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Simone's OncOpinion

The Underappreciated and Unheralded

Simone, Joseph V. MD

doi: 10.1097/01.COT.0000472800.80357.79

As I write this at the end of August, I was struck by an op-ed piece in the New York Times, which I read just about the same time as an autobiography written by a colleague and friend reached my desk; more on him later. The Times piece, by Stuart Eizenstat, was titled, “Jimmy Carter's Unheralded Legacy” (25 Aug 2015; and was prompted by the announcement that President Carter has metastatic melanoma.

Eizenstat had been a White House advisor for Presidents Carter and Clinton, and his description of Carter as a man—and, more important, his character—is beautifully written.

While Carter's term is viewed as a failure by many Democrats as well as Republicans, Eizenstat dissects Carter's time in office, its challenges, and, to a surprising degree (to me), the cornucopia of important accomplishments that Carter's administration achieved.

A brief—and incomplete—list:

  • Elected after Watergate when trust in government fell dramatically, Carter took steps to restore trust—for example, installing gift limits and financial disclosures for all his appointees;
  • While in office he stayed faithful to his message of uplifting the poor of all races at the risk of losing his white Southern base, which abandoned him in his failed run for reelection;
  • He established the Department of Education, and increased college tuition grants for needy students;
  • He had a dogged determination to awaken the American public and Congress to the dangers of our growing dependence on foreign oil: He phased out federal price controls for natural gas and crude oil, which ultimately led to increasing independence from foreign energy, and he created the Department of Energy and began tax incentives for home insulation and solar energy (30-plus years ago!); and
  • He brokered the first Middle East peace treaty between Israel and Egypt at Camp David, which remains a touchstone of U.S. security policy in the region.

Carter certainly had failures, as do all presidents. In some ways his term resembled Harry Truman's. Both were widely unpopular at the end of their presidencies, but history has shown that Carter, like Truman, is often now seen as a paragon of honesty, decisiveness, and achievement. Truman was President Carter's idol; he put a plaque on his desk with Truman's slogan, “The Buck Stops Here.” Eizenstat ends the column by saying: “Truman and Carter's plain-spoken decency, integrity, and courage are too often lacking among political leaders today.” Amen.

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Walter T. Hughes, Jr., MD

Awards and accolades are common in medicine, perhaps too many, some deserved and some not. But now and always there have been people with “plain-spoken decency, integrity, and courage” in the field of medicine. And some of these men and women, like Truman and Carter, have been unheralded and underappreciated by the medical professions.



One of the best examples that I know and worked with for over two decades is Walter T. Hughes, Jr., MD. Walter is a pediatrician and scientist with a remarkable record of accomplishment. His autobiography, “From Wales to Pneumocystis and AIDS, Centuries of Serendipity,” was published earlier this year on his 85th birthday. He is one of those who accomplished a great deal but for whatever reason has received relatively little recognition for his innovative work.

St. Jude Children's Research Hospital opened in 1962. I was recruited there five years later, and Walter was appointed the head of infectious disease services in 1969. His recruitment by Dr. Donald Pinkel, the director who recruited both of us, was the result of the increasing problems with immunosuppression and dangerous infections in our patients receiving chemotherapy. We began to see patients in remission of their cancer fatally infected with opportunistic microbes.

Walter completely revamped the facilities and procedures to try to minimize infections and to react quickly when infections appeared. Some staff and parents of patients resented some of his rules, but he was supported strongly by Don Pinkel and most of the doctors.

And then an epidemic broke out at St. Jude: Children developed a severe pulmonary disease from the then mostly obscure organism Pneumocystis carinii. It was first identified in rats in 1912 that were thought to have another type of infection. The first human epidemic in the U.S. occurred at St. Jude in immunosuppressed children.

Walter identified the agent in our patients and worked diligently to keep them alive, using “iron lungs” that had been used for children with paralytic poliomyelitis to support their respiration; these clinical approaches had only modest success, however, and we are still losing patients.

Only one drug, pentamidine, was known to have some effect against the organism. By 1974 we were seeing 20 to 40 cases a year with the pneumonia, by which time the symptoms and characteristics of the disease were worked out by Walter and his colleagues.

Walter combed the literature looking for a possible animal model of the disease that he could experiment with. He found an article from the German literature showing that one could induce P. carinii pneumonia in rats by simply giving them corticosteroids. The agent was widespread in these animals, but they did not contract the disease until their immunity was suppressed. He repeated the experiments and had his model.

He developed a vaccine that failed to prevent the pneumonia, so he abandoned that route. He then began to search for an antimicrobial drug. In the meantime, it had become clear that P. carinii was a protozoon in the same family as Plasmodia species (malaria et al), so antiprotozoal drugs were tried.

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The team hit the jackpot when they tried trimethoprim-sulfamethoxazole (TMP), which had been developed for treating urinary tract infections. TMP prevented the Pneumocystis infection in all rats given corticosteroids.

TMP had already gone through human testing in Europe and found to be relatively safe, so Walter and his team did the clinical trial. Patients were given either TMP or pentamidine and both were shown to be effective. But pentamidine had major side effects while TMP caused few, and TMP was given orally and pentamidine was given by intramuscular injection. So TMP was given to all patients as a prophylactic treatment.

The results confirmed the excellent results in animals, and one of our nightmares was about to be over. TMP has remained the drug of choice for 35 years for the prevention and treatment of Pneumocystis pneumonia.

Walter's studies became broadly read because by this time AIDS had become an epidemic and P. carinii infections became common in those patients because the disease suppressed the immune system—the same problem caused by chemotherapy in children. He dove into the AIDS problem and used the animal model and clinical trials to identify two additional drugs (atovaquone and dapsone) now in general use. Currently, more than four million HIV/AIDS patients receive the drug for prophylaxis.



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Hit a Home Run, but...

To explain so briefly what a feat Walter pulled off may suggest that the work was facile and easy. Not so. He identified the bug, developed a rodent model to test it, found the right drug, tested it carefully in animals and children, and hit a home run.

For that he received little recognition; he was nominated by colleagues several times for membership in the Institute of Medicine and was turned down. In typical Walter fashion, though, he just continued plugging away, saving lives and shedding light on other medical problems.

I showed him this manuscript before sending it to the editorial office. He corrected a few facts, but said he preferred that I omit the mention of the IOM. I pondered over that, but ultimately decided to leave the information in.

In some small way this column recognizes him—and, more importantly, he is silently heralded by the many patients he was instrumental in enabling to survive two killers: cancer and a deadly pneumonia.

The children (and adults with AIDS) saved by Walter's work are legion, and I think they should be heard. I am sure he would say he preferred that to any other prize or honor.

Walter Hughes is a great man by any measure—one of the finest gentlemen you would ever meet, and one of the best friends and colleagues I have ever had. Just as with the two underappreciated presidents, Walter's decency, integrity, courage—and I would add modesty—in his work and life is a model for any physician-scientist.

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