There just aren’t enough new antibiotics currently under development to fight the threat of antimicrobial resistance.
That’s the warning being issued by world leaders.
In a news release last month, officials at the United Nations (UN) and World Health Organization (WHO) said that most of the drugs currently under development are just modifications of existing drugs and won’t work on a long-term basis.
“Antimicrobial resistance is a global health emergency that will seriously jeopardize progress in modern medicine,” said WHO Director-General Dr. Tedros Adhanom Ghebreyesus in the release.
An expert interviewed by Healthline explained some of the difficulties in developing new classes of antibiotics while expressing optimism for the future of drug development.
Antimicrobial resistance 101
Over time, microorganisms in the human body gradually evolve to become resistant to the drugs that are used against them.
When a microorganism becomes resistant to a drug, that trait tends to spread across other similar microorganisms.
That’s when resistance can really get out of hand.
How bad could the problem get?
“Well, it’s a serious problem,” Dr. Kou-San Ju, assistant professor with a joint appointment in the Department of Microbiology and the Division of Medicinal Chemistry and Pharmacognosy at The Ohio State University Wexner Medical Center, told Healthline.
“It’s been estimated that if this trend continues, it’s possible that we could go back to an era where simple medical procedures can cause life-threatening infections,” he added. “So the threat is there, but it’s a complicated situation of not only how we use the medicines themselves, but also our ability to find new ones and replenish our medicine cabinet.”
Like a needle in a haystack
To discover new drugs, scientists traditionally cultivate microorganisms from soil or water because they are isolated from common places.
These lab-grown microbes are studied to find which ones can produce a substance that inhibits an undesired pathogen.
After purifying that substance, the scientists are left with an antibiotic molecule that can eventually be developed into a consumer-friendly drug.
“The challenge with this discovery process is that it’s been played over so many times that we tend to find the same molecules over and over again,” said Ju. “In the industry, research is done with strains on the order of millions at a time. So the number of strains that you have to screen to find a truly novel molecule that hasn’t been found before, using this method, is pretty mind-boggling.”
While this process can be time-consuming and yields diminishing returns, scientists are now using alternative research methods, such as genomics.
Because every organism has a virtual genomic blueprint of its pathways, researchers are finding ways to sift through a microorganism’s properties by studying its various characteristics.
Scientists are also finding new ways to grow naturally occurring genomes in a laboratory setting.
“A challenge of microbiology is that about 98 or 99 percent of all microbes are, quote-unquote, ‘uncultivatable.’” said Ju. “It’s not that we can’t grow them. It’s that we haven’t figured out the conditions in which they can be propagated in a laboratory setting. So there’s an effort to figure out how these environmental microbes can be coaxed into the laboratory — and there’s been some success in this area.”
“We’ve been able to find that a lot of these strains that we’re able to bring or domesticate into the lab are wildly different than anything we’ve studied before, and by that nature they have quite a variety of new and unexplored genes and pathways, so that’s been another successful source of new molecules,” he added. “Thinking about antibiotic discovery, natural products are a new source of next-generation pharmaceuticals.”
Bridging the gap
The UN and WHO may have put out a call for new and better antibiotics, but getting these drugs to market is a complicated issue.
For starters, it takes years for drugs to be properly tested and eventually gain approval from the U.S. Food and Drug Administration (FDA).
There’s also the matter of drug manufacturers.
“From the industry side, it’s kind of a catch-22, because we have these tremendously important medical problems. But from a commercial point of view, it’s something where you can take a medicine, and then hopefully the problem goes away,” said Ju.
“So it’s unlike a systemic illness or other type of physiology where you need continual treatment. From a commercial point of view, you have to ask, is this a long-term, economically viable endeavor? I think this is why a lot of large pharmaceutical companies divested away from the early discovery aspects of their pipeline.”
This doesn’t necessarily mean that drug companies aren’t interested in making antibiotics, says Ju, but does mean that they’ve stepped away from the early trial-and-error research process.
“It takes such a tremendous effort to find these effective lead compounds,” said Ju. “They want the leads. They just don’t want — in my opinion — the riskier parts of investing in early discovery.”
With various international agencies sounding the alarm over antibiotic resistance, combined with new technology in microbe research, there is reason for optimism.
“Advances in technology, DNA sequencing and analytical chemistry methods are really allowing us to access these untapped resources faster,” said Ju. “I think as a society, we’ve recognized the importance of this challenge, and it’s going to take a lot of hard work, but I personally feel that the future in this area is actually quite bright.
“We hear that the golden age of antibiotic discovery, when we found many important drugs that we still use today, was in the ’40s and ’50s,” he added. “But I like to think that with what we’re doing nowadays, with new technologies, genomics, and analytical methods — and the renewed commitment from everyone — that we’re going to find many, many new molecules, and the best discoveries are going to come in the very near future. I’m pretty optimistic, actually.”