Smallpox: the facts

On this day in 1796, British doctor Edward Jenner administered the first smallpox vaccination to James Phipps, an eight-year-old boy. To mark the anniversary, we speak with Martin S. Hirsch, MD, FIDSA. Dr. Hirsch is editor-in-chief of The Journal of Infectious Diseases, professor of medicine at Harvard Medical School, professor of infectious diseases and immunology at the Harvard School of Public Health, and a physician at Massachusetts General Hospital.

What impact did Edward Jenner’s accomplishments with smallpox vaccination have on the world’s response to the disease and to infectious diseases in general?

Jenner discovered the basic principle that one could become immunized against certain transmissible infectious agents by previous exposure to related agents. In this case, he used cowpox to protect individuals against the highly lethal smallpox. It is remarkable that this advance came without any knowledge of virology or immunology, although it did build on earlier experiences with variolation, a procedure whereby material from actual smallpox lesions was used to protect others against serious disease; variolation had been employed both in England and America during the early 18^th century, prior to Jenner’s monumental work. Jenner’s careful studies established the framework for the entire field of vaccinology, which has dramatically changed the world for the better. Over the past 100 years, not only has smallpox been eliminated from the globe, enormous progress has been made towards reducing the world burden of other infections, including poliomyelitis, measles, mumps, and rubella, among others.

I understand you saw a case of smallpox while in India in the 1960s, making you one of the few living US physicians today to have seen patients with the disease. How did that experience affect your understanding of smallpox and its impact?

While in medical school in 1963, I was fortunate enough to spend seven months in Calcutta, India. While there, not only did I see a patient with smallpox, I was able to spend a fascinating evening traveling from door to door with a group of public health workers who were vaccinating susceptible individuals in order to help eradicate smallpox virus from India. Fortunately, these efforts succeeded, as well described in the book by Dr. William Foege, House on Fire: The Fight to Eradicate Smallpox. The major lesson I learned from these activities is that with organized and cooperative international efforts, even highly infectious agents with great public health impact can successfully be controlled. Let us hope that similar approaches can be successfully mobilized against current scourges, such as malaria and HIV.

How much of a concern should smallpox be to the world today, and does it still pose a threat to public health?

Although no cases of human smallpox have been reported in decades, there remains a risk that residual stocks of variola (smallpox) virus in the wrong hands could pose a threat to humankind. We know of existing stocks at the CDC in the USA and in Russia; we don’t know if there are virus stocks stored secretly elsewhere. There have been ongoing discussions for many years regarding disposal of known smallpox virus stocks in the world, with arguments made either to eliminate them in order to reduce the risk of transmission, or to keep them in order to make better antiviral drugs or vaccines in case of virus reemergence. This issue has been debated by the WHO and the US Institute of Medicine, among other groups, but no resolution has yet emerged.

What important research advances have been made regarding this disease recently? Is there still more to learn?

Smallpox vaccines are still administered to some recipients, e.g., military populations in certain parts of the world. These vaccines have risks of their own, particularly in immunocompromised populations. Considerable research is ongoing to understand the mechanisms of immunity to variola virus and to prepare safer vaccines against it. In addition, work is underway to develop safer and more effective antivirals against the virus, as well as against related viruses (e.g., monkeypox) that still pose a problem to populations in certain parts of the world. The importation of monkeypox viruses to the US was demonstrated several years ago, and led to numerous cases in our country, reminding us that continued vigilance is necessary to prevent new infections in the years ahead.

Dr. Hirsch is editor-in-chief of The Journal of Infectious Diseases, professor of medicine at Harvard Medical School, professor of infectious diseases and immunology at the Harvard School of Public Health, and a physician at Massachusetts General Hospital.

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