Tag Archives: Human Physiology

September 13, 1848 (a Wednesday)

Phineas Gage skull diagram 1868 (left) and skull (right).

Phineas Gage (1823-1860) is one of the earliest documented cases of severe brain injury. He is the index case of an individual who suffered major personality changes after brain trauma. As such, Gage is a legend in the annals of neurology, which is largely based on the study of brain-damaged patients.

On this date, 25-year-old Phineas Gage and his crew were working on the Rutland and Burlington Railroad near Cavendish, Vermont. Gage was preparing for an explosion by compacting a bore with explosive powder using a tamping iron. While he was doing this, a spark from the tamping iron ignited the powder, causing the iron to be propelled at high speed straight through his skull. It entered under the left cheek bone and exited through the top of the head, and was later recovered some 30 yards from the site of the accident.

Gage recovered almost entirely from his physical disabilities, except for loss of sight in one eye. It is surprising, of course, that Gage survived such a traumatic event at all, but more surprising is the fact that his personality was completely changed as a result of the accident. Gage’s doctor describes how “the equilibrium or balance, so to speak, between his intellectual faculty and animal propensities” had been destroyed. The changes became apparent as soon as the acute phase of brain injury subsided. He was now “fitful, irreverent, indulging at times in the grossest profanity which was not previously his custom, manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times perniciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned. . . .” .

These new personality traits contrasted sharply with the “temperate habits” and “considerable energy of character” Phineas Gage was known to have possessed before the accident. Previously, he had “a well balanced mind and was looked upon by those who knew him as a shrewd, small businessman, very energetic and persistent in executing all his plans of action.” So radical was the change in him that friends and acquaintances could hardly recognize the man. They noted sadly that he was “no longer Gage.”  In fact, he was so different that his employers had to let him go shortly after he returned to work. The problem was not lack of physical ability or skill – it was his new character.

References:

  • Damasio, Antonio R. Descartes Error: Emotion, Reason and the Human Brain, New York: Avon, 1994.

Location of the Mind Remains a Mystery

ResearchBlogging.orgWhere does the mind reside? It’s a question that has occupied the best brains for thousands of years, including the Buddha’s.

Recent advances in functional magnetic resonance neuroimaging, a technique that measures brain activity in the hope of finding correlations between mental functions and specific regions of the brain, have led to a wealth of studies that map particular functions onto regions. Self-awareness is defined as being aware of oneself, including one’s traits, feelings, and behaviors. Previous neuroimaging studies had suggested that self-awareness (SA), which is central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). This proposal predicts that damage to these regions should disrupt or even abolish SA — an afflicted individual should be like a zombie, according to David Rudrauf, a neurologist at the University of Iowa in Iowa City.

University of Iowa researchers studied the brain of a patient with damage to three regions long considered integral to self-awareness — left to right, the insular cortex, anterior cingulate cortex, and medial prefrontal cortex. Image credit: UI Department of Neurology.

So when Rudrauf and his team heard about patient R, they immediately thought he could help set the record straight. Patient R is a 57-year-old man whose brain was damaged in 1980 following a severe episode of herpes simplex encephalitis. His brain damage is bilateral, more extensive on the right, and encompasses the target regions mentioned above: the insular cortex, the ACC, and the mPFC. Rudrauf et al reasoned that if any of the structures that are damaged in this patient are indeed critical for the different aspects of SA implicated by the hypothesis described above — i.e., insula, ACC, mPFC — the patient should show clear disruptions of the corresponding functions. Conversely, if these structures are not critical, R should show largely preserved SA.

In fact, R displays a strong concept of selfhood. Rudrauf’s team confirmed this by checking whether he could recognize himself in photographs and by performing the tickle test — based on the observation that you can’t tickle yourself. They concluded that many aspects of R‘s self-awareness remained unaffected. “Having interacted with him it was clear from the get go that there was no way that [the theories based on neuroimaging] could be true,” says Rudrauf. R also has an IQ within the normal range, although he does have severe amnesia, which prevents him from learning new information, and he struggles with social interaction.

