The Future of Antimicrobial Resistance

The Project

While most of our attention is spent on the present or dwelling on the past, thinking about and predicting potential futures is a worthwhile exercise to guide us towards decisions that help assure future successes. While this is true to our daily lives, it is especially true for research, the sciences, and academics.

In this multi-part series, Rob Dunn invites conversations with leaders in several fields, tasking them to see into the future – 10, 25, 50, 100 years – in an effort to help shape decisions that steer their fields of research to more fruitful scenarios for students, researchers, and stakeholders alike.

Antimicrobial Resistance

Muhammad H Zaman is a Howard Hughes Medical Institute Professor of Biomedical Engineering and International Health at Boston University. The following conversation with Dr. Zaman was facilitated by Maya Afilalo and Mayookh Barua, MFA students studying Creative Writing at NC State. The conversation was edited by Lauren Nichols, a researcher in the Department of Applied Ecology, and Maya Afilalo.

Maya Afilalo: I wanted to start off by asking you to talk about your research. I know you focus on global health—specifically antimicrobial resistance. Can you speak about that?

Muhammad H Zaman: Recently, the majority of our work within global health has focused on health in refugee camps; in camps of people who are displaced because of conflict, persecution, and climate change; as well as in urban slums, where a lot of refugees live. Some of my forthcoming books focus on access to healthcare, emergence of disease, and the challenges in managing disease in those contexts.

We’re very interested in antimicrobial resistance—less so on the mechanisms, which would be the focus of a molecular, cellular, or microbiology lab—but more so at the interface of public health and biology. We study the environmental factors that contribute to antimicrobial resistance—the social dimensions of public health. We became interested in this because of the emergence of antimicrobial resistance in communities that have a high level of usage of poor quality, fake, substandard medicines, because of poverty, social injustice or corruption of the state. We’re still interested in the work that happens in the laboratory—the mechanisms of resistance and genetic mutations—but that’s no longer the only element we’re looking at. We work closely with partners on the ground in Pakistan and southeast Asia and in conflict zones to study how real-world factors, which are often not present in the laboratory, contribute to a pathogen becoming resistant to frontline antibiotics.

Determining which antibiotics to use in a refugee camp is more difficult than it would be in a hospital in Durham or Boston or London, where you have more information about which antibiotics people are resistant to already. In a refugee camp, you’re dealing with a new population and an environment with no testing available. Because of the lack of testing, you don’t know the baseline level of resistance within the community. So how do you plan? We don’t know the answer yet. Our research is focused on answering these sorts of questions.

Mayookh Barua: I’d like to talk more about the lab and the field. Obviously those are two different research spaces. I’m curious what you see as the benefits and drawbacks of each? 

Muhammad H Zaman: I think work in the lab and field must be connected. For example, vaccines are only possible because of discoveries in the lab. But the reason people in many countries lack access to vaccines is something you couldn’t predict solely by working in the lab. So, if you worked only in the field, you wouldn’t have vaccines. And if you worked only in the lab, you wouldn’t know what challenges exist in getting vaccines to rural parts of the world, which is why both approaches are needed.

Oftentimes, there are huge silos in research. There’s almost no translation of work in the lab to work in the field, and vice-versa. We’re trying to be a group that bridges an understanding of tools and methods in the lab with policies and fieldwork. Each is inadequate on its own, but both are essential for making progress. If there’s a new strain of an infectious disease , you need people in the field to identify it. Then, in order to address that new strain, you need somebody back in the lab to develop a new vaccine. Too often, the cycle is very slow, and that creates problems. But the cycle is necessary.

Mayookh Barua: What kinds of policymaking is your lab mostly interested in?

Muhammad H Zaman: I was a part of the national health task force in Pakistan, reporting directly to prime minister of Pakistan on health reform. I’m part of the epidemic preparedness program in Uganda, which also reports directly to the prime minister. We work closely with the World Health Organization, and we work with think tanks to come up with specific policy briefs.

Policy work happens on two levels. On one level, you work with an institution that has asked you for a recommendation,“What should the policy be here?” On the other, you believe a policy is appropriate based on your research, you suggest it, and it may or may not be picked up. One is like a request, a contract, an opportunity to sit at the decision-making table. In the other, you’ve seen yourself what policy is needed, you write about it, and you send it to an institution like the WHO and say, “You have been doing things this way, perhaps think about it differently.”

I’ll give an example. One of the groups we have worked with is the UN High Commission for Refugees, on their management of antimicrobial resistance in Palestinian and Syrian refugee camps. Some of our scientific papers have a long section of specific policy recommendations on what needs to be done in terms of surveillance and assistance. We also have a project with UNICEF. There’s science, and there’s also tangible, specific recommendations that they can choose to adopt, and in some cases, they have.

