Thierry Crouzet

For now, only available for special orders (Bragelonne is looking for a publisher outside France)

April 2017
Novel

Presentation

EVERYTHING IN THIS BOOK, EVEN THE MOST TERRIFYING PARTS, IS BASED ON SCIENCE.

The passengers of a yacht are suddenly stricken by a super-bacterium, resistant to antibiotics. Except Katelyn, a young medical student. Why is she the only survivor? Recruited by the Anti-Bioterrorism Center, she is assigned the mission of finding the disease’s carrier, even if it means becoming intimate with him. But the man she is hunting awakes contradictory feelings inside her. Perhaps he’s not killing blindly…

Novelist, essay writer, and blogger, Thierry Crouzet is fascinated by issues located at the nexus of technology, politics, and literature. His works in French include Le Peuple des connecteurs [The Connected People], a reflection on our networked society; J’ai débranché [How I Unplugged], a tale of digital burnout; and La Quatrième Théorie [The Fourth Theory] a thriller by tweets. His scientific account, Clean Hands Save Lives, has been translated in eighteen languages, winning him hundreds of thousands of readers across the world.

Citations

“Antibiotic-resistant bacteria are gaining ground throughout the world. If nothing is done, they will kill more people than climate change.” Prof. Didier Pittet, director of the Infection Control Program (University Hospitals of Geneva) and the WHO Collaborating Centre on Patient Safety

"The problem of microbes becoming increasingly resistant to the most powerful drugs should be ranked alongside terrorism and climate change on the list of critical risks to the nation." Dame Sally Davies, UK Government's Chief Medical Officer

« We cannot wait for a highly communicable bacterium that is resistant to all of our antibiotics to hit before taking action. » Professeur Martin Blaser

If the worst happens, are we ready?

Translation: Sheryl Curtis and Tom Clegg

Antibiotics and book chronology (spoiler inside)

-4.6 billion years ago Formation of Earth.

-3.7 billion years ago Oldest fossils indicating the presence of bacteria, cells with no nuclei or procaryotes (in the same manner as viruses and archaea).

-2.2 billion years ago First eucaryotes (cells with nuclei).

-2.1 billion years ago First multi-cell organisms.

-600 million years ago First animals during the Ediacaran period.

-200,000 First Homo sapiens.

-2000 The Egyptians apply kohl, an antibacterial mineral powder to their eyes as make-up. They use henna, which has an antimicrobial effect (an antimicrobial acts against all germs, an antibacterial acts only against bacteria). They disinfect wounds with honey containing hydrogen peroxide, another powerful antimicrobial. [I use these ancestral practices for Katelyn’s character.]

0 In several cultures, wounds are disinfected with moldy bread that secretes penicillin.

1000 Resistant bacterial is already infecting the intestines of our ancestors (in particular, traces are found in Incan mummies).

1640 Apothecary John Parkington, the herbalist for the King of England, suggests treating infections with mold.

1674 Antoni van Leeuwenhoek (1632-1666) manufactures a small microscope and discovered the existence of germs.

1796 Edward Jenner (1749-1823) observes that women who milk cows do not generally contract small pox, but only a milder form of the disease, the “vaccine”. He discovers that, by injecting the “vaccine” into his patients, he protects them against small pox. This is the start of immunotherapy and vaccination (small pox would be declared eradicated in 1980, and the last known case dates back to October 26, 1977).

1847 Ignaz Semmelweis (1818-1865) demonstrates that disinfecting hands prevents the spread of puerperal fever (childbed fever). He is the father of antisepsis.

1854 Filippo Pacini (1812-1883) demonstrates the microbial origin of cholera, while John Snow (1813-1858) discovers that the London epidemic was caused by contaminated water.

1862 Louis Pasteur (1822-1895) refutes the theory that germs arise out of spontaneous generation. He demonstrates that they are organisms in their own right.

