Category: Methodology

Major Cancer Drugs Have Come from Unexpected Sources

(p. 182) Starting in the last decades of the twentieth century, last decades of the twentieth century, sophisticated genetics and molecular biology have been aimed toward a more precise understanding of the cell’s mechanisms. Yet, even here, chance has continued to be a big factor. Surprising discoveries led to uncovering cancer-inducing genes (oncogenes) and tumor-suppressing genes, both of which are normal cellular genes that, when mutated, can induce a biological effect that predisposes the cell to cancer development. A search for blood substitutes led to anti-angiogenesis drugs. Veterinary medicine led to oncogenes and vaccine preparations to tumor-suppressor genes. In one of the greatest serendipitous discoveries of (p. 183) modern medicine, stem cells were stumbled upon during research on radiation effects on the blood.
Experience has clearly shown that major cancer drugs have been discovered by independent, thoughtful, and self-motivated researchers–the cancer war’s “guerrillas,” to use the reigning metaphor–from unexpected sources: from chemical warfare (nitrogen mustard), nutritional research (methotrexate), medicinal folklore (the vinca alkaloids), bacteriologic research (cisplatin), biochemistry research (sex hormones), blood storage research (angiogenic inhibitors), clinical observations (COX-2 inhibitors), and embryology (thalidomide).

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Model Flaws Result in No Useful Climate Consensus

At the end of the first page of the commentary quoted below, the following biographical credentials were provided for the author of the commentary:

(p. C1) Dr. Koonin was undersecretary for science in the Energy Department during President Barack Obama’s first term and is currently director of the Center for Urban Science and Progress at New York University. His previous positions include professor of theoretical physics and provost at Caltech, as well as chief scientist of where his work focused on renewable and low-carbon energy technologies.

(p. C1) The idea that “Climate science is settled” runs through today’s popular and policy discussions. Unfortunately, that claim is misguided. It has not only distorted our public and policy debates on issues related to energy, greenhouse-gas emissions and the environment. But it also has inhibited the scientific and policy discussions that we need to have about our climate future.
. . .
(p. C2) We often hear that there is a “scientific consensus” about climate change. But as far as the computer models go, there isn’t a useful consensus at the level of detail relevant to assessing human influences.
. . .
• Although the Earth’s average surface temperature rose sharply by 0.9 degree Fahrenheit during the last quarter of the 20th century, it has increased much more slowly for the past 16 years, even as the human contribution to atmospheric carbon dioxide has risen by some 25%. This surprising fact demonstrates directly that natural influences and variability are powerful enough to counteract the present warming influence exerted by human activity.
Yet the models famously fail to capture this slowing in the temperature rise. Several dozen different explanations for this failure have been offered, with ocean variability most likely playing a major role. But the whole episode continues to highlight the limits of our modeling.
. . .
• A crucial measure of our knowledge of feedbacks is climate sensitivity–that is, the warming induced by a hypothetical doubling of carbon-dioxide concentration. Today’s best estimate of the sensitivity (between 2.7 degrees Fahrenheit and 8.1 degrees Fahrenheit) is no different, and no more certain, than it was 30 years ago. And this is despite an heroic research effort costing billions of dollars.
These and many other open questions are in fact described in the IPCC research reports, although a detailed and knowledgeable reading is sometimes required to discern them. They are not “minor” issues to be “cleaned up” by further research. Rather, they are deficiencies that erode confidence in the computer projections. Work to resolve these shortcomings in climate models should be among the top priorities for climate research.
Yet a public official reading only the IPCC’s “Summary for Policy Makers” would gain little sense of the extent or implications of these deficiencies. These are fundamental challenges to our understanding of human impacts on the climate, and they should not be dismissed with the mantra that “climate science is settled.”

For the full commentary, see:
STEVEN E. KOONIN. “Climate Science Is Not Settled.” The Wall Street Journal (Sat., Sept. 20, 2014): C1-C2.
(Note: italics in original; ellipses added.)
(Note: the online version of the commentary has the date Sept. 19, 2014.)

“Discovery Cannot Be Achieved by Directive”

(p. 170) As early as 1945 the medical advisory committee reporting to the committee reporting to the federal government on a postwar program for scientific research emphasized the frequently unexpected nature of discoveries:

Discoveries in medicine have often come from the most remote and unexpected fields of science in the past; and it is probable that this will be equally true in the future. It is not unlikely that significant progress in the treatment of cardiovascular disease, kidney disease, cancer, and other refractory conditions will be made, perhaps unexpectedly, as the result of fundamental discoveries in fields unrelated to these diseases…. Discovery cannot be achieved by directive. Further progress requires that the entire field of medicine and the underlying sciences of biochemistry, physiology, pharmacology, bacteriology, pathology, parasitology, etc., be developed impartially.

Their statement “discovery cannot be achieved by directive” would prove to be sadly prophetic.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: italics in original.)

“Folkman Persisted in His Genuinely Original Thinking”

(p. 141) As detailed by Robert Cooke in his 2001 book Dr. Folkman’s War, the successful answers to these basic questions took Folkman through diligent investigations punctuated by an astonishing series of chance observations and circumstances. Over decades, Folkman persisted in his genuinely original thinking. His concept was far in advance of technological and other scientific advances that would provide the methodology and basic knowledge essential to its proof, forcing him to await verification and to withstand ridicule, scorn, and vicious competition for grants. Looking back three decades later, Folkman would ruefully reflect: “I was too young to realize how much trouble was in store for a theory that could not be tested immediately.”

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: italics in original.)

