3.0 THE ORIGINS OF IMMUNOTHERAPY
As it applies to cancer, immunotherapy might be considered a revolutionary form of medicine but its roots actually go back as far as 1778, when Edward Jenner, an English physician, administered the first vaccine, which was targeted against smallpox. Jenner observed that milkmaids who contracted cowpox, a relatively mild disease, seemed protected from the deadly smallpox infection. To test this hypothesis, he injected some material from a pustule on the body of a milkmaid infected with cowpox into the arm of a small boy. After the boy had recovered from the cowpox infection, Jenner inoculated him with smallpox. As Jenner had expected, the boy never developed the disease. Jenner named his technique “vaccination,” a term derived from the Latin word “vacca” for cow. Even without a scientific understanding of why his method worked, Edward Jenner had discovered an effective way to prevent people from developing a serious disease.
It was not until the late 19th century that medical science disclosed the reason: Jenner had created a condition of acquired immunity in the boy. When the child contracted the less serious disease of cowpox, his immune system had mounted an attack against the invading virus. Later, when the boy was inoculated with the smallpox virus he did not contract the disease because the memory lymphocyte (T and B cells) of his immune system “remembered” the cowpox infection and were able to stimulate the immediate production of the specific antibodies needed to kill the related but more deadly smallpox virus. This pioneering immunological work eventually gave rise to a number of other vaccines against such diseases as rabies, diphtheria, yellow fever, polio, mumps, hepatitis B, measles, rubella, influenza, whooping cough, and tetanus. These days, this type of immunotherapy is in widespread use to protect against microbial infection.
The connection between cancer and the immune system was first uncovered nearly 100 years ago; long before an in-depth knowledge of the intricate workings of the immune system existed. In the early 1890s, Dr. William B. Coley, a New York physician, became intrigued by the dramatic disappearance of malignant tumors that he observed in cancer patients who had contracted acute streptococcal infections. Suspecting that the onset of bacterial infection was in some way responsible for the regression of the tumor, he decided to try an experiment in which he injected live streptococci into a patient with inoperable cancer to see whether the patient’s tumor would regress. After he had tried administering three different bacterial cultures to the patient, he finally injected a fourth that resulted in the complete disappearance of the tumor.
Dr. Coley continued to pursue his approach and ultimately developed a mixture of killed bacteria that became known as Coley’s mixed bacterial toxin. He and other physicians treated over 1,000 cancer patients with this substance, with varied success. His results were unpredictable however, and neither he nor the medical community at large could explain precisely why his mixture worked in some patients. This was due to the fact that the science of immunology was in its rudimentary stages at that time. Thus, his results were disregarded and virtually forgotten for years.
Scientific interest in Coley’s work has been accumulating since his daughter, Helen Coley Nauts, started compiling and disseminating information on his remarkable observations. Gradually, scientists began to understand why Dr. Coley’s preparation worked—the bacterial products of which it was composed had acted as immune potentiators. In other words, they had stimulated certain immune cells to kill the cancer cells directly or through cancer-killing factors. With the founding of the Cancer Research Institute by Mrs. Nauts in 1953, resources were provided to pursue research into the link between cancer and the immune system. Today, cancer immunology is a rapidly advancing field and Dr. Coley has come to be regarded as the “father of cancer immunotherapy.”
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