Sledge, George W. Jr., MD
There are few more tired metaphors than “The War on Cancer.” We have been fighting this war, if Richard Nixon had it right, since 1971. Practically from the beginning there were those who opposed the “war” metaphor's use. The objections were many: too bloodthirsty, too masculine, and too scary for kids with cancer (wars are about death and dying)—even, some would have it, unbiologic and simplistic and unhelpful.
Figure. GEORGE W. SL...Image Tools
Add to this the failed promise—the war would be over in 10 years—and the metaphor wore out its welcome long ago. No less an expert than the Director of the National Cancer Institute, Harold Varmus, has said “It's inaccurate, in my view, to think of a war on cancer as though cancer were a single, individual enemy—nor is the metaphor of war exactly right.”
Part of the issue was that wars, like cancers, differ greatly. Some end quickly, with lightning strikes (the Six-Day War between Israel and the Arab nations), while some drag on forever (the Hundred Years War between England and France). Some wars end in total victory—perhaps the World War II veteran Nixon was thinking in these terms—while some end in a negotiated surrender on terms. Some require total mobilization of resources (World War II, again, but think high-dose chemotherapy and bone marrow transplantation) while some are hardly noticed by the citizens of at least one of the combatants (the U.S. in Afghanistan, many carcinomas in situ). Some are wars of annihilation, while some are almost polite and rule-bound. So the metaphor isn't just tired, it is inexact and confusing.
Paul Kennedy's new book on World War II, Engineers of Victory, has made me re-think the “war” metaphor. Kennedy, a Yale historian, is perhaps best known for his The Rise and Fall of the Great Powers, one of the cultural zeitgeist books of the late 1980s and early 1990s. The book is his take on why the Allies beat the Axis powers in World War II.
The standard narrative of how the Allies won involves, respectively, the blood of millions of Russians, the overwhelming industrial might of the United States, and the bulldog tenacity of the British. Popular histories focus on defining moments, turning points, that together were said to decide the war: Midway, Stalingrad, El Alamein, Normandy, and a few others. Or, alternatively, they suggest that some “killer app” (to use an anachronistic term) like Bletchley Park's code-breaking efforts were responsible for victory.
Kennedy does not deny the importance of any of these, but he considers them both inadequate and too focused on nationalistic mythologies. Reality was far too complex, and this complexity leads him to resist “all efforts at reductionism, such as that the winning of the war can be explained by brute force, or by some wonder weapon, or by some magical decrypting system.”
Instead he thinks of World War II as a series of engineering problems, where many of the important “battles” were fought far from the front lines, through new solutions to seemingly intractable problems: How do you stop a Blitzkrieg? How do you overcome the “tyranny of distance” to defeat a country on the other side of the Pacific Ocean? How do you get a fleet of bombers to Berlin and back against determined resistance? How do you get a convoy across the Atlantic through submarine wolf packs?
Kennedy details how there was almost never a single “killer app.” Rather, the means of victory always required many separate solutions, from multiple sources, coming together to unravel complex problems.
An example, one among many, is the defeat of the German Air Force by British and American forces. The P-51 Mustang fighter plane was the closest thing to a “killer app” for this problem—a guardian for the bombers headed for the Reich, it prevented the collapse of the Allies bomber forces in 1944. Prior to the Mustang, no fighter could make it all the way and back, so the bomber forces were regularly slaughtered whenever they travelled over Germany.
But the Mustang was very much a series of linked events, rather than a solitary invention: originally a British-ordered American design with a weak engine, it only became powerful enough to take on German fighters when it received a replacement British Rolls Royce engine. And it was only able to fly to Berlin because of the invention of drop tanks that extended its range, a remarkably low-tech solution that somehow eluded the Air Forces for years.
Leadership mattered. The Mustang was bitterly opposed by the powers that be for some time—the original “Not Invented Here” syndrome that occurred because of its hybrid British-American lineage. It was not until a high-ranking Air Force officer took on the problem that the Mustang was put into production. Thousands of Allied airmen died while the leaders dithered.
But Kennedy is at pains, even in describing the Mustang's path to Berlin, to insist that this was only one part of the eventual solution, with dozens of other decisions along the way playing a part.