In Finding Cure for Ulcers, Marshall Was Not Constrained by the Need to Obtain Approval or Funding

(p. 113) Marshall was a youthful maverick, not bound by traditional theory and not professionally invested in a widely held set of beliefs. There is such a thing as being too much of an insider. Marshall viewed the problem with fresh eyes and was not constrained by the requirement to obtain approval or funding for his pursuits. It is also noteworthy that his work was accomplished not at a high-powered academic ivory tower with teams of investigators but instead far from the prestigious research centers in the Western Hemisphere.
The delay in acceptance of Marshall’s revolutionary hypothesis reflects the tenacity with which long-held concepts are maintained. Vested interests–intellectual, financial, commercial, status–keep these entrenched. Dogmatic believers find themselves under siege by a new set of explanations.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Ideas Should Not Be Rejected Just Because They Disagree with Reigning Theory

(p. 107) . . . Claude Bernard, the nineteenth-century founder of experimental medicine, . . . famously said, “If an idea presents itself to us, we must not reject it simply because it does not agree with the logical deductions of a reigning theory.”

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: ellipses added.)

Needed Revolutionary Ideas Often Come From Outsiders

(p. 103) . . . where knowledge is no longer growing and the field has been worked out, a revolutionary new approach is required and this is more likely to come from the outsider. The skepticism with which the experts nearly always greet these revolutionary ideas confirms that the available knowledge has been a handicap.”

Source:
W. I. B. Beveridge as quoted in Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: ellipsis added.)

Medical Innovator “Maintained a Healthy Skepticism Toward Accepted Wisdom”

(p. 103) Barry Marshall, a lanky twenty-nine-year-old resident in internal medicine at Warren’s hospital, was assigned to was assigned to gastroenterology for six months as part of his training and was looking for a research project. The eldest son of a welder and a nurse, Marshall grew up in a remote area of Western Australia where self-sufficiency and common sense were essential characteristics. His personal qualities of intelligence, tenacity, open-mindedness, and self-confidence would serve him and Warren well in bringing about a conceptual revolution. Relatively new to gastroenterology, he did not hold a set of well-entrenched beliefs. Marshall could maintain a healthy skepticism toward accepted wisdom. Indeed, the concept that bacteria caused stomach inflammation, and even ulcers, was less alien to him than to most gastroenterologists.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

“It Is Often Essential to Spot the Exceptions to the Rule”

Baruch Blumberg was awarded the Nobel Prize in 1976:

(p. 98) . . ., Blumberg learned an invaluable lesson: “In research, it is often essential to spot the exceptions to the rule–those cases that do not fit what you perceive as the emerging picture…. Frequently the most interesting findings grow out of the ‘chance’ or unanticipated results.”

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: ellipsis added.)

Theory Said Giant Bird Could Not Fly, But It Flew Anyway

(p. A3) Scientists have identified the largest flying bird ever found–an ungainly glider with a wingspan of 21 feet or more that likely soared above ancient seas 25 million years ago.
Until now, though, it was a bird that few experts believed could get off the ground. By the conventional formulas of flight, the extinct sea bird–twice the size of an albatross, the largest flying bird today–was just too heavy to fly on its long, fragile wings.
But a new computer analysis reported Monday [July 7, 2014] in the Proceedings of the National Academy of Sciences shows that the bird apparently could ride efficiently on rising air currents, staying aloft for a week or more at a stretch.
. . .
“You have to conclude that this animal was capable of flapping its wings and taking off, even though it is much heavier than the theoretical maximum weight of a flapping flying bird,” said Luis Chiappe, an expert on flight evolution at the Los Angeles County Natural History Museum, who wasn’t involved in the project. “Our modern perspective on the diversity of flight is rather narrow,” he said. “These were very unique birds.”
. . .
“This was a pretty impressive creature,” said avian paleontologist Daniel T. Ksepka at the Bruce Museum in Greenwich, Conn., who conducted the analysis of the bird’s biomechanics. “Science had made a rule about flight, and life found a way around it.”

For the full story, see:
ROBERT LEE HOTZ. “U.S. NEWS; Giant Bird Was Able to Fly, Scientists Find; Computer Analysis Shows Ancient Glider Could Get Off the Ground, Defying Conventional Theories of Flight.” The Wall Street Journal (Tues., July 8, 2014): A3.
(Note: ellipses, and bracketed date, added.)
(Note: the online version of the article has the date July 7, 2014.)

Serendipitous Discoveries Are Made by “Accidents and Sagacity”

(p. 6) “Accident” is not really the best word to describe such fortuitous discoveries. Accident implies mindlessness. Christopher Columbus’s discovery of the American continent was pure accident–he was looking for something else (the Orient) and stumbled upon this, and never knew, not even on his dying day, that he had discovered a new continent. A better name for the phenomenon we will be looking at in the pages to follow is “serendipity,” a word that came into the English language in 1754 by way of the writer Horace Walpole. The key point of the phenomenon of serendipity is illustrated in Walpole’s telling of an ancient Persian fairy tale, The Three Princes of Serendip (set in the land of Serendip, now known as Sri Lanka): “As their highnesses traveled, they were always making discoveries, by accidents and sagacity, of things they were not in quest of.”
Accidents and sagacity. Sagacity–defined as penetrating intelligence, keen perception, and sound judgment–is essential to serendipity. The men and women who seized on lucky accidents that happened to them were anything but mindless. In fact, their minds typically had special qualities that enabled them to break out of established paradigms, imagine new possibilities, and see that they had found a solution, often to some problem other than the one they were working on. Accidental discoveries would be nothing without keen, creative minds knowing what to do with them.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: italics in original.)