1. Sledge, George W. Jr. MD

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Nobel Prize season finished last month with the Awards Ceremony on Dec. 10, and once again the Swedes have failed to recognize my many contributions to peace, medicine, literature or physics (OK, the last one is a bit of a stretch). I watched my cell phone for days, but no phone calls from country code +46. What is with those guys?

GEORGE W. SLEDGE JR.... - Click to enlarge in new windowGEORGE W. SLEDGE JR., MD. GEORGE W. SLEDGE JR., MD, is Professor of Medicine and Chief of the Division of Oncology at Stanford University.His

But as happens every year, a Nobel Prize has an interesting story, and a back-story behind that story. And this story has to do with malaria and war.


The prize for Physiology or Medicine (its quaint name) went to three investigators, with the common theme of tropical disease. Satoshi Omura and William C. Campbell received half of the prize "for their discoveries concerning a novel therapy against infections caused by roundworm parasites" and the delightfully named Dr. You-You Tu received the other half for her discovery of the anti-malarial drug artemisinin.


It was the malaria story that caught my attention. Dr. Tu received the prize for the discovery of artemisinin. During the Vietnam War, our Vietnamese opponents suffered horrendously from malaria. Chairman Mao, a fan of traditional Chinese medicine, encouraged studies of Chinese herbs as treatment for the disease.

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Dr. Tu examined the Chinese herbal tradition and found that compounds derived from the sweet wormwood plant could treat the disease in mice. She then isolated artemisinin from the herb, and an exceptionally important antimalarial was born. Today over half of malaria worldwide is chloroquine-resistant. Artemisinin is the lifeline for patients suffering from resistant malaria.


As an undergraduate I had a classmate who had served as an infantryman in Vietnam. He had come home with what I would now recognize as quartan malaria, with recurrent fevers and chills and just the most miserable feeling on earth. He had that far-away look of someone who had spent too many days seeing things 19-year-olds shouldn't see. But it was the malaria that dragged him down.


'Whatever Works'

Patients often ask what I think of complementary and alternative medicines. My answer is always the same: whatever works. I prescribe drugs derived from mold, tree bark, and sea sponges. It isn't the origin of the drug that matters. If it passes rigorous scientific tests (so-called "Western medicine") demonstrating clinical utility, I am happy to prescribe it. The scientific method doesn't care if you are Chinese or American, nor whether your drug is a natural product or a synthetic chemical. It doesn't even care if it is a drug.


But the artemisinin story interested me for other reasons. The first was the long history of tropical medicine, particularly malaria, and the Nobel prize. One of the very first Nobel prizes for Medicine (in 1902) was given to Dr. Ronald Ross for his discovery of its transmission via the mosquito. Five years later Dr. Alphonse Laveran received the prize for his discovery of the malarial protozoan. Both the Englishman and the French doctor served their overseas colonial empire. In 1897, the year Ross published his work, approximately one-third of British troops in the Indian Raj were incapacitated by malaria.


Malaria represented an endemic disease in the American South for much of the first half of the 20th century. While common wisdom holds that the problem was solved through liberal dousing with DDT (another outcome of war), in fact it began its retreat during World War I. With large numbers of American soldiers receiving basic training in Southern cities, the U.S. Government was concerned that they would contract malaria before shipping overseas to France.


Extra-Cantonment Zones

The government's response was to set up so-called extra-cantonment zones, areas within which it assumed responsibility for public health. Mosquito eradication, the techniques for which had been pioneered in the Spanish-American War and its aftermath, was used in a widespread fashion for the first time in the American South, considerably reducing malaria incidence and setting the stage for the subsequent New Deal-era near-eradication (pre-DDT) of malaria in the United States.


For anyone interested in this story, read the definitive account by Daniel Sledge, my political scientist son, of whom I am very proud: "War, Tropical Disease, and the Emergence of National Public Health Capacity in the United States" (Studies in American Political Development 2012;26:125-162).


DDT also earned its discoverer, the Swiss Dr. Paul Muller, a Nobel prize in 1948. The Swiss shared Muller's discovery with the United States in the midst of World War II, and the U.S. military rapidly introduced it into war zones, dramatically reducing deaths due to malaria, typhus, and the panoply of other insect-borne disease, not just for soldiers but for civilians.


But the larger back-story is the connection between war and scientific progress in general, and medical progress in particular. Alfred Nobel himself personifies this connection. Nobel, as is well known, made his riches through the creation of dynamite, which he hoped would be used for peaceful purposes only. His subsequent recognition of, and his horror over, the co-option of his discovery for lethal military purposes led to his creation of the Peace Prize.


Alexander Fleming's discovery of penicillin languished until World War II, when two British scientists rediscovered it and brought it forward to treat wounded soldiers, the work supported by infusions of cash from the British and American governments.


One can make too much of these connections, of course. No malaria patient cares that artemisinin came out of a nasty jungle war. No one in a doctor's office getting any of penicillin's follow-on antibiotics cares that the antibiotic revolution was a byproduct of history's bloodiest war. They just want to be treated and cured, and not re-infected.


But it seems inescapable that the link between medical progress and war is a real one. Trauma medicine had its origins in military surgeons, and even the DaVinci robot so prized by urologic surgeons caring for prostate cancer patients had its beginnings in a DARPA contest to create a battlefield-ready automatic surgeon.


And cancer patients, as we all learn early in our training, owe a debt to war: the first effective chemotherapy agents were discovered as a result of a ship full of poison gas blowing up in Naples harbor in 1944. In short order the lymphopenic sailors served as the model for treating leukemia in children.


Someday, one hopes, such expensive advances, paid in the blood of innocents as well as the gold of governments, will no longer prove necessary. But for the moment, the essential tension embodied by the Nobel prizes, with their celebration of life paid for by the archetypal merchant of death, continues to vex us.