Historical antecedents to experimental Ebola treatments

We had the chance this week to sit down with physician and historian Scott Podolsky to discuss the history of serum therapy, the treatment for Ebola first provided to Americans Kent Brantly and Nancy Writebol and now given to three health workers in Liberia. Podolsky is Associate Professor of Global Health and Social Medicine at Harvard Medical School and Director of the Center for the History of Medicine at the Countway Medical Library.

Golden: You've written about the history of serum therapy. Now that it is back in the news with a serum treatment being tried for Ebola, what can you tell us about its history?

Podosky: Serum therapy, from the 1890s onward, was based on the finding that our blood has "antibodies" (later found to be produced by certain cells of the immune system), that these can be directed at microbes or their toxic products (and help defend us against infection), and that these antibodies could be stimulated by injecting laboratory animals with particular microbes.  With this in mind, scientists tried different types of immunotherapy to treat infectious diseases.  This included "active" vaccine therapy, where an infected patient was vaccinated with parts of a microbe so as to further stimulate the patient's own immune system (this differed, in principle, from preventive vaccination, where the hope is that the immune system can be stimulated to ward off future infection).

It also included "passive" serotherapy, where serum containing already-made antibodies, specific to the infecting microbe at hand, were given to the patient.  At the time, such serum was generated by infecting a particular animal – rabbits and horses were often used (and Lederle Laboratories, by 1930s, had 28,000 rabbits producing such serum) – with a particular microbe. Blood would be extracted from the animal, the serum (the part of the blood containing antibodies and other proteins) would be separated from the blood, and further steps could be taken to maximize the antibody content of the serum.  An entire science of production and standardization was developed to facilitate – and, in many instances, commercialize – this process.

The production of the

» READ MORE: monoclonal antibodies

used to treat patients with Ebola is similar in its outcome, though very different in the process used to reach it.

» READ MORE: Genes that direct the production of a specific type of antibody directed against the Ebola virus have been inserted into tobacco plants, whose own machinery then produces the proteins (the antibodies) that are harvested.

For more on experimental treatments and vaccines for Ebola go

» READ MORE: here.

Golden: What does serum therapy do inside the body?  How does it work?

Podolsky: The antibodies, once in the body, can attach to the desired target (virus, bacteria) and either destroy the microbe directly, or enhance the ability of the host's own immune system to destroy the microbe.

Golden: What serum therapies were used in the past and are there any in use today?

Podolsky: Serotherapy, in the pre-sulfa drug and pre-antibiotic era (before the mid-1930s), was used for a wide range of infectious diseases, some successfully, some less so.  It was first used widely against diseases like diphtheria and tetanus, where the toxins produced by the microbes were the targets.  It was then applied to a host of infections where the microbes themselves were considered directly toxic.  The treatment of pneumococcal pneumonia was the most widespread of such treatments, with 32,000 people treated with antiserum in 1937, before the advent of the sulfa drugs for pneumonia.

In the antibiotic era, we still see serotherapy (or, more precisely, extracted antibodies) applied to patients exposed to such infectious diseases as hepatitis B, tetanus, and rabies.  More generally pooled antibodies, in a treatment called IVIG, or intravenous immunoglobulin, can be given to those with deficient immune systems.  Also, given its impact on altering the immune system more generally, IVIG has been given to those with autoimmune diseases.

Monoclonal antibodies have been generated to treat a wide arrange of diseases, ranging from cancers (where the antibodies target the cancer) to autoimmune diseases such as Crohn's Disease, where such modern-day immunotherapy is again considered to alter the working of the immune system.

Scott Podolsky is a primary care physician and internist at Massachusetts General Hospital, as well as Associate Professor of Global Health and Social Medicine at Harvard Medical School and Director of the Center for the History of Medicine at the Countway Medical Library.  He is the co-author of Generation of Diversity: Clonal Selection Theory and the Rise of Molecular Immunology,  author of Pneumonia before Antibiotics: Therapeutic Evolution and Evaluation in Twentieth-Century America and author of the forthcoming The Antibiotic Era: Reform, Resistance, and the Pursuit of a Rational Therapeutics.

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