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C
Claas Kirchhelle
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James Ebdon
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Martha Clokie
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Claas Kirchhelle:我主要关注噬菌体的历史和发展。从20世纪初科学家们注意到细菌消失的现象开始,到Félix d'Hérelle对噬菌体的独立发现和命名,再到George Eliava将噬菌体疗法带到格鲁吉亚,建立了Eliava研究所。噬菌体研究经历了不同的阶段,从最初的治疗和诊断应用,到后来的基因组学研究,以及对微生物世界和遗传机制的理解。二战期间,噬菌体分型技术被用于绘制微生物多样性图谱,这在国家安全和公共卫生方面都具有重要意义。如今,历史档案中的信息为我们理解微生物环境的变化提供了宝贵的资源。 Martha Clokie:我的研究主要集中在噬菌体在人类健康中的应用。由于抗生素耐药性的日益严重,噬菌体疗法重新受到关注。噬菌体具有高度特异性,这意味着需要针对不同的细菌菌株选择特定的噬菌体。开发噬菌体疗法比开发青霉素更复杂,因为需要了解致病菌的具体类型和噬菌体的感染模式。噬菌体可以用于治疗各种细菌感染,包括肺部疾病、肠道疾病和尿路感染等。此外,噬菌体还可以用于动物保健,以减少抗生素的使用和抗生素耐药性的传播。 James Ebdon:我主要研究噬菌体在环境中的作用以及其在水质监测中的应用。噬菌体是地球上数量最丰富的生物体,它们在调节细菌种群数量方面发挥着重要作用。噬菌体具有两种生命周期:裂解循环和溶原循环。裂解循环导致细菌细胞裂解,而溶原循环则导致噬菌体基因组整合到细菌基因组中。噬菌体在环境中比细菌更持久,这使得它们成为有效的环境指标。我们可以通过检测噬菌体来确定饮用水中是否存在粪便污染,并追踪污染物的来源。此外,噬菌体还代表着地球上最大的未开发遗传变异库,我们对它们的了解还非常有限。

Deep Dive

Key Insights

What are bacteriophages and why are they significant?

Bacteriophages, or phages, are viruses that specifically infect and destroy bacterial cells. They are the most abundant life form on Earth and play a crucial role in regulating bacterial populations in various environments, including the human gut. Phages have significant potential in treating bacterial infections, especially in the context of antibiotic resistance, and have been instrumental in advancing our understanding of molecular biology and genetics.

Who first discovered bacteriophages and what were their initial observations?

The phenomenon of bacteriophages was first observed in the late 19th century. In 1896, Ernest Hankin noted that cholera bacteria in the Ganges River were being lysed by something in the water. Frederick William Twort in 1915 and Félix d’Herelle in 1917 independently identified and studied these lytic agents. Twort observed a glassy dot that could destroy bacteria, while d’Herelle coined the term 'bacteriophage' and demonstrated their ability to infect and kill bacteria.

How did bacteriophages contribute to the understanding of DNA?

Bacteriophages played a pivotal role in uncovering the nature of DNA. In 1952, Alfred Hershey and Martha Chase used phages to demonstrate that DNA, not protein, is the genetic material. This experiment, known as the 'blender experiment,' showed that phages inject DNA into bacterial cells, leading to the replication of the phage. This discovery was foundational for the later elucidation of the DNA double helix structure by James Watson and Francis Crick.

Why is there renewed interest in bacteriophages for treating infections?

The rise of antibiotic resistance has spurred renewed interest in bacteriophages as a potential treatment for bacterial infections. With millions of people dying annually from infections that antibiotics can no longer treat, phages offer a promising alternative. Advances in genomic tools now allow researchers to better understand and tailor phages for specific bacterial targets, making them a viable option in modern medicine.

What challenges exist in developing phage-based treatments?

Developing phage-based treatments is challenging due to their specificity. Each phage targets a specific strain of bacteria, requiring precise identification of the pathogen. Additionally, phages must be carefully selected to avoid lysogenic cycles where they integrate into bacterial DNA rather than killing the host. Regulatory and patent issues also complicate their development and commercialization, as phages do not fit neatly into existing drug development models.

How are bacteriophages used in environmental monitoring?

Bacteriophages are used in environmental monitoring to detect fecal contamination in water. Unlike traditional indicator bacteria, phages can identify the source of contamination (e.g., human vs. animal). They are also used to study the behavior of other enteric viruses, such as norovirus, in water systems. Phages are highly abundant in wastewater and can persist longer than bacteria, making them effective tools for water quality assessment.

What is the relationship between bacteriophages and bacterial evolution?