The UI researchers estimate that R has ten percent of tissue remaining in his insula and one percent of tissue remaining in his anterior cingulate cortex. Some had seized upon the presence of tissue to question whether those regions were in fact being used for self-awareness. But neuroimaging results presented in the current study reveal that R’s remaining tissue is highly abnormal and largely disconnected from the rest of the brain.

The authors of the report conclude that:

R is a conscious, self-aware, and sentient human being despite the widespread destruction of cortical regions purported to play a critical role in SA, namely the insula, anterior cingulate cortex, and medial prefrontal cortex.

“Self-awareness corresponds to a brain process that cannot be localized to a single region of the brain,” says Rudrauf. “In all likelihood, self-awareness emerges from much more distributed interactions among networks of brain regions.”

Patient R demonstrates that the mind remains as elusive as ever.

References:

  • Philippi CL, Feinstein JS, Khalsa SS, Damasio A, Tranel D, & et al. (2012). Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices Plos ONE, 7 (8) DOI: 10.1371/journal.pone.0038413

July 27, 1921 (a Wednesday)

On this date at the University of Toronto, Canadian scientists Frederick Banting and Charles Best successfully isolated insulin from canine test subjects — a hormone they believed could prevent diabetes — for the first time. On November 14, following successful trials on diabetic dogs, the discovery was announced to the world.

At that time, the only way to treat the fatal disease was through a diet low in carbohydrates and sugar and high in fat and protein. Instead of dying shortly after diagnosis, this diet allowed diabetics to live — for about a year.

On 11 January 1922, Banting and Best gave 14-year-old Leonard Thompson an injection of a reasonably pure extract of insulin from the pancreases of cattle from slaughterhouses. His blood sugar levels dropped significantly, but an abscess developed at the injection site making him acutely ill. A refined extract was again administered on 23 January, causing a drop in blood sugar levels from 520 mg/dl to 120 mg/dl within 24 hours. Leonard lived for 13 years, taking doses of insulin, before dying of pneumonia (another disease for which no cure was available in those days).

Within a year of isolating the hormone, the first human sufferers of diabetes were receiving insulin treatments, and eventually countless lives were saved from what was previously regarded as a fatal disease. By early 1923, insulin had become widely available, and Banting and Macleod were awarded the Nobel Prize in Physiology or Medicine for that year.

References:

June 6, 1822 (a Thursday)

Alexis St. Martin with his wife in his later years.

Alexis St. Martin with his wife in his later years.

On this date, Alexis St. Martin was working at a fur-trading post in Mackinac Island in Lake Huron when he was accidentally shot with a gun at close range. The charge of the gunshot blew a fist-sized hole through his side and into his stomach. The following account from Gurdon S. Hubbard is the only eyewitness description of the incident.

This St. Martin was at the time one of the American Fur Company’s engages, who, with quite a number of others, was in the store. One of the party was holding a shotgun (not a musket) which was accidentally discharged, the whole charge entered St. Martins body. The muzzle was not over three feet from him — I think not over two. The wadding entered, was well as pieces of his clothing; his shirt took fire; he fell, as we supposed, dead.

William Beaumont, a US Army surgeon stationed at a nearby army post, treated the wound. Although St. Martin was a healthy 28-year-old [1], he was not expected to recover due to the severity of his wound. Nevertheless, he did so under Beaumont’s care, and when the wound healed itself, the edge of the hole in the stomach had attached itself to the edge of the hole in the skin, creating a permanent gastric fistula. The strong stomach acid essentially disinfected the wound from the inside out, making it safe to not sew it up.

The trading post where St. Martin was shot still stands today in Michigan.

The trading post where St. Martin was shot still stands today in Michigan.

Beaumont recognized the wonderful opportunity he had in St. Martin to investigate the mysterious process of digestion. For centuries, the stomach was thought to produce heat that somehow cooked foods. Alternatively, the stomach was imagined to be like a mill, a fermenting vat, or a stew pan. Beaumont performed two kinds of experiments on the digestive processes from 1825 to 1833. First, he observed the fluids discharged by the stomach when different foods were eaten (in vivo). Second, he extracted samples of the stomach’s content and put them into glass tubes to determine the time required for “external” digestion (in vitro).

