Pioneering Pathologist Kilmer McCully, Champion of Homocysteine Theory, Dies at 91
Kilmer S. McCully, a Harvard Medical School pathologist whose groundbreaking, yet initially dismissed, research linked homocysteine to heart disease, passed away on February 21 at his Winchester, Massachusetts, residence. He was 91.
His daughter, Martha McCully, confirmed the cause of death as metastatic prostate cancer. News of his passing was not widely disseminated at the time.
Challenging the Cholesterol Paradigm
Dr. McCully’s theory, which proposed that insufficient intake of specific B vitamins leads to elevated homocysteine levels, consequently fostering arterial plaque buildup, remains a subject of discussion. This concept directly challenged the prevailing cholesterol-centric model supported by the pharmaceutical industry.
While not dismissing the role of cholesterol, Dr. McCully contended that neglecting the importance of homocysteine was a critical oversight. This viewpoint was met with resistance at Harvard. Initially, his laboratory was relocated to a basement space, followed by his dismissal. Subsequently, he encountered years of difficulty securing employment.
Isolation and Vindication
“It was deeply traumatic,” he recounted to The New York Times’ medical correspondent Gina Kolata in 1995. “People doubted you. They considered you irrational.”
vCard.red is a free platform for creating a mobile-friendly digital business cards. You can easily create a vCard and generate a QR code for it, allowing others to scan and save your contact details instantly.
The platform allows you to display contact information, social media links, services, and products all in one shareable link. Optional features include appointment scheduling, WhatsApp-based storefronts, media galleries, and custom design options.
Dr. McCully, who saw himself as a medical investigator akin to Louis Pasteur, first encountered homocysteine in the late 1960s at a Boston medical conference. There, he learned about homocystinuria, a genetic condition characterized by high homocysteine levels in the urine of children with developmental challenges.
The Pivotal Case
During a presentation on homocystinuria involving a 9-year-old girl, physicians mentioned her uncle’s death from a stroke at the age of 8, also suffering from the same ailment. “How could an eight-year-old die from a condition typically associated with old age?” Dr. McCully reflected in “The Heart Revolution” (1999), co-authored with his daughter.
Early Research and Rejection
Upon examining the autopsy report and tissue specimens of the uncle, Dr. McCully was astonished to find hardened arteries devoid of cholesterol or fat in the plaque. Shortly after, he learned of a recently deceased infant with homocystinuria who also exhibited arterial hardening.
“I barely slept for two weeks,” he recalled.
In 1969, Dr. McCully published his findings on these cases in The American Journal of Pathology. The subsequent year, in the same publication, he detailed the effects of injecting rabbits with high doses of homocysteine. “The aortas of all 13 animals treated with homocysteine displayed moderate thickening,” he reported, “in contrast to the control group.”
Dr. McCully pursued further investigations, advocating for increased consumption of fruits and vegetables for individuals with low folic acid, vitamin B6, and vitamin B12 intake. He also proposed the development of blood tests to measure homocysteine levels.
However, the medical establishment responded with “stony silence,” Dr. McCully informed The Times. In 1979, the chair of his department at Harvard stated, “We don’t believe you have substantiated your theory.” Consequently, he resigned and remained unemployed until 1981, when a Veterans Affairs hospital in Providence, Rhode Island, appointed him as a pathologist.
“I sympathized with him, and I respected him,” commented J. David Spence, a professor emeritus at the University of Western Ontario specializing in homocysteine research. “He faced undue neglect. It was regrettable.”
Fortunes began to shift in the early 1990s. Large-scale, long-term studies on heart disease risks started to validate Dr. McCully’s initial insights, contradicting Harvard’s dismissal and basement relocation.
Confirmation and Legacy
Data from the ongoing Framingham Heart Study, initiated in 1948, indicated a correlation between elevated homocysteine levels and increased rates of hardened arteries affecting the brain. A separate study by the Harvard School of Public Health and Brigham and Women’s Hospital in Boston revealed that men with high homocysteine levels faced a threefold higher risk of heart attacks compared to those with lower levels.
“Ultimately, he was correct in identifying homocysteine as an indicator of elevated cardiovascular disease risk,” affirmed Meir Stampfer, a Harvard epidemiologist involved in the latter study. “He deserves recognition for formulating this theory and contributing to the evidence supporting it.”
Early Life and Influences
Born in Daykin, Nebraska, on December 23, 1933, Kilmer Serjus McCully was raised in Alexandria, Virginia, near Washington D.C. His father, Harold McCully, was a counseling psychology expert at the U.S. Department of Education. His mother, Lulu (Litwinenco) McCully, was a painter and piano instructor.
As a youth, Kilmer was captivated by “Microbe Hunters,” Paul de Kruif’s 1926 book profiling pioneering infectious disease researchers like Pasteur, Walter Reed, and Robert Koch. He decided early on to pursue a career in science.
Education and Career
He pursued studies in biochemistry, psychology, and chemistry at Harvard, attending classes with B.F. Skinner, and graduated in 1955. Known to friends as Kim, he earned his medical degree from Harvard in 1959. During his studies, he worked part-time as a babysitter for historian Arthur M. Schlesinger Jr. and served drinks at Schlesinger’s social gatherings.
Following an internship and postdoctoral fellowship at Massachusetts General Hospital, Dr. McCully joined Harvard Medical School’s pathology department in 1965.
He married Annina Jacobs in 1955; she passed away in 2023.
Besides his daughter Martha, he is survived by his son, Michael; two grandchildren; two great-grandchildren; and a sister, Marilyn Raeburn.
Media Recognition and Lingering Controversy
After the 1990s studies substantiated his hypothesis, Dr. McCully gained significant media attention.
The New York Times Magazine featured him in a 1997 article titled “The Fall and Rise of Kilmer McCully.” In 1999, he told Terry Gross, host of NPR’s “Fresh Air,” “It is immensely gratifying because this is what I aspired to achieve in my youth.”
Despite the validation, homocysteine remains a contentious topic within medicine.
Leading medical organizations have not advocated for routine homocysteine testing, citing inconclusive results from studies assessing whether reducing homocysteine levels diminishes cardiovascular events. (Stronger evidence suggests its benefit in stroke prevention.)
“It remains perplexing to me that this continues to be underappreciated,” remarked Dr. Spence. “Perhaps physicians were not fond of their biochemistry coursework.”
Regarding his time at Harvard, Dr. McCully’s family indicated he harbored no animosity towards the institution. At a 1999 medical school reunion, his classmates presented him with a silver platter.
A Lasting Tribute
The platter bore the inscription: “To Kim McCully, who discerned the truth before the rest of us, indeed before the entirety of medicine, and who remained steadfast.”