Part II

This week, we continue our discussion of the concept of cancer as being a disease of the cell. We have described several instances in which cancer cells have been passed from one individual to another inadvertently and a new tumor developed. This is a unique property of cancer, in contrast to other diseases.

Perhaps the best known studies of cancer cell transmission in humans come from the work of Chester Southam, a medical oncologist and early immunologist who, at the time he did this work, was at Memorial Sloan-Kettering Cancer Center. Southam was born in 1919 and did his undergraduate degree at the University of Idaho before earning his MD at Columbia’s College of Physicians and Surgeons in 1947. He did his medical internship at Columbia Presbyterian Medical Center before moving on to Memorial Hospital, where he did his training in oncology and then remained on staff.

In the early 1950s, Southam initiated a series of studies that involved the injection of live tumor cells into patients with cancer at Memorial. The sites of injection were generally well demarcated and observed and were in patients thought to be terminal. In most instances, tumor nodules would arise at the sites of injection, which would be excised and studied to see if they corresponded to the same tumor that was injected. Patients were not told of the purpose of the injection or of what was injected into them—they were told it was an immunological test of some sort.

Southam then wanted to test whether this would occur in healthy individuals as well. So he went to the Ohio State Penitentiary and asked for volunteers. I believe that something like 100 volunteers or more were injected but again were not informed of the exact nature of the experiments. In this case, most of the injections did not result in tumors and Southam surmised that he was witnessing some form of an immune response.

In 1963 he arranged to inject elderly patients at the Jewish Chronic Disease Hospital in Brooklyn, a large facility serving the needs of primarily geriatric patients with chronic diseases (cancer, arthritis, neurologic disorders), now part of Kingsbrook Medical Center and Brookdale. The plan was again to inject these patients without their knowledge or consent.

Four resident doctors were instructed by the hospital’s director to administer the injections. One resident doctor complied, but three Jewish doctors (Avir Kagan, David Leichter, Perry Fersko) refused to participate, citing the experiments of the Nazis and the then already extant Nuremberg Code, an early guide to rules for the proper conduct of human experimentation, although it was not yet widely known and had not yet achieved the rule of law.

Nonetheless, 22 patients ended up getting injected. These three doctors resigned and sent their letter of resignation to the press as well as to the New York State Board of Regents. [I have been unable to find out what became of these three ethical heroes, so if any readers can let me know what their fates were professionally and otherwise at [email protected], I will pass it on to our readers in a future article.]

The hospital director and Southam both had their medical licenses suspended for one year. Despite the fact that this scandal became one of the most widely known ethical scandals in medical history, along with Tuskegee, it had little long-term impact on Southam’s career. He was subsequently elected as president of the American Association of Cancer Research, which remains until today the leading cancer research association in the U.S., and he also became a vice president of the American Cancer Society.

It is of note that the cancer cells that Southam used in his experiments were HeLa cells, which themselves have an ethical cloud over their heads. (See the book and movie “The Immortal Life of Henrietta Lacks.”) But what was learned was that tumor cells could transfer from one human to another, and the immune system could resist them.

We have now discussed the concept that cancer is a disease of the cell for two articles. What is its real significance? To answer that, we need to consider how information is carried in the cell.

The answer is the genome. The fact that a single cell can carry all the information necessary to create a tumor emphasizes the importance of the genome as a central element in the manifestation of malignancy by a tumor. The gene itself, the epigenetics, how the genes are translated ultimately to proteins, how all of that interacts and integrates with the environment is central to the pathophysiology of cancer. Until Watson and Crick and the innumerable discoveries that resulted from their work, this part of cancer was a closed book. And more than any other disease, with the possible exception of actual genetic disorders, molecular genetics is at the core of understanding the cancer phenotype (mak-eup) and much of its etiology, natural history, treatment and outcomes.

We will pursue this topic in our next episode of Thoughts on Cancer.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.