So that’s how the policy domain works. It’s not one-size-fits all. Sometimes it’s just developing awareness based on your science, disseminating your results. Sometimes it’s making recommendations based on your results, or people asking you what to do. It works in different dimensions.

Maya Afilalo: Looking toward the future, I’m thinking about the fact that we’re training medical students now who are going to hit their career peak in, say, 2050. Those are going to be the doctors who treat the people you talked about—refugees, displaced people, people living in urban slums. What do you think the future of antimicrobial resistance and managing resistance could potentially look like in the near future, let’s say the next 10 years, around 2030? And even beyond?

Muhammad H Zaman: We’re going to see more of what we’re already seeing in some parts of the world: an increase in drug resistance and a decrease in the number of tools we have to treat disease and infection. Infections that were previously treatable with six or ten antibiotics, are now only treatable with two. A specific case is the emergence of extensively drug resistant typhoid in Pakistan. Ten years ago, we had several drugs at our disposal that could be used to treat typhoid. Now there are only two left, only one of which is affordable, the other being too expensive. This sort of scenario could become more common in the future and people at the lowest end of the socio-economic spectrum will be at the highest risk. We also have new data showing evidence that microbial resistance has increased because of COVID. People going to the hospital for COVID symptoms have been prescribed antibiotics to protect them from infection.

In the near future, people going to the hospital for routine procedures—C-sections, dental implants, elective surgeries, etc.—could also be at higher risk of contracting an antibiotic resistant infection. The book that I wrote (Biography of Resistance) starts with the story of a woman in her seventies who travels to India, slips, breaks a bone, is treated in a hospital in India, comes back to Nevada, and develops a particular infection. All 26 available antibiotics were used – every single one – and she couldn’t get better. Unfortunately, she passed away. I think situations like this are going to happen much more frequently. Infections that were previously treatable will become untreatable, or will prolong your treatment in the hospital. People will be sicker for longer, people will have fewer options to get better, and the cost of care will increase. 

In the future, more people may also die from secondary bacterial infections that are resistant to antibiotics. During the Great Influenza or the Spanish Flu, viral and bacterial infections combined to create a much bigger problem. Most of the Spanish Flu deaths were not actually caused by a virus. They were caused by secondary bacterial infections, and at that time, antibiotics didn’t exist. I think that kind of challenge is likely. If there were another COVID-like event, along with antimicrobial resistance, people would get really sick. 

Looking further into the future, the data we have for 2050 is highly speculative. It requires that we make many assumptions about what may or may not happen. I think looking five or ten years into the future is much more reasonable than trying to project into 2050. A classic case is that many scientists’ 2050 climate change projections are already happening now in many parts of the world. There’s value in those models, but I find them to be more instructive and less useful in making good predictions.

Maya Afilalo: One of the solutions to the problem of antimicrobial resistance is to keep creating new antibiotics. That’s often the focus of reporting on the problem. But, what other strategies should we be thinking about and planning for, that would be more effective and sustainable than creating new drugs? 

Muhammad H Zaman: I think creating new antibiotics is important, but it’s not a very fertile solution right now. There are serious challenges to antibiotic development. The reality is that most large pharmaceutical companies do not see it as a viable opportunity. Compared to medicines for cancer, neurological disorders, osteopathic issues, which people generally need to use for the rest of their lives, antibiotics aren’t as lucrative.You only need to take antibiotics for three, five, or ten days. Antibiotics don’t lend themselves to a lucrative business model.

Think about it this way: if there were a blockbuster antibiotic, in order to preserve its efficacy, the government would tell healthcare providers not to use it unless it was an absolute emergency. A pharmaceutical company would therefore spend a billion dollars making a drug that can only be used in very acute cases. That doesn’t make for a good business model.

In general, the success rate of antibiotics going from preclinical to final approval is about 2 percent. Right now, there are only 45 antibiotics in advanced clinical trials, which means that the likelihood of any one of them making it is almost zero. For some classes of antimicrobial resistance, we haven’t seen the development of a new drug in sixty years. There’s often a lot of hype around the potential for a new antibiotic, but the reality is much more challenging.

The next point ties into one of the facts about the evolution of antibiotic resistance that might surprise people: antibiotic resistance has existed since the beginning of time. It’s not a new concept.

There are some bacteria that produce antibiotics, and there are some bacteria that respond to it by becoming resistant. That tug of war has always existed. But, our overuse and abuse of antibiotics over the last eighty or ninety years has tipped the balance.

