Fuller Albright and Parkinson’s Disease


fuller albrightFuller Albright discovered more new diseases and their causes than any other person in the history of medicine. He founded modern endocrinology, the study of how glands work in your body. In his lifetime, he mentored most of the chairmen of the departments of endocrinology in North American medical schools. He was one of the most brilliant and innovative doctors who ever lived. He was also an outstanding athlete who had captained his high school football team and was one of the better senior tennis players in New England, even though he spent most of his time in his lab at the Mass General Hospital.

In 1937, at age 37, he developed Parkinson’s disease, with symptoms that grew gradually but relentlessly worse. At age 56, after 20 years of progressive loss of his ability to control his muscles, he underwent an experimental, and subsequently abandoned, brain procedure that left him hospitalized in a coma for the rest of his life. During my residency at the Mass General Hospital in the early 1960s, I saw one of the most brilliant physicians of all time lying unconscious in his room. In 1969, he died after spending the last 13 years of his life in a hospital bed.

Early Life and Career
Albright was born in Buffalo, NY, on January 12, 1900. His father was John J. Albright, a wealthy industrialist. John Albright’s first wife had died in 1895, and he hired Susan Fuller, a recent Smith College graduate, to educate his three children. Two years later, John and Susan married and had five children together, including a son they named Fuller. Fuller went to the Nichols School in Buffalo, which was founded by his father, and then to Harvard College. He left Harvard after 18 months to enlist in the Army to fight in World War I. During the 1918 pandemic, he was infected with influenza, which can cause Parkinson’s disease many years later.

In 1921, he went to Harvard Medical School and finished at the top of his class. He took his internship and residency at the Massachusetts General Hospital. In 1928, he went to Vienna to study with Dr. Jacob Erdheim, the man who showed the world that the parathyroid gland controls calcium metabolism. In 1929, he returned to the Mass General Hospital and established the world-famous Ward 4, a 10-bed research unit where over the next 15 years, he described many new diseases and was one of the most loved and followed teachers at Harvard Medical School. His students remember this wonderful teacher always dressed in an old tweed jacket, baggy trousers, and a bright-colored bow tie.

He married Claire Birge in 1932, and they had two sons. One of the sons, Birge Albright, was a classmate of mine at Harvard (Class of 1957).

List of Firsts
Try to imagine how one person could make so many breakthroughs in our understanding of how the human body functions. Fuller Albright was the first person to:
• describe the functions of the parathyroid gland,
• associate an overactive parathyroid gland with kidney stones,
• explain the modern diagnosis and treatment of kidney stones,
• develop a method for measuring sex hormones in the urine,
• explain what causes women to have irregular periods or even stop menstruating,
• describe various male sex hormone deficiencies,
• show how certain types of diarrhea cause vitamin deficiencies,
• describe renal tubular acidosis and its treatment,
• show how menopause weakens bones,
• use estrogen to prevent a woman from releasing an egg, setting the stage for the first birth control pills,
• show that progesterone can prevent uterine cancer in women who lack that hormone,
• demonstrate the cause of overactive adrenal glands (Cushing’s syndrome),
• warn how dangerous adrenal steroids can be.

He was also the first to describe or characterize the following syndromes, tests and treatments:
• Forbes-Albright syndrome (breast milk and absence of periods caused by a brain tumor)
• Jaffe-Lichtenstein syndrome (painful, swollen deformity in one bone that fractures easily)
• Klinefelter’s syndrome (a genetic disorder that causes males to be tall and have small testes with low testosterone, delayed puberty, breast enlargement, reduced facial and body hair, and infertility)
• Lightwood-Albright syndrome (acidic blood caused by a kidney defect)
• Martin-Albright syndrome (inability to respond to the parathyroid hormone, short stature, short fingers, round face, and mental retardation)
• McCune-Albright syndrome (a genetic disease characterized by deformed, easily broken bones, premature sexual maturity, enlargement of the adrenal glands and the overproduction of cortisol)
• Morgagni-Turner-Albright syndrome (partial or complete absence of one X-chromosome, ovaries that fail to respond to pituitary hormones so they do not produce adequate estrogen, short stature, absence of secondary sexual characteristics, webbing of the neck and inconsistent heart problems)
• Ahumada-del Castillo syndrome (women with breast milk not associated with nursing and the absence of menstrual periods due to not releasing an egg each month)
• Albright’s anemia (anemia in advanced overactive parathyroidism)
• Albright’s prophecy (in 1945 Albright wrote that preventing ovulation prevents pregnancy and explored the possibility of birth control by hormone therapy)
• Albright’s syndrome II (Albright hereditary osteodystrophy in which a person has normal levels of parathyroid hormone, but cannot respond to that hormone)
• Albright’s test (a kidney function test to see how much acid kidneys can clear)
• Albright-Butler-Bloomberg disease (a metabolic syndrome marked by dwarfism and other severe developmental anomalies)
• Albright-Hadorn syndrome (softening and bending of bones associated with abnormally low concentrations of blood potassium levels)
• Chiari-Frommel syndrome (over-production of breast milk and absence of periods for more than six months after giving birth.)

