Gerry Wright, professor of biochemistry and biomedical sciences, holds a petri dish in the Wright Lab at McMaster University on Jan. 27.Nick Iwanyshyn/The Globe and Mail
On Tuesday, professor of biochemistry and biomedical sciences Dr. Gerry Wright and The Globe’s health science reporter, Jennifer Yang, answered reader questions about the fight against dangerous antibiotic-resistant superbugs.
Superbugs are bacteria and other pathogens that have become resistant to available drugs; collectively they represent one of the gravest public-health threats of our time. Antimicrobial resistance (AMR) has been projected to be the cause of 10 million deaths annually by 2050 – more than cancer’s current toll.
Dr. Wright and his team at McMaster University in Hamilton, Ont., have been working to find new antibiotics capable of killing drug-resistant bacteria – sometimes by digging through the dirt themselves. Yang reported on the Wright Lab’s efforts to stave off the rise of the superbug.
Readers asked about how Dr. Wright’s lab operates, what citizens can do to help with research and the difficulties of getting new medications released to the public. Here are some highlights from the Q&A.
The fight against superbugs
What bacteria and its disease currently pose the greatest threat of antimicrobial resistance to current available antibiotics?
Dr. Gerry Wright: Organizations like Health Canada and the WHO have their “most wanted” bugs. Drug-resistant Gram-negative bacteria (which are surrounded by two distinct membranes, making drug penetration especially difficult) are a major concern right now. Organisms such as E. coli, Klebsiella, Pseudomonas and Acinetobacter are particularly worrisome. Though staph infections (caused mostly by Staphylococcus) are also very problematic when drug-resistant. Sexually transmitted diseases like gonorrhea are also increasingly resistant to existing drugs and can be widely spread outside the hospital.
Jennifer Yang: Just to chime in with something hopeful: gonorrhea is one that I’ve reported on over the years because it really is on the verge of incurability. But some new antibiotics for gonorrhea are finally coming online; I reported on one last April.
Postdoctoral fellow Xuefei Chen inspects plates of fungal pathogens with Dr. Wright on Jan. 27.Nick Iwanyshyn/The Globe and Mail
What do you wish people knew about how drugs become commercialized?
Wright: What people don’t appreciate is that the attrition rate from discovery in the lab to the patient is very high. This is because potential drugs need to be both effective and safe. A discovery in our lab must be tested extensively in preclinical studies to demonstrate efficacy (an ever more challenging task as bacteria become increasingly drug-resistant) and to assess its behaviour in animal models.
For example, are there any unexpected issues with metabolism or drug accumulation? Does it reach the right tissues, e.g., the lungs for pneumonia, and at a high enough dose to kill the target organisms? How should the drug be delivered? Pills, intravenously? What dose and at what frequency? This takes years of investigation and cannot be done easily by a single lab; teams of experts need to be recruited.
Assuming all that works well with no safety concerns in animals, and you can manufacture the drug candidate in sufficient quantity, you now need to test it in people. You can see that for an effective drug where everything goes well, this takes years and is expensive.
Given the source of super bugs from zoonotic illnesses transmitted from animals, would an overall transition to cell-grown meat and promotion of plant-based diets be a huge supplement to the work you are doing?
Wright: You touch on an important point. Antibiotic use in agricultural and food animal production accounts for most antibiotic use worldwide. The selection pressure driving the emergence of resistance reflects antibiotic use, so there is a link for sure. Also, if antibiotics are used, say in pork production, and the manure is then used on vegetable fields, there is the opportunity for contamination not only of zoonotic infectious organisms but also antibiotic resistance genes.
This is why we consider AMR a “One Health” issue – it impacts humans, animals and the environment. While there are strict regulations on antibiotic use in food animals in Canada, we import a lot of our food from countries around the world, which may be less stringent than ours. I’m not familiar with cell-grown meat, but I expect it will be challenging to scale to meet the planet’s population, so improving antibiotic use reduction in agriculture in the meantime is important.
A tray of natural products, chemical compounds produced by different microorganisms, from the compound library in the Wright Lab.Nick Iwanyshyn/The Globe and Mail
Ten million deaths by 2050 seems like a scarily high number. Why isn’t every alarm bell sounding off on this?