Resistance has always existed, and bacteria will eventually develop resistance to any drug, even a new one. So how do you address resistance? You extend the runway of existing antibiotics. I am in strong favor of developing new antibiotics. But I want to make sure people recognize that if we change our behavior, our existing antibiotics can last a lot longer than they will at the current rate. For example, if we decrease the use of antibiotics in the veterinary sector, develop a better understanding of antibiotics in the environment, enact better prescription laws, etc, then even the antibiotics we’ve become resistant to have the potential to be used effectively again. We’ve seen this type of intervention work in Sweden, the Netherlands, and in Norway. I think behavior changes are where some short term gains can be made.

Point of care testing is another solution that I think is particularly relevant when you’re dealing with larger global realities and looking at countries like India, China, Thailand, Bangladesh, Pakistan, and elsewhere. The problem is that in many places, there are no capacities for point of care testing. So if you have a fever, you have no idea whether it’s bacterial or viral, and people start taking antibiotics without any real testing. There is an opportunity to develop technology that separates a fever of viral origin and a fever of bacterial origin. That way, antibiotics are only prescribed to treat bacterial infections, for which they are actually effective, which would decrease the use of antibiotics significantly. 

Of course, a lot of people have also written about better use of antibiotics in the animal sector and better surveillance. I think all of these solutions have to be implemented, along with new vaccines that are coming out for typhoid, new opportunities using phage therapy, etc. There isn’t going to be a single new antibiotic that resolves the problem of resistance. I don’t think anybody believes there will be. A piecemeal approach that focuses on human behavior and recognizes a diversity of solutions is what can make a difference.

Mayookh Barua: What can we do at home, in our daily lives, to slow the evolution of antimicrobial resistance, or at least not be on the wrong side of the situation, and remain healthy? 

Muhammad H Zaman: There are a handful of adjustments people can make in their daily lives that won’t solve the problem, but can help. The first is better hygiene and prevention against infection in general. 

Secondly, when it comes to diet, if people eat meat, choosing antibiotic-free meat is important. Not just because it’s organic, but because it creates the financial incentive in the meat-producing industry to use fewer antibiotics. So you are creating a demand.

A third shift people can make applies in particular to those with kids. We often want—and rightfully so—quick solutions for the people who we love most. If our child has a fever, we go to the doctor and we sort of nudge them to give our child an antibiotic. This is not just a problem in India and Pakistan and Colombia, it’s a problem in Boston. Doctors are under tremendous pressure from parents to prescribe antibiotics. There’s a psychological element. We push the doctors. And the doctors are also responding to their market demands. They shouldn’t, but they are. They’re saying, “If we don’t prescribe an antibiotic for this ear infection, even if we’re not sure it’s bacterial, our patient is dissatisfied with us. And the patient will go to another doctor who will be happy to prescribe an antibiotic.” I think it’s important to hold back, develop knowledge, and say “Well, if the kid doesn’t have a bacterial infection, let’s not push the doctor to give an antibiotic.” This is absolutely important for ourselves, for our kids, for our partners, for our families. Ask the question: is it a bacterial infection? Should we get an antibiotic here? Or is that unnecessary? Of course, we should ask this in a way that is polite and respectful, but it needs to happen.

Fourth, I think we can learn from countries that are handling the problem reasonably well. The Netherlands, Norway, Sweden, and Scandinavia in general, provide some promising examples. In some ways, the lives of people in these countries are not very dissimilar from ours. What are they doing differently? Some of it has to do with trust in the public health system. In the U.S., we don’t have the same level of trust in our healthcare system. There are a variety of reasons for this distrust, which I don’t want to go into. But there is a sense of independence in the U.S.—we define freedom to be personal freedom—and that permeates other areas, including health. There have been many political discussions about this: vaccines, masks, gun control, for example. I think perhaps we need to revisit what freedom means for us, and to a certain extent, develop a sense of trust in the public health system.

These four behaviors aren’t going to solve all our problems, but they can create a culture of taking antimicrobial resistance seriously. This then increases the runway of good ideas, policies, and strategies. Good things are happening now. New discoveries are happening, some runways are increasing—but general behavior is undermining their efficacy. General behavioral and cultural changes are where we can make a difference.

Maya Afilalo: I sent you this question in advance and we already touched on it, but I want to see if there’s anything you’d like to add. What aspects of the evolution of resistance do you think would surprise people today? 

Muhammad H Zaman: I think it would surprise people to know that antimicrobial resistance has always existed, and we have always coexisted with it healthily. It’s a natural process. It’s tricky, because if you tell people that antimicrobial resistance has always been around, they say, “Then what’s there to worry about?” But the problem is we’ve tipped the scales by aggressively using antibiotics. Our overuse, including within the animal sector and even with plants, has given resistant organisms free rein.

