Penicillin and Oxygen

 

It is often said that the discovery of penicillin was the greatest advance made in the 20th century but it is little known that its commercial production depended on using high levels of oxygen.

Fleming's paper, describing the inhibition of the growth of Staphylococci by a mould, was discovered in 1941 by a group in Oxford led by Howard Florey. He collaborated with Ernst Chain and Norman Heatley to refine penicillin and the pure substance was tested on mice. Eight were inoculated with Streptocci and four were then given penicillin: they survived but the four control animals died.

British drug companies did not express interest and so Florey and Heatley left for the USA. A potent source of the mould was discovered and a nutrient substrate developed but yields on the flat mesh screens were minimal. Joseph Bombardino, a Pfizer chemist thought that if oxygen was bubbled through the corn syrup broth the yields may be increased - they were - and Pfizer set up a manufacturing facility in Brooklyn in time for penicillin to be made available for troops injured in the D day landings. So Pfizer, now the biggest drug company in the world began growing by using more oxygen.

The use of tubes to transport oxygen into the nutrient broth mirrors the development of the tubular network of blood vessels we use to convey oxygen to our three trillion cells.

But the story does not end there: Florey and his team would have been astonished to learn that oxygen is the antibiotic of the body. The very property of electron acceptance that allows oxygen to provide us energy from glucose is used by the white blood cells called neutrophils to form oxygen free radicals to kill microbes.

In 1965 a group in Glasgow found that hyperbaric oxygenation enhances this defence mechanism using mice inoculated with pneumococci. They did not know of the role of neutrophils and simply thought that molecular oxygen was toxic. By this time it had been recognised that the bacteria responsible for gas gangrene are anaerobic and hyperbaric oxygen treatment is life saving in this infection.

 

Review

Abstracts from the book review by Dr. Jane Orient M.D in the Journal of the American Association of Physicians and Surgeons, Summer 2017.

Physicians learn something about oxygen transport in physiology class and have been using oxygen with patients since the earliest days of their clinical rotations. They may think that they already know everything they need to know about this essential gas, but they would be wrong. This book challenges some of the basic dogma that most of us were taught during our residencies. It also offers the prospect of path-breaking advances in the treatment of otherwise hopeless conditions. Many of these possibilities were discovered decades ago and then forgotten.

A key purpose of the book is to promote hyperbaric oxygenation therapy (HBOT) as a treatment for conditions going beyond the well-accepted ones for decompression sickness and wound healing. One barrier is the insistence on randomized double-blind controlled trials (RCTs) for new indications. James argues that RCTs are not only inappropriate, but often actually unethical for HBOT. Oxygen is, after all, a necessity, not an “adjunct.”

The book is extensively and brilliantly illustrated. The many historical photographs include John Scott Haldane, whose work in the field was seminal, testing his breathing apparatus in a coal mine. Photomicrographs, gross pathology specimens, retinal photographs, and the latest in neuro-imaging studies (pre- and post-treatment) help make a convincing case for James’s unifying theory on the pathophysiology of many neurologic conditions.

James not only reviews the history and the science of HBOT but has been making history himself with his pioneering work. His disruptive ideas could make billions of dollars of research based on the wrong theories obsolete, posing a serious threat to lucrative drug therapies. In short, this book is revolutionary.


The medical use of oxygen in treatment has a long history and the comments below by Dr SM Birch about using oxygen treatment are just as relevant today as when they were written - in 1857.

Demanding evidence from "controlled trials" is the defensive position adopted by many medical practitioners and derives from the need to test drugs of unknown value. The value of oxygen is not open to question and evidence from just one patient is valid.

Science is about measurement and oxygen levels can be measured in our tissues. Lack of oxygen identified by the presence of lactic acid in tissues can be assessed in the brain by Magnetic Resonance Spectroscopy.

Evidence of a deficiency of oxygen? There is a duty of care to correct it - by increasing the concentration a patient is breathing above the level obtained from breathing air.

The term "hyperbaric oxygen" is grammatically incorrect and is taken by some to imply that the oxygen somehow differs from the oxygen in the air. It is just the same: Our cells cannot know where an oxygen molecule came from: the correct term is hyperbaric oxygenation.

The power of the body to heal is miraculous but only possible when critical substances are present, oxygen being the most important.

     

      

 

         ON THE THERAPEUTIC USE OF OXYGEN

                                               by S.B. Birch, M.D.

                                                   The Lancet

                                                 August 1, 1857

 

The therapeutic use of this gas, either alone or as an adjunct, in various intractable diseases, is a subject of vast importance. 

 

This gas, although so well known in its physiological relations, has been practically little better than a “secret” in its therapeutic bearings.

 

the patient needs plenty of pure air, more air  (in other words more oxygen)  than he can possibly obtain under many circumstances and in many diseased states from the atmosphere.

 

It would not be too difficult to show cause why the use of this remedy has been neglected. It involves some trouble and loss of time to the practitioner.

 

...... the very want of practical knowledge still existing may be justly attributed to the neglect to carry out fair trials on a sufficient scale in practice.

 

The profession has been led to overlook or ignore  oxygen as a medicine even though chemical science tells us decidedly that it ought to be a most valuable remedial agent

 

A single trial, or several trials on several patients, are no evidence, if they fail, against its value; they are only proof either that it was not suited to the case, or that it was not properly exhibited.