1870: Bert's experiments advance respiratory wisdom

Paul Bert (1833-1886)

"It can be said of Paul Bert as it has been of Vesalius, Harvey and Boyle, that the full significance of his work could not be fully appreciated until long after his death." (8, page v)

This was a quote from John F. Fulton, who wrote the forward to the 1843 edition of Bert's book "Barometric Pressure."

Bert's experiments would have a broad and lasting impact on surgery, aviation, mountain climbing, deep sea excursions, mining, pressure breathing machines, and even the definition of asthma.

He was born in Auxerre, France, on October 17, 1833, attended school in Paris, and received his medical degree in 1863. (2)(8, page V)

Fulton said that while in Paris he was assistant to Dr. Claude Bernard in his laboratory.  Fulton said "Bernard recognized his ingenious mind and predicted a brilliant future." (8, page VI)

Denis Jourdanet (1815-1892)

His thesis on grafting of animal tissue gained him public acclaim, and this helped him to quickly earn fame in the medical community. (2)(8, page VI)

Animal grafting, and later skin grafting, was "an operation consisting of the removal of a living part and transplanting it so that it shall continue to live on another part of the same individual or on another individual," said the authors of an 1888 biography of Dr. Bert in Popular Science Monthly.(2)(8, page V)

In 1865, the Academy of Sciences awarded him a prize in experimental physiology for his work on animal grafting and skin grafting.  This work was significant because it allowed physicians to perform plastic surgery on soldiers injured during the war of 1870.  (2)(5, page ?)(8, page V-VI)

In 1867 he was appointed to a chair in the Faculty of Sciences at Bordeaux where he taught zoology.  Then he became Bernard's successor in December of 1869 when he was named Professor of Physiology at the Faculty of Sciences in Paris. (2)(8, page VI)(13, page 599)

In 1870 Bert became interested in respiratory disorders, such as asthma, chronic bronchitis, and emphysema.  He performed experiments to learn more about these diseases, and to find methods of helping people with these diseases.   (1, page 194)(8, page VII)

In 1854 Alton Wintrich performed experiments that seemed to disprove the spasmotic theory of asthma in favor of the diaphragmatic theory of asthma.  For 16 years Wintrich gained many followers.  But Bert aimed to prove him wrong.

In 1870 he attempted, with improved methods of scientific research compared to that used by Williams and Longet, to stimulate the vagi of dogs.  As he expected, this indeed produced dyspnea.  His experiment reaffirmed for the medical community the spasmotic theory of asthma.   (10, page 10)(11, page 37)(12, pages 5-6)(13, page 16)(14, page 599)

According to W.H. Geddings in 1885, along with demonstrating that respiration could be "arrested by irritation of the pneumogastri (vagi)," it could also be arrested by irritation of the "laryngeal nerves or the Schneiderian membrane of the nose (membrane lining the maxillary sinus cavity)." (1, page 194)

In 1855, Ludwig Traube came to a similar conclusion.

Bert's experiment was important because it prevented physicians from spending what minimal time and money was dedicated to asthma form being wasted on areas that were already disproved.

Around this time, said Fulton, a friend of his, Dr. Denis Jourdanet, had just returned from an excursion to Mexico where he had spent time in the mountains at great heights and suffered mountain sickness.  The two decided that Bert should dedicate his time performing experiments on the effects of pressure on plants, animals and humans. Jourdanet was a wealthy man, and he offered to provide any funds that Bert needed. (8, page VII)

Bert's first experiment was performed on April 15, 1874.  He sent three balloon enthusiasts and equipment in a hot air balloon called Zenith.  The mission was to collect data from the the upper atmosphere.  Another goal, however, was to exceed 24,000 feet, which was the height accomplished by an English balloonist named Glaisher in 1862.

At 26,000 feet all of the men were unconscious.  Upon the Zenith's return to the earth, two of the men had perished, and the third was insensible.  Bert hypothesized the reason was due to lack of oxygen to the brain (2)(5, page 112)(8, page VII)

This was a set back for Bert in which none of the equipment, and obviously none of the men, were able to function at that height due to cold and rarified (negative pressure, suction) air.  Most of the equipment was also damaged in the efforts made to get the balloon back down to earth, so no data could have been obtained anyway.  (2)(5, page 112)(8, page VII)

While this was a set back, it did not keep him from marching forward.  Instead of using humans to perform his studies from here on out, he did them in his laboratory using small animals.  Only when perfected his experiments did he resort to using humans.  (2)(5, page 112)(8, page VII)

