0033 // Our Mortal Drugs: Looking for the Birth of New Antibiotics

Our
Mortal
Drugs

Looking for the Birth of New Antibiotics
David Mogolov

A great poetic tragedy sits at the heart of one of our greatest medical breakthroughs. Antibiotics, the life-saving drugs that have shaped our modern world as surely as our technology, are as mortal as we are.

Antibiotics, though not alive, are the product of living things. The first known modern antibiotic, penicillin, was found oozing from a fungus in a petri dish. The others have all come from similar micro-organisms.

Though these drugs derive from genetically primitive processes, it is beyond our current ability to invent them: we can only synthesize and modify them once we’ve discovered them. Discovery at such a miscroscopic scale, it turns out, is hard to come by.

We’ve always known that these drugs – drugs which look more like magic than any discovery in the history of medicine – were going to decline in efficacy and would eventually fail to control the infections they’ve so carefully tamed. Antibiotics – mortals, all – could beat back our bacteria for a while, but the germs? The germs are machines, tiny Schwarzeneggerian killing machines. We knew they’d learn and adapt.

Alexander Fleming, whose accidental discovery of penicillin in 1928 kicked off the golden age of antibiotics, warned of this decline at the conclusion of his 1945 Nobel Lecture. “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.”

The end was written into the beginning.
‍The source of our amnesia about Fleming’s warning is in our victories: Look at the Murderer’s Row of diseases reduced to memories or inconveniences through the use of antibiotics: Tuberculosis. Pneumonia. Whooping cough. Syphilis. Rheumatic Fever. Gonorrhea. Diphtheria.

Paired with a revolution in vaccine development, the mid-20th century saw the eradication or control of most bacterial illnesses. Doctors now had the upper hand where once they’d only been able to throw them up and say, “Let me give you something for the pain.”

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From roughly the 1940s until the 1980s, doctors received a windfall of new antibiotic classes, discovering drugs and enhancing those we already had.

Some, like penicillin, attack the proteins in bacterial cell walls, utterly destroying live infections.

Others, like ciprofloxacin, disrupt the microbes’ abilities to reproduce their DNA, preventing the spread of infection.

Still others, like sulfonamides, act almost as a counter-infection within the microbe, disrupting its cellular metabolism, causing it to dwindle and die.
All of this happens without harming the patient’s own cells: the antibiotics target cellular features particular to bacteria.

During the golden age of antibiotic discovery, more or less from the 1950s to the 1980s, first-world life expectancy has increased by 20 to 30 years. It’s impossible to say exactly how much this is due to antibiotics rather than, say, vaccines, sanitation, or safety engineering, but ask the next hundred doctors you see.

Then ask them if they’re worried about antibiotic resistance. They are. It’s one of the biggest problems in medicine. You might wonder how we haven’t prepared. After all, you ask...
“Didn’t Dr. Fleming warn us this was going to end?”

He did. In that same Nobel Lecture, he said, “Moral: If you use penicillin, use enough.” And he was right. We’ve trained our germs to punch penicillin in its wall-destroying face. Underdosage was only the start.

We’ve distributed antibiotics for low-level illnesses that weren’t serious, or for which they weren’t even effective (“Doc, give me an antibiotic for this virus”). We’ve pumped our livestock full of them, as a preventative measure. We’ve put them in hand soaps. Dr. Fleming had no idea how much we’d take his miracle for granted.

Antibacterial resistance, once a condition only observable in a petri dish, is now observable daily in hospitals worldwide. The CDC reports that 40% of strep infections are caused by bacteria that are immune to at least one antibiotic. Methicillin-resistant Staphylococcus aureus, making headlines worldwide as MRSA, is an antibiotic-resistant infection that’s already mutated into varieties resistant to nearly the entire antibiotic arsenal.
The problem is acute. Better control over our use of antibiotics will help prolong their efficacy and will slow the evolution of antibiotic-resistant bacteria, but what we need more than anything else is new antibiotics.

That’s one reason the January 2015 announcement of teixobactin was so exciting. After 30 years without the discovery of a new class of antibiotics, here was the potential for one. It attacks the fat in bacterial cell walls, a mechanism we’ve never seen before. In the lab, it’s been tremendously effective.
Teixobactin is not in clinical trials yet. We don’t know how it will work in the human body. We don’t know how it can be effectively cultivated and produced. It may never be part of our arsenal against bacteria. But it is exciting.

Developing medicines from micro-organisms is a delicate process, and the lab has killed many more than it has bred. Teixobactin was found and cultivated using a tiny device inserted into the soil, outside the lab. Regardless of the drug’s success, the potential for antibiotic discovery seems greater than it has in decades.

We should be rooting for teixobactin, because we need new drugs. The danger of a world with unchecked antibiotic-resistant infection is the stuff of dystopian fiction (or, if you only have 15 minutes, an early episode of the podcast
"Meanwhile in the Future").

Our relationship with antibiotics and bacteria will never be a settled one. Bacteria will continue to adapt and thrive. If we want to do the same, we can’t forget the mortality of our drugs.

The germs certainly won’t.