August 7, 2022

Hitting the books: an ode to the joy of antibiotics

The stress and uncertainty surrounding the COVID pandemic, along with misinformation about the life-saving vaccines developed in response, has shattered many weak minds over the past two years, leading people to try everything, to inject themselves. bleach and inhale nebulized hydrogen peroxide, to bring down horse dewormer in misguided attempts to thwart modern medicine. Surprise, none of this actually works. The worst part is that this kind of behavior is not new. Quack homeopathic remedies have been around for centuries – curing bubonic plague by bleeding, self-flogging, or sitting in hot drains to chase away a fever, for example – and supported by little more than anecdotal evidence.

In their latest book, Patient Zero: A Curious History of the Worst Diseases in the World, Dr Lydia Kang and Nate Pedersen delve into the fascinating history of some of mankind’s deadliest diseases and the societal preservation work of scientists who have developed cures, vaccines and treatments to counter them. In the excerpt below, we take a look at the deployment of antibiotics and antitoxins in the fight against diphtheria, anthrax, and other deadly diseases.

Publishing worker

Extract of Patient zero: A curious history of the worst diseases in the world by Lydia Kang, MD, and Nate Pedersen. Workman © Editions 2021

Besides putting barriers between us and the plagues, the next main approach to defeating them was to attack them directly, thanks to the scientific breakthroughs that created and discovered antibiotics and antitoxins. Some of these drugs are not just used against microorganisms like bacteria, but also work as antifungals, antivirals, and antiparasitics. Today, there are more than a hundred types of drugs in this group. The World Health Organization (WHO) maintains a list of drugs deemed essential for a country’s health system to best care for its citizens, and many of these essential drugs fight infectious diseases.

Some might assume that penicillin was the first definitive weapon discovered in our fight against pathogens, but several preceded it and significantly innovated when they were discovered.

Emil von Behring, born in Prussia, was a doctor and assistant to the famous Robert Koch at the Institute of Hygiene in Berlin. In 1888 he developed a way to treat people with diphtheria and tetanus. An unfamiliar disease these days, diphtheria is prevented by a vaccine that is usually combined with your routine tetanus injection. In the 1800s, diphtheria was a terrible killer that inflamed a victim’s heart, caused paralysis, and caused a suffocating membrane to cover the throat. In Spain, the disease was so widespread in 1613 that it was dubbed El Año de los Garrotillos, or “The Year of Strangulation”.

Much of the disease caused by diphtheria is caused by the toxin created by Corynebacterium diphtheriae. Von Behring infected rats, rabbits and guinea pigs with weakened (attenuated) forms, then collected their serum – the liquid fraction of their blood, minus the red and white blood cells. This clear honey-colored liquid, which contained antibodies to diphtheria toxin, was then injected into another group of animals that were sickened by fully virulent diphtheria bacteria.

Newly infected animals given the serum did not die because they acquired a passive form of protection against the toxin with the donated serum. In 1891, the life of a child was saved for the first time thanks to this new method. Serum has been produced in large quantities using animals such as sheep and horses. At a time when 50,000 children died of diphtheria each year, it was a miracle cure.

Tetanus serum was created soon after, becoming a feasible treatment in 1915. Today, antitoxins are used to treat botulism, diphtheria, and anthrax. The same principles of antitoxin therapy are used for antivenom therapy to remedy bites from poisonous animals, including those from black widow spiders, scorpions, box jellyfish and cobras. A treatment called passive antibody therapy, in which serum from patients recovered from infection is given to other sick patients (also called convalescent plasma therapy), may have been helpful during the COVID-19 pandemic, although the data is still available. Antibodies to infections can not only treat illnesses like toxic shock syndrome, but also prevent infections during exposure, such as hepatitis A and B and botulism. But the antibodies themselves have been used to treat more than bites, stings, and infections. Intravenous immunoglobulins from pooled donors treat a variety of disorders, such as ITP (immune thrombocytopenia) and severe immunodeficiency diseases.

