The Friday Evening Lectures at the MBL in Wood’s Holl, as it was then called, descend from a series of public lectures that began in 1889, the year after the lab was founded. And over the next decade, Jacques Loeb (1859–1924) gave several of these, published in Biological Lectures at MBL Wood’s Holl. Based on his summer experiments at the MBL on sea urchin sperm and eggs, in 1909 he issued a challenge:
Whoever claims to have succeeded in making living matter from inanimate will have to prove that he has succeeded in producing nuclear material which acts as a ferment for its own synthesis and thus reproduces itself.
Doudna and the other “heroes of CRISPR,” as geneticist Eric Lander called them, met that challenge just over a century later. The CRISPR-Cas method uses “inanimate RNA” and protein to snip out the old “nuclear material” (DNA) to add the new which can “act as ferment” for its own reproduction. Going viral, we might say.
CRISPR-Cas HAS ALSO GONE VIRAL in the scientific literature. According to the website Web of Science, the topic of CRISPR-Cas went from a few dozen citations in 2005 to over ten thousand on the eve of Doudna’s lecture. Her seminal 2012 paper with Charpentier has itself been cited over fifteen hundred times. (To put this into current pop perspective: one notes that one tweet by Kim Kardashian has reproduced itself 137,369 times.)
As for Jacques Loeb, he went as far as one could in the pre-viral days. His papers were cited fifteen hundred times in his lifetime, thrice the number of his contemporary, Paul Ehrlich. He was also a figure in the press: “Loeb Tells of Artificial Life,” proclaimed the Chicago Daily Tribune in 1900. In1907, under the headline “Believes Germ of Life Will Be Discovered,” the San Francisco Call reported that “Professor Jacques Loeb . . . in a bulletin issued today from the office of the president, makes the statement that he believes the germ of life can be discovered, provided the chemical reactions surrounding the process of fertilization, are investigated.”
Loeb’s public persona also went viral in his role as the fictional Dr. Gottlieb, the mentor in Arrowsmith. The novel by Sinclair Lewis won a Pulitzer Prize, and the film was nominated for an Oscar. Lewis described how Gottlieb and Martin Arrowsmith (Ronald Colman on screen) not only discovered bacteriophage, but used it to stem an outbreak of plague (Y. pestis) on a tropical island.
BACTERIOPHAGE AND THE PLAGUE may have been brought to modern attention in 2005 when French scientists found phage-like DNA sequences at the CRISPR locus of plague bacilli, but Martin Arrowsmith got there first! His story was patched together from Paul de Kruif’s memories of work at Rockefeller Institute (now Rockefeller University) and Sinclair Lewis’s progressive politics. De Kruif and Lewis made a joint 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.
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
