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As antibiotic resistance builds, Dartmouth research works on an alternative

  • Antibiotic resistance Courtesy—World Health Org.

Monitor columnist
Published: 3/2/2020 2:29:36 PM

The scariest thing happening in the world these days is climate change, but there’s a close second: Antibiotic resistance.

The global impact of the COVID-19coronavirus shows how bad things can get when a contagious disease that we can’t treat enters our interconnected world. Alarmingly, such diseases are on the rise as more bacterial pathogens become resistant to treatment, thanks to evolution and our own stupidity in overusing and misusing antibiotics.

The medical world is aware of the problem and starting to tackle it, whether through education of the health community, such as the state’s annual Antimicrobial Stewardship Symposium, or technical approaches, such as a device at the N.H. Veterinary Diagnostic Lab with their weird name of MALDI-TOF that helps quickly identify diseases in animals, to focus treatment.

What would really help, though, are some good alternatives to antibiotics. This is easier said than done, so I was interested to learn of efforts to make use of a different molecular mechanism at the Thayer School of Engineering at Dartmouth.

I was interested partly because I think of Thayer as a place where researchers work with software or steel rather than proteins and cells. Very wrong, says Karl Griswold, an associate professor of engineering.

“I came to Dartmouth specifically because of the Thayer School and the environment. There are world-famous biological engineers here,” Griswold said. “There’s some really strong bioengineering component here; more specifically focused in the medical space on immunology and immuno-engineering.”

Before we go on, a reminder of why antibiotic resistance develops.

When disease enters your system it consists of lots of bacteria or viruses – millions of them. By sheer chance, a few of these nasties will be genetically different because of DNA copying errors or an errant cosmic ray.

Very occasionally, one of those differences will allow the bug to shrug off the antimicrobial treatment that kills its colleagues. This is very rare, but when you are talking about millions and millions of fast-replicating beings, rare things happen pretty often.

This new resistant pathogen thrives because the antibiotic or medicine kills the competing microbes, allowing it to replicate at high speed. Do this often enough among enough people or animals, and you’ve created an entire population of resistant pathogens. Our medicine is now worthless.

It’s evolution in action, with populations shaped by a changing environment over multiple generations, just as apes were shaped by the environment to become humans. The difference here is that we are creating the environment.

Humanity has used these “miracle drugs” willy-nilly for decades, creating multiple populations of drug-resistant pathogens, to the point that public health officials fear we’re entering a “post-antibiotic world” where once-conquered diseases will again wipe out millions of us.

Antibiotic resistance isn’t a surprise, by the way. Alexander Fleming, the guy who discovered penicillin, warned about it during his 1945 Nobel Prize acceptance speech. But avoiding it would require self-control and global cooperation, which are in short supply among human beings.

So we’re looking for science to save us. Which brings me back to Griswold at Thayer School.

I talked to Griswold after learning of his lab’s work from a lecture he gave at UNH-Manchester, another Granite State location where biomedical research is taking off. He walked me through a whole category of medical research involving lysins, a type of enzyme produced by phages, which are viruses that attack cells.

The phages inject lysins into cells of our body, where they “chew up the wall from inside and cause the bacteria to explode” creating all sorts of havoc, Griswold said.

What we want to do is use some lysins to attack cells of specific diseases rather than cells in our organs.

This sounds straightforward – “You take enzymes out of the phage and add those externally to target bacteria,” Griswold explained – and to an extent it is. “The lysin molecule was discovered back in 1964 and went into human trials in ’67, I think.”

But lysins were put aside because of problems and as other antibiotics were developed, until resistance caused us to give them another look.

So what’s holding them back? Our own immune system.

Lysins are proteins, a type of molecule that our body has learned to be wary of. Griswold explained that you can give lysin-based treatment to a patient one time and even if it works, the immune system will have learned what it looks like. If you give it to the patient a second time, it will trigger an immune response with possibly disastrous results. (The next time you hear some herb or supplement seller blather about “strengthening your immune system” remember that many serious diseases are caused by immune system over-reaction. Usually we don’t want to strengthen it!)

Griswold’s lab is developing its own lytic enzyme that it thinks can sidestep the issue, creating an antibiotic alternative that can be used multiple times.

Research, some done at the Dartmouth Regional Tech Center incubator, is being licensed through a startup, with grants from the National Institutes of Health allowed pre-clinical studies. Griswold said the hope is that it will lead not just to one new treatment but a method to develop many new treatments.

“We have a platform technology that we think can apply to any drug, not just lysin. … Any drug that’s got an immunogenicity problem or risk, we can run that through our platform technology and help to de-risk it,” he said.

Sounds awesome! But Griswold concludes with a cautionary note: Evolution never stops and we can’t, either.

“I think the science and the technology is standing ready to help address this problem. We’ve got the tools we need to help address the crisis,” he said. “But this is an eternal problem. We’re never going to come up with a silver bullet that will be the therapy for hundreds of years.

“It’s a moving target we’re going to need to continue to address,” he said. 

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If you want more geek in your week, subscribe to David Brooks’ free weekly newsletter at GraniteGeek.org. You can also listen to him talk about his stories on the GraniteGeek podcast, granitegeek.concordmonitor.com/podcast, or talk with Chris Ryan on WKXL radio at soundcloud.com/wkxl/

(David Brooks can be reached at 369-3313 or dbrooks@cmonitor.com or on Twitter @GraniteGeek.)



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