A COMIC NOVELIST'S GREAT TRAGEDY

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Peter De Vries (1910–1993)—writer for the New Yorker, Poetry editor, once widely acknowledged as the top American comic novelist of his era—was best known for his clever wordplay, irreverent humor, and extended riffs on a broad range of human foibles.^1–3 But despite De Vries' reputation for puckish wit and for the skewering bon mot, his greatest novel is a tragedy—one that is all the more haunting because it is stuffed with autobiographical detail.

The Blood of the Lamb, ⁴ published in 1961, describes the growing estrangement of the main character (Don Wanderhope) from his origins in a close-knit, blue-collar, Chicagoland Dutch immigrant community. The death of a sibling, parental mental illness, and the strains of a volatile marriage contracted too hastily were heavy stones that stressed the increasingly rickety structure of Wanderhope's boyhood religious faith, until that faith finally collapsed beneath the crush of a singular and devastating loss, re-emerging as something more ambiguous. Emily De Vries—her literary counterpart is Carol Wanderhope—De Vries' youngest child and a chief existential consolation, died in September 1960, just a few days before her 11th birthday and 2 years after she was diagnosed with acute lymphoblastic leukemia (ALL).¹

Through the filter of his prodigious literary gifts, De Vries poured out the monstrous, idiosyncratic grief of a bereft father, of a man who has lost something that really matters. The Blood of the Lamb was published just a year after Emily's death, and the rawness of emotion sears its pages: often bitter, sometimes elegiac, and with scattered patches where the writing is less polished, less subtle than is typical for De Vries.⁴ The author's seething anger over the unfairness of the world is frequently channeled into frustration at a paternalistic and ultimately impotent medical establishment, which provided plenty of facile reassurances, even as it failed to save his innocent “lamb” of a daughter from her own poisoned blood.

De Vries eventually returned to writing comic novels after The Blood of the Lamb, but always with darker undertones, echoing the futility and chaotic meaninglessness of life that he felt so acutely during Emily's terminal illness.^1,2 These stylistic changes parallel the intellectual evolution of Charles Darwin a century earlier, after a similar event: Darwin lost his beloved daughter Annie in 1851, also at age 10 years from an unexplained illness—possibly tuberculosis, which was just as frightening and incurable in the 1850s as leukemia a century later.⁵ Darwin's great-grandson suggests that the feelings of randomness and lack of ultimate purpose engendered by Annie Darwin's untimely death pushed the great naturalist towards a reluctant full acknowledgment of the terrifying metaphysical implications of his mechanism of natural selection.^5,6 The legacy of a child's premature death can be long indeed.

THE ILLNESS OF EMILY DE VRIES

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If the detailed descriptions in The Blood of the Lamb are faithful to how events actually unfolded at the De Vries family home in suburban Connecticut at the end of the late 1950s—to credit, even though some details are clearly altered (eg, the character Carol became sick at age 11, a milestone that the real Emily De Vries never reached)—the girl's illness began with progressive fatigue and a low-grade fever that antibiotics could not eradicate. A blood test ordered by a general practitioner revealed an elevated white count. An initial attempt at a bone marrow exam was unsuccessful—it was a sternal aspirate, as most marrow studies still were in the late 1950s—but a second bone marrow specimen obtained the following day showed “a strong suggestion of leukemia.”

Consistent with the ethos of the era, the nature of the illness was kept secret from the patient. Emily/Carol was urgently referred to a specialist, Dr. Scoville (recognizable from descriptions as cancer chemotherapy pioneer Joseph Burchenal, about whom more later) at Westminster Hospital in New York City (ie, Memorial Hospital, which merged with Sloan-Kettering Research Institute in 1960).

By the time Carol was seen in the pediatric oncology clinic, her spleen was palpable, her hemoglobin was dropping rapidly, and, in the words of the oncologist, her condition was “getting touch-and go.” Don Wanderhope/Peter De Vries was instructed to tell his daughter that she had anemia—leukemia was considered too frightening a word to mention to a child—and was given a roll of hemostatic yarn to use in case she developed epistaxis. Indeed, before the first planned follow-up clinic visit to talk about experimental chemotherapy, the girl's nose bled profusely, and she was briefly hospitalized for treatment with transfusions and a corticosteroid—a drug previously described by the physician as an “ace in the hole,” to be used only in an emergency.

