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Louis Pasteur’s scientific discoveries in the 19th century revolutionized medicine and continue to save the lives of millions today

On World Rabies Day – which is also the anniversary of French microbiologist Louis Pasteur’s death – a virologist reflects on the achievements of…

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Louis Pasteur was a pioneer in chemistry, microbiology, immunology and vaccinology. pictore/DigitalVision Vectors via Getty Images

Some of the greatest scientific discoveries haven’t resulted in Nobel Prizes.

Louis Pasteur, who lived from 1822 to 1895, is arguably the world’s best-known microbiologist. He is widely credited for the germ theory of disease and for inventing the process of pasteurization – which is named after him – to preserve foods. Remarkably, he also developed the rabies and anthrax vaccines and made major contributions to combating cholera.

But because he died in 1895, six years before the first Nobel Prize was awarded, that prize isn’t on his resume. Had he lived in the era of Nobel Prizes, he would undoubtedly have been deserving of one for his work. Nobel Prizes, which are awarded in various fields, including physiology and medicine, are not given posthumously.

During the current time of ongoing threats from emerging or reemerging infectious diseases, from COVID-19 and polio to monkeypox and rabies, it is awe-inspiring to look back on Pasteur’s legacy. His efforts fundamentally changed how people view infectious diseases and how to fight them via vaccines.

I’ve worked in public health and medical laboratories specializing in viruses and other microbes, while training future medical laboratory scientists. My career started in virology with a front-row seat to rabies detection and surveillance and zoonotic agents, and it rests in large part on Pasteur’s pioneering work in microbiology, immunology and vaccinology.

A black and white illustration of Pasteur with a group of patients.
An illustration of Louis Pasteur, right, supervising the administration of the rabies vaccine at the Pasteur Institute in Paris in 1886. Library of Congress/Interim Archives via Getty Images

First, a chemist

In my assessment, Pasteur’s strongest contributions to science are his remarkable achievements in the field of medical microbiology and immunology. However, his story begins with chemistry.

Pasteur studied under the French chemist Jean-Baptiste-André Dumas. During that time, Pasteur became interested in the origins of life and worked in the field of polarized light and crystallography.

In 1848, just months after receiving his doctorate degree, Pasteur was studying the properties of crystals formed in the process of wine-making when he discovered that crystals occur in mirror-image forms, a property known as chirality. This discovery became the foundation of a subdiscipline of chemistry known as stereochemistry, which is the study of the spatial arrangement of atoms within molecules. This chirality, or handedness, of molecules was a “revolutionary hypothesis” at the time.

These findings led Pasteur to suspect what would later be proved through molecular biology: All life processes ultimately stem from the precise arrangement of atoms within biological molecules.

Wine and beer – from fermentation to germ theory

Beer and wine were critical to the economy of France and Italy in the 1800s. It was not uncommon during Pasteur’s life for products to spoil and become bitter or dangerous to drink. At the time, the scientific notion of “spontaneous generation” held that life can arise from nonliving matter, which was believed to be the culprit behind wine spoiling.

While many scientists tried to disprove the theory of spontaneous generation, in 1745, English biologist John Turberville Needham believed he had created the perfect experiment favoring spontaneous generation. Most scientists believed that heat killed life, so Needham created an experiment to show that microorganisms could grow on food, even after boiling. After boiling chicken broth, he placed it in a flask, heated it, then sealed it and waited, not realizing that air could make its way back into the flask prior to sealing. After some time, microorganisms grew, and Needham claimed victory.

However, his experiment had two major flaws. For one, the boiling time was not sufficient to kill all microbes. And importantly, his flasks allowed air to flow back in, which enabled microbial contamination.

To settle the scientific battle, the French Academy of Sciences sponsored a contest for the best experiment to prove or disprove spontaneous generation. Pasteur’s response to the contest was a series of experiments, including a prize-winning 1861 essay.

Pasteur deemed one of these experiments as “unassailable and decisive” because, unlike Needham, after he sterilized his cultures, he kept them free from contamination. By using his now famous swan-necked flasks, which had a long S-shaped neck, he allowed air to flow in while at the same time preventing falling particles from reaching the broth during heating. As a result, the flask remained free of growth for an extended period. This showed that if air was not allowed directly into his boiled infusions, then no “living microorganisms would appear, even after months of observation.” However, importantly, if dust was introduced, living microbes appeared.

Through that process, Pasteur not only refuted the theory of spontaneous generation, but he also demonstrated that microorganisms were everywhere. When he showed that food and wine spoiled because of contamination from invisible bacteria rather than from spontaneous generation, the modern germ theory of disease was born.

