Bestiary of human epidemics and the Struggles of digitisation in Microbiology
The coronavirus epidemic has become a great challenge for all of us for many reasons. Some lost their jobs, others experienced an acute lack of human communication during quarantine. But of course, those who experienced complications from the disease, lost relatives and friends, or died from a cytokine storm caused by covid were the most unlucky. Sars-cov 2 caused previously unthinkable changes in our daily lives, dealt a blow to the economy, the healthcare system, and exerted enormous psychological pressure on the entire society.
The coronavirus pandemic has caused consequences that no one was prepared for. Humanity has managed to build a developed healthcare system, pharmaceuticals and implemented a hygienic revolution. We have vaccination, antibiotics, and a system for diagnosing infectious diseases, which has allowed us to drive the deadliest microorganisms into remote areas of Africa or Asia. And even there, in the conditions of almost complete absence of civilisation, these diseases mainly affect animals, occasionally infecting people. And out of nowhere, a new virus appears, which quarantines the entire planet, kills millions of people and causes hysteria of the whole society.
Dear reader, I have some bad news for you. This is just the beginning of a future cycle of epidemics, each of which will be scarier than the previous one. Pathogenic microorganisms have always been living with us, they will always keep evolving, adapting to us, bypassing our system of protection against them. The goal of any pathogenic microbe is to live, eat and reproduce at our expense, but be less harmful for us, to keep the chance of their survival is much higher. But sometimes mutations happen that turn an almost harmless microorganism into a real killing machine, destroying half of humanity and changing the course of history. And today we will figure out how to properly keep a record of the occurrence of such mutations, how to predict them, how useful it is to study these microorganisms, and most importantly, look at how specialised software will help us in the eternal struggle against microbes.
For starters, lets recall some of history’s most significant epidemics in recorded history, and how they were contained.
1. For a general understanding of the scale of each disease, let’s start with covid. The epidemic began in 2019 and continues to this day (April 2023). During all this time, the virus has killed from 7 to 29 million people, depending on the source of information, which is 0.1–0.4% of the human population. The measures to combat the virus included vaccination (which lead to the development of immunity against the virus), quarantine (isolation of the population at the place of residence), and the use of personal protective equipment in the form of latex gloves and respiratory masks. These measures were primarily aimed at reducing the rate of spread of the virus, which was necessary to reduce the burden on hospitals. But even in such conditions, we often faced cases of shortage of places in some hospitals.
2. The disease is very similar to today’s covid — Spanish flu, which, according to various sources, killed up to 100 million people, which is about 5% of the world’s population in the period from 1918 to 1920. The respiratory virus killed mainly young people with strong immunity, causing a cytokine storm — a condition that causes the destruction of the tissues of the focus of inflammation, at the same time the reaction spreads to neighbouring tissues and, as it develops, acquires a systemic character, covering the entire body. In part, the spread of the virus was facilitated by the military actions of the First World War. Soldiers with a mild form of the disease remained in the trenches, and with a severe form they went to hospitals. In both cases, there was a very rapid spread of the virus due to the mass congestion of people. Stress, hunger and migration also contributed to the development of the epidemic. Quarantine, social distancing, and wearing face masks were used as measures to counteract the spread of the disease. There have been attempts at vaccination, but they were mistakenly carried out against bacteria found in patients, and not against the virus.
3. HIV. A real pandemic that has engulfed the entire planet, but does not cause acute panic among the population due to a long latent period, as well as the fact of a long period from the moment of infection to the death of the patient, which can last for decades. At the moment, 40 million people have become victims of HIV, and about the same number are carriers of it. According to one of the scientific hypotheses, HIV was transmitted to humans from primates in the late 19th — early 20th century, and only in 1981 the first case of human infection was officially registered. HIV is transmitted through unprotected sexual intercourse, through blood, breast milk, as well as during pregnancy and childbirth from mother to child. HIV kills by weakening the immunity of its carrier, resulting in death even from those microorganisms that do not pose a danger to a healthy person.
The methods of combating the virus include antiretroviral therapy, which reduces the viral load on the patient to zero. An HIV-infected patient receiving such treatment can have unprotected sexual contacts without the risk of infecting a partner, and is also able to conceive and, in case of pregnancy, give birth to an unaffected child. However, it is impossible to completely cure a person at the moment, the virus remains in the body and when treatment is canceled, the disease continues to progress. The development of accessible diagnostics is extremely important, because due to the long latency period, millions of people are unaware of the presence of the disease and participate in its spread.
