Cancer Research

Cancer is the Latin word for crab. Karkinos, the Greek original, is the same animal. The constellation Cancer — the fourth zodiac sign — is the same word. Galen of Pergamon, around 150 CE, said tumors had swollen veins radiating from the body like a crab’s legs. The earliest physicians named the disease after what it looked like, because what it looked like was all they could see.

The whole technical vocabulary descends from physical appearance, not from cause. Tumor — Latin tumere, to swell. Oncology — Greek onkos, originally a burden, a heavy weight, the thing one carries. Metastasis — Greek for “a standing-after,” a transposition. Sarcoma — flesh-thing. Carcinoma — crab-thing. Leukemia, coined by Rudolf Virchow in 1845, named for what he saw at autopsy when the white blood cells outnumbered the red and reversed the color.

The two evaluative words are Latin. Malignant — badly born — male- + -gnāre. Benign — well born. The morality is embedded in the diagnosis. The most common word every cancer patient hears about their disease names how it was born, before any treatment has begun.

The Edwin Smith Surgical Papyrus is the oldest surviving medical text. The 4.7-meter scroll preserved at the New York Academy of Medicine dates to roughly 1600 BCE and copies an earlier text some scholars date to the Old Kingdom, around 3000 BCE. Edwin Smith bought it in Luxor in 1862. James Henry Breasted translated it in 1930. It contains forty-eight case descriptions of injuries and surgical conditions.

The scribe describes each case in the same format: a presentation, a diagnosis, a recommended intervention. Almost every case carries a prescription — splints for the fractures, manipulations for the dislocations, bandages and salves for the wounds, prayers and incantations where the surgical art runs out. One condition does not. Case 45 describes “bulging tumors on the breast” — large, hard, cool to the touch, no inflammation. The recommendation is a single line:

“There is no treatment.”

It is the only condition in the entire papyrus that the author marks as untreatable. Of forty-eight cases, the scribe is willing to try something on forty-seven. On cancer, he resigns.

On the evening of December 2, 1943, the German Luftwaffe attacked the Allied harbor at Bari, Italy. The raid sank or damaged seventeen of twenty-eight ships in port — the largest single Allied cargo loss at sea in the war. One of the ships, the SS John Harvey, was secretly carrying two thousand M47A1 bombs, each loaded with sixty to seventy pounds of sulfur mustard. It was the Allied chemical-weapons stockpile, prepositioned in case the Germans broke their own restraint. The John Harvey exploded. Mustard dispersed into the water and the city.

Sailors swam through the contaminated harbor. Many had not been told what their ship carried. Civilians in Bari breathed the cloud. Hospital staff treated the casualties for ordinary war injuries. Stewart Alexander, an American medical officer dispatched from Algiers, traced the delayed-onset symptoms — eye and skin burns, then lethal collapse of bone marrow days later — to mustard exposure. He examined autopsy tissue and found massive lymphocyte depletion. He filed his report on December 11, 1943.

The report reached Cornelius “Dusty” Rhoads at Memorial Sloan-Kettering. It joined, in Rhoads’s thinking, a parallel program already running secretly at Yale. In December 1942 — twelve months before Bari — pharmacologists Louis Goodman and Alfred Gilman had given nitrogen mustard intravenously to a lymphoma patient at Yale-New Haven Hospital. The tumor regressed in forty-eight hours. The patient died weeks later. Wartime classification held the Yale result until 1946. Mustargen — mechlorethamine — became the first FDA-approved chemotherapeutic in 1949.

Sidney Farber (1903–1973) was a Boston Children’s Hospital pathologist — third of fourteen children of Polish Jewish immigrants — who by the late 1940s had committed an unusual move for his discipline. He had left the autopsy room to treat living patients. Childhood acute lymphoblastic leukemia was, in 1947, universally fatal within weeks to a few months. Children arrived; children died.

In November 1947 Farber began administering aminopterin — a folic-acid antagonist supplied by Yellapragada Subbarow at Lederle Laboratories — to sixteen children with ALL. The first patient, Robert Sandler, age two, started daily aminopterin on December 16, 1947. By spring of 1948 ten of the sixteen children had shown measurable clinical remissions: falling white-cell counts, retreating bone marrow infiltration, returning energy, restored appetite. The remissions lasted weeks to months. Every one of the children eventually relapsed and died. The principle had been demonstrated: a chemical could selectively kill cancer cells in a living human being. Farber published the result in the New England Journal of Medicine on June 3, 1948. The paper is the founding document of medical oncology.

Mary Lasker (1900–1994), New York advertising widow, joined the cause after her husband Albert died of colon cancer in 1952. She had what Farber did not: access, money, and political instinct. For the next two decades they ran what Lasker called the “Lasker syndicate” — a coalition of researchers, philanthropists, journalists, and senators that lobbied Congress year after year for federal cancer-research funding. Lasker personally lobbied every U.S. President from Truman through Carter. The Children’s Cancer Research Foundation in Boston — later the Dana-Farber Cancer Institute — was their joint creation.

