In 1934, a doctor at a private boy’s school in Pennsylvania tried a unique method to stave off a potentially deadly measles outbreak. Dr. J. Roswell Gallagher extracted blood serum from a student who had recently recovered from a serious measles infection and began injecting the plasma into 62 other boys who were at high risk of catching the disease.

Only three students ended up contracting measles and all were mild cases.

The method, while relatively novel, was not new to science. In fact, the very first Nobel Prize in Physiology and Medicine was awarded in 1901 to Emil von Behring for his life-saving work developing a cure for diphtheria, a bacterial infection that was particularly fatal in children. His groundbreaking treatment, known as diphtheria antitoxin, worked by injecting sick patients with antibodies taken from animals who had recovered from the disease.

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Von Behring’s antitoxin wasn’t a vaccine, but the earliest example of a treatment method called “convalescent plasma” that’s being resurrected as a potential treatment for COVID-19. Convalescent plasma is blood plasma extracted from an animal or human patient who has “convalesced” or recovered from infection with a particular disease.

“Convalescent plasma has been used throughout history when confronting an infectious disease where you have people who recover and there’s no other therapy available,” says Warner Greene, director of the Center for HIV Cure Research at the Gladstone Institutes. “There must be something in their plasma—i.e. an antibody—that helped them recover.”

Convalescent plasma interacts differently with the immune system than a vaccine. When a person is treated with a vaccine, their immune system actively produces its own antibodies that will kill off any future encounters with the target pathogen. That’s called active immunity.

Convalescent plasma offers what’s called “passive immunity.” The body doesn’t create its own antibodies, but instead “borrows” them from another person or animal who has successfully fought off the disease. Unlike a vaccine, the protection doesn’t last a lifetime, but the borrowed antibodies can greatly reduce recovery times and even be the difference-maker between life and death.

“Convalescent plasma is the crudest of the immunotherapies, but it can be effective,” says Greene.

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After von Behring’s antitoxin was distributed worldwide to treat diphtheria in 1895, doctors experimented with the same passive immunity technique for curing measles, mumps, polio and influenza.

During the pandemic influenza outbreak of 1918 known as the “Spanish flu,” fatality rates were cut in half for patients who were treated with blood plasma compared to those who weren’t. The method seemed particularly effective when patients received the antibodies in the early days of their infection, before their own immune systems had a chance to overreact and damage vital organs. In the 1930s, doctors like Gallagher used convalescent plasma effectively against measles.

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By the 1940s and 1950s, antibiotics and vaccines began to replace the use of convalescent plasma for treating many infectious disease outbreaks, but the old-fashioned method came in handy yet again during the Korean War when thousands of United Nations troops were stricken with something called Korean hemorrhagic fever, also known as Hantavirus. With no other treatment available, field doctors transfused convalescent plasma to sickened patients and saved untold numbers of lives.

Greene says that convalescent plasma was even deployed against 21st century outbreaks of MERS, SARS and Ebola, all novel viruses that spread through communities with no natural immunity, no vaccine and no effective antiviral treatment. Today, the best treatment for Ebola is still a pair of “monoclonal antibodies,” individual antibodies isolated from convalescent plasma and then cloned artificially in a lab.

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One of the best-known modern uses of convalescent plasma is for the production of antivenom to treat deadly snake bites. Antivenom is made by injecting small amounts of snake venom into horses and allowing the horse’s immune system to produce antibodies that neutralize the poison. Those equine antibodies are isolated, purified and distributed to hospitals as antivenom.

In March 2020, doctors at Johns Hopkins University began testing convalescent plasma as a promising stop-gap treatment for COVID-19 while the search continued for a permanent vaccine. The advantage of convalescent plasma is that it can be drawn from recovered patients using the same plasma separation technology used at blood banks.

"It's all doable,” says immunologist Arturo Casadevall, lead researcher on the COVID-19 study, “but to get it done it requires effort, organization, resources… and people who have recovered from the disease who can donate the blood."

READ MORE: See all pandemic coverage here.