After a few days of prednisone therapy, Carol's spleen was no longer palpable, her platelet count rose from 65 × 10⁹/L to over 100 × 10⁹/L, her pallor had resolved, and the nosebleeds stopped. At the next clinic visit, she started taking mercaptopurine (MP). Today, children with ALL usually take MP at bedtime, but Emily's mother was instructed to wake her to give her the drug at precisely 3 o'clock each morning, and she became so anxious about missing the alarm and harming her daughter that she required a mild sedative to fall asleep.²

Within 3 weeks, the child's blood counts had normalized, and a sternal marrow showed a “solid remission” (remissions were rather loosely defined in the early days of leukemia therapy). But this first remission lasted less than 6 months. The marrow blast proportion rose to 20%, then 40%, and finally 50%; (sternal aspirates were taken every 3 weeks throughout the entire course of her disease) before methotrexate was substituted for the MP, again resulting in remission. The 1950s were an era of sequential treatment for cancer, with the first randomized clinical trials of combination chemotherapy reported only at the very end of the decade.^7–9

Three months after Carol began taking methotrexate, she developed headaches and blurry vision. These frightening symptoms heralded the onset of meningeal involvement by leukemia, which was confirmed with a spinal fluid exam (CNS prophylaxis in ALL would not become routine for another decade¹⁰). Intrathecal chemotherapy solved that problem, but the systemic disease quickly returned. Carol then began taking a new experimental drug, never named in the book, which briefly dropped her marrow blast count to 6%.

The Blood of the Lamb hints about specific additional chemotherapeutics on the horizon, like floxuridine, which proved relatively ineffective in leukemia,¹¹ and the vinca alkaloids (vincristine was US Food and Drug Administration approved in 1963 for ALL and several other tumors¹²). But Carol never got a chance to try any of those other drugs. A virulent opportunistic infection swept through the Memorial Hospital children's cancer ward, and she caught it, too. The final scenes of the child's life are described in heartbreaking detail. Despite treatment with chloramphenicol, the “big gun” antibiotic of the era, Carol developed septic shock with the stigmata of purpura fulminans. As she slipped into a coma with her parents at her bedside, Dr. Scoville poked his head in the door of her room briefly to report that the new drug she'd taken was proving a bust in a clinical trial – and also mentioned that he'd just cancelled an order for another tank of oxygen, since the dying girl wouldn't need it. The doctor then turned his back and walked away. This was his last appearance in the book.

EVOLUTION IN THE TREATMENT OF CHILDHOOD LEUKEMIA

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The outcome of many illnesses is highly dependent on historical context, and rarely is this more obvious than for ALL. Had Emily De Vries developed leukemia 10 years earlier than she did, her death would have been much quicker and accompanied by minimal medical intervention, and The Blood of the Lamb would lack much of its drama. Had her illness been diagnosed 10 years later, there is a chance she would still be alive today: by 1968, durable remissions were achieved in more than 80% of children with ALL,¹³ and in the early 1970s, the possibility of “cure” began to be spoken of openly.¹⁴

In unpublished notes, Emily's mother, the poet Katinka Loeser, captured the feeling of impatience engendered by a time of rapid medical progress that has not yet moved far enough along to cure a loved one:

The child is put on the critical list and nobody knows how it will turn out this time. There have been past recoveries, haven't there, and you have taken your child home, haven't you? Meantime the rats and mice next door may have demonstrated something which even now is being evaluated, and at any moment the phone may ring, the New York Times have a front page story, the newscasters have a startling announcement to make. (Loeser K: Who cried in goose, alas—Notes on the death of a child. Unpublished manuscript).

Emily De Vries's story is of special interest to oncologists because it occurred during a unique transitional period in the history of cancer therapy, when the first effective nonsurgical treatments for neoplasia were being developed, and leukemia was treatable but not yet curable – a transition that is still taking place for some other types of cancer. Her father's skills of observation and expression provide a unique window into what it was like for patients and their families in the early days of cancer chemotherapeutic experimentation, before there were any cancers that had been conquered to provide a hopeful example. As De Vries pithily observed, summing up what ALL meant in 1959:

So death by leukemia is now a local instead of an express. Same run, only a few more stops. But that's medicine, the art of prolonging disease. ⁴

Notably, Emily's story is also intertwined with that of Joseph Burchenal (1912–2006), past president of the American Association of Cancer Research and a pioneer in medical therapy of neoplasia.¹⁵ I have not been able to find other essays that make this connection.

