Thinking about science like Louis Pasteur

Scientific discoveries and achievements from centuries past are often portrayed as a set of fully-fledged concepts and perfect results. The exacting trial-and-error processes and frequent setbacks we know from modern-day science are rarely mentioned. Why could this be – was science ‘easier’ in the past?

Dr Keith Turner and Professor Marvin Whiteley of the University of Texas at Austin were intrigued by this phenomenon and looked at 19^th century microbiology as a case study. To get a better insight into what really happened in laboratories a century and a half ago, they studied a paper by Louis Pasteur, one of the founding fathers of modern microbiology. Written in 1877, it is entitled Charbon et septicémie (Anthrax and septicaemia, an inflammatory response of the body to severe infections). The manuscript is written in Pasteur’s native French, so the researchers enlisted the help of Dr Turner’s wife, who translated the original text into English. Together, they have published their thoughts on Pasteur’s paper in the Journal of Medical Microbiology.

In Pasteur’s day, anthrax was a disease common in both humans and livestock – a far cry from its modern associations with bioterrorism in the aftermath of the 11 September 2001 attacks. One of the main microbiological challenges of the late 19^th century was to ascertain whether anthrax was caused by bacteria or by even smaller entities that were invisible to the microscopes of the time – entities that we today know as viruses. If bacteria proved to be the culprits, the secondary challenge was to show whether or not the bacterium we call Bacillus anthracis was the one that caused anthrax.

Charbon et septicémie was a response to an earlier investigation from 1865 that attempted to shed light on the cause of anthrax by inoculating a healthy rabbit with blood from a cow that had died of the disease at a slaughterhouse. The rabbit quickly died, but the scientists found no sign of anthrax symptoms or of B. anthracis; they therefore concluded that the bacterium could not be the cause of anthrax.

Twelve years after the publication of these controversial findings, Pasteur neatly dissected the earlier study’s reasoning using two simple arguments:

• Blood from any animal dead for more than a few hours will putrefy, becoming deadly for other organisms irrespective of anthrax; the scientists could not know how long the cow had been dead when they took their blood sample.
• The microbes that grow in putrefying blood are deadly not just to humans but also to B. anthracis, which is why the anthrax bacterium was not found in the dead rabbit.

As Turner and Whiteley argue, this simple yet insightful criticism epitomises the critical thinking and sceptical approach that are essential in science. Not content with debunking his fellow microbiologists’ reasoning, however, Pasteur also responded with his own experimental findings. He used urine, which remains mostly sterile unless microbes are artificially introduced, as a basis for isolating a pure culture of B. anthracis bacteria. Indeed, a guinea pig he infected with this pure culture died of anthrax very shortly after. More importantly, filtering this anthrax culture to remove B. anthracis rendered it completely avirulent, proving that it was the anthrax bacterium that caused the disease.

Besides presenting these important findings in their own right, Charbon et septicémie also laid the groundwork for Pasteur’s anthrax vaccine, to which we owe a largely anthrax-free world today. The paper is also a description of an early application of Pasteur’s pure-culture method to medical microbiology. Pure culture forms the basis of 20^th-century microbiology, much of which focused on studying microbes in isolation using purification methods similar to those Louis Pasteur pioneered.

In contrast to pure culture, Professor Whiteley’s lab studies the role polymicrobial communities – those consisting of multiple species coexisting – play in human infection. They believe that pure culture does not reflect the intricacies of real, natural interactions between microbes and the impacts such interactions have on individual cells. Can the two seemingly conflicting scientific approaches of pure culture and the study of polymicrobial communities be reconciled?

Dr Turner and Professor Whiteley argue that they can. They are keen to acknowledge the transformative impact that Pasteur’s work has had on microbiology. However, they believe that modern microbiology has focused on Pasteur’s isolation methods so much that studies of the interactions between microbes in their natural environment have been neglected. They therefore see their work as complementary to Pasteur’s, not as contrasting. Turner and Whiteley aim to apply the insightful reasoning and logical rigour of Pasteur to the study of two or more microbial species interacting. After all, exploring in new directions and not taking existing knowledge as infallible is key to driving science forward and advancing our understanding of the world around us. Charbon et septicémie, they argue, is not merely a summary of scientific findings but an example of the kind of incisive, critical thinking all scientists should use when considering the results of others – or their own. As such, Turner and Whiteley’s praise for Pasteur’s work should be seen first and foremost as a sign of great respect for a fellow scientist from another era.