Ernest Starling's Revolutionary Physiology
The hidden chemical messengers that control your body were first revealed by a brilliant, determined English physiologist.
Imagine a world where we didn't understand how the heart automatically pumps harder during exercise, where the concept of chemical messengers in our blood was unknown, and where doctors had no scientific explanation for fluid balance in the body. This was the medical landscape before Ernest Henry Starling (1866-1927), a British physiologist whose groundbreaking discoveries fundamentally changed our understanding of the human body 1 2 .
Principles of fluid exchange across capillary walls
First hormone identified and the concept created
Law of the Heart explaining cardiac regulation
Starling, a professor at University College London, made at least four monumental contributions to physiology that remain cornerstones of medical science today: the principles of fluid balance across capillary walls, the discovery of the first hormone and the very concept of hormones, the "Law of the Heart" that explains how the heart regulates its output, and fundamental insights into kidney function 1 6 . His work transformed physiology from a qualitative description to a quantitative science and laid the foundation for modern endocrinology .
Starling's first major contribution came from his investigation into how fluids move between blood vessels and tissues. He demonstrated that the capillary wall acts as a semipermeable membrane, with hydrostatic pressure forcing fluid out into tissues and the osmotic pressure of plasma proteins pulling fluid back in 2 4 .
These opposing forces, now known as "Starling forces," explained the formation of lymph and tissue fluid and provided doctors with their first scientific understanding of edema (swelling) 1 6 . Before this discovery, physicians lacked the basic knowledge to understand what caused fluid accumulation in tissues, a common symptom in many medical conditions.
In 1902, Starling and his brother-in-law William Bayliss made a discovery that would create an entirely new field of biology 1 5 . They were investigating how the pancreas is triggered to release digestive juices when food enters the intestine. The prevailing theory, championed by Russian physiologist Ivan Pavlov, was that this was exclusively controlled by nerve signals 5 .
Their crucial experiment on January 16, 1902, demonstrated that a chemical substance released from the intestinal lining stimulated pancreatic secretion, even when all nervous connections were severed.
They took an anesthetized dog and isolated a segment of its small intestine, cutting all nervous connections to this segment while preserving its blood supply.
When they introduced acidic material (simulating stomach acid) into this denervated intestine, the pancreas still responded by secreting digestive juices.
Realizing this defied nervous explanation, Starling exclaimed, "Then it must be a chemical reflex!"
They quickly prepared an extract from the intestinal lining that had been exposed to acid and injected it into the dog's jugular vein.
The pancreas responded with even greater secretion than before.
They had discovered that a chemical substance, which they named secretin, was released from the intestinal lining into the bloodstream and traveled to the pancreas to stimulate secretion 5 .
In 1905, Starling needed a word to describe chemical messengers like secretin. After consulting with colleagues, including a Greek scholar, he proposed the term "hormone" from the Greek word hormon, meaning "to excite" or "to set in motion" 4 5 . He introduced this term during his Croonian Lectures at the Royal College of Physicians, stating:
"These chemical messengers, however, or 'hormones' as we might call them, have to be carried from the organ where they are produced to the organ which they affect by means of the blood stream" 4 .
This marked the beginning of endocrinology as a scientific discipline. The discovery was initially met with skepticism, particularly from Pavlov's school, but eventually the evidence became undeniable .
| Year | Researcher | Discovery | Significance |
|---|---|---|---|
| 1902 | Bayliss & Starling | Secretin | First identified hormone |
| 1905 | Starling | Term "hormone" | Created concept of endocrine system 4 |
| 1849 | Thomas Addison | Adrenal insufficiency | Early clinical description of endocrine disorder 4 |
| 1890s | George Oliver & Edward Sharpey-Schäfer | Vascular effects of adrenal extract | First demonstration of hormonal action in humans 4 |
| 1922 | Banting & Best | Insulin | Diabetes treatment building on hormone concept 5 |
Starling's third great contribution came from his work on cardiovascular function. Using an isolated heart-lung preparation from dogs, he demonstrated that the heart has an intrinsic ability to adjust its output based on the volume of blood returning to it 1 .
What we now know as the Frank-Starling Law of the Heart states that "the force of muscular contraction of the heart is directly proportional to the extent to which the muscle is stretched" during filling 2 3 .
In simpler terms, the more the heart fills with blood (within physiological limits), the more forcefully it contracts, automatically adjusting to pump out whatever blood comes back to it from the veins.
Starling himself used an analogy to explain this phenomenon: "It is as if we had a motor vehicle, which automatically opened the throttle as soon as the road began to go uphill" .
Relationship between ventricular filling and cardiac output
This self-regulating mechanism ensures that our circulation efficiently meets the body's changing demands, whether we're resting or exercising.
| Component | Function in Experiment |
|---|---|
| Isolated mammalian heart and lungs | Maintained functional relationship outside body |
| Artificial systemic circulation | Connection from aorta to right atrium replacing body circulation |
| Resistance regulation system | Allowed researchers to control hemodynamic resistance |
| Blood sampling capability | Enabled analysis of blood composition during experiments |
| Temperature control | Maintained appropriate physiological conditions |
Starling's groundbreaking discoveries were made possible through careful experimentation with various biological preparations and reagents. The table below highlights some essential materials from his research.
| Material/Preparation | Function in Research |
|---|---|
| Anesthetized dog model | Provided intact physiological system for studying integrated bodily functions |
| Heart-lung preparation | Isolated cardiopulmonary system to study heart function without confounding variables 1 |
| Duodenal mucosal extract | Source of secretin containing the first identified hormone 5 |
| Capillary pressure measurement | Quantified forces governing fluid exchange between blood and tissues 1 |
| Denervated intestinal loops | Isolated chemical signals from nervous control to prove hormone existence 5 |
Starling's career was not without controversy. He and Bayliss became embroiled in the "Brown Dog affair," a heated public debate about vivisection that culminated in a libel suit won by Bayliss 1 6 . Starling was also a passionate reformer of medical education, advocating for stronger science curriculum in medical training, and played a significant role in implementing rationing in Britain during World War I based on nutritional principles 1 .
Despite being nominated for a Nobel Prize, Starling never received the award, though many of his contemporaries and successors did for work building on his discoveries 1 .
Starling advocated for stronger science curriculum in medical training and helped reform medical education in Britain.
He died unexpectedly in 1927 while on a Caribbean cruise, but his legacy continues through the fundamental physiological principles that bear his name 1 3 .
Starling's work exemplifies how basic scientific research into seemingly obscure physiological mechanisms can transform medical practice. His discoveries provided the foundation for understanding fluid balance in illness, created the entire field of endocrinology, explained the heart's fundamental regulation, and advanced our knowledge of kidney function—all pillars of modern medicine. As his colleague Henry Dale noted, "it is impossible to think of physiology in the last thirty years without Starling as the central figure of inspiration" 1 .