The first order of business for Bert was to invent a device for measuring pressure and put together compression chambers.  He used a smaller compression chamber for small animals, and a larger one for himself and his friends.  (see figures)(2)(8, page VI)

In a laboratory experiment Bert placed a sparrow in the compression chamber made of pneumatic glass bells and exposed it to low pressures.  When it started to suffer he administered oxygen, at which point the bird "at once became himself again."  Upon this success, he performed the same experiment on himself, and he observed at higher pressures that his heart would beat faster and he'd have palpitations.  At one point he wanted to write in his tablet, but could not.  When he inhaled oxygen these symptoms went away. (7)

By these experiments he concluded that the lower the atmospheric pressure (as what would occur with high altitudes) results in oxygen tensions in the air and blood too low to support life. Instead of inhaling 21% oxygen which is present in normal room air, he was inhaling a lower percentage of oxygen.  (7)

High altitudes, or high atmospheric pressures, subject humans to the risk of suffocation or asphyxia. Early symptoms are increased heart rate,weakness, malaise, nausea, and vomiting. The colder the air the earlier these symptoms appear. For instance, the symptoms appear earlier in the Alps than in the Himalaya, Bert said. (7)

The remedy here would be "the respiration of an air sufficiently rich in oxygen to maintain the tension of that gas at its normal value." (2)

In another laboratory experiment Bert placed a sparrow in the compression chamber made of pneumatic glass bells and exposed it to high pressures (compression).  He then decompressed the bird rapidly to atmospheric pressure, at which time the bird suddenly died.  Upon inspection of the body he found air bubbles in the arteries and heart.  The same effect resulted during similar experiments performed with rats and small dogs. (5, page 115)

Robert Boyl had observed bubbles in the eyes of a snake he placed in a compression tank he invented, although no further investigations were made at that time into the nature or cause of the bubbles.  Bert, however, benefited from improved laboratory equipment.  (5, page 116)

Bert concluded that higher atmospheric pressures (as what would occur as one travels deeper under water) result in increased oxygen tensions in the air and blood.  The remedy here would be avoidance of too high a pressure (such as greater than 5-6 atmospheres), and gradual decompression back to atmospheric pressure (1 atmosphere). (2)

He observed that the effects of high pressures may kill not only humans and animals, but plants too.  (2)

While the significance of this work may not have been immediately known, the value of it was immediately recognized by the scientific community.  For this work the Academy of Sciences awarded him a prize of twenty thousand francs. (2)

His experiments would have an impact in many areas of science and medicine.

His conclusions about the effects of diminished pressure resulted in equipment, such as oxygen tanks and masks that made aviation possible.  For this reason, he is often referred to as the father of aviation medicine.

Improved methods of storing and delivering oxygen was also thought to benefit people with respiratory disorders, and so research was eventually done in this regard, some of it by Bert himself.

His conclusions about the effects of increased pressure resulted in better knowledge of decompression sickness or bends.

Bends occurs when a person moves from deep water (where the pressure is higher) to the surface (where the pressure is lower) too fast.  This causes bubbles to escape into the blood and tissues, and can cause symptoms such as headache, joint pain, nose bleeding, vertigo, shortness of breath, nausea, vomiting, and sometimes death.

This is a small compression chamber made of a pneumatic glass jar.
Bert was able to use it to expose a sparrow to low pressures.
He reduced the pressure using a manometric tube,
observing at what point the bird started to suffer.
He used the India rubber bag to administer oxygen to the bird,
and "at once the bird becomes himself again," he wrote.
He concluded that at high altitudes, where the pressure was low,
: "it appears it is not the lowering of mechanical pressure
that produces the symptoms, but the low tension of oxygen
of the dilated air, which low tension prevents the oxygen from
entering the blood in sufficient quantity." (7)

So Bert became interested in helping people with breathing difficulties during the early 1870s.  He said it was already known (such as by the works of Tavarie) that compressed air (higher pressure) helped people with anemia, chronic bronchitis, and emphysematous asthma. The result was easier breathing, and a lower heart rate. (7)(8 page VII)

Improved knowledge of the effects of high pressure on the human body resulted in Bert, and various other physicians, trying to invent machines that would adjust the pressure of inspired air to relieve the feeling of air hunger. Such machines would be experimented on patients of various lung disorders, including asthma.