4. The absolute record holder in terms of the number of victims is the black death or the plague, which claimed the lives of up to 200 million people or 54% of the world’s population in the period from 1346 to 1353. Although this is the most massive plague epidemic, but far from the only one, about 80 plague epidemics have swept the world, so the number of victims in the entire history of mankind is much greater. Bacterial infection is transmitted through the bites of rat fleas, and subsequently by airborne droplets from person to person, causing a pulmonary form of the disease. Trade and migration contributed to the spread of the disease, as black rats migrated along with people whose fleas were the main source of infection. Unsanitary conditions among the population, additional concomitant infections, hunger, and large crowding of the population in cities also contributed to the rapid spread of the disease.
The symptoms of the plague include general malaise, nausea, vomiting, high fever and fever, joint pain, cough, sputum with blood. Most often, people die between two and seven days after infection. This epidemic has left a huge mark on world history, affecting all spheres of life — from art and religion, to economics and scientific and technological progress.
It was to protect against the plague by the XVII century that probably the most charismatic protective suits in history appeared, the image of which is still popular in art.
If we discard useless methods of treatment based on the stereotypical thinking of people of that time, namely prayers, bloodletting, cauterisation of bubons and the use of dried toads, then quarantine can be attributed to the most adequate methods of preventing the spread of the disease, for example, strangers were not allowed in some cities, self–isolation — some people went away from cities and lived alone, successfully waiting out the epidemic. Also an important factor was the timely detection and disposal of the corpses of former patients.
The main question that arises after studying each epidemic is why did it end? Why did the Spanish flu or the black death suddenly come to naught and disappear? Of course, this is partly due to measures aimed at treating patients and against the spread of the disease. It is also worth mentioning natural selection — people who are prone to infection and a severe form of the disease die, but those who are resistant, and able to transfer the disease in a mild form, or who cannot get infected remain. An important factor is the adaptation of the microorganisms themselves. The fact is that it is not profitable for any parasite to kill its host, but it is better to use it unnoticed and for as long as possible. A deadly virus that kills any carrier in 24 hours is doomed to extinction along with its hosts, and a microorganism that is almost invisible to the carrier is doomed to success and a long life on this planet. That is why a deadly microorganism “understands” that it has made a mistake and rearranges its genome using natural mechanisms so as to be less harmful.
The question of the nature of the pathogen of a future new pandemic is quite interesting. The most massive epidemics of the past were more often associated with bacterial infection. Plague, anthrax, cholera are caused by bacteria, against which we have developed a powerful weapon — antibiotics. But increasingly, information about antibiotic resistance appears in scientific publications. For example, Mycobacterium tuberculosis, the bacteria that cause tuberculosis, is already resistant to most readily available antibiotics, and there are more and more such resistant bacteria. Right now, in real time, we can observe, perhaps, the most significant war in the history of mankind, in which there is a constant arms race between world pharmacology and bacteria adapting to all the weapons of humanity directed against them.
Another pathogen that poses a danger to a reasonable person are viruses. The Spanish flu, HIV and coronavirus have dealt humanity a big deal of trouble. Unlike most pathogens, viruses mutate quickly, are easily transmitted and simply penetrate into the human body, which makes their spread very fast. Nowadays, specific antiviral drugs are being developed that block the receptors of healthy cells, preventing the virus from invading, or making it impossible for the virus to reproduce in the host cells. But the simplest and most studied way to resist viruses is vaccination, which does not guarantee 100% protection, but gives a good chance not to get sick. With the help of vaccination, we were able to defeat polio, measles and smallpox.
For the record, the world has never faced a pandemic caused by a fungal infection. Yes, outbreaks of fungal diseases often occur, massively destroying animals, but as a rule this applies to cold-blooded ones, we are too hot for mushrooms, so far our body temperature protects us. We are used to looking at fungal infections as frivolous diseases that are not spoken aloud, because in our minds they affect the genitals, feet or nails, but already about 1.5 million people die from fungal infections in the world every year. Yes, fungi mutate thousands of times slower than viruses, which does not allow them to take so many forms and adaptations to infect humans, and the number of fungi contagious to humans is only about 200 species, but science has not studied these pathogens enough, and funding for antifungal drugs has always been insufficient. As a result, we know how to fight viruses and bacteria, but our military strategy against fungal infections is only at the beginning of its formation. Most recently, WHO published a list of the 19 most pathogenic fungi, with the allocation of a “critical group”: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans and Candida auris. Candida auris is already terrorizing US hospitals, aggravating the condition of patients with other infections and those with weakened immunity, as well as outbreaks of infection occur in other countries.
The role of software in containing pandemics
Humanity has faced epidemics too many times that have affected the course of history, destroyed entire cities and left a deep mark on world culture in this regard. In order to protect our future and minimise the future harm dealt from new pandemics, collections of pathogenic microorganisms have been created around the world. A little later, when the genetic foundations of the pathogenicity of microbes were discovered, digital databases of genomes of bacteria, viruses and fungi began to emerge. Below is a roundup of digital platforms created to study and fight against pathogenic microorganisms.