Yang: Honestly – they’ve been sounded off! Public health folks have a tendency toward conservative language but if you look at public statements that have been made over the years, they’ve been very alarming in tone.
When I first started reporting on AMR, I remember being struck by statements from Dame Sally Davies, the UK’s special envoy on antibiotic resistance. She described antimicrobial resistance as an existential threat akin to global warming; in one interview, she described an “apocalyptic scenario” in the near future, where someone like her would need a new hip but wind up dying from a routine infection because we’ve run out of antibiotics. In 2015, the then-director of the WHO, Margaret Chan, described a post-antibiotic era as “the end of modern medicine as we know it.”
Even this year at Davos, the director of the Global Fund to Fight AIDS, Tuberculosis and Malaria was making statements like this: “AMR is a pandemic with a probability of 100%. It is guaranteed to happen. It is already happening. Yet we have failed to mobilize significant resources to mitigate it.”
I think what you’re really asking, though, is why hasn’t the world responded in kind?
I mentioned that Dame Sally Davies has compared AMR to global warming, and I do think these crises are comparable. They’re both slow-moving emergencies. They’re both “super wicked problems” with causes that are many and complex, and solutions that require the coordination, leadership and sacrifices of many. It’s a tragedy of the commons, where everyone acts independently and rationally in their own best interest – but, in doing so, they deplete a shared resource, which is the effectiveness of our global antibiotic supply.
AMR is also an example of public health working so well that people stop appreciating the danger. Infection used to be a leading cause of death but now, we no longer really see it as a threat. But as Gerry points out, we don’t necessarily know when a person has died of infection; cancer patients sometimes die from infection, but that gets logged as a cancer death, not a death from infection.
Postdoctoral fellow Manoj Jangra prepares samples for animal studies in the Wright Lab.Nick Iwanyshyn/The Globe and Mail
Your lab is located at McMaster University. Do students and postdocs get involved? How does that impact the work?
Wright: Yes! Students and postdocs are the lifeblood of our work! Undergrads play a big role here, too. One of the most satisfying parts of my job is working with young people who have tremendous energy and excitement for research.
Yang: I think many people in the general public don’t realize how central postdocs and students are to the scientific output of academic labs. Gerry is what’s known as the “principal investigator” of his lab, the Wright Lab; a PI comes up with the big scientific questions, leads the research, comes up with the funding and provides guidance and leadership to his team. The buck stops with him or her. But oftentimes, the scientists performing the experiments and running the data analyses are postdocs, grad students and technicians. You can read more about the various roles inside an academic lab here.
How to talk about research
How important is being proficient at science communication in research work? What difference does it make to be able to make science research accessible to understand?
Yang: Speaking as a health reporter, I personally think science communication is a critical skill that every scientist should prioritize learning and honing over their career. So much of science is publicly funded, for starters, so I think scientists have a duty to explain and describe their work to the general public. And there’s no point to doing science in a vacuum; it needs to be translated into the real world in order to have an impact.
The work I do simply wouldn’t be possible if not for scientists like Gerry who know how to explain their research in accessible language, but also take the time to speak with reporters like me. Gerry spent six-plus hours patiently answering my many questions and follow-up questions; he didn’t have to do that but, if he hadn’t, I could have never written my feature about the AMR research being done by him and other scientists.
Jennifer, how do you go about writing a detailed article like this about such a complex topic?
Yang: Thanks for this question, truly, because I think many people don’t realize how much work goes into a feature like this! This story took about two months to come together. Gerry was both my starting point and most invaluable source. I spent two days at McMaster University in Hamilton, Ont., where I visited the Wright Lab and interviewed many of Gerry’s colleagues and postdocs. I conducted interviews with outside experts as well, like Kim Lewis in Boston, in addition to some who were never quoted or mentioned in the piece.
Beyond that, I read countless scientific papers, newspaper articles and books on this topic. It took several rewrites to figure out how to structure this article. I also worked with a graphics designer to create the charts, maps and infographics. And I spent many, many hours fact-checking (and re-fact-checking).
Antimicrobial resistance is a truly challenging topic to write about, in part because you’re forced to include words like “Acinetobacter baumannii” that make readers go cross-eyed while also taking up so much real estate on the newspaper page.
I’ve been covering antimicrobial resistance on and off since 2012, and I still have so much to learn.