In fact, in his 1877 article "Atmospheric pressure and life," Bert said:

The great influence that may be exerted upon living beings by atmospheric pressure is now questioned by none, and there is even a disposition to exaggerate its importance. If the barometric column rises or falls a few millimetres, nervous people affected with the asthma perceive phenomena, whether of a beneficial or of a noxious kind, which they do not hesitate to attribute to the weight or to the lightness of the atmosphere. But if this were the only cause of their sensations, then they should experience the same symptoms whenever they subject themselves to equal variations of pressure, as in passing from the level of the sea to a point only a few feet above it, or vice versa. (7)

In his 1878 book "Barometric Pressure," he published the results of his experiments on barometric pressure. He dedicated the book to his friend, and the man who funded the project, Dr. Jourdanet.

This is a compression chamber that allowed Bert to measure
the effects of barometric pressure on himself and others.
Inside was an Indian rubber bag so he could inhale oxygen.
Access points allowed him to take blood samples
to determine changes in blood oxygen tensions.
He exposed himself to decreased pressures.  Once he
started to feel symptoms he inhaled oxygen.  He wrote:
"But all these symptoms disappeared as by enchantment
so soon as I respired some of the oxygen in the bag;
returning, however, when I again breathed the air in
the cylinder."  (7) 

There would be many devices invented, and many failed experiments, over the next hundred years, before a truly effective, and mass producible, device would be invented to truly help patient's with respiratory disorders.  Yet it was Bert's work that got it all started.

He also performed work using anesthetics such as chloroform, and to administer it he devised an apparatus that allowed the patient to inhale an ideal percentage of the compound.   (2)(3, page 427)

Along with being a successful physician and scientist, he was also a successful politician.

As Bert was performing his experiments on pressure,
he started to wonder how the world was created.
In regards to animals dying due to compression, he wrote:
"Thus it is the oxygen that is to blame.  Oxygen at too high
a tension destroys animal life.  Long I hesitated to characterize
as a poison the 'nursing father' of everything that lives, but there
was no help for it.  Oxygen, which gives us life, slays also,
when administered in too strong a dose.  I have had to study
thoroughly this paradoxal poison to determine the different
effects of varying doses, and its action upon our tissues. (7)

So after Williams, Longet and Bert all performed experiments to prove the spasmotic theory of asthma, you probably thought the subject was settled.  Well, not quite. There still remained skeptics with credible arguments against it.

J.B. Berkart, in his 1878 book "On Asthma," explained that, during his work on asthma, Bert had a difficult time getting the air passages to contract until he realized that he had been over inflating the lungs.

Berkart said it was only when he provided less inflation that he was finally able to induce the air passages to...

"contract... upon electrical irritation, applied either directly to it or to the pneumogastric nerve.  But the contractions were so feeble and slow as to induce Bert to think that they had no active share in the mechanism of respiration.  Moreover, the paralysis of the bronchial muscles, following the section of the vagus, did not appear to influence in that least the function of nutrition of the lungs.  Thus the integrity of those muscles, not being indispensable to an efficient ventilation of the lungs, it seemed not unreasonable to conclude that their spasmodic contractions could hardly have the effect generally assigned to them."  (4, page 42-43)(9,page 5)

Berkart said that Bert's experiments did not initially demonstrate contraction of the lungs because he over inflated them.

Berkart believed that Bert's experiments demonstrated proof that the air passages may constrict as Williams proved, but this did not occur in asthma because most asthmatics also present with emphysema, which is essentially over inflation of the lungs.  (4, page 103)

Berkart's theory was respected among the medical community, although it did not have a long lasting influence.

In 1886 Bert was appointed governor-general of Tonquin, and soon thereafter his health started to fail.  On a return to France during the year he gave a farewell speech at a meeting of the Academy of sciences, supposedly because he knew he was ill. He died of dysentry on November, 11, 1886. (2)

References:

1. Geddings, W.H., author of the chapter on "Bronchial Asthma," in the book  "A System of Practical Medicine," edited by William Pepper and Louis Star,Volume 3, 1885, Philadelphia, Lea Brothers and Co.
2. "Sketch of Paul Bert," Popular Science Monthly," July, 1888, Volume 33, compliments of wikisource.org, http://en.wikisource.org/wiki/Popular_Science_Monthly/Volume_33/July_1888/Sketch_of_Paul_Bert, accessed 2/6/14
3. Waller, A., "Meeting of the society of Anaesthetists: Dosage in Anaesthetics," The Clinical Journal, April 6, 1898, pages 426-430, volume XI, October 27- April 20, 1898, Sixth Year, Edited by L. Eliot Creasy, 1898, London, The Medical Publishing Company
4. Berkart, J.B., "On Asthma: It's pathology and treatment," 1878, London, J. & A. Churchill
5. Phillips, John L., "The Bends," 1998, Yale University
6. Tissier,Paul Lewis Alexandre, edited by Solomon Solis Cohen, "Pneumotherapy: Including Aerotherapy and inhalation methods," volume X, 1903, Philadelphia, P. Blakiston's Sons and Co., pages 296-224.  If the profession of respiratory therapy existed in their era, we would be reading their books.  However, as it was, their books were written for the medical profession. All of the material from this post is from Tissier's book unless otherwise noted in the above paragraphs. Tissier page 72
7. Bert, Paul,  "Atmospheric pressure and life," Translated from the French by J. Fitzgerald, Popular Science Monthy, July, 1877, volume 11, http://en.wikisource.org/wiki/Popular_Science_Monthly/Volume_11/July_1877/Atmospheric_Pressure_and_Life, accessed 2/8/14
8. Fulton, John F., author of the Forward to Paul Bert's book "Barometric Pressure," 1843, Columbus, Ohio, The F. J. Heer Printing Company
9. Bert, Paul,  "Barometric Pressure," 1843, Columbus, Ohio, The F. J. Heer Printing Company
10. Dobell, Horace, "On Asthma: It's nature and treatment," 1886, London, Smith, Elder and Co
11. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company
12. Thorowgood, John Charles, "Notes on Asthma," 1878, 3rd edition, London, J and A Churchill
13. Thowowgood, John Charles, "The Lettsomian Lectures: delivered at the Medical Society of London, 1879, on bronchial asthma: it's causes, pathology and treatment," 1879, London, Bailliere, Tindall, and Cox
14. West, Samuel Hatch, "Diseases of the organs of respiration," volume II, 1902, London, Charles Griffin & Company, Limited 

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1841: Romberg verifies nervous theory of asthma

Moritz Heinrich Romberg (1795-1873)

By 1841 there seemed to be quite a bit of evidence in support of the nervous theory of asthma.  It was in this year that Dr. Moritz Heinrich Romberg verified this evidence, hence proving once and for all that asthma was definitely nervous, or so many supporters of the theory believed.

In the 17th century Jean Baptiste van Helmont and Thomas Willis came up with the idea that asthma was nervous.  In the 18th century William Cullen further supported this theory. Then, in the 19th century, the experiments of various physicians seemed to provide the evidence in support of the nervous theory of asthma.  (1, page 506)

In 1835 Francis Ramadge wrote papers, in 1836 Joseph Bergson and Amedee Lefevre wrote prize essays, all of which seemed to provide support for the nervous theory of asthma.  Based on this evidence, Romberg also supported this theory, and he did experiments to put an end to any arguments once and for all. (1, page 506)

J.B. Berkart, in his 1878 book "On Asthma," said Romberg described "two affections of the vagus... of which are productive of dysponeal attacks:

• Bronchial spasm:  He generally referred to this as "bronchial cramp" or spasmus bronchialis.  (2, page 28)(3, page 4) 
• Paralysis: This was essentially paralysis of the muscles of respiration, or emphysema (2, page 28)

There were also later studies that likewise verified the works of Romberg.  Alfred Wilhelm Volkman (1801-1877) and M. M. Valentin proved that irritation of the pneumogastric, or vagus, nerve causes contraction of the air tubes, or bronchioles. (4, pages 5-6

Orville Brown, in his 1917 book, described Volkman's experiment:

Volkmann tied a tube into the trachea of an animal and set a candle before the opening and then stimulated the vagus and the flame showed that air was thereby caused to come from the lungs. (2, page 33)

These results were verified again by Ludwig Traube, Paul Bert, and others.

These men confirmed that asthma was nervous, and this influenced the remedies used to treat it, often resulting in physicians prescribing such medicines that calmed the nerves and relaxed the mind in order to prevent and treat asthma. (4, pages 5-6)

The experiments of these men helped enshrine the image of asthma as nervous for greater than the next hundred years. 