Global pathogen analysis service
A platform based on cloud data storage. A participating laboratory can upload raw genome sequencing data of a pathogenic microorganism to the platform and obtain an aligned sequenced genome after a short period of time. In addition, the platform automatically compares the genome of “your” pathogen with the genomes of pathogens of the same species all over the planet, which allows you to find new mutations, practically, in real time, which is very useful for tracking morbidity and further forecasting.
PANDEM-2
A project funded by the European Union, designed to protect European citizens from future epidemics. The project is also based on a database that collects information about the spread of the pathogen, on the basis of which it is possible to quickly obtain data on the course of the pandemic, make forecasts and make decisions on combating the source of infection.
Mypathogen
A database for searching, downloading, storing and exchanging data on bacterial genetics. Mypathogen is a useful tool for analysis and management in genomic research, especially for clinical centers for disease Control and epidemiological studies. It allows specialists from all over the world to “be closer” and exchange information faster, make forecasts and take measures to combat epidemics.
The National Center for Biotechnology Information (NCBI)
https://www.ncbi.nlm.nih.gov/genome/microbes/
A huge database with a mapped genome of microorganisms. When studying the genome of a particular microorganism, it is possible to use scaling, which allows you to follow the sequence of the genetic code in detail.
A standard for future pathogen analysis software
After analysing the currently available solutions and databases, we can conclude about the necessary qualities that a universal program should exhibit to provide the necessary tools to solve the problems of modern epidemiologists:
1. International coverage. A specialist who has confirmed qualifications on the website should be able to upload, download and compare data from anywhere in the world.
2. A said researcher must have a personal account with work history, projects, and an archive. The database should be relatively open, so that data is accessible to biology enthusiasts who visited the site. Uploading to new data into the database and changing data should be restricted for qualified specialists.
3. The genome must be mapped and divided into chromosomes if the genome of the microorganism meets basic platform requirements. A specialist should be able to study any chromosome, using scaling to find the right gene and analyse it.
4. A manual and automatic genome comparison toolkit should be available
5. There should be an ability to create projects for scientists located in different parts of the world, but performing similar projects.
6. Detailed information about the owner of the data uploaded to the database, as well as the restrictions of the copyright holder imposed on this data. Some researchers will allow you to use your information as you like, and someone will want to give you the opportunity only to look and compare, but not to make primers for PCR or DNA probes for FISH research based on the data. Just like github, but for researching microorganisms.
7. Automatic alignment and sequencing of the genome by downloadable reads. This feature will especially attract customers and save them a lot of time.
What can be improved?
There are laboratories and even countries out there with their own pathogen databases, which, sometimes, are merely plain spreadsheets with data. Now, despite the untidiness of this approach to the creation, design and storage of pathogen databases, the value of their scientific information remains invaluable to the scientific community, however, we believe that the advent of a new global platforms with a multifunctional interface that leverage existing taxonomic data can give a boost to the efforts of the global scientific community studying pathogens.
Why do we need such platforms? Well, one of the most straightforward answer is for a successful choice of treatment strategy in case of an outbreak. For example, one of our researchers at HMND was involved in the study of antibiotic resistance of helicobacter pylori, a phenomenon in which bacteria are not susceptible to antibiotic treatment, respectively, a different strategy is chosen for their destruction. And it was the analysis of scientific literature and open databases that made it possible to construct the necessary DNA probe to detect mutations of resistance to clarithromycin in bacteria by the FISH method. And of course, after achieving the desired result, the sequence of this probe forever replenished our personal collection of working oligonucleotides.
Now what if all or at least some of the above tools were consolidated on a single platform that studies pathogenic microorganisms in a manner similar to kaggle?
With readily available, detailed study of many species and strains of microorganisms, combined with some knowledge of natural biological laws, it is possible to predict the vector of development of a particular microorganism, which means to develop the right vaccine in time, or take the necessary protection measures at the state level in advance. With the above, it would also become possible to track the spread of infection, determine the origin and potential zero patient.
Another important factor is the determination of the type of animals that can carry this or that infection. For example, the plague that has been defeated on most of the planet may be in remote parts of the world in the organisms of rats, cats, camels or ground squirrels, developing new deadly properties and waiting in the wings to start a new pandemic that will once again reformat humanity and world history.
We cannot know in advance when the next epidemic will start and where the pathogen will come from. Perhaps it will be bacteria preserved in the now melting glaciers, or a virus from the virgin forests, where people will come in search of cheap resources, or perhaps it will be a fungus from the tomb of some ancient king, whose rest will be disturbed by archaeologists. In any case, we must prepare in advance for future blows of evolution, not only by developing pharmacology and hygiene, but also through uniting our efforts and preparing a collaborative digital platform for the study of pathogenic microorganisms as a weapon for our next battle with pathogenic microorganisms.