Again and again, in Kennedy's telling, it was the mid-level engineers (he uses the term in a very broad sense) who came up with the solutions, often creative types low on the totem pole. The cavity magnetron, the basis for centimeric radar, arguably the most important invention in the war, was created by two Birmingham scholars using materials scrounged from a local scrap metal dealer.
So back to the “War on Cancer.” Maybe the problem is not that the metaphor is tired, but that we never really understood what the metaphor actually implies, and what it takes to win the sort of global war that it will take to defeat the disease.
When Kennedy speaks of over-simplistic appeals to “brute force,” to “wonder weapons,” or to “some magical decrypting system,” the student of cancer can readily translate these as “high-dose chemotherapy,” “kinase inhibitor,” or “genomics.”
Some lessons from Kennedy's book, applied to the “War on Cancer”:
1. Don't focus just on “Turning Points.” We automatically think in terms of imatinib for CML or trastuzumab for HER2-positive cancer. Not to gainsay those great, and very real, victories, but neither drug ended the war. The war is much larger than CML or HER2-positive breast cancer, and the tools needed for those victories are not the tools that will be applicable to most other battles, nor do they even represent a final defeat for those diseases. One is tempted to remember Churchill's description of El Alamein: not the beginning of the end, but the end of the beginning.
2. No single solution exists. This doesn't mean just that imatinib won't cure every cancer, but also that no single category of solutions (kinase inhibitors, antibodies, chemotherapeutics, radiation, surgery) will ever do the trick. Instead, we need to accept the need for combinations of solutions, not just to win the war, but also even to win individual battles. Every problem requires a different solution, or collection of solutions (multidisciplinary clinics, anyone?). Magic bullets didn't end World War II and won't end the “War on Cancer.”
3. Continuous improvement cycles matter. We went from a 20 percent cure rate to a 90+ percent cure rate for ALL without introducing any new drugs. Sometimes learning how to use imperfect tools better (the Mustang was nearly tossed away early on because of its imperfections, as were cisplatin and trastuzumab) is a large part of the solution for some problems. Though not all: remember 20 maddening years of 5-FU studies in colorectal cancer.
4. Logistics matter more than Great Generals. The Germans lost at El Alamein with the war's best general (Rommel) because they could not get enough supplies to their troops. We still lose all too many cancer “battles” because of access and supply issues. It does not matter that we can cure childhood ALL if the dirt-cheap drugs cannot make it to an American clinic, or to Sub-Saharan Africa.
5. Solutions are often either low-tech (drop tanks for the Mustang, arsenic trioxide for APL) or emerge from a place at the bottom of the hierarchy. Often, in both World War II and the War on Cancer, it is the sergeants or the Assistant Professors who find a solution.
6. The role of leadership is to identify problems, and then enable the solutions of others; making sure that the best solutions (not the perfect solutions, for they don't exist) are adequately resourced. And for heaven's sake, when a solution exists, leaders should at least have the good sense to get out of the way and let it bubble up to the top. Churchill, for instance, had an almost uncanny ability to discover and enable low-level problem-solvers over the best (worst?) efforts of his own bureaucracy, in Kennedy's telling.
7. The experts are not always the best judges of what works. Kennedy discusses the lack of functioning American torpedoes for the first two years of World War II: if they didn't work, it was the fault of the “practitioners” (in this case, the submariners), according to the Navy bureau that created the devices. It turns out that the Navy bureau didn't actually understand the problem in “the clinic.” Their models were wrong, better suited to Rhode Island than the South Pacific.
Sound like anything we've dealt with? Effective translational science (bench to bedside to bench) is not an invention of the “War on Cancer.” The necessity of getting the end-users together with the basic researchers was learned through bitter experience in the 1940s.
8. Strategy matters, but only if solutions exist. Brute force rarely does the trick: in Kennedy's words, it is the intelligent application of force that matters. If anyone believes we have applied our forces intelligently (at either a scientific or societal level), I have a bridge I would like to sell you.
So the “War on Cancer” may well be the right metaphor. We just didn't understand what the metaphor actually required of us: a committed effort to complexity, the rejection of simplicity, the enabling of talent at every level, and the effective delivery of the right resources to those fighting in the trenches against a deadly and vicious foe.
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