Pasteur’s discoveries resonate to this very day.

The origins of vaccination in the 1800s

In the 1860s, when the silk industry was being devastated by two diseases that were infecting silkworms, Pasteur developed a clever process by which to examine silkworm eggs under a microscope and preserve those that were healthy. Much like his efforts with wine, he was able to apply his observations into industry methods, and he became something of a French hero.

Even with failing health from a severe stroke that left him partially paralyzed, Pasteur continued his work. In 1878, he succeeded in identifying and culturing the bacterium that caused the avian disease fowl cholera. He recognized that old bacterial cultures were no longer harmful and that chickens vaccinated with old cultures could survive exposure to wild strains of the bacteria. And his observation that surviving chickens excreted harmful bacteria helped establish an important concept now all too familiar in the age of COVID-19 – asymptomatic “healthy carriers” can still spread germs during outbreaks.

After bird cholera, Pasteur turned to the prevention of anthrax, a widespread plague of cattle and other animals caused by the bacterium Bacillus anthracis. Building on his own work and that of German physician Robert Koch, Pasteur developed the concept of the attenuated, or weakened, versions of microbes for use in vaccines.

In the late 1880s, he showed beyond any doubt that exposing cattle to a weakened form of anthrax vaccine could lead to what is now well known as immunity, dramatically reducing cattle mortality.

A computer-generated image of the rabies virus, colored brown in this illustration and resembling a pinecone.
The deadly rabies virus. Although preventable by vaccination, rabies still kills approximately 59,000 people worldwide every year. Nano Clustering/Science Photo Library via Getty Images

The rabies vaccine breakthrough

In my professional assessment of Louis Pasteur, the discovery of vaccination against rabies is the most important of all his achievements.

Rabies has been called the “world’s most diabolical virus,” spreading from animal to human via a bite.

Working with rabies virus is incredibly dangerous, as mortality approaches 100% once symptoms appear and without vaccination. Through astute observation, Pasteur discovered that drying out the spinal cords of dead rabid rabbits and monkeys resulted in a weakened form of rabies virus. Using that weakened version as a vaccine to gradually expose dogs to the rabies virus, Pasteur showed that he could effectively immunize the dogs against rabies.

Then, in July 1885, Joseph Meister, a 9-year-old boy from France, was severely bitten by a rabid dog. With Joseph facing almost certain death, his mother took him to Paris to see Pasteur because she had heard that he was working to develop a cure for rabies.

Pasteur took on the case, and alongside two physicians, he gave the boy a series of injections over several weeks. Joseph survived and Pasteur shocked the world with a cure for a universally lethal disease. This discovery opened the door to the widespread use of Pasteur’s rabies vaccine around 1885, which dramatically reduced rabies’ deaths in humans and animals.

A Nobel Prize-worthy life

Pasteur once famously said in a lecture, “In the fields of observation, chance favors only the prepared mind.”

Pasteur had a knack for applying his brilliant – and prepared – scientific mind to the most practical dilemmas faced by humankind.

While Louis Pasteur died prior to the initiation of the Nobel Prize, I would argue that his amazing lifetime of discovery and contribution to science in medicine, infectious diseases, vaccination, medical microbiology and immunology place him among the all-time greatest scientists.

Rodney E. Rohde has received funding from the American Society of Clinical Pathologists (ASCP), American Society for Clinical Laboratory Science (ASCLS), U.S. Department of Labor (OSHA), and other public and private entities/foundations. Rohde is affiliated with ASCP, ASCLS, ASM, and serves on several scientific advisory boards. See https://rodneyerohde.wp.txstate.edu/service/.

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Expanding the arsenal of drugs against COVID-19

Researchers from Tokyo Medical and Dental University (TMDU) have developed novel compounds with potential as drug treatments for COVID-19 by modifying…

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Researchers from Tokyo Medical and Dental University (TMDU) have developed novel compounds with potential as drug treatments for COVID-19 by modifying a previous “hit” compound that was active against the SARS-CoV virus

Credit: Department of Medicinal Chemistry, TMDU

Researchers from Tokyo Medical and Dental University (TMDU) have developed novel compounds with potential as drug treatments for COVID-19 by modifying a previous “hit” compound that was active against the SARS-CoV virus

Tokyo, Japan – The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been devastating the entire world. While the vaccination program is advancing, drug treatments for COVID-19 are still highly important for those who become infected. Now, a team at Tokyo Medical and Dental University (TMDU), National Center for Global Health and Medicine (NCGM), Tohoku University, NCI/NIH, and Kumamoto University has designed and synthesized compounds that have the potential to be novel drugs targeting SARS-CoV-2.