Another antibody therapy, monoclonal antibodies, has been a game-changer in treatments over the last decade or so, the first approved by the FDA in 1986. These specially designed antibodies are used to treat several types of cancer (melanoma, cancer). and breast cancer). stomach, among many others) and autoimmune diseases (including Crohn’s disease, rheumatoid arthritis, and psoriasis). The antibodies themselves are Y-shaped proteins that bind to a specific protein. In doing so, they can cause a whole series of effects: activating or deactivating cascades of the immune system, destroying cells, blocking or initiating cellular activities. The antibodies only bind to a single antigen, therefore “mono”, and are produced by clones of cells which produce the antibodies in large quantities. Sometimes they can also be bound to radioactive particles, delivering radioactivity directly to a cancer cell. Others may be linked to a chemotherapy agent. Often they work alone.

In the field of cancer therapy, most of us have some understanding of chemotherapy. But the origin of the term chemotherapy itself actually came from the struggle to treat infections, not cancer. By the turn of the twentieth century, antibiotics had not yet established themselves as a cure for infections. That changed with a doctor and scientist named Paul Ehrlich. He was born in 1854 in East Prussia (now Poland) where his father ran a lottery office. During his career he took advantage of the boom in the German dye industry to experiment with the appearance of cells stained with different chemicals. His love of color has led to some notable idiosyncrasies, such as carrying bits of colored pencils in his pockets. But Ehrlich’s work led to what would become the famous Ziehl-Neelsen acid-fast dye for tuberculosis. (Unfortunately, he also stained his own TB bacteria from his sputum, although he luckily survived the disease.) Later he collaborated with Nobel Prize-winning physiologist Emil von Behring on serum therapy. tetanus and diphtheria.

But Ehrlich’s most notable discovery may have happened by accident as he searched for a chemical cure to treat a specific disease – “chemotherapy”. Specifically, he hoped to cure sleeping sickness, a disease caused by a microscopic parasite called Trypanosoma brucei. He had worked with a chemical called atoxyl (meaning “non-toxic”), ironically an arsenic compound. Ehrlich coined the term “magic bullet” linked to his hope of finding that perfect chemical that would hopefully kill a very specific pathogen, the Trypanosome parasite, not the patient. He ended up testing nine hundred variants of arsenic compounds on mice. None were particularly effective, but he revisited # 606 because it appeared to have an effect on a newly discovered bacteria believed to cause syphilis. In 1910, the drug called Salvarsan (sometimes simply called “606”) proved effective: it killed the syphilis spirochete and left guinea pigs, rabbits and mice alive.

In the coming decades, new research would be applied to fight not only old pandemics, but also everyday infections that could disrupt people’s lives. A scratch or bite can kill if these Staphylococcus Where Streptococcus the infections got out of hand. A German scientist named Gerhard Domagk began working with a group of chemicals called azo dyes that had a characteristic nitrogen double bond. Azo dyes can color textiles, leather and foods in various shades of bright orange, red and yellow. When an azo compound had a sulfonamide group attached (a nitrogen and sulfur bond with two oxygen atoms doubly bonded to sulfur, if you need to impress friends at a party), they knew they had found something special. The sulfonamide group inhibits a bacteria’s ability to make folate, a necessary B vitamin. Humans, on the other hand, can get folate through their diet. And that’s how another magic bullet was born. The new compound appeared to work in mice infected with Streptococcus, otherwise known as streptococcus.

Domagk used the new drug, called KL 730 and later patented as Prontosil, on his own daughter Hildegard. Suffering from a severe strep infection, she was injected with Prontosil and recovered, although the drug left a telltale reddish discoloration at the injection site.

The “sulfa” drugs would then be used in a variety of drugs, including antibiotics (trimethoprim and sulfamethoxazole, aka Bactrim), diabetes drugs (glyburide, a sulfonylurea), diuretics (furosemide or Lasix), pain relievers (celecoxib or Celebrex), and are also used today to treat pneumonia, skin and soft tissue infections, and urinary tract infections, among others.

Domagk’s work won him the Nobel Prize in 1935. However, the Nazis, who disapproved of the way the Nobel Committee had tried to help German pacifist Carl von Ossietzky, had Domagk arrested by the Gestapo for accepting the prize. and forced him to return it. He was able to receive it later in 1947.

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