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An Interview with Professor Manuel Varela: Who Was Pierre Paul Emile Roux? And what do we owe to him?

Nov 26, 2018 by

Michael F. Shaughnessy –

1) Professor Varela- the word “diphtheria” sends waves of fear into physicians, nurses and obviously the general public. What exactly is diphtheria and how is it communicated or transmitted?

Diphtheria is a bacterially-caused infectious disease in humans. There are essentially two forms of the disease, a respiratory-based and a cutaneous-based version. Even though the work of Dr. Roux and others led to an effective diphtheria vaccine, the bacterial pathogen retains its presence within human populations, as the microbes are carried by individuals who do not exhibit the disease but may transmit it to unsuspecting people.

The diphtheria-causing microbe can be harbored in the throat or on the skin of asymptomatic human carriers. The human carrier may then cough, emitting droplets of phlegm containing the pathogen into the air, whereupon another individual person will breathe the microbe into their own respiratory tract. Once the pathogenic microbe acquires access to the throat of the patient, the diphtheria disease takes hold.

Alternatively, the human carrier may have a close contact with another individual, transmitting the microbe onto the skin of the new soon-to-bediphtheria patient. The newly transferred microbe will then grow on the skin of the recipient, perhaps gaining entry into the patient through a break in the skin and eliciting the disease.

Outbreaks of the diphtheria can occur worldwide. The ailment is especially found in areas where conditions of poverty, overcrowding, and lack of adequate vaccinations are prevalent. In the U.S., the diphtheria is presently rare, and credit is given to the vaccine usage. Its role in the success of reducing the disease numbers in humans in the U.S. is attributed directly to active vaccination programs. For example, it is recorded that, in 1921, over 200,000diphtheria cases occurred in the U.S. whereas a clinical case of the diseaseh as apparently not been observed since 2003.

2) Emile Roux, apparently worked closely with Louis Pasteur on an anti-diphtheria medication. It is interesting that such great minds were able to work together.But who ultimately was given the credit for discovering the microbial causes of diphtheria?

Although it is generally accepted that Profs. Edwin Klebs and Fredrich Loeffler satisfied Koch’s postulates in determining that the diphtheria disease was caused by a microbe, it was Dr. Emile Roux who was ultimately key to discovering that the disease was generated by toxin that was secreted by the Klebs-Loeffler bacterium. Dr. Roux worked in the laboratory of Prof. Louis Pasteur. In the late 1880s, Dr. Roux worked alongside Dr. Alexandre Yersin. First,the trio collaborated on the project, focusing on the toxin formed by the Klebs-Loeffler bacterial pathogen, named Corynebacterium diphtheriae. Together, Drs. Roux and Yersin demonstrated that the bacterium could make the diphtheria toxin. They published the work in 1888.

With the diphtheria toxin in hand, work began in earnest to produce ananti-toxin. They injected laboratory animals with the toxin and let the animals use their immune systems to produce the anti-toxin, which we now know to be the antibody. The antibodies are proteins that are induced to be synthesized upon exposure to an antigen, which in this case is the diphtheria toxin.  The antitoxin in this scenario is the antibody.

Blood samples were then taken from the laboratory animals that had been immunized with the diphtheria toxin. The blood samples were allowed to clot,whereupon the blood clot was discarded. The remainder was centrifuged to removed cell debris and other confounding factors, leaving behind the so-called diphtheria anti-serum.  The  the diphtheria antitoxin was then isolated. This substance figured prominently in the development of the novel serum therapy, for which Dr. Roux was to be famous for having had a direct role in its discovery.

3) Tetanus–another feared word–linked with lockjaw- and stepping on rusty nails (correct?) What was his contribution in this realm?

Dr. Roux’s work with the tetanus, a universally feared disease, began in the early 1890s, when he had already been a long-time assistant in the famous laboratory of Dr. Pasteur. In the tetanus project, Dr. Roux worked closely with another assistant, Dr. Louis Vaillard. Together they found that they could attenuate the tetanus toxin using a solution of potassium iodide (KI).  The attenuated form of the tetanus featured adenatured tetanus toxin protein such that the pathogenicity was lost but heimmunogenicity was retained.

The tetanus toxin is known in modern times as tetanospasmin, which is a type of neurotoxin.  This tetanus neurotoxin works to mediate its pathogenic condition on a patient by preventing the release of neurotransmitters called glycine (an amino acid) and gamma-aminobutyric acid (GABA). These neurotransmitters cannot, therefore, mediate their activities. They normally function to facilitate neuromuscular relaxation, as opposed to muscular contraction. Without the ability of the muscles to relax,they instead stay abnormally in a contracted condition.  Lockjaw is a good example of such an abnormal muscular contraction.  This lockjaw type of muscle contraction is often one of the first symptoms to be manifested during tetanus.