1867 Joseph Lister (1827-1912) introduces the use of antiseptics in surgery. Applied to the surfaces of living tissues, they limit infections by attacking all germs, but they cannot be used to treat internal infections since they are toxic for the organism.

1870 Sir John Scott Burdon-Sanderson (1928-1905) observes that culture broths covered with mold do not produce bacteria.

1871 At the initiative of Sir John Scott Burdon-Sanderson, Joseph Lister takes an interest in mold. He observes that urine samples contaminated with mold do not allow bacteria to grow. He also describes the antibacterial action of a mold he names Penicillium glaucum on human tissue and successively uses it to heal a nurse at King’s College Hospital, whose wounds did not respond to the antiseptics.

1874 William Roberts (1830-1899) discovers that bacteria do not generally contaminate cultures of Penicillium glaucum.

1875 John Tyndall (1820-1893) demonstrates the antibacterial action of a fungus of the Penicillium genus.

1877 Louis Pasteur and Jules François Joubert (1834-1910) demonstrate that Bacillus anthracis causes anthrax. In this manner, they prove the bacterial origin of many diseases. They note that when they inject the bacillus into animals along with ordinary bacteria, the ordinary bacteria prevent the bacillus from developing. Pasteur evokes the idea of bacterial antagonism.

1878 Charles-Emmanuel Sédillot (1804-1883) coins the term “microbe” to designate all pathogenic microscopic agents.

Pasteur discovers staphylococcus.

1880 Robert Koch (1843-1910) discovers the salmonella that causes typhoid.

1881 Robert Koch invents a technique for cultivating bacteria on an agar gel.

1882 Robert Koch discovers the bacillus that causes tuberculosis.

Ilya Ilitch Metchnikov (1845-1916) discovers phagocytosis or how white blood cells help the organism fight against bacteria, by provoking an inflammation (he received the Nobel prize for physiology and medicine in 1908).

1884 Hans Christian Gram (1853-1938) invents a staining method that serves to distinguish two groups of bacteria: a negative Gram stain has a triple wall that does not preserve the stain after rinsing (colibacillus, gonococcus, salmonella, Escherichia coli…), unlike the positive Gram stains (streptococcus, staphylococcus…).

1887 Julius Richard Petri (1852-1921) perfects Koch’s culture technique using the Petri dish.

Paul Ehrlich (1854-1915) develops an immune response theory focusing on the interaction between antigens and antibodies (he shared the Novel prize for physiology and medicine with Ilya Ilitch Metchnikov in 1908, for his work in immunology). After discovering that the dyes kill certain microbes, he tried to use them for therapeutic purposes.

1888 Eduard von Freudenreich (1868-1935), Rudolf Emmerich (1856-1914) and Oscar Loew (1844-1941) discover that Pseudomonas aeruginosa stops the proliferation of other bacteria. This is the first antibiotic discovered, but it was almost impossible to use it on humans (an antibiotic is an antibacterial of microbial origin).

1889 Jean Paul Vuillemin (1861-1932) uses the term “antibiosis” to refer to the fact that an organism can be antagonistic to other organisms with which it lives.

1893 In a book published posthumously, Karl Wilhelm von Nägeli (1817-1891) describes the oligodynamic effect, the antimicrobial effect of certain metals, including copper, mercury and silver.

1895 Vincenzo Tiberio (1869-1915) attempts unsuccessfully to treat infected animals with extracts of Penicillium.

1897 Ernest Duchesne (1874-1912) describes the antibiotic power of Penicillium glaucum molds and evokes their possible therapeutic use (his research was ignored).

1900 Paul Ehrlich imagined the concept of the “magic bullet”: a medication that would kill dangerous bacteria without damaging other cells.

Pneumonia, tuberculosis and diarrhea are the first three causes of death and kill one person out of three. The world mortality rate is 17.2 ‰, with half those deaths being attributed to infectious diseases.

