Hematology

 
The Latona Fountain in the gardens of Versailles

1. We will begin by revisiting a criminal investigation that took place in France in 1668. Jean-Baptiste Denis was the son of the chief hydraulics engineer to Louis the XIV, and was famous for creating an elaborate system of pumps that transported water from the Seine to the great fountains of Versailles. Rather than become an engineer himself, Jean-Baptiste decided to combine the family craft with the field of medicine. During his time as a lecturer in physics, mathematics, and medicine, he came across the work of William Harvey, and became fascinated with the possibility of blood transfusions. On June 15th 1667, he conducted the first ever animal to human transfusion using 13 ounces of lamb's blood and a series of goose quills as an I.V. line. His work made him a Parisian celebrity, but also earned him a fair number of enemies within the French Medical Academy. They were vehemently against the procedure and jealous of his position as personal physician to the king.

After a couple more "successful" trials, he performed his fourth animal-human transfusion on a madman named Antoine Mauroy, who died soon after the procedure. However, the case was wrought with suspicious behavior, especially from the man's wife who buried her husband herself to avoid the inevitable autopsy. At Denis' trial there was a witness who described Mauroy's death. Apparently he became very pale and started having seizures and may have shown evidence of GI irritation and discoloration of his nails (leukonychia striata). There was no jaundice, splenomegaly, hematuria, or fever. The judge was smart enough to know that these were the signs of overdose from a type of syphilis treatment common in those days. Denis was set free, and the wife was convicted of murder. Unfortunately the case left such a stain on Denis' reputation that he quit medicine, and the idea of transfusing blood disappeared for 150 years. Can you name the substance that killed Mauroy? What would be the cause of death from xenotransfusions?


A diagram of Denis' method

2. Most people know Pythagoras of Samos for his work on the triangle, but he was also one of the first documented polymaths. He was said to have studied medicine in Egypt, he wrote music, made extensive contributions to philosophy, and even started a kind of mystic mathematical cult called Pythagoreanism. In 529 BC he established a school near the southern Italian town of Crotone with a small group of his followers. They lived an aesthetic lifestyle, spent their free time practicing music and math, and ate an exclusively plant-based diet (interestingly, before the 1800s vegetarianism was known as The Pythagorean Diet). There was however a very strict rule against eating beans, which was likely the result of Pythagoras witnessing episodes of severe hemolytic anemia among some of his male followers. Today, the same area around Crotone is known to have the highest incidence of a certain Mediterranean genetic defect linked to this phenomenon. What is it? What is the genetic term we use to describe what happened with the Pythagoreans?


Pythagoreans celebrate sunrise by Fyodor Bronnikov


We've been here before. Pythagoras teaching music in Raphael's School of Athens

3. In 1932 two men excavated a temple in England from the 4th century AD. The temple was dedicated to the god Mars and it was written that any of his followers suffering from weakness could come drink from the temple waters and acquire some of the god's strength. Also of note was that the temple waters were frequently discolored on account of the high mineral content of the nearby soil. They even appeared red at times (hence the Mars-red connection). The two archeologists uncovered an interesting statue at the site, displaying one of the typical symptoms one might find among these weak followers. What did people come to the temple to treat? What is name of the symptom shown below?


Hand uncovered at Lydney, Gloucestershire

4. Now time for some political intrigue. In 1974 the Shah of Iran noticed a swollen lymph node in his neck, and was secretly treated by two French physicians for the next five years. He kept it a secret even from his wife until 1979, when he became severely ill at his villa in Mexico. He suddenly developed jaundice, nausea, chills, and a fever. Local doctors confused his symptoms with malaria, so an American doctor was brought in from Cornell to consult. Unfortunately he also made an incorrect diagnosis, thinking it was gallstones. But when the Shah began rapidly deteriorating his French doctors finally spoke up, and President Jimmy Carter made the very controversial decision to allow the Shah into the U.S. for treatment at Sloan-Kettering. In the hospital he received a full workup, and they discovered that he had a very unusual type of cancer characterized by an increased blood viscosity without lytic bone lesions, as well as other features typical of lymphoma. When news got out that the Shah was in the U.S. for treatment, the Ayatolla Khomeni became furious, and pro-revolutionary student groups began protesting outside of the U.S. embassy in Tehran. A quite well-known hostage crisis ensued, decades of political strife followed, and an overrated movie was made. What was the specific disease that set all of this off?


The Pahlavi Family

5. One of the greatest pianists of the 20th century is also one of the least well known. Dinu Lipatti was praised in his own lifetime by some of the most famous musicians of his age. Francis Poulenc called him "an artist of divine spirituality", and Herbert von Karajan described his playing as "no longer the sound of the piano, but music in its purest form." Though sadly, at the age of 29 he began suffering from a mysterious illness that started as a persistent fever and weight loss. After a number of incorrect diagnoses and random treatments, his doctors began administering x-ray therapy, which he said helped immensely. He also went through a trial of mustard gas injections, which caused swelling and disfigurement in his left arm. At 31 he began requiring weekly blood transfusions, and stopped chemotherapy after it destroyed one of his lungs. He remained positive and calm throughout, saying his swollen left arm gave "such formidable sonorities in the bass," and he continued touring, captivating audiences with "a different kind of expression." Based on his age and treatment, which disease was he suffering from?

 
Dinu Lipatti, Romanian classical pianist and composer (1917-1950)

In the midst of his final decline, and against the advice of his doctors, Lipatti decided to give one last recital in the French city of Besançon. Barely able to walk onstage, he gave a performance that has entered into legend, displaying an artistry that epitomized his musical purity. Towards the end of the concert, he found himself too weak to finish a series of Chopin waltzes, and ended with a simple Bach Chorale instead. The audience knew this was a final prayer from a man at the end of his life, and were moved to tears by the performance. Lipatti died ten weeks later at his home in Geneva, at the age of 33.

Listen to Dinu Lipatti's performance of J.S. Bach's Chorale, Jesu Joy of Man's Desiring:

ANSWERS (highlight to see):
1. Arsenic, autoimmune hemolytic anemia. Rumor has it members of the Paris Faculty of Medicine supplied the wife with arsenic in an attempt to frame Denis.
2. Glucose-6-phosphate dehydrogenase deficiency (G6PD), founder effect
3. Iron deficiency anemia, koilonychia. Mythology states that Iron was a gift from Mars to mankind.
4. Waldenstrom's macroglobulinemia
5. Hodgkin's Lymphoma