The nail need not be rusty in order for tetanus to gain a foothold on a patient. The nail need only to be contaminated with the bacterial pathogen, called Clostridium tetani.  After gaining entry into a host, perhaps by a nail puncture of the skin, this tetanus-causing bacterium will then secrete the tetanospasmin, and it will mediate its own entry of the active part of the toxin into a host cell to disturb the normal  release of the neuro-muscular neurotransmitters. If severe in its onset, all of the unfortunate patient’s muscles may be affected, maintaining a profound contracted state, a seriously painful situation called opisthotonos. A patient experiencing the opisthotonos can suffocate to death if not promptly and vigorously treated! 

4) Apparently after Pasteur died- Roux took over his institute. What were some of his later discoveries or what did he work on besides diphtheria?

Perhaps one of the earliest contributions by this great scientist was accomplished almost immediately after Dr. Roux started working in the laboratory of Dr. Pasteur, in 1880.  In this scenario, Dr. Roux worked with Dr. Pasteur to attenuate the causative agent of the chicken cholera. They cultured the bacteria in broth culture conditions at room temperature for weeks at a time, allowing the bacteria to mutate into relatively harmless forms but at the same time retain the immunogenic property of the microbe. Here, they were able to enhance the growth in culture of a less virulent form of the chicken cholera bacteria, called Pasteurella multocida. It is now widely believed by historians of science that it was Dr.Roux himself who performed the animal injection studies using their attenuated Pasteurella multocida bacteria.

It is also at this time that the term vaccination was invoked to honor the work of Dr. Edward Jenner, who used an attenuated cowpox agent to provide protective immunity against the smallpox disease. Dr. Roux was directly involved in the work that led to this attenuation approach towards vaccine development.

Dr. Roux also played a key role in the studies aimed at developing an anthrax vaccine, in 1881. Here, he collaborated with Drs. L. Pasteur and Charles Chamberland. Together, the three scientists attenuated the Bacillus anthrac is bacterium by letting the cultures sit a somewhat higher than normal body temperatures.  Under these laboratory conditions, the anthrax bacterium became attenuated, making it a good candidate for vaccine development.

It is recorded that Drs. Roux and Chamberland were directly involved in the world famous and legendary experiment of Pouilly-le-Fort, in 1894. The incident was a public demonstration of the efficacy of their anthrax vaccine, a discovery that had been widely disbelieved. The public show, though initially risky (it may not have worked) was ultimately successful and quite dramatic in its findings.  They demonstrated that the non-immunized animals died from the pathogen while the immunized animals survived a lethal dose of the anthrax. The public show converted even the harshest of skeptics, even the unbelieving Dr. Hippolyte  Rossignol, a veterinarian and fierce opponent of the efficacious nature of the anthrax cause and its vaccine.

In 1898, Dr. Roux had studied a condition known then as pleurop neumonia. The painful inflammatory condition involves infection of the lungs and of the membranous lining, called the pleura, that surrounds the lungs. It is clear today that the pathogenic microbe is a bacterium called My coplasma pneumoniae, a tiny bacterium. However, because Dr. Roux and his collaborator, Dr. Edmond Nocard, had observed that the causative microbe could pass through laboratory filters, they mistakenly referred to the agent as a virus. The error pushed back the progress towards the scientific studies on the disease and its microbe.

At the turn of the 20th century, Dr. Roux became the second director of the Pasteur Institute, taking the post that had been vacated by his famous supervisor. It was at about this time that Dr. Roux studied the transmission of syphilis between laboratory animals.

5) Looking back on his life and contributions- was he acknowledged for his work and how is his work viewed today?

Dr. Roux was both fortuitous and astute in his approach to his scientific studies. He was fortuitous in the sense that he had been in the right place at the right time in history by becoming closely involved in the famous works of Prof. Pasteur.  Likewise, Dr. Roux was astute in his uncanny abilities to perform definitive experiments, the results of which had convinced longtime skeptics of the causes disease or of approaches to prevention of disease.

Though Dr. Roux did not receive the Nobel for any of his scientific contributions, he was awarded, in 1917, the renowned Copley Medal, a prestigious honor bestowed upon him by the Royal Academy. Since 1731, the Copley Medal has been awarded to scientists who havemade significant contributions.  Theaccolade is in vogue, even to this day.

Despite the overwhelmingly legendary status of his director, Dr. Pasteur, the contributions of Dr. Roux have made a significant mark on scientific history.  Thanks to the work of Dr. Roux, tetanus,anthrax, and diphtheria are terribly rare commodities in developed regions of the world. In modern times, Dr. Roux is given a prominent status in the textbooks dealing with the topics of microbiology, bacteriology, immunology,and the biomedical sciences. It is clear that the works of Dr. Roux will no doubt continue to benefit humankind for generations to come, when each of the infectious diseases he studied will eventually become eradicated.

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