the microbiome in history

This is not a comprehensive overview of the development of microbiome science, instead it emphasizes key techniques and conceptualizations of the science in an attempt to trace the origins of contemporary ideas of the microbiome

1670s-1680s

Antonie van Leeuwenhoek (Dutch businessman/scientist) visualized microorganisms (what he called “animalcules”) using the new technology of microscopes

1884

Robert Koch (German physician, later Professor of Hygiene at Berlin University) cited microbial infection as causative agents of many diseases

1888

Sergei Winogradsky (Russian botanist, worked at Swiss Polytechnic Institute in Zurich, later as Chief of Microbiology at Imperial State Institute of Experimental Medicine, St. Petersburg)

He utilized ecological approaches (environmental microbiology) to microbiology and studied the importance of beneficial effects of microorganisms in the environment (ex. in soil) and how microbes were connected through metabolic processes.

He developed the “Winogradsky column” which attempted to study certain microbes within their natural environment (i.e. a long clear plastic tube that was filled with non-sterilized soil and water; different bacteria would separate into sections based on their metabolic type – aerobic vs. anaerobic; could study how they interacted with eachother)

This was against the paradigm of growing isolated bacteria on sterile medium in petri dishes utilized by others like Koch

Feminist science scholar Stephanie Maroney (2018) calls our contemporary time the “probiotic present”, or the current shift in science and popular culture of microbes as mostly beneficial and no longer pathogenic as established by the legacies of the work of Koch and Pasteur

Given the microscopic nature of the microorganisms that comprise a microbiome, the anthropologist Amber Benezra (2018) notes how understandings of the microbiome are intimately connected to the technologies developed to see them, from microscopes to sequencers.

Historian of Science Mathias Grote (2018) argues that although the scientific dominance of the “purity” of isolated cultures was a dominant technique, the “diversity” and ecological approach to microbiology was still present and though recently experienced increased interest (ex. of museum exhibits on microbiomes that show the use of these columns)

1940s

Gnotobiotic rodent models

Technological advancements (i.e. simplified chambers) expanded the accessibility of studying “germ free” animals, a general concept recognized since Pasteur (late 1800s)

“Germ-Free”

no other detectable organism on or in the animal, born through caesarean and raised in sterile environments “Gnotobiote”

animal with known associated microorganisms (ex. produce a germ-free animal then introduce specific bacteria)

Act as scientifically controlled models to isolate causal functions of specific microorganisms; the basis for association and potential causality studies between certain diseases and the microbiome

Historian of Science Robert Kirk (2012) writes that the standardized germ-free isolator system developed by James Arthur Reyniers (microbiologist at Laboratories of Bacteriology at Notre Dame) envisioned germ-free animals as “ideal basic experimental tools” – intended to mass produce and supply for research

In World War II, these isolators were used for biological warfare research (to isolate pathogens inside) -

(U.S military investment in the lab and technique) (248)

After WWII "presenting germ-free life as an essential new tool for the fast-expanding biomedical sciences was a deliberate strategy adopted by Reyniers intended to integrate his work with the promise of future improvements in health and well-being. In the laboratory, germ-free life promised new understandings of aging as well as providing the vehicle by which new treatments would be discovered for diseases as diverse as tooth decay and cancer, promising healthier, happier, and longer futures for all.”

(Kirk 2012, 248-249)

1965

Schaedler et al. utilized germ-free mice for the study of microbiota transfers, gut colonization processes, and effects of host/microbiome interactions

1977

Carl Woese & George Fox (University of Illinois at Urbana-Champaign, USA) utilized comparisons of specific regions of the 16S rRNA gene to distinguish bacteria from archaea

1996

Kenneth Wilson & Rhonda Blitchington (Infectious Disease Department at Duke University, NC, USA) were the first to use sequencing of the 16S rRNA gene in bacteria to identify different species within a human stool sample

Frederick Sanger (governmental Medical Research Council Laboratory of Molecular Medicine - Cambridge, England) developed the Sanger Sequencing Technique, which accurately gives the sequence of long DNA due to breaking it up into fragments then piecing back together. This technique won the 1980 Nobel Prize in Chemistry.

Considered “First Generation Sequencing”

This is the foundation of how most DTC test kit companies sequence the microbes in your stool sample

(ex. Atlas, Ombre)

2005-2006

Next Generation Sequencing (NGS)

Produced by private companies, new automated technologies can sequence many small fragments at the same time, instead of one large fragment at a time

Massive increase in sequencing capacity – 1 gigabase (1 billion [10^9] base pairs) per run now versus 84 kilobase (1,000 [10^3] base pairs) per run previously.

(Note ~3 billion base pairs in a human genome.)

2008

RNA-sequencing emerges as technique to study the transcriptome. Several studies concurrently published utilized next generation sequencing of mRNA transcripts produced in various eukaryotes (not bacteria) to obtain sequences of active genes

This is foundation of how some DTC test kit companies sequence the presence and activity of microbes in your stool sample (ex. Viome)

references

Benezra, Amber. 2018. "Making Microbiomes." In Handbook of Genomics, Health & Society, edited by Sahra Gibbon, Stephen Hilgartner, Janelle Lamoreaux, Barbara Prainsack, 283-290. New York, NY: Routledge.

Berg, Gabriele et al. 2020. “Microbiome definition re-visited: old concepts and new challenges.” Microbiome 8, no. 103. https://doi.org/10.1186/s40168-020-00875-0

Goins, Janet. 2019. "Microbiomes: An Origin Story." American Society for Microbiology, March 8 2019. https://asm.org/Articles/2019/March/Microbiomes-An-Origin-Story

Grote, Mathias. 2018 “Petri dish versus Winogradsky column: a longue duree perspective on purity and diversity in microbiology, 1880s– 1980s.” History and Philosophy of the Life Sciences 40:11. https://doi.org/10.1007/s40656-017-0175-9

Illumina. n.d. "History of Sequencing by Synthesis." Illumina, n.d. https://www.illumina.com/science/technology/next-generation-sequencing/illumina-sequencing-history.html

Kirk, Robert G. 2012. “’Life in a germ-free world’: isolating life from the laboratory animal to the bubble boy." Bulletin of the History of Medicine 86, no. 2 :237-75. doi: 10.1353/bhm.2012.0028.

Maroney, Stephanie. 2018. "Eat for Your Microbes: Reimagining Diet, Health, and Subjectivity in the Probiotic Present." PhD Dissertation, University of California Davis.

Nature Milestones. 2019. "Human Microbiota Research." Nature Milestones, June 2019. https://www.nature.com/collections/bhciihjhei#:~:text=The%20human%20body%20is%20home,archaea%2C%20viruses%2C%20and%20fungi.

Sanger, Frederick et al. 1977. “DNA Sequencing with Chain-Terminating Inhibitors.” Proceedings of the National Academy of Sciences USA 74, no. 12: 5463-5467.

Snyder, Michael et al. 2009. “RNA-Seq: A revolutionary tool for transcriptomics.” Nature Reviews Genetics 10, no. 1: 57-63.

Turbaugh, Peter J. et al. 2007. “The Human Microbiome Project.” Nature 449: 804-810. doi:10.1038/nature06244

Wilson, Kenneth H. and Rhonda B. Bilchington. 1996. “Human Colonic Biota Studied by Ribosomal DNA Sequence Analysis.” Applied and Environmental Biology 62, no. 7: 2273-2278.