President Nixon signed the National Cancer Act of 1971 into law on December 23, 1971. The American institutional architecture of cancer research has two parents: a Boston pathologist who had given folic-acid antagonists to dying children, and a Manhattan socialite who had decided after her husband’s funeral that the country needed a different relationship with cancer. Farber died of cardiac arrest in his Dana-Farber office on March 30, 1973. Lasker outlived him by twenty-one years.

Henrietta Lacks — born Loretta Pleasant in Roanoke, Virginia, on August 1, 1920, raised on a Clover tobacco farm, mother of five — arrived at Johns Hopkins Hospital in segregated Baltimore in January 1951 with vaginal bleeding. Diagnosis: cervical adenocarcinoma, driven (as would later be understood) by an integrated HPV-18 genome. She received radium treatments. She died on October 4, 1951, at age thirty-one.

A small sample of her tumor was taken without her knowledge — standard practice in 1951, and not in itself unusual. The tissue went to George Gey, who had been trying for years to establish a continuously dividing human cell line. Every previous sample had failed. Lacks’s cells divided. They kept dividing. Gey distributed them freely to other researchers, and HeLa — named for the first two letters of her first and last names — became the first immortal human cell line and the most-used cells in all of biology.

By the mid-2020s HeLa had been the subject of more than 110,000 scientific publications, and it now sits behind more than 17,000 patents. The cells were used in Jonas Salk’s polio vaccine trials in 1955, the first cloned human cell, in-vitro fertilization research, the identification of cancer-causing viruses, the early AIDS research, and the COVID-19 mRNA vaccines. If the cumulative biomass of every HeLa cell ever cultured were piled in one place, the figure quoted in Rebecca Skloot’s The Immortal Life of Henrietta Lacks is above fifty million metric tons. The cells now have seventy-six to eighty chromosomes (humans have forty-six), have diverged enough through seventy years of culture pressure that the evolutionary biologist Leigh Van Valen proposed in 1991 that HeLa should be classified as a new species, Helacyton gartleri.

The Lacks family did not learn of HeLa until 1975. They were not asked, not paid, not formally acknowledged for two decades. Lacks’s children worked menial jobs in Baltimore while their mother’s cells flew to space, became the basis of the polio vaccine, and seeded labs in every country with a biomedical research budget. The family began legal action against Thermo Fisher Scientific in 2020; the case settled in 2023 with undisclosed terms.

In 1910, a poultry farmer brought a Plymouth Rock hen with a large breast tumor to Peyton Rous, a thirty-year-old pathologist at the Rockefeller Institute. Rous removed the tumor, ground it up, passed the slurry through a filter fine enough to exclude bacteria, and injected the filtrate into other healthy chickens. They developed sarcomas. The 1911 paper in the Journal of Experimental Medicine reported the result with what would prove to be massive understatement: a cell-free filtrate could induce cancer in another animal. Rous had identified the first cancer-causing virus.

The medical establishment ignored it. The prevailing view held that cancer was a heritable cellular abnormality — viral causation seemed conceptually incompatible. The chicken result couldn’t be replicated in mammals. Rous shifted to other problems; he ran a major series of studies on liver physiology and helped develop the modern blood bank.

Then, in 1970, Howard Temin at Wisconsin and David Baltimore at MIT — working independently — discovered reverse transcriptase, the enzyme by which an RNA virus produces a DNA copy that integrates permanently into the host genome. Suddenly the Rous result was conceptually possible. The Nobel Committee awarded Peyton Rous the 1966 Nobel Prize in Physiology or Medicine — fifty-five years after his original paper, at age eighty-seven. It is the longest discovery-to-Nobel lag in the history of the Prize, and Rous remains the oldest Medicine laureate. He died sixteen months after the award.

The conceptual closure came in 1976. J. Michael Bishop and Harold Varmus at UCSF showed that v-src — the viral oncogene carried by Rous sarcoma virus — was not really a viral gene at all. It was a stolen mutated version of c-src, a normal cellular gene present in healthy vertebrates including humans. Their 1989 Nobel established that cancer is fundamentally a disease of normal cellular genes that have gone wrong. The chicken sarcoma virus had been carrying a hijacked growth-regulation gene the whole time. The 1910 poultry farmer had brought Peyton Rous a seventy-eight-year head start on human oncogene biology.