The SARS-CoV-2 virus contains an enzyme called the “main protease”, or Mpro, that cleaves other proteins encoded in the SARS-CoV-2 genome as part of viral activity and replication. Mpro is an important and appealing target for drugs treating COVID-19 because it is both essential for viral replication and very different from any human molecules, so drugs targeting Mpro are likely to have few side effects and be very effective.

When testing a panel of compounds known to have inhibitory activity against SARS-CoV, the virus responsible for the 2002 SARS outbreak, the team identified a compound named 5h/YH-53 that showed some activity inhibiting SARS-CoV-2 Mpro, but was inefficient and unstable. Therefore, they used 5h as a starting point to develop other compounds with increased efficiency and stability. “Our strategy involved introducing fluorine atoms into the part of the molecule responsible for inhibiting Mpro to increase its binding affinity, as well as replacing a bond within 5h that is easily broken down by the liver with a different structure to increase biostability,” explains lead author Kohei Tsuji.

“Of the compounds we developed, compound 3 showed high potency and was able to block SARS-CoV-2 infection in vitro without any viral breakthrough,” explains senior author Hirokazu Tamamura. “Compound 4, a derivative of compound 3 in which an easily broken-down amide bond had been replaced with a stable thioamide bond, also showed remarkable anti-SARS-CoV-2 activity.” Although compound 4 had lower Mpro inhibitory activity than compound 3, the increased stability meant that the overall activity of compound 4 was comparable to that of compound 3.

When they tested these novel compounds on a variety of strains of SARS-CoV-2, compound 3 was as effective on mutant strains of the virus as on the ancestral Wuhan strain. Additionally, neither compound 3 or 4 showed any toxicity to cultured cells. These data suggest that these compounds show high potential as drug treatments for COVID-19.

A repertory of drug choice is important for treating disease, and so the development of efficient drugs to target the novel SARS-CoV-2 virus is highly important. This work identifies two compounds as potential drugs, and further development of these compounds continues. It also proves the principle that easily broken-down amide bonds can be replaced with thioamide bonds in drug development to increase the stability of the resulting compounds. Taken together, this is an important advance in both the wider drug development field as well as for drugs to treat COVID-19.

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The article, “Potent and Biostable Inhibitors of the Main Protease of SARS-CoV-2”, was published in iScience at DOI: 10.1016/j.isci.2022.105365
 


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Team undertakes study of two-dimensional transition metal chalcogenides

Two-dimensional materials, like transition metal dichalcogenide, have applications in public health because of their large surface area and high surface…

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Two-dimensional materials, like transition metal dichalcogenide, have applications in public health because of their large surface area and high surface sensitivities, along with their unique electrical, optical, and electrochemical properties. A research team has undertaken a review study of methods used to modulate the properties of two-dimensional transition metal dichalcogenide (TMD). These methods have important biomedical applications, including biosensing.

Credit: Nano Research Energy, Tsinghua University Press

Two-dimensional materials, like transition metal dichalcogenide, have applications in public health because of their large surface area and high surface sensitivities, along with their unique electrical, optical, and electrochemical properties. A research team has undertaken a review study of methods used to modulate the properties of two-dimensional transition metal dichalcogenide (TMD). These methods have important biomedical applications, including biosensing.

 

The team’s work is published in the journal Nano Research Energy on November 23, 2022.

 

The team’s goal is to present a comprehensive summarization of this promising field and show challenges and opportunities available in this research area. “In this review, we focus on the state-of-the-art methods to modulate properties of two-dimensional TMD and their applications in biosensing. In particular, we thoroughly discuss the structure, intrinsic properties, property modulation methods, and biosensing applications of TMD,” said Yu Lei, an assistant professor at the Institute of Materials Research, Shenzhen International Graduate School, Tsinghua University.

 

Since graphene was discovered in 2004, two-dimensional materials, such as TMD, have attracted significant attention. Because of its unique properties, two-dimensional TMD can serve as the atomically thin platforms for energy storage and conversion, photoelectric conversion, catalysis, and biosensing. TMD also displays a wide band structure and has unusual optical properties. Yet another benefit of two-dimensional TMD is that it can be produced in large quantities at a low cost.

 

In public health, reliable and affordable in vitro and in vivo detection of biomolecules is essential for disease prevention and diagnosis. Especially during the COVID-19 pandemic, people have suffered not only from the physical disease, but also from the psychological problems related to extensive exposure to stress. Extensive stress can result in abnormal levels in biomarkers such as serotonin, dopamine, cortisol, and epinephrine. So, it is essential that scientists find non-invasive ways to monitor these biomarkers in body fluids, such as sweat, tears, and saliva. In order for health care professionals to quickly and accurately assess a person’s stress and diagnose psychological disease, biosensors are of significant importance in the diagnostics, environmental monitoring, and forensic industries.

