The Fevers of Reason. Gerald Weissmann

field trip to the West Indies, which gave Lewis the setting for an epidemic of plague in a colonial context; it also set the stage for an exercise in bioethics.

      Plucked from an earnest career as a Midwest clinician, Martin Arrowsmith is taken up by the McGurk (read Rockefeller) Institute, where he stumbles on filterable “Factor X,” which seems to kill bacteria, staph at first. But then, Gottlieb (Loeb) steps in:

       “Why have you not planned to propagate it on dead staph? That is most important of all.”

       “Why?” Gottlieb flew instantly to the heart of the jungle in which Martin had struggled for many days: “Because that will show whether you are dealing with a living virus.”

      Martin continues the work and finds not only that this virus kills several kinds of bacteria but also that he can make batches of the purified material to test in infected animals. He’s ready to publish his work, when Gottlieb brings bad news—in a German accent:

       “Vell. Anyvay. D’Hérelle of the Pasteur Institute has just now published in the Comptes Rendus, Académie des Sciences, a report—it is your X Principle, absolute. Only he calls it ‘bacteriophage.’ . . . Bacteriophage, the Frenchman calls it. Too long. Better just call it phage.”

      Martin goes on to further basic, laborious studies on phage and, lo and behold, he discovers a century before Doudna’s work that his phage “can cause mutations in bacterial species.” He plugs on but is soon confronted by the director of the McGurk Institute, Dr. Tubbs (read Simon Flexner, the first director of the Rockefeller Institute), who faults Martin for not making his discoveries go viral and makes a suggestion:

       “D’Hérelle’s discovery hasn’t aroused the popular interest I thought it would. If he’d only been here with us, I’d have seen to it that he got the proper attention. Practically no newspaper comment at all. . . . I think it may now be time for you to use phage in practical healing. I want you to experiment with phage in pneumonia, plague, perhaps typhoid.”

      As expected, Martin gets phage to cure plague in experimental animals—and people come next. There’s plague in the Caribbean, on the quarantined island of “St. Hubert,” a colony beset by rats and shiftless administrators. Arrowsmith heads there with a team of microbe hunters and volunteers, including his faithful wife, Leora (Helen Hayes in the film). They’ll try to stem the epidemic with a batch of Yersinia phage that’s cured plague in rats.

      The team faces personal tragedy and ethical conflict. For any new treatment, science demands controls, but can an investigator willfully deprive anyone of lifesaving measures? Does protocol trump empathy? Arrowsmith, book and film, throws a curveball: Martin’s beloved Leora dies from the plague and a depressed Martin stands down from his task. Others prevail, and Yersinia phage is finally given to one and all. Since this is fiction, the effort succeeds and the plague is quenched.

      A tear-filled Martin returns to New York, where the McGurk honchos are in bliss: the newspapers have gone viral with news of the phage and the plague. The director congratulates Martin:

       “You have done what few other men living could do, both established the value of bacteriophage in plague by tests on a large scale, and saved most of the unfortunate population.”

      In Martin Arrowsmith’s fictional experiments with phage, empathy ran ahead of clinical science. In the case of CRISPR-Cas9, bacterial immunity to phage, the opposite may be true. Doudna and others, David Baltimore among them, have argued that since CRISPR can be used to hand-pick the DNA of our gonads, human evolution could be played out at the lab bench. If the science has moved too fast for the ethics, perhaps the time has come to stop and think about Lionel Trilling’s warning:

       The apparatus of the researcher’s bench is not nature itself, but an artificial . . . contrivance much like the novelist’s plot, which is devised to foster or force a fact into being.

      The plot of CRISPR is before us, but we’re only into the first chapter of this book—and we’re not talking fiction.

       2.

       Ebola and the Cabinet of Dr. Proust

       The death of millions of people whom we do not know barely touches us, and almost less unpleasantly than a current of air.

      —Marcel Proust, Remembrance of Things Past (ca. 1916)

       Cordon sanitaire—we call it a cordon when someone who presents any symptoms of that disease is transferred, if their condition permits, to a hospital or to an equivalent place designated by the local authorities.

      —Adrien Proust, “Essay on International Hygiene” (1873)

       We believe these new measures [taking temperatures and administering questionnaires at JFK and other airports] will further protect the health of Americans, understanding that nothing we can do will get us to absolute zero risk until we end the Ebola epidemic in West Africa.

      —Thomas R. Frieden, Centers for Disease Control and Prevention (October 8, 2014)

      WE’VE LEARNED FROM THE EBOLA OUTBREAK of 2014 that to stop pandemics, we must regulate the transport of host and virus alike. Public transmission and cellular invasion depend on the unimpeded traffic of people across borders and of viruses across cell membranes. Barring the traffic of people across the Atlantic from Liberia would certainly have prevented the first four cases of Ebola in the United States. Blocking the traffic of the virus in human cells would have prevented thousands of cases worldwide. The Ebola epidemic in West Africa presented a major challenge not only to our public health system but also to our capacity to develop antiviral drugs. Thanks to cell and molecular biology, we already understand some of the critical pathways of virus entry and replication. We’ve also learned that these conduits can be blocked by novel drugs such as dynasore [sic] and Dyngo (no kidding) that are slowly coming to the clinic. To everyone’s surprise, papers by Harper et al. and Masaike et al. showed that bisphosphonates, drugs widely used to treat osteoporosis, also inhibit the traffic of Ebola virus in cells.

      So now that we have the tools available—dynasore, vaccines, adenosine analogues, inhibitors of RNA dependent-RNA polymerase, and so on (as shown by Oestereich et al.)—isn’t it time to launch a major effort, like those against smallpox, polio, and AIDS, to bring the benchwork of pharmacology to the bedsides of West Africa?

      IF DRUGS OR VACCINES HAVEN’T BEEN DEVELOPED for an infectious disease, there are only two time-tested ways to quell an epidemic: quarantine and sanitation. In the case of Ebola, the first step would have been to stop reliance on thermometers and telephones to keep infected victims from transmitting the disease. Temperatures vary, Tylenol can mask fever, and reliable information via telephones depends on who’s asking and who answers. Those protocols didn’t work in Dallas in the case of the first victim, the unfortunate Thomas Eric Duncan. Also fallible was the CDC’s policy of voluntary self-monitoring by people exposed to active Ebola victims: ask the many passengers between Dallas and Cleveland. The third American Ebola victim, Amber Joy Vinson, got permission for flights between Dallas and Ohio “because her elevated temperature of 99.5 degrees was below the no-fly threshold of 100.4 degrees,” the New York Post reported. Once it became known that Ms. Vinson had been involved in Mr. Duncan’s care, Dr. Frieden of the CDC confessed that “she should not have traveled on a commercial airline”—let alone take a taxi or visit a popular bridal shop. In contrast, quarantine of Mr. Duncan’s immediate family seemed to have worked.

      The CDC and the White House presented cogent arguments against a strict ban on flights from Liberia, Guinea, and Sierra Leone, arguing that such a ban would wreck the fragile economies of the area. “Trying to seal off an entire region of the world—if that were even possible—could actually make the situation worse,” said President Barack Obama. A ban would also have curtailed free passage of sanitary supplies and