In the 1770s, British physician Edward Jenner began noticing a strange phenomenon.

It was known that milkmaids sometimes caught a disease from the cows, called "cowpox," similar to smallpox in the red boils it produced, but not nearly as dangerous. More importantly, once milkmaids had recovered from cowpox, they seemed to be immune from smallpox.

After studying the problem, Jenner eventually developed a relatively safe and effective method for "vaccination," from the Latin root of vacca, for cow. Breaking open swollen blisters from the milkmaids' hands, Jenner produced a primitive vaccine and injected it into the arms of his patients.

It worked in 1796. And less than two hundred years after Jenner's first vaccine, doctors can claim to have completely wiped out smallpox infections.

Over the next century, scientists such as Louis Pasteur, Robert Koch and Paul Ehrlich developed more vaccines to diseases such as diphtheria, in the process saving countless millions of lives.

But how did scientists get there? What properties of the body's immune system allow such careful engineering to work? And what goes into making a vaccine?

The job of a vaccine is to impart immunity against a given disease to a person by educating the immune system. The idea is to expose a person to an antigen without causing the full-blown effects of the disease normally associated with it.

Thanks to the immune system's capacity for memory, when the individual encounters the virus or bacteria later on in their lives, their immune system can respond quickly and efficiently to prevent the disease.

Such memory is generated on the basis of interactions between specialized cells, known as T and B lymphocytes, and antigens. Upon first "seeing" a given antigen, in the phase known as the "primary response," just a handful of the millions of cells can actually recognize, or bind, the antigen. The system is thus incapable of mounting a truly effective response.

But upon subsequent infection with the same antigen, the immune system leaps into action against the already familiar enemy, and immobilizes it with a much stronger "secondary response."

The trick for vaccine designers is to find an antigen which fools the immune system into thinking it is a dangerous foe, but is actually a harmless look-alike.

The Shots Hurt Around the World

Realizing this, in the early 1950s, Dr. Jonas Salk used injections of dead polio viruses as a vaccine against the crippling and sometimes fatal disease, which rose to epidemic proportions each summer to strike victims such as Franklin Delano Roosevelt '04. On April 12, 1955, U.S. health officials proclaimed the vaccine a success.

Today, research into the production of new vaccines is a major undertaking, involving academic researchers, government agencies, and pharmaceutical and biotechnology firms all working to provide newer and safer prevention of disease by infectious agents, allergens, and even some forms of cancer.

Physicians use vaccines against viruses, such as the measles, polio, mumps, or rubella, against bacteria, such as typhoid and salmonella, and against bacterial toxins, such as pertussis, tetanus and diphtheria. Each type of antigen, however, requires its own strategy.