Symptoms of Parkinson’s Disease
In 1937, at age 37, when he was one of the most productive, respected and well known physicians in the world, Albright noticed that his hands started to shake and would become even more shaky when he used them. For example, when he raised a glass of water to his mouth to drink, the shaking would increase as the glass came closer to his mouth. He noticed a progressive slurring of his words as he talked. This former athlete had to walk more slowly because the faster he walked, the more he would lose control of his legs and start to fall. These symptoms progressed very slowly over the next 20 years. He appeared to accept the challenges and did everything he could to overcome his increasing disability. He forced himself to work even harder and discovered many new syndromes and basic mechanisms of how hormones work during this period.

By his early forties, he could not write, and by his mid-forties, he could no longer speak clearly. In his fifties he could not drive a car, so the medical students assigned to him were given the family’s second car to drive him to and from the hospital. They also wrote notes for him at work. Many of these students became famous researchers themselves.

Parkinson’s Disease Experimental Treatment Disaster
In 1952, Irving Cooper, a New York University neurosurgeon, reported that he could reduce the symptoms of Parkinson’s disease by injecting small amounts of alcohol into a part of the brain called the globus pallidus. Because Albright knew that he was losing his ability to reason in addition to losing his ability to eat, dress, write or speak, he went ahead and had the treatment in June 1956. Virtually all of his Harvard colleagues and even Dr. Cooper himself had discouraged him from having the procedure done. After his right side was injected, he noticed less rigidity and better control. He was able to walk comfortably and use his left hand more effectively. He was so encouraged that he had his left side injected, but this procedure resulted in extensive bleeding into his brain. He never recovered and was unable ever to speak again. He spent the next 13 years in a coma, living in a private room at the Massachusetts General Hospital. In 1962, I was in residency training there and saw him, but he was unable to respond to me or anyone else. He died on December 8, 1969.

What is Parkinson’s Disease?
When you move a muscle, your brain sends electrical messages between nerves and muscle fibers. When an electrical message reaches the end of a nerve, it releases chemicals called neurotransmitters that travel to the next nerve or muscle fiber to continue the message. Your fine muscle movements are controlled by a chemical neurotransmitter called dopamine that sends messages by passing primarily between two brain areas called the substantia nigra and the corpus striatum.

Most of the movement-related symptoms of Parkinson’s disease are caused by a lack of dopamine due to loss of dopamine-producing cells in the substantia nigra. The lower the level of dopamine, the less control you have of your muscles.

We do not know the cause of the loss of dopamine-producing cells. A small percentage of Parkinson patients have other members of their family with the same disease. However, more than 90 percent of people with Parkinson’s disease do not have any family history of that disease, so most cases of Parkinson’s disease appear to be caused by something in the environment, not by a genetic condition. Risk factors for Parkinson’s disease include:
• Toxins: Exposure to manganese, carbon monoxide, cyanide and other chemicals (Curr Med Chem, 2018;25(19):2198-2214). Some pesticides and herbicides inhibit dopamine production. Farmers are at increased risk for Parkinson’s disease (Int J Environ Res Public Health, Sep 2016;13(9):881).
• Medications such as antipsychotics for treating severe paranoia and schizophrenia
• Synthetic heroin
• Declining estrogen levels: Post menopausal women and women who have had their ovaries removed are at increased risk.
• Viruses: For example, people who survived exposure to influenza in the 1918 flu pandemic were at increased risk for Parkinson’s disease many years later.
• Structural problems: Strokes and fluid buildup in the brain may increase risk of Parkinson’s disease.
• Low levels of folic acid: A few studies suggest that folic acid deficiency may cause some cases of Parkinson’s disease.
• Head trauma: Any damage to the head, neck, or upper spine increases risk. Boxer Muhammad Ali developed Parkinson’s disease in his forties (Neurology, May 15, 2018; 90 (20)).
• Lack of exercise (Clin Pract Epidemiol Ment Health, 2018; 14: 89–98).
• Advancing age: Parkinson’s disease affects one percent of people over 60 years of age. Risk increases with age.
• Gender: Men are more likely to suffer from Parkinson’s than women, possibly because they have greater exposure to other risk factors such as toxins or head trauma.
• Genetic factors: A Mayo-Clinic-led international study revealed that the gene alpha-synuclein may play a role in the likelihood of developing the disease. Studies showed that individuals with a more active gene had a 1.5 times greater risk of developing Parkinson’s. These findings support the development of alpha-synuclein suppressing therapies, which may in the long run slow or even halt the disease.

Parkinson’s Disease and Colon Bacteria
Researchers don’t know what causes Parkinson’s disease, but recent studies show that it may originate in the intestines and be affected by the types of bacteria that live in the colon (Parkinsonism & Related Disorders, June, 2016;27:1-8). If that is true, then all the factors that help to prevent inflammation may help to prevent this dreaded disease.

Fuller Albright
January 12, 1900-December 8, 1969