Expressing his dislike for his role, St. Martin periodically disappeared. In 1832, to secure his experimental subject, Beaumont signed St. Martin to a 1-year contract. Per the contract, St. Martin was to “obey, suffer and comply with all reasonable and proper orders or experiments” for $150 and room, board, and clothing. In 1833, St. Martin went home to Canada, never to return to Beaumont’s care. The difference in social status and wealth makes Beaumont’s use of St. Martin ethically questionable.

Beaumont published the first results of his experiments on St. Martin in the Philadelphia Medical Recorder for January 1825, and full details in 1838 as Experiments and Observations on the Gastric Juice, and the Physiology of Digestion. He ended his treatise with a list of fifty-one inferences based on his 238 separate experiments. Although working away from the centers of medicine, Beaumont used findings from Spallanzini, Carminiti, Viridet, Vauquelin, Tiedemann and Gmelin, Leuret and Lassaigne, Montegre, and Prout. Even with their information, he still obeyed the scientific method, basing all his inferences on direct experimentation.

Beaumont proved once and for all that digestion in the stomach was chemical — a product (mostly) of the gastric juice itself which Beaumont surmised, correctly, was composed largely of hydrochloric acid. Beaumont’s important experiments quickly reached an international audience. In the United States, Dunglison’s 1844 second edition of Human Health included a 3-page appendix of Beaumont’s “…time required for the stomachal digestion of different alimentary substances,” and Cutter’s popular Anatomy and Physiology Designed for Academies and Families (1848) included Beaumont’s results for the mean times for digesting foods. In France, Claude Bernard cited Beaumont’s work in his 1865 Introduction to the Study of Experimental Medicine.

Beaumont’s accomplishment is even more remarkable because the United States, unlike England, France, and Germany, provided no research facilities for experimental medicine. Beaumont, a “backwoods physiologist,” inspired future studies of gastric emptying, intestinal absorption, electrolyte balance, rehydration, and nutritional supplementation with so-called sports drinks.

[1] For some reason, St. Martin’s age at the time was given by Beaumont as 18 years, and the error was not corrected until the Canadian Physiological Society marked his grave in 1962. Often referring to his patient as a “lad,” the doctor was actually just nine years his senior. It is possible that Alexis for some reason falsified his age throughout his dealings with Beaumont, or even that someone else stated the age and the wounded man was never actually asked. On the other hand, others think that it was not an error. “I doubt that Beaumont, who showed himself to be a notoriously accurate observer, would not have noticed the difference between a youth of 18 and a grown man of 28,” said Sylvio Leblond, MD. “I do not believe that Alexis had any reason to state that he was ten years younger than his correct age, and I feel certain that the thought would never have occurred to him…It is reasonable to conclude, then, that he was…18 or 19 in 1822.”

References:

April 1, 1578

William Harvey

On this date, the English physician and scientist William Harvey was born. He is credited with being the first in the Western world to describe correctly and in exact detail the systemic circulation and properties of blood being pumped around the body by the heart. Harvey published his discovery in a treatise entitled Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (On the Motion of the Heart and Blood in Animals) in 1628. Brief, well argued, and clearly written, De Motu Cordis is very probably the one and only great classic of Western science written before 1800 that is still widely read today. His discovery was dramatically confirmed later in the seventeenth century by microscopist Marcello Malpighi’s discovery of capillaries.

Functional knowledge of the heart and the circulation had remained almost at a standstill ever since the time of the Greco-Roman physician Galen – 1,400 years earlier. With Harvey, life began to receive mechanistic explanation. The essential idea of mechanistic explanation is that “natural” events have “natural” causes and can be explained by cause-and-effect relationships that do not involve special action of supernatural agency. This is fundamental to modern science.

Title page of *De Motu Cordis*

Just as important was Harvey’s methodology. De Motu Cordis quickly became understood as a rejection of traditional methods. It was viewed as challenging the traditional system of deductive reasoning via syllogisms, instead advocating experimentation and sensory experience. The empirical methodology observable in Harvey’s work is now the acknowledged scientific method and has been universally adopted across all science and medicine.