Bacteriophages and bacteria engage in a constant evolutionary arms race. Phages infect and kill bacteria, but bacteria can evolve resistance mechanisms. This dynamic regulates bacterial populations and drives genetic diversity. Phages can also transfer genetic material between bacteria through lysogeny, where phage DNA integrates into the bacterial genome, potentially conferring new traits such as antibiotic resistance or virulence factors.

What historical role did bacteriophages play in the Soviet Union?

In the Soviet Union, bacteriophages were extensively used for treating bacterial infections, particularly during the 1920s and 1930s. George Eliava, a Georgian scientist, collaborated with Félix d’Herelle to establish the Eliava Institute in Tbilisi, which became a center for phage research and therapy. Phages were used to treat diseases like typhoid, diphtheria, and the plague, but their use declined with the advent of antibiotics.

Why are bacteriophages considered a 'treasure trove' of genetic diversity?

Bacteriophages are considered a treasure trove of genetic diversity because they are the most abundant biological entities on Earth, with trillions of unique phages. Their genomes contain vast amounts of undiscovered genetic information, much of which is unlike anything previously known. This diversity makes phages a rich resource for understanding microbial ecosystems, developing new therapies, and advancing biotechnology.

How can bacteriophages be used alongside antibiotics?

Bacteriophages can be used alongside antibiotics to enhance their effectiveness. Phages can target and destroy biofilms, which often protect bacteria from antibiotics, allowing the antibiotics to reach their target. Additionally, phages can be used to treat infections caused by antibiotic-resistant bacteria, providing a dual approach to combating bacterial infections. Studies have shown that combining phages with antibiotics can eradicate infections that are otherwise untreatable.

Chapters
The discovery of bacteriophages, viruses that infect and kill bacteria, was a serendipitous observation made by scientists in the early 20th century. Initially observed as a mysterious phenomenon causing bacterial cultures to disappear, further research by scientists like Frederick Twort and Félix d'Hérelle revealed the existence and nature of these 'bacteria eaters'. D'Hérelle's dramatic description of his discovery highlights the excitement and novelty of this finding.
  • Early 20th-century scientists noticed bacteria disappearing in their labs.
  • Bacteriophages, or phages, were identified as viruses that infect and kill bacteria.
  • Félix d'Hérelle coined the term 'bacteriophage' and made significant contributions to early phage research.

Shownotes Transcript

Melvyn Bragg and guests discuss the most abundant lifeform on Earth: the viruses that 'eat' bacteria. Early in the 20th century, scientists noticed that something in their Petri dishes was making bacteria disappear and they called these bacteriophages, things that eat bacteria. From studying these phages, it soon became clear that they offered countless real or potential benefits for understanding our world, from the tracking of diseases to helping unlock the secrets of DNA to treatments for long term bacterial infections. With further research, they could be an answer to the growing problem of antibiotic resistance.

With

Martha Clokie Director for the Centre for Phage Research and Professor of Microbiology at the University of Leicester

James Ebdon Professor of Environmental Microbiology at the University of Brighton

And

Claas Kirchhelle Historian and Chargé de Recherche at the French National Institute of Health and Medical Research’s CERMES3 Unit in Paris.

Producer: Simon Tillotson

In Our Time is a BBC Studios Audio Production

Reading list:

James Ebdon, ‘Tackling sources of contamination in water: The age of phage’ (Microbiologist, Society for Applied Microbiology, Vol 20.1, 2022)

Thomas Häusler, Viruses vs. Superbugs: A Solution to the Antibiotics Crisis? (Palgrave Macmillan, 2006)

Tom Ireland, The Good Virus: The Untold Story of Phages: The Mysterious Microbes that Rule Our World, Shape Our Health and Can Save Our Future (Hodder Press, 2024)

Claas Kirchhelle and Charlotte Kirchhelle, ‘Northern Normal–Laboratory Networks, Microbial Culture Collections, and Taxonomies of Power (1939-2000)’ (SocArXiv Papers, 2024)

Dmitriy Myelnikov, ‘An alternative cure: the adoption and survival of bacteriophage therapy in the USSR, 1922–1955’ (Journal of the History of Medicine and Allied Sciences 73, no. 4, 2018)

Forest Rohwer, Merry Youle, Heather Maughan and Nao Hisakawa, Life in our Phage World: A Centennial Field Guide to Earth’s most Diverse Inhabitants (Wholon, 2014)

Steffanie Strathdee and Thomas Patterson (2019) The Perfect Predator: A Scientist’s Race to Save Her Husband from a Deadly Superbug: A Memoir (Hachette Books, 2020)

William C. Summers, Félix d`Herelle and the Origins of Molecular Biology (Yale University Press, 1999)

William C. Summers, The American Phage Group: Founders of Molecular Biology (University Press, 2023)