Chemeq - a replacement for antibiotics

15 September 2002

Published in The Age


At the start of World War Two, the work of Australia’s Howard Florey inaugurated the age of antibiotics. In 1945, Florey shared a Nobel Prize for having isolated and manufactured the active ingredient in penicillin - which subsequently saved millions of lives.

Even so, the millennia-old “arms race” between humans and their bugs did not pause for long. By the 1950s it was noticed that bugs were mutating in ways which were making them resistant to the new wonder drugs.

Today, perhaps half the world’s antibiotics are used in animals for human consumption. Though such use is thought to be understated by food producers, there’s no doubt that penicillin, tetracycline and other antibiotics have now been fed to animals for more than 40 years. The practice is less common in sheep (which are less intensively bred), common in cattle, and near-universal in pig and poultry breeding. As a result, many target bugs have mutated into “superbugs” - bugs resistant to antibiotics.

In New York City, reports Barry Kreiswirth of its Public Health Research Institute, some tuberculosis strains are now resistant to as many as nine drugs, and “some cases of TB are virtually untreatable”. In a 1994 study in the New England Journal of Medicine, one in seven new TB cases was resistant to the two most common TB drugs, and one in five of these patients died.

The European Union, among other jurisdictions, is now acting to restrict animal antibiotic use - but it may be too little too late.

And it’s a fair assumption that drug companies will continue to promote antibiotics for human use. One GP says government spending cuts mean “continuing medical education, which all doctors have to perform to maintain their Medicare payments, is now commonly run by the pharmaceutical companies - who host dinners, weekend updates and conferences where a topic is presented which has relevance to their product.”

Given our slow-acting farm regulators, and the bias now creeping into medical training, what are the chances we can avoid a disaster with antibiotics?

Well, Dr Graham Melrose - Chairman and CEO of the Australian company Chemeq Ltd - has come up with what medical science is increasingly seeing as an exciting breakthrough.

Melrose, former research director at Johnson & Johnson, has invented a “polymeric antimicrobial”, which he sees as a safe alternative to human antibiotics. Melrose told The Age:

“It’s usual that antimicrobials are strong in safety, and weak in efficacy - or vice-versa. If it’s got enough grunt, it’s too toxic. If it’s safe enough, it hasn’t got enough grunt.

“We approached safety problem by making a polymer - it’s a very big molecule, like a string of sausages. And being big, it doesn’t easily go across membranes like skin or intestines. So it won’t go into the bloodstream like a normal drug will. Not getting to the bloodstream means it cannot manifest any toxicity.

“The other trump card is that our drug works differently from antibiotics. An antibiotic’s action is akin to a lock and key. The lock is the germ, and the key is the antibiotic. But if the germ mutates - that is, if the lock changes its shape - the key won’t fit any more. That gives you a super-bug - one where the antibiotic doesn’t work. But our material reacts with protein - an ever-present component of the outer membranes of germs, whether they’re bacteria, viruses, fungi or whatever. Indeed it ruptures the protein. And whilst proteins can mutate, they’re still protein. So our material is not upset by a mutation.”

Melrose has also proposed the product as a disinfectant, an antiseptic and a preservative.

“However after trying everything, we’ve decided our best application is in the animal area. The two main animals of interest are pigs and poultry. Together they represent 72% of the meat consumed by humans worldwide. It’s a very big market - about $8 billion between them - and for us an opportunity for a very large margin, with regulators gradually stopping the use of antibiotics.

“Those figures are applicable to just one germ, E. coli bacteria. If we found that it were active against salmonella, up would go the market by about another $4 billion.

“Environmentally, the product has some real advantages. Because it can’t get across the membranes, it doesn’t harm animals or humans [who eat them]. When animals excrete it, our material is not antimicrobially active any more. That’s because the germs it attacks - the E. coli - are right up the top of the intestine. The excess drug goes down further into the intestine, and when it hits the protein and gunk down there it gets neutralised. So it doesn’t upset the good flora further down, like antibiotics do.”

Dr Melrose’s product for the animal market is called Chemeq polymeric antimicrobial. Double-blind trials were carried out by David Hampson, Professor of Veterinary Microbiology at Murdoch University, and Chemeq’s Dr Alistair Murdoch. The trials were on pigs suffering from gut E. coli infections. They showed that the drug reduced animal deaths to zero, and significantly reduced illness. Three groups of “control” animals - fed regular antibiotics, E. coli vaccine and “no treatment” - all had deaths, and more illness.

Professor Hampson told The Age there was presently “no evidence” of toxicity in the drug, and that bacterial resistance “is not likely - but only prolonged use in the field will tell”.

“There are theoretical reasons and early experimental data that suggest it may be effective in several different contexts - for example against Helicobacter in the stomach. Only further work will tell whether this promise will be fulfilled.”

As to the future: “Certainly [the drug] is likely to be useful against a number of pathogenic bacteria infecting the gastrointestinal tract in animals like pigs, chickens and dogs. Its use in ruminants - cattle, sheep etcetera - will probably be limited by its potential effects on the ruminal microflora.” Down the track, he feels, “it may have some use for skin infections”.

“Currently things are looking good for the company,” Professor Hampson acknowledges.

“Our aim really,” says Chemeq’s Dr Melrose, “is to save antibiotics. Antibiotics are designed for us. But routinely farmers give animals just a small dose - which means resistant germs are built up, and then they come back through the food chain on the carcass to us. They end up in our hospitals. If we keep up that practice, we will be out of effective antibiotics.”

Scientists are not the only ones to smell success with Chemeq: the company’s share price has gone from 40c to over $3.40 in a year.

Last year, testing of Chemeq’s product was fast-tracked by the US Food and Drug Administration, one of the world’s toughest regulators. The product has already been approved in South Africa for use in pigs, and approvals in the US, Europe and Australia are possibly not far away. The product is patented in the 23 countries which represent the bulk of its global market. Chemeq’s Western Australian factory opens in 2003.

Longer-term, Dr Melrose says, “one could reasonably project that we might enter into the human area”.

Thanks to Howard Florey, Australia has a proud history in the global fight against the bugs which kill us. Maybe we’re about to do it again.