How scientists revived an old-school treatment for a 21st century pandemic
A few weeks after the new coronavirus arrived on U.S. shores, Dr. Arturo Casadevall hatched a plan to beat back the outbreak with a medical advance so powerful it had earned a Nobel Prize.
That's when Dr. Emil Adolf von Behring was honored for pioneering the use of so-called convalescent serum as a treatment for diphtheria. In 1892, the Prussian bacteriologist infected horses with the pathogen that causes the deadly disease. If the beasts recovered, Von Behring harvested their blood, removed its red blood cells and clotting proteins, and introduced the resulting antibody-rich fluid into the bloodstreams of human diphtheria patients.
Until a diphtheria vaccine came into broad use in the 1930s, Von Behring's daring experiments saved countless lives. At the end of the 19th century, diphtheria, known as "the strangling angel," was the 10th most common cause of death in the United States, and a pitiless killer of children.
Convalescent serum would go on to become a mainstay of treatment for measles, mumps, tetanus, smallpox and polio before the "era of vaccine" began in the late 1940s.
"It's a beautiful history," Casadevall, a microbiologist and physician at Johns Hopkins University, said with wistful ardor. "It was the birth of immunology."
Amid a pandemic response that promises marvels of genetic engineering, vaccines developed at "warp speed" and artificial intelligence at the bedside, it takes courage for a scientist to dust off a remedy from the history books and propose it as modern medicine.
The yellowish elixir now drawn from the blood of recovered COVID-19 patients is plasma, which retains some clotting factors. It has been tried against the Ebola virus and novel strains of influenza, only to be shelved when vaccines became available.
Reviving the 19th century invention to fight a 21st century pandemic is no job for the faint of heart. It will generate neither profits nor scientific glory. Yet to navigate a gauntlet of clinical trials and logistical challenges, it does require a mighty intellect, a heap of energy, the ability to muster an army of skilled recruits and a knack for fundraising.
And so, nearly every night for five months, Casadevall and two longtime colleagues — Dr. Michael Joyner of the Mayo Clinic and Dr. Liise-anne Pirofski of Albert Einstein College of Medicine — have met online to plot the potential comeback of convalescent plasma. They hope it can become both a treatment for COVID-19 and a way to protect people at high risk of coronavirus infection from becoming ill.
All in their 60s and well into accomplished careers at leading medical institutions, this trio might have spent the pandemic engaged in quieter pursuits. Instead, the three are putting immune system proteins from recovered patients through modern scientific trials, hoping to buy time for other medical advances to come along.
They've created the National COVID-19 Convalescent Plasma Project, a consortium of 260 doctors and scientists from 57 institutions around the country. Members of their coalition have launched more than 50 laboratory studies and clinical trials, and as of Thursday, 79,059 patients had been treated under the project's experimental "compassionate use" program. Preliminary findings are expected soon.
Their passion has them living on "COVID time," practicing science at all hours of the night and day as kids and spouses hover near their makeshift home offices. The pace of research has been compressed beyond recognition.
Joyner, who handles the project's day-to-day management, wakes at 4 a.m. and works for 16 hours, crushing sets of 50 push-ups between meetings and falling asleep at his desk. Casadevall and Pirofski oversee trials, recruit scientific talent and build support for the national effort.
If their work demonstrates even a modest benefit, convalescent plasma could help get children back to school safely and allow more of the economy to reopen. Successful results could also hasten vaccine development by making it possible to infect testers deliberately, which would speed up the evaluation process.
The initiative has reached well beyond the premier academic medical centers where most clinical trials are run. Dozens of doctors and patients in small and mid-sized community hospitals have had a chance to join in.
Dr. Shmuel Shoham, a participant from Johns Hopkins who normally treats transplant and cancer patients with compromised immunity, put it this way: "We're crowdsourcing a cure."
'A lightbulb moment'By mid-February, the novel coronavirus had ravaged Wuhan, China, and spread to Egypt, Iran, South Korea and most of Europe. Instances of community spread were being reported in the United States, prompting Casadevall to assess his profession's readiness to treat the respiratory plague.