1907 In New York, George Soper (1870-1948) discovers that Mary Mallon (1869-1938) is a healthy carrier of typhoid. [I based the vampires and particularly the character of Yash on her. I replaced the Salmonella typhi which must have infected Mary Mallon with the imaginary Curitiba adversus.]

1908 In Tunisia, Charles Jules Henri Nicolle (1866-1936) and Louis Manceaux discover the Toxoplasma gondii parasite in a rat.

1910 Paul Ehrlich discovers that a dye derived from arsenic, namely salvarsan, has an antibiotic effect and can be used to treat patients with syphilis, despite its numerous undesirable effects.

Ilya Ilitch Metchnikov studies intestinal flora and encourages a diet based on Bulgarian yogurt in order to maintain a more balanced microbiota during aging.

1915 Frederick Twort (1877-1950) discovers bacteriophages.

1917 Félix d’Hérelle (1873-1949) re-discovers bacteriophages and invents phagotherapy.

1922 Alexander Fleming (1881-1955) discovers lysozyme, an enzyme with an antibacterial effect that is found in tears, saliva, mother’s milk… and egg whites.

1923 George Eliava (1892-1937) founds a virology institute in Tbilisi where, he develops phagotherapy in collaboration with Félix d’Hérelle; phagotherapy would be used throughout the Soviet Union.

Clodomiro Picado Twight (1887-1944), noticed the antibiotic effect of Penicillium.

1925 André Gratia (1893-1950), while working in New York on phages, discovers colicin, the first bacteriocin, a molecule which, while not an antibiotic, has antibacterial properties comparable to those of lysozyme isolated by Fleming.

1927 Discovery of a second bacteriocin, nisin, an antibacterial peptide used since that time as a food preservative under the name E234. It would later be discovered that eukaryotes release antibacterial peptides which in turn can also produce bacteriocins.

1928 After several days of vacation, Fleming returns to his lab at St. Mary’s Hospital on September 3. He notices that his staphylococcus cultures were contaminated by the Penicillium notatum mold grown by a colleague in the same building. Clear halos surrounded the growths. The obvious conclusion: a substance released by the mold killed the staphylococcus. Fleming called it penicillin, but he quickly abandoned his research because he could not produce enough penicillin.

1932 Gerhard Domagk (1895-1964) discovers sulfamides, the first antibacterial medications that could be commercially viable, particularly for fighting against streptococcal infections; unfortunately, they were only moderately effective. Gerhard Domagk received the Nobel prize in medicine in 1939.

1936 Marketing of the first sulfamide: Prontosil.

1938 Howard Florey (1898-1968) discovers Fleming’s article on penicillin. Along with Ernst Chain (1906-1979) and Norman Heatley (1911-2004), he managed to produce enough penicillin to test it on mice.

1940 First resistance to sulfamides identified.

1941 At Oxford, after scratching his face, Albert Alexander (1897-1941) received the first four injections of penicillin in history, but the dosage would not be enough to save him.

1942 First large-scale test of penicillin in Boston following the Coconut Grove fire, which convinces the pharmaceutical industry to start large-scale production.

1943 Selman Abraham Waksman (1888-1973) discovers streptomycin, the first antibiotic effective against Koch’s bacillus, which could be used to treat tuberculosis. He referred to this new medication as an “antibiotic”. He received the Nobel prize for medicine in 1952.

1944 Mass production of penicillin: 650 billion units each month.

1945 Alexander Fleming, Ernst Boris Chain and Howard Walter Florey share the Nobel prize in medicine. In an article in the New York Times, Fleming warns of the dangers of resistance (in the laboratory, he has seen the emergence of resistant staphylococcal infections).

Benjamin Minge Duggar (1872-1956) discovers aureomycin, first antibiotic in the tetracycline class, a broad-spectrum antibiotic with no undesirable effects.