JOSEPH BURCHENAL AND THE INFANCY OF CHEMOTHERAPY

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Joseph Burchenal joined the newly founded Sloan-Kettering Institute for Cancer Research in New York, NY, after he left the army in 1945.¹⁶ Along with Sidney Farber in Boston, MA,¹⁷ and a tiny cadre of like-minded physicians, Burchenal began to view leukemia not as an inevitable prefiguration of death, but as a disease just like any other—one that might be successfully treated with drugs in the same way that infections had begun to yield to antibiotics during his residency in Baltimore, MD, in the 1930s.¹⁶ Burchenal turned his attention to leukemia in 1948, confirming the temporary effectiveness of nitrogen mustard compounds¹⁸ as well as Farber's promising results with folate antagonists, and then embarking on murine experiments and clinical studies with a series of other antimetabolites. The assistance of George Hitchings and Gertrude Elion at Wellcome Research Laboratories in Tuckahoe, NY, proved critical: MP, a purine nucleoside analog synthesized by the team at Burroughs-Wellcome, was Burchenal's first major clinical success, and won a Nobel Prize for Hitchings and Elion along with Sir James Black in 1988.¹⁹

A seminal paper in Blood in that journal's inaugural year (1953) described good clinical and hematological remissions, albeit brief, in one third of 45 children who received MP.²⁰ When this article appeared, Burchenal had already witnessed the introduction of corticosteroids into leukemia treatment around 1951,²¹ and by 1961, he and others had successfully added alkaloids of Vinca rosea to the standard treatment sequence of methotrexate and MP. In 1962, the first “Total Therapy” regimen for acute leukemia, combining all known effective agents to induce and maintain remission, was introduced at the new St. Jude Children's Research Hospital in Memphis, TN, by Donald Pinkel⁷ (There were other advocates of combination therapy besides Pinkel and Burchenal, such as Frei and Freireich at the National Cancer Institute, Bethesda, MD, and Holland at Roswell Park Cancer Institute, Buffalo, NY). Now, of course, the beast that killed Emily has been mostly chained: contemporary ALL therapy induces remissions in more than 90% of children, and the long-term cure rate is nearly as good.

The picture of Dr. Scoville in De Vries' novel is one of insensitive bluster, illustrated by a typical exchange between doctor and father:

Dr. Scoville: “Chemotherapy—drugs—is the scent we're on now, and it's only a few years ago we didn't have anything at all. It's quite a game of wits we're playing with this beast. The 6-MP, for example, breaks the cells up nutritionally by giving themselves counterfeit doses of the purine they like to gorge themselves on. I hope we'll have some other pranks to play on him soon, and if there are, you may be sure the clinic downstairs will be the first to try them out. There's nothing hot at the moment, but who knows? It's an exciting chase, though I can't expect you to look at it that way at the moment.”

Don Wanderhope: “Do you believe in God as well as play at him?”

Dr. Scoville: “Between my work at the clinic and tearing around to every other hospital in the country, I sometimes go for weeks without seeing my own children. I have no time to think about such matters…I think we'd better run another bone marrow. As you probably know, that's where blood is manufactured and where the villain's headquarters are.”⁴

Likewise, in the unpublished reflections of Emily's mother:

I have had her for nine years, this pretty, gentle little daughter, and I know all about her. I also know that when her father and I took her to the specialist last year and he spoke of her as one of ‘these dying children’, I wanted to kill him. (Loeser K: Who cried in goose, alas—Notes on the death of a child. Unpublished manuscript).

But this is not the Joe Burchenal fondly remembered by his trainees and former colleagues, who describe him not as a man of hubris or insensitivity, but of thoughtfulness and humility—always ready to listen, and keen to learn right up to his death.^15,16,22 Burchenal himself was no stranger to sorrow, having lost his first wife in 1943, and his stepmother to osteosarcoma while he was a college student.

The Blood of the Lamb indicates that Emily's parents were not alone at the hospital in their anger and grief. In addition to a scene in which the novelist intervenes when a frustrated father attacks a physician, De Vries describes a pessimistic father of another child with leukemia—a man he calls Stein” who is full of fatalistic apothegms:

“They'll never get it, cancer. They'll never conquer it. Do you see what it is, that sluggishly multiplying anarchy? A souvenir from the primordial ooze. The original Chaos, without form and void.”⁴

For contemporary patients with cancer, it is a relief that Stein's poetic cry of despair has proven, at least in part, untrue. Eradication of cancer-related mortality remains a distant dream, but after 50 years of work following the model of Burchenal and other early investigators, many individual neoplasms are now curable. As Burchenal himself once stated when asked after his retirement whether cancer could ever be defeated, “I'm the wrong man to ask…I've always thought something could be found.”²²

Peter De Vries' 1961 tragic novel The Blood of the Lamb is a moving account of one family's experience of childhood leukemia during a transitional period in that cancer's treatment. While it may be critical or unfair to one treatment pioneer, the book retains much of its power a half century after its debut.

The author(s) indicated no potential conflicts of interest.