 

The team reviewed the use of two-dimensional TMD as the functional material for biosensing, the approaches to modulate the properties of TMD, and different types of TMD-based biosensors including electric, optical, and electrochemical sensors. “Public health study is always a major task in preventing, diagnosing, and fighting off the diseases. Developing ultrasensitive and selective biosensors is critical for diseases prevention and diagnosing,” said Bilu Liu, an associate professor and a principal investigator at Shenzhen Geim Graphene Center, Shenzhen International Graduate School, Tsinghua University.

 

Two-dimensional TMD is a very sensitive platform for biosensing. These two-dimensional TMD based electrical/optical/electrochemical sensors have been readily used for biosensors ranging from small ions and molecules, such as Ca2+, H+, H2O2, NO2, NH3, to biomolecules such as dopamine and cortisol, that are related to central nervous disease, and all the way to molecule complexities, such as bacteria, virus, and protein.

 

The research team determined that despite the remarkable potentials, many challenges related to TMD-based biosensors still need to be solved before they can make a real impact. They suggest several possible research directions. The team recommends that the feedback loop assisted by machine learning be used to reduce the testing time needed to build the database needed for finding the proper biomolecules and TMD pairs. Their second recommendation is the use of a feedback loop assisted by machine learning to achieve the on-demand property modulation and biomolecules/TMD database. Knowing that TMD-based composites exhibit excellent performance when constructed into devices, their third recommendation is that surface modifications, such as defects and vacancies, be adopted to improve the activity of the TMD-based composites. Their last recommendation is that low-cost manufacturing methods at low temperature be developed to prepare TMD. The current chemical vapor deposition method used to prepare TMD can lead to cracks and wrinkles. A low-cost, low-temperature method would improve the quality of the films. “As the key technical issues are solved, the devices based on two-dimensional TMD will be the overarching candidates for the new healthcare technologies,” said Lei.

 

The Tsinghua University team includes Yichao Bai and Linxuan Sun, and Yu Lei from the Institute of Materials Research, Tsinghua Shenzhen International Graduate School and the Guangdong Provincial Key Laboratory of Thermal Management Engineering and Materials, Tsinghua Shenzhen International Graduate School; along with Qiangmin Yu and Bilu Liu from the Institute of Materials Research, Tsinghua Shenzhen International Graduate School, and the Shenzhen Geim Graphene Center, Tsinghua-Berkeley Shenzhen Institute & Institute of Materials Research, Tsinghua Shenzhen International Graduate School.

 

This research is funded by the National Natural Science Foundation of China, the National Science Fund for Distinguished Young Scholars, Guangdong Innovative and Entrepreneurial Research Team Program, the Shenzhen Basic Research Project, the Scientific Research Start-up Funds at Tsinghua Shenzhen International Graduate School, and Shenzhen Basic Research Project.

 

##

 

About Nano Research Energy 

 

Nano Research Energy is launched by Tsinghua University Press, aiming at being an international, open-access and interdisciplinary journal. We will publish research on cutting-edge advanced nanomaterials and nanotechnology for energy. It is dedicated to exploring various aspects of energy-related research that utilizes nanomaterials and nanotechnology, including but not limited to energy generation, conversion, storage, conservation, clean energy, etc. Nano Research Energy will publish four types of manuscripts, that is, Communications, Research Articles, Reviews, and Perspectives in an open-access form.

 

About SciOpen 

 

SciOpen is a professional open access resource for discovery of scientific and technical content published by the Tsinghua University Press and its publishing partners, providing the scholarly publishing community with innovative technology and market-leading capabilities. SciOpen provides end-to-end services across manuscript submission, peer review, content hosting, analytics, and identity management and expert advice to ensure each journal’s development by offering a range of options across all functions as Journal Layout, Production Services, Editorial Services, Marketing and Promotions, Online Functionality, etc. By digitalizing the publishing process, SciOpen widens the reach, deepens the impact, and accelerates the exchange of ideas.

 


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Climate-Change Lockdowns? Yup, They Are Actually Going There…

Climate-Change Lockdowns? Yup, They Are Actually Going There…

Authored by Michael Snyder via The End of The American Dream blog,

I suppose…

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Climate-Change Lockdowns? Yup, They Are Actually Going There...