1946 Joshua Lederberg (1925-2008) and Edward Tatum (1909-1975) discover the phenomena of conjugation or how bacteria exchange genes horizontally, including among non-related species (this is how resistant genes spread). When two bacteria touch, the plasmids, bits of DNA floating in their cytoplasm, can trade hosts and potentially be integrated into their genome.

In London, in one of the first hospitals to use penicillin, 14% of the staphylococcal infections were resistant.

1947 Discovery of chloramphenicol, a broad-spectrum antibiotic in the phenicol family.

1948 Discovery of cephalosporines, a class of antibiotics of the beta-lactam genus.

Nutritionist Robert Stokstad (1913-1995) and biochemist Thomas Jukes (1906-1999) discover that, by administering a low dose of aureomycin to chickens, they grow 24% faster and their body mass increases 2-6%. They open the way to the use of antibiotics as growth factors.

Creation of the World Health Organization (WHO), a specialized institution of the United Nations Organization (UN).

1949 In London, staphylococcal resistance to penicillin increases to 49%.

Discovery of colistin, called a “last-resort antibiotic”. Unfortunately, although it is very powerful, it has many undesirable effects and is only used for desperate cases.

Discovery of macrolides, antibiotics that spread throughout all tissues, even inside cells, and can as a result attack intracellular infections.

1953 James Watson (1928) and Francis Crick (1916-2004) discover the double helix structure of DNA.

1954 Marketing of vancomycin, a last-resort antibiotic, starts.

1955 There is no longer any doubt about resistance to penicillin and, in most countries, penicillin is no longer available without a prescription.

1959 Discovery of methicillin, an antibiotic of the beta-lactam genus and the penicillin family, used to fight Staphylococcus aureus, in particular in cases of resistance to penicillin.

1960 Marketing, in France, of metronidazole (antibiotic that is often prescribed and self-prescribed following a bout of turista).

1961 Development of ampicillin, a broad-spectrum antibiotic of the beta-lactam class.

Discovery, in Great Britain, of the first strain of Staphylococcus aureus that is resistant to methicillin (MRSA), only two years after the introduction of methicillin.

1962 Discovery of quinolones.

Theodore Rosebury (1904-1976) proposes the concept of amphibiosis: a symbiotic relationship that can be either positive, or negative.

1963 For the first time, greenhouse gases are evoked as most likely being responsible for climate change (almost 20 years after Fleming warned that resistance to antibiotics would become a major problem for humankind).

Demonstration that antibiotics promote growth by affecting the microbiota. Researchers divide chickens into two groups, raising those in the first group in ordinary conditions, while confining those in the second group in an aseptic environment so as to eliminate the microbiota. These two groups are then separated into two sub-groups, one of which is given antibiotics and the other is not. Therefore, there are four categories of chickens: the normal ones, the normal ones that are treated, the aseptic ones and the aseptic ones that are treated. The normal chickens treated with antibiotics grow more than the normal chickens that are not treated; the aseptic chickens treated with antibiotics develop at the same rate as those that are not treated. In conclusion, the antibiotics do not act directly on the animals, but on the bacteria in their microbiota. They promote growth because they destroy the bacteria that burn sugars and fats. Result: the muscle mass of the animals increases by up to one-tenth at less cost.

1967 Clindamycin synthesized.

1968 In Guatemala, an epidemic caused by a strain of Shigella diarrhea resistant to four antibiotics kills 12,500 people (the doctors, who were unaware of the problem of resistance, thought they were dealing with a parasite).

1969 Discovery of fosfomycin.

1970 Adding a fluorine atom to quinolones produces fluoroquinolones.

It is the time of the Vietnam war. Discovery of resistant strains of Neisseria gonorrhoeae in American soldiers, causing a sexually transmitted disease, a form of blennorrhagia. The investigation reveals that, in the Philippines prostitutes are using penicillin as a preventive means, which promoted the resistance of the bacteria.

1972 Marketing of amoxicillin, one of the most commonly used antibiotics, particularly for children.

The first Earth Summit takes place in Stockholm, at the initiative of the UN. These summits take place every ten years.

