Q&A: The end of the antibiotic age?

Antibiotics have saved millions of lives – but there is now growing concern that their misuse and overuse is making them less effective as bacteria develop resistance. Despite scientists’ warning, antibiotic prescriptions in many countries continue to grow.

Venki Ramakrishnan, a Nobel Prize-winning chemist based at the Laboratory of Molecular Biology in Cambridge University, tells us about the importance of gaining a better understanding of the use and misuse of these wonder drugs.

The world seems to be running out of antibiotics. If in the middle of the 20th century, more than 20 new classes of antibiotics were marketed, since the 60s only two new classes have reached the market. Why is that the case?

It’s not entirely clear. Because of the effort to make penicillin during the World War II, and its success, there was a strong motivation to look for other antibiotics. So in the 40s and 50s there were lots of new antibiotics that were being discovered.

But then it became a law of diminishing return for the number of new compounds that could be effective. Because to be effective, an antibiotic has to be able not just to kill bacteria, but you have to be able to make it cheaply, and it has to be safe. So the number of really new compounds has diminished and a lot of drug companies were modifying known antibiotics, trying to make them better and more effective.

There have been recent reports of a breakthrough – a new antibiotic that “kills pathogens without detectable resistance”. What do you think of this advance?

Indeed, there was a very interesting report on an antibiotic from a soil bacterium that does represent a new class. Many bacteria cannot be cultured, but the researchers used a clever trick to obtain a reasonable amount of this bacterium and isolate a new class of antibiotics from it. How useful it will be in humans still remains to be seen, because it still has to go through the clinical trials.

The other issue is resistance. In the paper they claim that this antibiotic, because of the way it acts, is unlikely to lead to resistance. But people have said this about many different things before, and eventually resistance seems to develop. I would be a little cautious to say that no resistance will ever develop to anything, because natural selection is very powerful and has a way of defeating even the most powerful tools. Still, it seems very promising.

Researchers are now waging a war against antibiotic-resistant bacteria. What exactly is being done?

There are several aspects to the problem of antibiotic resistance. It’s very important to have highly specific targets, which kill the particular bacterium that’s causing the disease rather than using a spectrum of antibiotics that should only be used as a last resort when you don’t know what the disease is caused by and you don’t have time.

But there’s a larger problem – the problem of resistance is also due to an abuse of antibiotics. Many people will go to a doctor and demand an antibiotic when they have a cold or a flu, for which these antibacterial compounds are useless. In many countries, it is possible to buy antibiotics over the counter. Often, if people are poor, they will not take the full dose – all of that leads to resistance.

In countries like India, people will give you antibiotics prophylactically, as a way to prevent infection. This should only be done in very extreme cases, because it’s again spreading resistance.

So is the problem limited mostly to the developing world?

Not at all. In addition to also prescribing antibiotics for the flu, the West, in agriculture uses antibiotics in cattle feed to fatten up the cattle – that’s an abuse of antibiotics. This leads to the spread of resistant strains, rendering current antibiotics useless if resistance spreads too much.

We need better diagnostics, to allow us to very quickly diagnose a bacterium that is causing a particular disease, to then treat it specifically with a narrow spectrum of antibiotics. And finally, there’s a whole issue of better public hygiene.

People now move all over the world so if resistance emerges in one place it can very quickly spread to other places. So it needs a concerted attack – it is a broad social problem.

Are you confident we can win this war against resistant bacteria?

I am an optimist. I think that when things get serious, people have a habit of responding. And I’m hoping that people don’t wait for a big crisis to respond because then a lot of people will die and eventually things will get corrected and improve.

I would prefer that governments in a worldwide agreement establish certain guidelines for antibiotics use, for public health, for hygiene, for use of antibiotics in the animal industry, and also will promote science – get better diagnostics, better understanding how bacteria cause disease, and for the development of new antibiotics.

What would a world without antibiotics look like?

I don’t think there ever will be a world without antibiotics. In a worst-case scenario, if resistant strains emerge to all known antibiotics, there will be large epidemics until new antibiotics are found. It won’t be like returning to the dark ages because now we have a huge amount of knowledge about how bacteria work, about molecular biology, genetics, microbiology, and about how to make antibiotics. But we have to be proactive.

Are there any alternatives to antibiotics?

Antibiotics should be used as a last resort. Apart from general preventive measures like public health and hygiene, vaccines can be of enormous benefit. If we can develop good vaccines for many serious diseases, that would be wonderful. However vaccine development is a difficult enterprise and it can take a long time in any given case. Sometimes it has failed despite many years of work.

Bacteriophages – naturally occurring viruses that attack specific bacteria – have sometimes been mentioned as possible tools. Although they were discovered in the early 20th century, their clinical use has so far been limited to some efforts in Russia, Georgia and Poland. This is partly because they are large biological agents and delivering the phage to the appropriate target is not as straightforward as administering a small-molecule antibiotic. Phages and bacteria can also mutate, rendering them ineffective. However, it is possible that future research may pave the way for greater use of phages to treat bacterial infections.

Are governments and the public beginning to understand the problem with resistant bacteria and do something about it?

I think so. Of course, when resistance becomes a huge problem and starts affecting the middle class and the rich, there will be an outcry. But I think things are already changing. In India, for instance, I see a lot of opinions calling for stricter regulations of antibiotics and for their better use. But India has a huge problem of providing proper sanitation and public health and that’s a big problem to be tackled.

It’s a multi-pronged approach. Measures like public health and hygiene will take a long time.

Do you think the production of drugs should be funded by governments – or private companies, as it is mostly the case today?

I personally believe that for certain things the private enterprise model is not going to work. It costs a huge amount of money to develop a new drug. But when you develop a new antibiotic, one of the first things you’re told is only to use it against resistant strains as a last resort. And that itself limits the number of patients who can take this medicine – and that limits your income.

If it’s a good antibiotic, the patient will be cured in a week or two – whereas ideally if you want to make a lot of money from a drug, it should be something the patient has to take all of their life. So antibiotics by their nature are not going to be the same class of money-maker.

So I think that governments really need to get involved in the development of new antibiotics. They have to think of this as something generally good for society, in the same way that governments fund education, roads, police, defence and so on. This is one case where governments need to act.

Interview by Katia Moskvitch for the World Economic Forum.

Author: Venki Ramakrishnan, a Nobel Prize-winning chemist based at the Laboratory of Molecular Biology in Cambridge University, is participating in the science programme of Davos 2015.

Venki Ramakrishnan is attending our Annual Meeting 2015 in Davos, and is a panel member in the session The End of Antibiotics, on 21/1 at 4.15pm.

Image: Various medicine pills in their original packaging are seen in Ljubljana February 14, 2012. REUTERS/Srdjan Zivulovic.