Authored by Michael Snyder via The End of The American Dream blog,

I suppose that we should have known that this was inevitable.  After establishing a precedent during the pandemic, now the elite apparently intend to impose lockdowns for other reasons as well.  What I have detailed in this article is extremely alarming, and I hope that you will share it with everyone that you can.  Climate change lockdowns are here, and if people don’t respond very strongly to this it is likely that we will soon see similar measures implemented all over the western world.  The elite have always promised to do “whatever it takes” to fight climate change, and now we are finding out that they weren’t kidding.

Over in the UK, residents of Oxfordshire will now need a special permit to go from one “zone” of the city to another.  But even if you have the permit, you will still only be allowed to go from one zone to another “a maximum of 100 days per year”

Oxfordshire County Council yesterday approved plans to lock residents into one of six zones to ‘save the planet’ from global warming. The latest stage in the ’15 minute city’ agenda is to place electronic gates on key roads in and out of the city, confining residents to their own neighbourhoods.

Under the new scheme if residents want to leave their zone they will need permission from the Council who gets to decide who is worthy of freedom and who isn’t. Under the new scheme residents will be allowed to leave their zone a maximum of 100 days per year, but in order to even gain this every resident will have to register their car details with the council who will then track their movements via smart cameras round the city.

Are residents of Oxfordshire actually going to put up with this?

[ZH: Paul Joseph Watson notes that the local authorities in Oxford tried to ‘fact check’ the article claiming they’re imposing de facto ‘climate lockdowns’, but ended basically admitting that’s exactly what they’re doing...]

I never thought that we would actually see this sort of a thing get implemented in the western world, but here we are.

Of course there are a few people that are loudly objecting to this new plan, but one Oxfordshire official is pledging that “the controversial plan would go ahead whether people liked it or not”.

Ouch.

Meanwhile, France has decided to completely ban certain short-haul flights in an attempt to reduce carbon emissions…

France can now make you train rather than plane.

The European Commission (EC) has given French officials the green light to ban select domestic flights if the route in question can be completed via train in under two and a half hours.

The plan was first proposed in 2021 as a means to reduce carbon emissions. It originally called for a ban on eight short-haul flights, but the EC has only agreed to nix three that have quick, easy rail alternatives with several direct connections each way every day.

This is nuts.

But if the French public accepts these new restrictions, similar bans will inevitably be coming to other EU nations.

In the Netherlands, the government is actually going to be buying and shutting down approximately 3,000 farms in order to “reduce its nitrogen pollution”

The Dutch government is planning to purchase and then close down up to 3,000 farms in an effort to comply with a European Union environmental mandate to slash emissions, according to reports.

Farmers in the Netherlands will be offered “well over” the worth of their farm in an effort to take up the offer voluntarily, The Telegraph reported. The country is attempting to reduce its nitrogen pollution and will make the purchases if not enough farmers accept buyouts.

“There is no better offer coming,” Christianne van der Wal, nitrogen minister, told the Dutch parliament on Friday.

This is literally suicidal.

We are in the beginning stages of an unprecedented global food crisis, and the Dutch government has decided that now is the time to shut down thousands of farms?

I don’t even have the words to describe how foolish this is.

Speaking of suicide, Canada has found a way to get people to stop emitting any carbon at all once their usefulness is over.  Assisted suicide has become quite popular among the Canadians, and the number of people choosing that option keeps setting new records year after year

Last year, more than 10,000 people in Canada – astonishingly that’s over three percent of all deaths there – ended their lives via euthanasia, an increase of a third on the previous year. And it’s likely to keep rising: next year, Canada is set to allow people to die exclusively for mental health reasons.

If you are feeling depressed, Canada has a solution for that.

And if you are physically disabled, Canada has a solution for that too

Only last week, a jaw-dropping story emerged of how, five years into an infuriating battle to obtain a stairlift for her home, Canadian army veteran and Paralympian Christine Gauthier was offered an extraordinary alternative.

A Canadian official told her in 2019 that if her life was so difficult and she so ‘desperate’, the government would help her to kill herself. ‘I have a letter saying that if you’re so desperate, madam, we can offer you MAiD, medical assistance in dying,’ the paraplegic ex-army corporal testified to Canadian MPs.

“Medical assistance in dying” sounds so clinical.

But ultimately it is the greatest lockdown of all.

Because once you stop breathing, you won’t be able to commit any more “climate sins”.

All over the western world, authoritarianism is growing at a pace that is absolutely breathtaking.

If they can severely restrict travel and shut down farms today, what sort of tyranny will we see in the future?

Sadly, most people in the general population still do not understand what is happening.

Hopefully they will wake up before it is too late.

*  *  *

It is finally here! Michael’s new book entitled “End Times” is now available in paperback and for the Kindle on Amazon.

Tyler Durden Fri, 12/09/2022 - 06:30

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