1976 Discovery of carbapenems, antibiotics that are capable of fighting bacteria that are resistant to antibiotics in the beta-lactam class, such as penicillin.

William Griffiths (1940) develops the first really effective hydro-alcoholic solution, but few people use it.

Stuart B. Levy (1938) and his colleagues discover that the microbiota of the livestock breeders transforms when they administer tetracycline to their animals. They also show that the resistance genes spread from chicken to chicken and from chickens to humans.

1978 Paul Zamecnik (1912–2009) and Mary Stephenson demonstrate that antisense oligonucleotides inhibit protein synthesis and can, as a result, kill viruses and bacteria. Since that time, it has been hoped that they can be used as antibacterials.

1979 Robin Warren (1937) re-discovers Helicobacter pylori (bacteria already mentioned in 1875 in Germany).

First international conference on the climate in Geneva. Starting in 1995, under the name COP, this conference is held in a different country each year.

1980 Epidemic of multi-resistant Shigella dysenteria in Zaïre.

During this decade, Enterococcus faecium becomes one of the largest causes of nosocomial infections. Subsequent genetic tests reveal that the strain in question is of animal origin and that it diverged from its ancestors at almost the same time as antibiotics appeared 30 years earlier. The human and animal strains diverged 3,000 years ago, during a time of significant urbanization.

Targeted immunotherapy develops as a result of the knowledge acquired as part of the fight against AIDS and during the first successful tests for cancer treatments.

1981 Discovery of azithromycin.

The first international conferences on resistance takes place in Santo Domingo. It concludes with a Antibiotic Misuse Statement, which starts with the following words: “We are faced with a worldwide public health problem.” The declaration was published by all of the media. Nature published an editorial entitled “Save antibiotiocs from themselves”.

Creation of the Création of the Alliance for the Prudent Use of Antibiotics (APUA) at the initiative of Professor Stuart B. Levy.

1982 Robin Warren and Barry Marshall (1951) demonstrate that Helicobacter pylori occasionally causes gastritis and ulcers, that we can treat with antibiotics (they receive the Nobel prize in medicine in 2005).

1985 In Costa Rica, 68% to 97% of the Gram-negative bacilli are resistant to ampicillin, making this broad-spectrum antibiotic unusable.

1986 Sweden prohibits the use of antibiotics as growth factors.

Without the need for clinical trials, generic medications can be marketed as soon as they are similar to medications previously covered by patents. A patent lasts 20 years as of the time when the patent application is submitted, and is required before any clinical trials are undertaken.

1987 Martin Blaser (1948) and Guillermo Pérez-Pérez discover that the presence of Helicobacter pylori in the stomach results in the presence of antibodies in blood, which enables them to develop the first test for detecting this bacterium.

1990 In Bangladesh, more than 80% of the Type 1 Shigella dysenteria bacteria, responsible for bloody diarrhea, are resistant to ampicillin and to the combination of trimethoprime/sulfamethoxazole.

1991 Up until this date, erythromycin was a macrolide that was little used as a result of its undesirable effects, but clarithromycin (discovered in 1984) and azithromycine (discovered in 1980) appear on the market.

1992 The European Union and the United States implement a Supplementary protection certificate (SPC) that increases the term of the protection provided by a patent awarded to a medication by five years.

1993 In the United States, Escherichia coli O157:H7 epidemic at Jack in the Box.

1994 Just about everywhere in the world, maximum thresholds are implemented for antibiotics authorized in the food chain. For example, milk must not contain more than 100 micrograms of tetracycline per kilo.

1995 Didier Pittet (1957) and his team demonstrate that, in the intensive care unit at the HUG in Geneva, the care-giving staff does not have the time to disinfect their hands with soap and water. This marked the start of the use of hydro-alcoholic solutions to slow the spread of nosocomial infections.

