Identifying new antibiotics that can fight harmful bacteria is difficult and resource intensive because these substances can be literally ANYWHERE.
We’ve developed antibiotics in the past, so why it is now so difficult to discover and develop new antibiotics?
To find out, let’s look back to the “golden age” of antibiotic discovery from the 1940 to 1970s.
The majority of antibiotics we use at home or in hospitals today have their origins in natural products. The penicillins, cephalosporins, aminoglycosides, rifamycins, tetracyclines and glycopeptide-based antibiotics all came from bacteria or fungi. They are made by nature in response to selective evolutionary pressure over eons of “chemical warfare”, in which microorganisms battle to survive by killing off their competitors with antibiotics.
This method of screening soil microorganisms was overmined by the 1960s. Most antibiotics found during the “golden age” were from micro-organisms themselves, isolated from soil or plants and then cultured in the laboratory. They were easily screened on agar culture plates or liquid culture broths to see if they could kill pathogenic bugs.
The toolkit required was pretty simple: some dirt, a culture flask to grow the antibiotic-producing bacteria or fungi, a column to separate and isolate the potential new antibiotic, and a culture plate and incubator to test if the compound could kill a disease-causing pathogenic bacteria. Chemists were then able to “tweak” these new structures to extend their activity against different bacteria and improve their ability to treat infection in the clinic.
The problem is that using this trial error method over and over again, is time consuming and resource intensive. Synthetic approaches to produce antibiotics have been unable to replace this platform so far, however scientists are working on genetic sequencing technology to find new antibiotics.
The cost and time required to bring new drugs to market are staggering. Estimates for the time to bring a new antibiotic through the preclinical, clinical and regulatory approval process are in the order of 13 to 15 years and around US$1.2 billion. If the costs of failures are factored in, it is closer to US$2.5 billion.
Because we expect to pay $20 or at most $200 for a course of antibiotics (compared to more than $20,000 for many cancer treatments), and because we only take antibiotics for a week or two, almost all of the companies that were active in antibiotic discovery have left the field over the last 20 years.
So what’s happening now? Will we all die?
It’s not all doom and gloom. Scientists have now been looking further afield, turning to coral reefs, deep oceans and cave-dwelling bacteria to search for new promising molecules. Scientists have developed many innovative approaches to the search for new antibiotics, such as one recently reported in Nature, in which bacteria from soil are sealed into 10,000 separate miniature culture cells in a chip device, then buried in the soil they came from again to grow in their natural environment. The chip device is then dug up, and each cell screened for compounds that can kill pathogenic bacteria.
Philosopher Sun Tzu said “the supreme art of war is to subdue the enemy without fighting”. We are now in a protracted war against superbugs, as we have overplayed a key weapon against disease. Our unfortunate misuse and abuse of antibiotics means that bacteria have developed new ways to inactivate the drugs, to stop them getting to their targets within the bacteria cells, and to pump them back out of the cell when they do get in.
We need better stewardship of existing antibiotics, better diagnostic methods and new antibiotics that we can take better care of this time around. Unfortunately, we are dragging our feet in dealing with the superbug threat.
Yes, we’ve heard a lot lately about superbugs.
Now it’s time to act.
Which is where the vision for Post | Biotics comes in…
Post|Biotics toolkit handsover the power of empirical research in the hands of citizen scientists. Instead of relying on research institutions and pharmaceutical companies to do the first and most tedious phase of research in mining for antibiotics, we ask citizen scientists to do it by having them test specimens like plants, insects and any ‘specimen’ in their surrounding for antibiotic properties. The data of what citizens test in then uploaded on a global platform with the ambition of creating an open drug database. When a citizen using the kit spots a promising specimen, they can submit a sample of the substance in question to our team of Post | Biotics leaders. They’ll pass it along to a network of scientific collaborators for verification and further study. Scientific leaders will perform test on the compound to determine whether the substance has antibiotic properties and what chemical structure enables those properties.
“Not every compound will turn into a new antibiotic, But if we have enough experiments going on, in enough locations around the world, we think it’s possible that some will.”
– Mark Opal, a neurobiologist specializing in drug development
“I imagine Post|Biotics open drug database as a rich collection of all the existing wise remedies that we have been using from nature, ginger, honey, turmeric, red sage,…”
– Medical Herbalist
The dialogue through Post | Biotics is crucial. It democratises healthcare research, making citizens equal stakeholders in research, decision making and consumption of antibiotics.
inputs from :
by Matthew Cooper, Prof. Institute for Molecular Bioscience at The University of Queensland