Harvey clearly understood the implications of his work, for he wrote at the opening of Chapter VIII (“Of the abundance of blood passing through the heart out of the veins into the arteries, and of the circular motion of the blood”), in which he demolishes the core of the Galenic model:

Thus far I have spoken of the passage of the blood from the veins into the arteries….But what remains to be said upon the quantity and source of the blood which thus passes, is of a character so novel and unheard-of that I not only fear injury to myself from the envy of a few, but I tremble lest I have mankind at large for my enemies, so much has wont and custom become second nature. Doctrine once sown strikes deep its root, and respect for antiquity influences all men. Still, the die is cast, and my trust is in my love of truth and the candor of cultivated minds.

He also left a message in De Motu Cordis that is as true today as it was 500 years ago:

True philosophers, who are only eager for truth and knowledge, never regard themselves as already so thoroughly informed, [so that they do not] welcome information from whomsoever and from wheresoever it may come; nor are they so narrow-minded as to imagine any of the arts or sciences transmitted to us by the ancients, in such a state of forwardness or completeness that nothing is left for the ingenuity or industry of others. On the contrary, very many maintain that all we know is still infinitely less than all that remains unknown. [Nor] do philosophers pin their faith to others’ precepts in such [ways] as they lose their liberty, and cease to give credence to the conclusions of their proper senses. Neither do they swear such fealty to their mistress Antiquity, that they openly, and in sight of all, deny and desert their friend, Truth. [emphasis added]

In Exercitationes de Generatione Animalium (On the Generation of Animals) in 1651, Harvey was extremely skeptical of spontaneous generation and proposed that every living animal originally comes from an egg, introducing the oft-quoted phrase “ex ova omnia” (all [life] from eggs). [However, Harvey did not completely reject spontaneous generation.] His experiments with chick embryos supported the theory of epigenesis, which states that organisms develop from substances in the egg that differentiate during embryonic development.  This was in conflict with the now-descredited preformationist view that perfect miniature versions of offspring exist in the gametes and grow during development.  [Please note that the term ‘epigenesis’ carries different meanings. Here, it used used in the older sense, as a theory of animal and plant development. In more modern times, it refers to mechanisms by which gene regulation over generations is controlled by elements other than DNA.]

References:

  • Schultz, S.G., “William Harvey and the circulation of the blood: The birth of a scientific revolution and modern physiology,” News in Physiological Sciences 17: 175-180 (Oct 2002).

January 20, 1862 (a Monday)

In medical knowledge, Egypt leaves the rest of the world behind.

The Odyssey, Book 4 by Homer

Zen stones

The Edwin Smith Papyrus

On this date, in the city of Luxor, Egypt, the American Egyptologist Edwin Smith made an important historical discovery when he bought an ancient papyrus from a dealer named Mustapha Aga. After Smith died in 1906, his daughter, Leonora Smith, gave the papyrus to The New York Historical Society. In 1920, James Henry Breasted, founder of the Oriental Institute of Chicago, was asked to translate the papyrus. Finally, in 1930, Dr. Breasted published the English translation for The New York Historical Society (University of Chicago Press). The papyrus now resides at The New York Academy of Medicine, where it has been since December 2, 1948.

The Edwin Smith Papyrus is the first known medical document dating from the 17th century B.C.E. However, it is thought to have been based on earlier documents, possibly by the 27th century B.C.E. medical writer and architect Imhotep, among others, since the papyrus appears to be a compilation of work based on the writing of multiple authors. This would make it the oldest of all known medical papyri. According to Breasted, the papyrus is a copy of an ancient composite manuscript which contained, in addition to the original author’s text, a commentary added a few hundred years later in the form of 69 explanatory notes (glosses). The treatise contains 48 systematically arranged case histories, beginning with injuries of the head and proceeding downward to the thorax and spine, where the document unfortunately breaks off. These cases are typical rather than individual, and each presentation of a case is divided into title, examination, diagnosis, and treatment. The treatment of these injuries is rational and chiefly surgical; there is resort to magic in only one case out of the 48 cases preserved. The Edwin Smith Papyrus is of special interest to the anatomist because it describes the sulci and gyri on the surface of the brain, the meninges (coverings of the brain), and the cerebrospinal fluid for the first time in recorded history.