1996 In the United States, Odwalla fruit juices cause an epidemic of Escherichia coli O157:H7.

1998 In the British Medical Journal, Richard Smith (1953), compares the problem of antibiotic resistance to climate change.

1999 The European Union follows the example of Sweden and prohibits the use of antibiotics as growth factors.

Many articles evoke the use of antimicrobial peptides to fight against bacteria that are resistant to antibiotics.

It has become obvious that, during the transition from the paleolithic period to the neolithic, from the nomadic life of the hunter/gatherer to the sedentary one of the farmer, life expectancy decreased and, above all, living conditions deteriorated (traces of numerous diseases on skeletons, often caused by nutritional deficiencies). While the men and women of the paleolithic period generally died as a result of accidents, those of the neolithic period died of infectious diseases resulting from the proximity of people and animals. Jared Diamond declares that agriculture was the worst error of human history.

2000 Appearance of linezolid, first antibiotic in the oxazolidinone family. It is particularly active with respect to MRSA and enterococcal infections that are resistant to glycopeptides.

Ada Yonath (1939), Thomas Steitz (1940) and Venkatraman Ramakrishnan (1952) published a detailed chart of ribosome, a molecular machine that reads the RNA messenger in order to manufacture proteins. The model explains how certain antibiotics act. It makes it possible to consider the creation of new molecules. Yonath, Steitz and Ramakrishnan receive the Nobel prize in chemistry in 2009.

Discovery of signs of sexual arousal when rats infected by Toxoplasma gondii sniff cat urine, instead of the signs of fear usually observed in healthy individuals. [I imagine that adversus makes the vampires seductive in order to give them more opportunities to bite.]

2002 In France, start of the “Antibiotics are not automatic” campaign.

2003 Marketing of daptomycin in the United States, specifically to fight against staphylococcus aureus.

McDonald’s requires its meat suppliers to stop using the antibiotics that are vital for human medicine.

2004 Discovery that colostrum, the first milk, contains nisin. This antibacterial peptide had already been detected in the milk of numerous mammals.

2005 Stopping the administration of antibiotics as growth factors would only decrease pork or poultry production by 2%.

2007 Two years before receiving her Nobel Prize in economics, at the time of the 300th anniversary of the birth of Carl Linnaeus, Elinor Ostrom was give an honorary doctorate from the University of Uppsala. In her speech, she declared, “The issue [of bacterial resistance] is comparable to that of climate change, in the sense that both phenomena involve non-renewable global resources, both are caused by human activity and are intrinsically linked to our behaviour. The problem can only be addressed through international cooperation.” With the approval of Elinor Ostrom, this quote was later used by Otto Cars, Anna Hedin and Andreas Heddini in an article proposing action against resistance, as well as in a document intended to sound the alert about the antibiotic crisis.

2008 Identification in a Swedish patient of a bacteria with the New Delhi Metallo-beta-lactamase-1 enzyme coded by the NDM-1 gene, enabling it to resist carbapenems. [I imagine that Curitiba adversus carries the NDM-1 gene.]

2009 Creation of Walter Reed’s Multidrug Resistant Organism Repository and Surveillance Network (MRSN) which is intended to maintain a database of genes that confers resistance to antibiotics.

In the heart of the Amazon forest in Venezuela, first contacts with the Yanomami, hunters-gathers, who have a microbiota that is more diverse than that of Westerners, but also bacteria that are resistant to certain antibiotics.

Identification in Iran of strains of Mycobacterium tuberculosis resistant to all the antibiotics that can be used to fight this bacterium, which is responsible for tuberculosis.

Didier Payen and Ane-Claire Lukaszewicz demonstrate the usefulness of monitoring immunity to guide treatment using Interferon gamma and boost the immune system. [This therapeutic approach inspired the use of immunotherapy in the case of Johanna Rasmussen, which enabled her to overcome the infection].

