Sunday, June 05, 2016

The real drug problem that could cause a catastrophe

Count yourself lucky if you are laid low this winter. You probably won't die.

But not long ago you could have. Back in the 1930s before the widespread introduction of penicillin, infectious diseases were responsible for 5600 of Australia's 62,000 annual deaths. These days they bring about just 2600 of 148,000 deaths.

Nothing has improved health and brought down the cost of staying alive as much as antibiotics. But they are losing their power. A decade ago only 1800 Australians died of infectious diseases, but the death rate is climbing and is back to where it was in the late 1960s. Last month the United States was presented with its first patient carrying a bacteria resistant to the drug of last resort, Colistin.

There are literally no backups left, and for financial reasons, there is nothing on the horizon.

Australia has had several cases of Carbapenem-resistant Enterobacteriaceae, some brought in from overseas, and some transferred from patient to patient in hospital. It kills up to 50 per cent of the people it touches. If it gets a bigger foothold and becomes commonplace, we'll enter what the experts call the "post-antibiotic era".



It's true that to a large extent we've done it to ourselves. Right at the beginning of the modern era, accepting the Nobel Prize for his work on penicillin, Alexander Fleming forecast "the time may come when penicillin can be bought by anyone in the shops".

"Then there is the danger that the ignorant man may easily underdose himself, and by exposing his microbes to non-lethal quantities of the drug make them resistant," he went on.

"Here is a hypothetical illustration. Mr X has a sore throat. He buys some penicillin and gives himself not enough to kill the streptococci, but enough to educate them to resist penicillin. He then infects his wife. Mrs X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails. Mrs X dies. Who is primarily responsible for Mrs X's death? Why, Mr X whose negligent use of penicillin changed the nature of the microbe. Moral: If you use penicillin, use enough."

We haven't. We've often taken antibiotics only until we felt well. Then we've infected other people with the bugs that survived and no longer feared the antibiotic. And we've handed them out where they are not needed and dosed up pigs and chickens on overstocked farms in conditions that breed resistance. Carbapenem-resistant Enterobacteriaceae developed first in pigs before jumping to humans through raw pork.

As a business model, guaranteed obsolescence has worked well for the pharmaceutical industry. It has had to keep coming up with replacement drugs, each time getting new patents.

But what hasn't worked for it is the more important need to come up with a genuine antibiotic of last resort; something that is held in reserve and hardly ever used, because there's no incentive to make such a thing.

Patents typically last only 20 years. Even at an appropriately high price per unit sold, the manufacturer and developer of such a drug would be unlikely to get their money back. Tripling or quadrupling the patent term wouldn't much help.

Antibiotics aren't like other products, or other drugs. The less they are used, the bigger the pay-off. But our system of incentives encourages the reverse. It's in large measure an economic problem, with an economic solution.

The most promising is called "delinkage​". One its most influential proponents is Boston University law professor Kevin Outterson.

Under delinkage companies will no longer be paid according to sales. Instead they would be paid handsomely for developing drugs that weren't to be used. Promotion and free samples (usually the drug company's lifeblood) would be banned. Where the drugs were used, the drug companies would receive nothing other than the actual cost of producing them. Doctors might be given special payments ("bribes") tied to how little they prescribed them.

As an attempt to re-engineer a market it's on a par with carbon pricing, and about as important. Outterson says the long lead times involved mean we've got to act a decade before the need becomes urgent.

The UK government's review into antibiotic resistance has reached a similar conclusion. It believes that unless we act quickly, drug-resistant superbugs could kill as many as 10 million people per year by 2050, more than cancer kills now. Britain's prime minister David Cameron is talking to the group of seven leading industrial nations and to the G20 later this year. I'd like to hope we got on board.

In The Age and Sydney Morning Herald