References:

1. Whitaker, James Thomas, "The theory and practice of medicine," 1893, New York, William Wood and Company
2. Berkart, J.B., "On Asthma: It's Pathology and Treatment," 1878, London, J. & A. Churchill
3. Schmiegelow, Ernest, "Asthma, considered specially in relation to nasal disease," 1890, London, H. K. Lewis; he references the following source; Bergson, Das krampf. Asthma der Erwaohsenen, Nordhausen, 1850.
4. Thorowgood, John Charles, "Notes on Asthma: It's Nature, Forms, and Treatment," 1878, London, J. & A. Churchill

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1842: Longet's proves nervous theory of asthma

William Longett (1811-1871)

In 1808 Dr. Franz Reisseissen discovered muscular fibers wrap around the air passages in the lungs, and in 1840 Dr. Charles Williams proved these fibers spasm in the presence of certain stimuli.  Yet there remained one missing link necessary to prove the spasmotic and nervous theories of asthma.  The man up to the task was Dr. Francois Achille Longet of France. 

Longet did a variety of experiments on the anotomic nervous system, which is a system of nervous system that controls involuntary action, such as the beating of your heart, your rate of breathing, digestion, sexual arousal, dilation and contraction of the pupils, salivation, etc. In other words, it controls all the actions of the body that a person does not control (the brain controls them). 

In 1840 he must have heard of the experiments of Williams, so it was only a few years later, in 1842, that he aimed to see if he could find the missing link between the brain and the lungs to prove that the brain, or the nervous system, was responsible for asthma.  

Dr. J.B. Berkart, in his 1878 book "On Asthma," explains: 

Yet one link was wanted to complete the chain of evidence in favour of a bronchial spasm. As yet nothing was known of the innervation of the bronchi. Irritation (galvanization) of the vagus (pneumogastric) had produced no effect upon their calibres, and Dr. Williams was therefore led to conclude that "the muscular fibres seem not to be excitable through the nerves of the lungs".

Soon, however, Longet not only confirmed in the main the results obtained by Williams, but added that in his experiments irritation of the pneumogastric nerve always produced spasmodic contraction of the bronchi, whereas section of the nerve led to emphysema. Of the bronchial stricture he could satisfy himself by watching with a magnifying glass, but as to the occurrence of a similar process in the pulmonary tissue he had no means of judging. Still, he believed that such took place, although the presence of muscular fibres in the air-vesicles was then as doubtful as it is to-day. For, since section of the vagus causes emphysema, i.e., distension of the air vesicles, there must be muscular fibres which, if liable to paralysis, are liable also to spasm. (1, pages 26-27)

Now, just for the record here, the vagus nerve is a main nerve that runs down from the brain and supplies the heart, lungs and the various organs of the body. Longet proved irritation of this nerve would cause bronchospasm.

However, Berkart said that some of Longet's experiments, along with those of others, often led to incorrect speculations.  He said:

It cannot fail to be observed that those hasty applications of the results of the experiment to the pathology of asthma led here, as they always do, to unwarrantable conclusions. If, indeed, Longet were correct in this, that bronchial stricture and emphysema are due the one to a plus, the other to a minus state of irritability of the vagus, it would necessarily follow that, as asthma and emphysema are almost always associated, spasm and paralysis of the self-same muscles could co-exist at the same time, each independently of the other, manifesting itself in its own peculiar way. Such deduction necessarily follows from the premisses. (1, pages 28-29)

Regardless, while Williams proved irritation of the muscular fibers in the lungs may cause bronchospasm, Longet proved irritation of the vagus could cause bronchospasm. Thus, for the rest of the century various authors referred to the experiments of Williams and Longet as proving both the spasmotic and nervous theories of asthma.

The experiments of Williams and Longet were later verified by other physicians, including Moritz Heinrich Romberg, Alfred Wilhelm Volkman, Traube, Bernard, and Bert.  They all proved that irritation of the vagus caused "contractions of the air tubes."  (3, pages 5-6)

Based on this evidence, most authors on the subject of asthma believed in the nervous and spasmotic theories of asthma, citing Reisseissen, Williams, Longet and Volkman as promulgators of the evidence.

References:

1. Berkart, J.B., "On Asthma: It's Pathology and Treatment," 1878, London, J. & A. Churchill
2. Brown, Orville Harry, "Asthma, presenting an exposition of nonpassive expiration theory," 1917, St. Louis, C.V. Mosby Company
3. Thorowgood, John Charles, "Notes on Asthma: It's Nature, Forms, and Treatment," 1878, London, J. & A. Churchill

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