2010 Azithromycin becomes the most prescribed antibiotic in the United States. One American in five receives this antibiotic in a year, 10 million treatments are administered to children under the age of eight, two million to children under the age of two.

The agri-food industry consumes 63,000 tons of antimicrobials per year. This should surpass 100,000 tons in 2030.

In terms of computer science, we step fully into the Big Data era. A few leading-edge hospitals start to keep data on patients and test results. [In the novel, Katelyn uses these gigantic data-mines to locate the village of Salwala, a feat that will be possible when all the health care centers on the planet will be computerized and connected.]

2011 Epidemic of Escherichia coli O104:H4 in Europe, and particularly in Germany, initially attributed to cucumbers before being attributed to sprouts.

Discovery of resistant bacteria trapped in the permafrost, dating back 30,000 years.

Andrew Read and his team demonstrate that it may not be necessary to continue antibiotic treatments until all of the bacteria has been eradicated, which encourages the selection of the most resistant strains. He is interested in defining the minimal therapeutic dosages required to prevent the emergence of resistance, which has never been done.

2012 Emmanuelle Charpentier (1968) and Jennifer Doudna (1964) and their teams discover a revolutionary method, with CRISPR-Cas9 for making genetic manipulations (occasionally called a molecular Swiss knife).

In Mexico, in a grotto that has been isolated for four million years, discovery of bacteria that is resistant to more than 14 antibiotics, which demonstrates once again that resistance is a natural phenomenon.

2013 At least 50% of the antibiotics produced are administered to animals.

Four Americans out of five take antibiotics every year.

A study reveals that 65% of Australians believe that antibiotics cure colds.

Denise Monack resolves the mystery of Mary Mallon: her macrophages probably contain Salmonella typhi. [I imagine that Curitiba adversus hides in the vampires in the same manner.]

Since 1990, eight of the 11 largest pharmaceutical laboratories have abandoned their research into antibiotics.

2014 Discovery in Japan of lysocin E which acts on the Vitamin K2 in bacterial membranes and kills bacteria. This is a completely new class of antibiotic.

First WHO report on the resistance to antibiotics: “Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill.”

In France, the Agence nationale de sécurité du médicament (ANSM) considers the fecal microbiota a medication.

It is becoming more and more obvious that the microbiota influences the brain, that the intestinal bacteria can be linked to anxiety.

In Liberia, villages affected by Ebola are quarantined. [I based my creation of the village of Salwala on this crisis.]

In a report ordered by the British government, economist Jim O’Neill estimates that by 2050 resistant bacteria will kill 10 million people each year.

Xavier Duportet (1987) and David Bikard attack the generic bacteria machinery directly, using the CRISPR-Cas9 technique.

Richard Samuel Hotchkiss describes immune parallels between cancer and infectious diseases. The same tools can be used.

Martin Blaser publishes The Missing Microbe in which he reveals the disturbing links that exist between the use of antibiotics and many diseases, ranging from asthma to autism.

2015 Discovery of teixobactin which could inaugurate a new class of antibiotics.

A Chinese team discovers the MCR-1 gene in people and pigs; this gene allows bacteria to resist colistin. Escherichia coli carriers who have this gene are very quickly identified in China, Malaysia and Europe. [I imagine that Curitiba adversus carries the MCR-1 gene.]

The CRISPR-Cas9 genetic manipulation method starts to be of concern, since it authorizes manipulations that were unthinkable up to that point.

At the age of 16, Jack Andraka invents a cancer detector which takes only five minutes while being effective as of the early stages of the disease. [I used this feat for the character of Erlend Sander who creates a new generation, paper bacterial analyzer, based on the model of the one developed at the University of Southampton.]

The “World without Antibiotics” health summit takes place in Uppsala, Sweden in May. During his presentation, Ramanan Laxminarayan shows that antibiotics no longer generate profits for the agri-food industry.

The team of Laurent Debarbieux at the Institut Pasteur demonstrates that phages are just as effective as antibiotics.

