Gut and Liver: how did we get to know them well

Food is essential for life. A popular view, till 17th century was that our body absorbs food, that is directly converted by Liver into blood. While this view was later refuted (as blood is formed inside our bones), yet food does provide all the essential and required ingredients. Better nutrition, indeed is better health, and more red blood cells in circulation. As food is central to life, many diseases as well as their cures were linked with foods and our ability to digest various edible substances. Thus our stomach and intestines (or gut) were indeed central to all health processes as well as emotional state.

Insights into Gut Anatomy

Andreas Vesalius (1514-1564) first provided an actual description of gastrointestinal system or gut. This scientific foundation of medicine led his disciples to describe other important gut structures, such as ileocolic valve (Caspar Bauhin, 1605), Pancreatic duct (Johann Georg Wirsung, 1635), Liver anatomy (Francis Glisson, 1654), Duodenal glands (Johann Conrad Peyer, 1677).

How does our gut function

Over the next century, scientists studied physiology of digestion. Lazzaro Spallanzani (1729-1799) a researcher at Padua (Italy) described gastric physiology in detail. His views were later endorsed and developed further by an American physician William Beaumont (1785-1853). They established that unlike other parts of the gut, stomach is acidic. Later Claude Bernard (1813-1878) described physiology of Liver and Pancreas.

Ivan P. Pavlov (1849-1936) established neural control over gut secretions. He established that gut innervation triggers secretion of various gastric juices, at the very beginning of swallowing. He received Nobel Price in 1904 for his work in experimental gastroenterology. This was the first Nobel Prize related to gut physiology.

A polish Pharmacologist Leon Popielski (1866-1920) reported that gastric acid secretion depends on Histamine. This 1916 discovery met its nemesis in form of Histamine blocking medications (such as Ranitidine) in 1976. Later British pharmacologist Sir James Whyte Black was awarded 1988 Nobel Prize for his work on histamine receptors and its blockage.

Advent of Endoscopy

In early 19th century Phillip Bozzini made first endoscopes. These had small tubes, and used candle light, good to see uterus, rectum and throat. He called these Lichtleiter (or light-guiding instrument). About six decades later, in 1868, a German physician Adolf Kussmaul got inspired by watching a sword swallower. He developed first rigid gastroscope, that could help see inside the stomach.

In 1932, Rudolph Schindler developed a first semi-rigid gastroscope, that used a series of optical lenses at its distal end. Twenty five tears later, in 1957 Basil Isaac Hirschowitz developed a flexible endoscope. This invention really changed how we diagnose and treat diseases of the gut. Over the years technology has grown to make this procedure better and more perfect. Today we can see many parts of the gut, take biopsies, and even treat some diseases through an endoscope.

Gastroenterology becomes a distinct specialty

First Liver biopsy was performed in 1868, but the procedure was tedious and considered to be risky. In 1958 Giorgio Menghini developed a simple, quick, and safe method of percutaneous needle liver biopsy. Soon thereafter, advances in ultrasonography changed the way we diagnosed conditions of liver, gall bladder, pancreas and peritoneal cavity. In early 1960s, angiography techniques could help us see vessels supplying the gut. By early 1970s endoscopic therapies, ERCP, and diagnostic angiography contributed to gastroenterology emerging as a distinct specialty.

Another parallel development was understanding of Gastric pathology. Peptic ulcerations of the stomach were common. These were partly managed by histamine receptor blockers, that were discovered in 1976. In the same year George Sachs identified proton pump, as central to acid production in the stomach. In early 1980s we had our first proton pump blockers. Today these medicines (such as pantoprazole) is most used medicine.

In 1979 J. Robin Warren a Pathologist from Australia discovered an organism Helicobacter pylori. In 1983, his colleague B J. Marshall identified its relationship with peptic ulcer disease. This landmark discovery led to H pylori eradication therapy for peptic ulcer disease. In 2005 Warren and Marshall were jointly awarded Nobel prize for this work.

Liver – inseparable from the gut

All the nutrients we eat, are absorbed from the gut. These nutrients pass through the portal veins, and are carried to the Liver. In turn, liver uses these nutrients to make more useful molecules. Liver is also a storehouse of energy, and actively discards any substances it does not need. Till the Middle Ages, liver was seat of soul, emotions, feelings, desires, sexuality, and generator of blood (sanguification officina). Andreas Vesalius and Claude Bernard helped in our understanding of its Anatomy and Physiology.

Yet in the early 18th century, our understanding of diseases of Liver were scanty. Rudolf Virchow (1821-1902) coined the term Catarrhal Jaundice, for acute hepatitis. He suggested that jaundice is due to a disease of duodenum, rather than Liver.

In some long standing conditions of the liver, the organ becomes hard. Renne Laennec (1781-1826) linked it rightly to alcohol and coined the word Cirrhosis (skirros=hard; Kirrhos=yellow). William Osler (1849-1919) a physician coined the term Laennac’s cirrhosis in his honour. 

In 1913 Van-Den Berg identified that excess bilirubin in blood, that gives a yellow colour to the eyes. Other Blood tests for liver diseases (or what we know as liver function tests) were perfected only during 1950s. We developed first automated blood analyser in 1957. Meanwhile in UK in 1949, Sheila Sherlock (1918–2001) established a liver unit. This unit became an authority in Liver diseases, and remains a leader in new innovations till date.

Discovery of viral hepatitis

In 1965, Baruch Bloomberg chanced upon an unusual protein in a stored blood sample of an Australian aborigine. Bloomberg and his colleagues named it Australia antigen or Au. Initially they thought that Au is a protective antibody, and the same was also seen in blood samples from patients with Hemophilia, leukaemia (who recd blood transfusions), downs syndrome (who often lived in mental asylums), and also in many children in Willowbrook experiment.

In 1967, we knew that Australia antigen was indeed a particle from hepatitis B virus. This discovery was made on 28th July, which we observe as World Hepatitis day.

Today, hepatitis B infection is found in many people in Asia, Africa and Oceania. Yellow fever and small pox vaccinations, untested blood-units, unabated use of unsterile hypodermic needles, and intramuscular antibiotic campaigns – have all contributed to its spread. In 1969, Bloomberg and coworkers developed Hepatitis B vaccine. Bloomberg received 1976 Nobel Prize for these discoveries. Soon Hepatitis B had became a global concern

Blossoming of Gastroenterology

Gastroenterology is a newer science, with most cutting edge discoveries in the later half of 20th century. The growth of this specialty is also remarkable, driven by technology within the specialty as well as in radiology, pathology and virology. In a short span of about 75 years, we could expand our access to the gastrointestinal tract (endoscopy, biopsies, USG, CT scan), discover useful medications (H₂ receptor blockers, proton pump inhibitors, anti-inflammatory compounds), developed vaccine for hepatitis B (first vaccine to prevent a cancer), and perfected increasingly skilled abdominal surgery (laparoscopy and liver transplant). It is indeed a journey from a bud to a full blossom. Guts it is !!