Gerry Wright
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Antibiotics: behind the scenes, they enable much of modern medicine. We use them to cure infectious diseases, but also to safely facilitate everything from surgery to chemotherapy to organ transplants. Without antibiotics, even routine medical procedures can lead to life-threatening infections. And we’re at risk of losing them.

Antibiotics are chemicals that prevent the growth of bacteria. Unfortunately, some bacteria have become resistant to all currently available antibiotics. At the same time, we’ve stopped discovering new ones. Still, there’s hope that we can get ahead of the problem.

But first, how did we get into this situation? The first widely used antibiotic was penicillin, discovered in 1928 by Alexander Fleming. In his 1945 Nobel Prize acceptance speech, Fleming warned that bacterial resistance had the potential to ruin the miracle of antibiotics. He was right: in the 1940s and 50s, resistant bacteria already began to appear.

From then until the 1980s, pharmaceutical companies countered the problem of resistance by discovering many new antibiotics. At first this was a highly successful— and highly profitable— enterprise.

Over time, a couple things changed. Newly discovered antibiotics were often only effective for a narrow spectrum of infections, whereas the first ones had been broadly applicable. This isn’t a problem in itself, but it does mean that fewer doses of these drugs could be sold— making them less profitable. In the early days, antibiotics were heavily overprescribed, including for viral infections they had no effect on. Scrutiny around prescriptions increased, which is good, but also lowered sales. At the same time, companies began to develop more drugs that are taken over a patient’s lifetime, like blood pressure and cholesterol medications, and later anti-depressants and anti-anxiety medications. Because they are taken indefinitely, these drugs more profitable.

By the mid-1980s, no new chemical classes of antibiotics were discovered. But bacteria continued to acquire resistance and pass it along by sharing genetic information between individual bacteria and even across species. Now bacteria that are resistant to many antibiotics are common, and increasingly some strains are resistant to all our current drugs.

So, what can we do about this? We need to control the use of existing antibiotics, create new ones, combat resistance to new and existing drugs, and find new ways to fight bacterial infections. The largest consumer of antibiotics is agriculture, which uses antibiotics not only to treat infections but to promote the growth of food animals. Using large volumes of antibiotics increases the bacteria’s exposure to the antibiotics and therefore their opportunity to develop resistance. Many bacteria that are common in animals, like salmonella, can also infect humans, and drug-resistant versions can pass to us through the food chain and spread through international trade and travel networks.

In terms of finding new antibiotics, nature offers the most promising new compounds. Organisms like other microbes and fungi have evolved over millions of years to live in competitive environments— meaning they often contain antibiotic compounds to give them a survival advantage over certain bacteria.

We can also package antibiotics with molecules that inhibit resistance. One way bacteria develop resistance is through proteins of their own that degrade the drug. By packaging the antibiotic with molecules that block the degraders, the antibiotic can do its job.

Phages, viruses that attack bacteria but don’t affect humans, are one promising new avenue to combat bacterial infections. Developing vaccines for common infections, meanwhile, can help prevent disease in the first place.

The biggest challenge to all these approaches is funding, which is woefully inadequate across the globe. Antibiotics are so unprofitable that many large pharmaceutical companies have stopped trying to develop them. Meanwhile, smaller companies that successfully bring new antibiotics to market often still go bankrupt, like the American start up Achaogen. New therapeutic techniques like phages and vaccines face the same fundamental problem as traditional antibiotics: if they’re working well, they’re used just once, which makes it difficult to make money. And to successfully counteract resistance in the long term, we’ll need to use new antibiotics sparingly— lowering the profits for their creators even further.

One possible solution is to shift profits away from the volume of antibiotics sold. For example, the United Kingdom is testing a model where healthcare providers purchase antibiotic subscriptions. While governments are looking for ways to incentivize antibiotic development, these programs are still in the early stages. Countries around the world will need to do much more— but with enough investment in antibiotic development and controlled use of our current drugs, we can still get ahead of resistance.