If cancer is the stochastic accumulation of mutations in dividing cells, then larger and longer-lived animals should have catastrophic cancer rates. A blue whale has roughly a thousand times as many cells as a human and lives at least as long. Naive multiplication suggests near-certain lifetime cancer. The Oxford epidemiologist Richard Peto noticed in 1977 that the prediction was empirically wrong. Whales and elephants do not have substantially more cancer than mice. Naked mole-rats, which live ten times longer than the rodents of their size class, almost never develop cancer at all. The finding is now called Peto’s paradox.

The resolution is in the gene count. Joshua Schiffman and colleagues at the University of Utah, with Carlo Maley at Arizona State, showed in JAMA in 2015 that African elephants carry twenty copies of TP53 — the master tumor-suppressor gene that triggers cell-cycle arrest or apoptosis in response to DNA damage. Humans have one. Asian elephants have approximately thirty copies. Some of the extras are “retrogenes” that were reverse-transcribed back into the genome over millions of years of evolution. Elephant cells are biased toward death when they detect damage, where a human cell might try to repair and survive.

Naked mole-rats took a different route. Vera Gorbunova and Andrei Seluanov at Rochester showed in Nature in 2013 that mole-rat cells produce abnormally high-molecular-weight hyaluronic acid that triggers contact inhibition at unusually low cell densities. The cells stop dividing before a tumor can form. Same problem; different solution.

Multicellularity arose roughly six hundred million years ago in the late Ediacaran. Every multicellular lineage that survived has had to evolve mechanisms to police defection by individual cells. The defense mechanisms are everywhere we look in animal genomes. We do not have cancer despite having complex genomes; we have complex genomes in part because cancer has been there the whole time.

In March 1960, Rachel Carson — marine biologist, science writer, federal employee of the U.S. Fish and Wildlife Service for fifteen years — discovered a cyst in her left breast. A radical mastectomy followed in April. By December the cancer had metastasized; the next two years she would be writing through radiation therapy. She told only her closest friends.

Silent Spring was published by Houghton Mifflin on September 27, 1962. The book named synthetic pesticides — DDT especially — as harm to wildlife, ecosystems, and human health, citing rising cancer rates as one of the consequences of unregulated agricultural chemistry. One chapter was titled “One in Every Four.” The title was a contemporary cancer-incidence figure. The woman writing the chapter was already in the one-in-every-four.

Carson kept her cancer private as a deliberate strategic choice. The chemical industry was preparing a substantial counter-campaign; she believed that if her diagnosis became public, the industry would portray Silent Spring as the emotional outburst of a dying woman, not the carefully sourced scientific argument she had spent six years building. She testified before President Kennedy’s Science Advisory Committee and the Senate Commerce Committee in 1963 wearing a wig — she had lost her hair to radiation — and on crutches, having concealed both her cancer and the bone metastases that had reached her spine. The Kennedy committee’s report largely vindicated her claims.

She died at her home in Silver Spring, Maryland, on April 14, 1964, age fifty-six. The Environmental Protection Agency banned DDT for domestic agricultural use on December 31, 1972 — ten years after the book, eight years after her death. The institutional architecture of American environmental regulation is downstream of one book by a woman who hid her cancer to keep the book credible.

A Latin word for crab, calqued from the Greek, used by Galen because he thought tumors had crab-leg veins. A 4,600-year-old scroll that resigns on Case 45. A harbor in southern Italy where two thousand mustard-gas bombs exploded on December 2, 1943, classified for decades, and where a medical officer dispatched from Algiers traced the symptoms back to the lymphocytes the gas had destroyed. A Yale program from twelve months earlier where a lymphoma patient had received nitrogen mustard intravenously and the tumor regressed in forty-eight hours. A Boston pathologist who, in November 1947, gave folic-acid antagonist to sixteen children with leukemia and watched ten of them briefly come back. A New York advertising widow who lost her husband to colon cancer in 1952 and turned the rest of her life into a lobby. A National Cancer Act signed on December 23, 1971. A thirty-one-year-old Black tobacco farmer who died at Johns Hopkins on October 4, 1951, and whose cells are still alive in laboratories on every continent. A poultry farmer who in 1910 brought Peyton Rous a Plymouth Rock hen with a tumor; the discovery that waited fifty-five years for its Nobel and another decade for its conceptual closure. Elephants with twenty copies of TP53. Six hundred million years of multicellular life that has had to police its own cells. A book published in September 1962 by a woman who had hidden the disease she was writing about. Two papers on the same disease seventy years apart, the first temporarily slowing it in ten children, the second the first FDA-approved gene therapy in history.

Every one of these names a moment in the longest continuous medical project. The disease has been there since multicellularity. The vocabulary describes what it looked like. The treatments have arrived as accidents the field learned to recognize: the chicken, the harbor, the dying woman’s cells, the elephant’s genome, the chromosome that took forty-one years to become a drug. The first written words about cancer were “there is no treatment.” The most recent are not. The work is the difference.