2016 For the first time, a female American patient is infected by Escherichia coli that carries the MCR-1 gene.

In July, in Paris, the Hôpital Pompidou is forced to close nine of its 24 operating rooms as a result of a nosocomial infection.

It only takes a stay of two days in a foreign country for the resistant bacteria circulating there to infect our microbiota.

Discoveries of molecules that manage to block the mechanisms of certain bacteria, specifically MRSA, and make antibiotics that had become powerless effective once again.

Discovery of lugdunin, a new antibiotic, present in the nose of one human out of six.

The Autorité européenne de sécurité des aliments (EFSA) estimates that 25,000 people die each year in Europe as a result of resistant bacteria (a figure that is largely under-estimated, compared to the report by Jean Carlet and Benoît Shlemmer who estimate 12,500 deaths in France alone for 158,000 people contracting an multi-resistant bacterial infection).

Demonstration that phagotherapy can destroy multi-resistant Escherichia coli.

According to the most recent estimates, a person weighing 70kg. is made up of 30 billion cells and is home to 38 billion bacteria weighing 0.2kg. Therefore, we have approximately as many bacteria as human cells and not ten times more, as we often read. Returning to the ratio of one to ten, we must only count the eukaryote human cells and exclude the prokaryote cells, which are ten times more numerous, such as the red blood cells.

In September, an article in Nature suggests that antibiotics should be treated as a common good. A few days later, a “high-level” working meeting on resistance took place at the United Nations.

Two-speed medicine is developing with, for example, acne cream that is sold for close to $10,000 US per tube. [I used such excesses to imagine the prohibitive price of Milton Roy’s new antibiotic.]

According to the World Bank, the proliferation of resistant bacteria could cause a decrease of 1.1 % to 3.8% in the global GDP in 2050. The poorest nations will be the first victims of such a crisis, with an excepted drop of 5% in the GDP.

Shu Lam (1991) develops a star-shaped antimicrobial polymer, that is effective against multi-resistant bacteria. Generally, the bacteriocins, whether they are secreted by micro-organisms or are synthetic, appear to be a promising alternative to antibiotics.

Australian researchers discover that the milk of Tasmanian devils contains six new antimicrobial peptides whereas human mother’s milk contains only one. [I based Katelyn’s miracle flower on these developments.]

Michael Gillings from Macquarie University demonstrates that the biodiversity of the microbiota decreases with technological development. He evokes three major bacterial extensions. [Katelyn bases her speech on these events.]

The CRyPTIC project at Oxford uses artificial intelligence algorithms to identify strains of resistant tuberculosis and propose the appropriate antibiotic treatment. [I based Lord Thompson’s sequencer on this technology].

Good news: In France, in animals, the rates of resistance are stabilizing and the sales of antibiotics continue to decline.

A study conducted in California repudiates the growth factor effect of antibiotics in children and states, in return, that the more infections children have the more risk they have of being obese.

In September, death in the United States of a patient infected in India, following an operation, by a strain of Klebsiella pneumonia, that was resistant to the 26 antibiotics likely to be able to fight that bacterium. Nevertheless, the CDC pointed out that 90% of the multi-resistant infections observed in the United States can still be treated with at last one last-resort antibiotic. On the other hand, in India, 82% of the Acinetobacter bacteria can resist all antibiotics.

A report published in the Lancet estimates that climate change, by impacting agricultural production, could kill 500,000 people per year by 2050. A WHO report estimates that the annual death rate could increase to 250,000 deaths. Combined, all of these estimates indicate that climate change could have a total human cost of one million lives per year (a figure that could be much higher if climate change multiplies the conflicts). Resistant bacteria could, therefore, kill ten times more people.

2017 The world mortality rate is 8.1%. The population is approaching 7.4 billion individuals, with 60 million deaths. It is largely due to antibiotics that we have reduced this death rate by half compared to 1900, saving approximately 60 million people per year.