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A Q&A with Morton A Meyers about Happy Accidents: Serendipity in Modern Medical Breakthroughs, followed by some fun facts from the book
A Q & A with Morton A. Meyers, M.D.
Your view of the process of medical discovery may be considered
controversial. How would you summarize it?
In my book Happy Accidents: Serendipity in Modern Medical
Breakthroughs, I reveal that many of the major medical discoveries have
occurred simply through chance—through a surprising, unexpected finding or
observation that led research in a different direction, which resulted in a
discovery of far greater value than the original goal.
What are major examples?
I describe about one hundred instances. But most
people—scientists included—are astonished to realize that most of our
antibiotics to combat infections, chemotherapy drugs against cancer,
psychotropic drugs which modify mood disorders, and many advances in
cardiovascular treatments and procedures were stumbled upon. So many of these
chance discoveries, such as Valium, Lipitor, and Viagra, have become household
names.
These fields cover much of modern medicine. Are these advances
the results of specialized teams with large federally-supported grants?
The astonishing answer to that is a resounding "No!" Rather,
they were typically discovered by individual curiosity-driven researchers with
modest resources and funding. They had the sagacity to pursue a surprising
finding or an incidental happenstance. For instance, in going down a false trail
while testing the toxicity of a product, an unknown scientist working alone
stumbled upon the effectiveness of lithium as a treatment for bipolar disorder.
In another case, a researcher made what he thought was a frightening mistake
only to discover that he had pioneered a revolutionary approach that enabled
bypass surgery for heart disease. While conducting animal experiments for a
surgical procedure, a young resident chanced upon a new treatment for abdominal
aneurysms.
Why is this generally unknown?
Scientific articles are very cut and dry, following a
traditional format indicating a rigid, logical sequence. This is very often
misleading. Understandably, researchers and clinical investigators are loathe to
admit the element of chance for fear of compromising their status, tenure, and
ability to generate research funds. Only years later, toward the end of their
careers, after awards have been received, might the phenomenon of serendipity be
openly acknowledged. I have interviewed a number of Nobel laureates and
recipients of other prestigious awards who now feel they can speak with
refreshing candor.
Why is it important for us to know the true contribution of
serendipity in medical research?
Mainstream medical research stubbornly assumes that new drugs
and other advances will follow exclusively from a predetermined research path.
Many, in fact, will. Others, if history is any indication, will not. They will
come not from a committee or a research team but from individual scientists and
mavericks who view a problem with fresh eyes and who may find what they're
not looking for.
We must reconsider our allocation of research funds, now
directed almost exclusively to centrally directed programs. We must take a
chance on chance. We as a society need to take steps to foster the kind of
creative, curiosity-driven research that cultivates an openness to serendipity
and has the potential to accelerate medical discovery as never before.
What specific steps can you recommend?
Education at all levels should encourage creative thinking and
prepare minds to be open to the unexpected. We must recognize and support the
unconventional researcher and allow scientists to pursue surprising findings.
Big Pharma should return from being primarily marketing machines to its roots as
an engine for truly innovative research.
A Few Fun Facts
Pathologist Looking at Slides Happens to Notice Undetected Cancer
In 1928, the Greek-American pathologist George Papanicolaou was investigating
the reproductive cycle by using vaginal smears, when he happened to observe the
presence of cancer cells in people who were not known to be sick. This
accidental discovery of a way to detect a cancer so early in its development was
groundbreaking. Thanks to the now-famous Pap smear test that was routinely
adopted in the 1940s, cervical cancer, once the leading cancer killer among
women, is now a distant seventh.
Castration of Dogs Leads to Discovery of Hormone Therapy
Charles Huggins, a professor of surgery at the University of Chicago School
of Medicine, was collecting fluid from the prostates of dogs in whom malignant
prostate tumors had spontaneously arisen. His interest was in the biochemistry
of seminal fluid. After castrating some of the dogs to see what effect
testosterone injections might have on their production of prostate fluid, he
noticed something totally unexpected: Castration caused their tumors to regress.
Realizing that castration would, of course, not be a desirable option for
treating humans, he injected estrogen into some of the dogs, producing, in
effect, chemical castration, which also caused the tumors to regress. His work
led to a synthetic estrogen drug shown to work against cancer, and Huggins, who
had not been originally working on cancer, was awarded the Nobel Prize in 1966
for an invaluable finding that saved many lives.
