Thread by @THilalMD

First described by Dr. Burkitt as a sarcoma, this lymphoma is notorious for being rapidly fatal without treatment. Here is the remarkable history of the discovery of Burkitt’s lymphoma and the men and women behind it. #lymsm

Denis Burkitt was born on February 28th, 1911 in Enniskillen (Northern Ireland). He grew up in a Presbyterian family, and his faith influenced him greatly. He went to Trinity College in Dublin, with a goal to follow in father’s footsteps as an engineer.

He soon realized that engineering was not his calling. During that first year, he joined an evangelical group in College and was inspired by his uncle, a missionary physician stationed in Kenya, to pursue a career in medicine. He excelled in medicine, graduating in 1935.

Despite losing his right eye as a child when a stone shattered his eyeglasses during a fight, he wanted to become a surgeon. He was able to start training and became a fellow of Edinburgh’s Royal College of Surgeons in 1938.

His other passion of becoming a missionary physician was difficult to attain. After multiple attempts to join the Colonial Services in West Africa, he succeeded in becoming an army physician in 1943 at the end of World War II. He was posted in Kenya, where his uncle was.

After the war, he was accepted for Colonial Service and moved to Uganda where he would make his first medical contribution. He observed a high incidence of hydroceles in the East compared to the West. His paper in 1951 suggested a causal relationship with parasitic infestation.

Burkitt then moved to Kampala, where he worked at Mulago Hospital (pictured is Mulago today).

In 1957, he was asked to examine a 5 year old boy with large tumors around his jaw and neck. The tumors had grew rapidly and the child died several days later.

He encountered a similar case with an abdominal mass. These cases stood out to him. “A curiosity can occur once, but two cases indicated more than a curiosity”

This curiosity led him to report on all the cases seen at Mulago Hospital in his first paper about the disease.

These “jaw tumors” were previously described by multiple European physicians who spent time in Africa, and many pathologists as far back as the 1930s. Most famous among them was perhaps Sir Albert Cook, a missionary physician who was the founder of Mulago Hospital.

The following year, O’Conor and Davies, pathologists working with Burkitt in Kampala, examined many cases of this “sarcoma” and classified it as a lymphoma. Like Burkitt, they suggested a local causative favor.

In 1961, Burkitt and O’Conor published a compilation on lymphoma in African children in @JournalCancer. He traveled and gave lectures about his findings that were met with very little enthusiasm.

During one of his lectures in England, a medical virologist named M. Anthony Epstein took an interest. The distribution of the lymphoma and it’s association with temperature meant there was a biological cause, and to him, that meant a virus was behind it! 🦠

Epstein asked Burkitt for a tissue sample. He searched for a virus for 2 years but could not isolate one. He recruited Yvonne Barr and Berg Achong to help him. Lymphoma cell lines were cultured and named E-B 1, 2, 3, etc. after Epstein and Barr.

In the meantime, interested in the geographic distribution of the disease, Burkitt and two associates, Ted Williams and Cliff Nelson, visited over 60 hospitals in East and Southern Africa and examined all cases of kids with jaw tumors.

They found a higher incidence of the disease in regions where malaria was prevalent (i.e. temperate and humid climates), suggesting a mosquito-borne etiology. The region with the highest prevalence would later be called the “lymphoma belt”

In 1964, viral particles were found. The virus resembled herpes, but was unique to Epstein. He sent a batch of cells to his colleagues Gertrude and Werner Henle.

The Henles, who were renowned virologist in Philadelphia, confirmed Epstein’s findings and later named the virus Epstein-Barr virus. They would go on to discover that EBV was the cause of infectious mononucleosis (i.e. Mono)

In 1971, molecular studies by George and Yanka Monlov at the University of Lund, Sweden identified the reciprocal translocation between chromosome 8 and 14 that led to activation of the MYC oncogene.

Burkitt had a role in bringing chemotherapy to Africa. In the late 1950s, Dr. Joseph Burchenal, an oncologist known for treating leukemia with 6-MP, developed a protocol of methotrexate and cyclophosphamide to treat Burkitt’s lymphoma. Children were cured for the first time.

Despite having his name attached to this unique lymphoma, Burkitt became better known later in his life as a proponent of diets rich in fiber. He observed that Africans rarely suffered from gallbladder disease, diabetes, obesity, or colorectal disorders.

Burkitt hypothesized that refined carbohydrates were the culprit for many diseases of the West, including colorectal cancers. He was zealous with his belief and launched a campaign to increase consumption of fruits of vegetables. He was later nicknamed “Fibre Man”.

Burkitt received an Honorary Fellowship by the Royal College of Physicians and Surgeons in Canada in 1992, one year before his death.

The College wrote about him:

“What made him famous is his remarkable ability to observe disease patterns, to identify peculiarities and to develop concepts and hypotheses. Like many surgeons, Dr. Burkitt is rarely in doubt, but unlike the rest of us, he is consistently correct”

References and additional reading:
- Volume 156, Issue 6 of British Journal of Hematology
- ncbi.nlm.nih.gov/m/pubmed/70222…
- ncbi.nlm.nih.gov/pmc/articles/P…

This thread feels incomplete without tagging @DavidSteensma, who inspired me to look at the people behind the pathology slide.

Tagging some lymphoma folks @CaThompsonMD @graham74GC @tobyeyre82 @LymphomaMD @timfenske @StefanoLuminari @JudithTrotman1 @JohnPLeonardMD