Wyeth (now a wholly owned subsidiary of Pfizer Inc.) undertook the Herculean task of developing a vaccine against rotavirus in the 1980s.

Generally, the steps for developing a vaccine are as follows:

  1. Design a strain of the virus that does not replicate in humans
  2. Develop a process to manufacture this attenuated (weakened) strain
  3. Utilise analytics to determine the attributes of the vaccine that impart its efficacy
  4. Test it for safety in animals
  5. Test it in normal healthy humans for side effects
  6. Test it in humans to ensure it protects against infections and disease by comparing with a control (placebo) group of subjects
  7. Obtain approval from the regulatory agencies

Wyeth submitted the data package for approval in 1996. The process from design to approval took fifteen years and cost hundreds of millions of dollars.

Good Genes Gone Bad

Excerpted with permission from Good Genes Gone Bad, Narendra Chirmule, ebury.