Routine Lab Animal Experiment Leads to Discovery of Stem Cells
In the 1960s, Canadians Ernest McCollough and James Till were researching the
use of radiation and subsequent bone marrow transplants as a treatment for
cancers of the blood. During one of their experiments, they discovered several
clumps of cells on the spleens of their animal subjects. These nodules turned
out to be colonies of cells all derived from a single blood-forming cell.
McCollough and Till had serendipitously stumbled upon the first stem cell, a
discovery that set the stage for current research on adult and embryonic stem
cells and all of their great potential for curing diseases. Investigations on
the likelihood that stem cells may underlie some cancers are currently underway.
In 2005, the two men were given the Albert Lasker Award for Basic Medical
Research (often a precursor to the Nobel Prize)
Dirty Plates and Good Weather Bring the World Penicillin
Returning from a long summer vacation in 1922, Alexander Fleming, a
bacteriologist at St. Mary's Hospital in London, was cleaning up piles of old
bacterial growth plates, when he made an extraordinary observation in one. A
mold had settled on the surface and killed all the surrounding lethal bacteria.
The event had unfolded in this way thanks to an awesome sequence of lucky
circumstances, including the timing of the seeding of the original bacteria, the
likely moment of the accidental mold deposit, the type of mold, and fortuitous
weather changes during the interval. Miraculously, Fleming had discovered
penicillin, the first antibiotic.
Catheter Mishap Allows Doctors to See Circulation in Heart for First Time
In 1958 a terrifying event occurred in the life of Mason Sones, a
cardiologist at the Cleveland Clinic. Readying his patient for a heart X-ray, he
had introduced a catheter into the heart chamber and was injecting the dye that
would allow the heart to be visible on the X-ray. To his horror, he watched as
the tip of the catheter flipped around, allowing a large amount of the dye to
flow directly into a coronary artery, which doctors had never dared enter for
fear of causing immediate cardiac arrest. Assuming the worst, Sones prepared to
open his patient's chest to massage the heart but instead found, to his great
relief, that the man was fine. Sones is credited with discovering an invaluable
technique for obtaining clear and detailed pictures of the heart's circulation
system, opening the way to coronary bypass and angioplasty operations.
An Overzealous Radiologist Jams In a Catheter and Unblocks an Artery
In 1963, Charles Dotter, a radiologist at the University of Oregon in
Portland, was inserting a catheter through the skin into a major artery in the
pelvis of a patient for the purpose of taking X-rays of an arterial obstruction.
Being a little aggressive, he jammed the catheter in farther than was standard
practice and cleared up the obstruction. When it was made public that arterial
obstructions could be not only diagnosed but also treated directly by
radiologists, vascular surgeons in the United States, whose livelihoods were
threatened by the discovery, openly ridiculed Dotter. But European radiologists
enthusiastically embraced the technique and began referring to the new approach
as "dottering." The amazing discovery eventually led to the life-saving
technique known as angioplasty.
Effort to Increase Blood Flow to Heart Brings About Interesting Side Effect
In England in the early 1990s, men were undergoing a clinical trial for a new
medication for angina. Unfortunately, the medication did not quite do what it
was intended to do, which was to increase blood flow to the heart. However, it
did increase blood flow to another organ: the penis. Miraculously, the drug
restored erectile function to men who were experiencing dysfunction, and Viagra
was born.
A Psychiatrist Investigating the Wrong Cure Stumbles Upon the Right One
In 1948, John Cade, a psychiatrist in a mental institution in Australia,
hypothesized, incorrectly, that the manic depressive state might be due
to either an excess or lack of some metabolite. His crude experiments indicated
the culprit was most likely uric acid, so Cade began experiments with uric
acid's most soluble salt, lithium urate. As he administered the salt to manics,
he watched, thunderstruck, as their raging moods subsided. In time, the truth
emerged, that it was the lithium that was responsible for the positive effect,
not the uric acid. Lithium became, and remains, the first-line treatment for
manic-depressive illness, now more commonly known as bipolar affective disorder.
Tuberculosis Treatment Leads to First Anti-Depressants
In the early 1950s, a new drug, a nicotine derivative, called
iproniazid had been shown to be effective in treating tuberculosis, and studies
to further validate its usefulness were being conducted in Europe. What
emerged was the fact that it had one rather "troublesome" side effect, at least
from the doctors' point of view. The patients taking it felt too good.
The result was that they overexerted themselves and generally ignored the
medical safeguards their condition required. Nathan Kline, an American
psychiatrist, upon learning about the odd effect, saw the potential, and
conducted a clinical trial that quickly established iproniazid as the very first
anti-depressant.
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