experiment of Scottish surgeon James Lind, in which a controlled trial of
citrus fruit administration was shown to be effective in the prevention of
scurvy, a true randomized controlled trial had never been performed prior
to 1948.
“Alternate allocation” trials, in which every other patient is given an
alternating experimental remedy, are prone to error because clinicians
cannot undo selection bias when assigning patients to treatment arms, no
matter how stringent the assignment of patients is. The British
epidemiologist-statistician Austin Bradford Hill realized the shortcomings
of previous experimental designs, concluding that the only sound way of
evaluating a drug would be to blind both the clinicians and the patients. A
trial for streptomycin was designed in early 1947 in which a triple-blinded
design (patients, treating clinicians, and evaluators) would all be ignorant
to whether patients received the actual antibiotic or placebo medicine.
With the war having just ended and British funds at paltry levels, there
simply weren’t the resources to treat a large number of patients. In fact,
with supplies of streptomycin almost nonexistent and without much
research financing, a randomized trial of patients getting no medicine was
not only scientifically intriguing, it was necessary. Hill later wrote, “... in
this situation it would not be immoral to do a trial—it would be immoral
not to, since the opportunity would never come again.”^22 The world’s first
randomized controlled trial, intentional but fortuitous, was concluded six
months later, and the results were undeniable. Of the fifty-five patients
who received streptomycin, only four had died (and twenty-eight
improved); in the control group of fifty-two patients who received only
placebo drug, fourteen had died. (A follow-up study demonstrated a
reversal of the trend, and researchers would later conclude that resistance
was building to streptomycin. Later studies showed improved outcomes if
aspirin was concomitantly given, thus bolstering the case for
streptomycin.)
Streptomycin became an immense success story but not without its
controversies, including who should receive the credit for its development.
The most important wrinkle in the story of streptomycin is that it paved
the way for future chemotherapeutic development—both for antibiotics
and anticancer medicines. Most antibiotics are derived from bacteria from
the soil (not industrial dyes and chemicals), and increasingly, from bizarre
places in the world, including the ocean depths and from the air. But