Additionally, resistance is affecting health care in ways that might surprise people. Routine care—pregnancy, dental implants, routine surgeries—are all affected. Often, when people go to the hospital for surgery, they are told to spend as little time there as possible afterward. The risk of drug-resistant infection, due to increasing rates of evolution of resistance, is cutting patients’ time short in hospitals. It’s affecting people’s care. It’s not that people are dying, God forbid, but their overall health care is affected in many ways. 

Additionally, the risk of acquiring a resistant infection will impact people in the lowest socioeconomic strata most, as COVID did. Whether you were in New York, Detroit, Mumbai, or Karachi, the most vulnerable people were the most affected. It’s the same with antimicrobial resistance. People living in urban slums, people with limited healthcare options, people who can’t see a doctor because they don’t have insurance—they are given broad spectrum antibiotics, as opposed to ones that are specific. That increases the chances of developing resistance. The greater the threat, the bigger the impact—at least early on—on people who are most vulnerable.

Maya Afilalo: It sounds like addressing the social and economic inequities around the world will ultimately help us combat antimicrobial resistance. Everyone will benefit from it, even if you’re not part of those communities. Would that be fair to say?

Muhammad H Zaman: Absolutely. When you address equity, everybody benefits, regardless of their position on the socioeconomic scale—because the health system as a whole elevates. It becomes more effective and efficient. It also becomes more efficient financially, because people don’t return to hospitals again and again. So, greater equity allows for fewer dependencies on the public health system, which then helps everyone. And then that money could be used for advancement, like new research.

Mayookh Barua: I’m interested in your book, Biography of Resistance. We are writers, so we’re always thinking about how people write: what inspired them, what they were thinking about while writing, the potential challenges of putting together a book. How did you conceive of the project, do you feel you achieved what you set out to do?

Muhammad H Zaman: I like to write both in English and Urdu, short essays, creative nonfiction. It’s an opportunity to go beyond research papers, which tend to be conservative in their approach. In a research paper, you’re writing defensively, because you’re responding to what a reviewer might say. You don’t necessarily put out theories, ideas, etc.

I’ve been thinking about antimicrobial resistance for quite some time, ever since I started working in global health. I come from a family of historians, so I have a tremendous regard for looking back in time in order to better understand where we are now. My hope is that looking back will allow us to move forward. The book also challenges the notion that scientists or drug manufacturers have a monopoly on the solution. Broadly speaking, the key thesis is that everyone played a role in getting us to this point, and so everyone has a role to play as we move forward.

I also write because of a sense of public responsibility. I feel that more scientists and academics need to share what we know with the broader public—neighbors, family members, the people in your church or mosque, your kids’ high school teachers—and share these important issues in the form of a narrative. My writing often tends to focus on global issues, which makes it a harder sell—oftentimes, the publishers are not interested in that—but it is important. 

Did I achieve this goal? To a certain extent, yes. The book has been translated into multiple languages. It’s actually doing better in Japan and in Korea than it did in the US. Part of that had to do with the timing. The book came out in April 2020, and at that time there was a general fatigue about disease. Some people were curious, but many didn’t want to read about another public health emergency that could upend their lives. The book has done very well in the audio format—ten times better than in print—so I’m learning about how people now consume literature and books.

Maya Afilalo: I’m interested in what you mentioned about the role we each have to play in combating resistance. And it relates to one of the questions I sent you in advance. How can universities help societies anticipate and face the challenges of the evolution of resistance? Is it a problem that should matter when administrators are planning for the future?

Muhammad H Zaman: That’s a good question. I thought a lot about it. When it comes to health planning, I think universities are part of society and the community at large. We’ve seen that when universities try to create an impenetrable bubble, it doesn’t work out very well. The core mission of research-oriented universities in the U.S. is discovery, education, and knowledge dissemination. Universities should plan in terms of investing in new resources, in more awareness, in new ways of discovery. And they need to bring their research to local stakeholders—the town administrator, the mayor’s office, etc. But in terms of day-to-day planning, I don’t think more or less needs to be done. More should be done by everybody. That’s one part of the answer.

The second part, in my opinion, is that the universities have to recognize the fundamental multi-disciplinary nature of the problem of antimicrobial resistance. It shouldn’t only be a question in fields of health, microbiology, engineering, etc. It should also be addressed in economics, social work, law, and elsewhere. For example, what are the roles of patents and copyright? Universities have the opportunity and tools to engage people and make this issue an important part of the broader conversation. For example, what Rob [Dunn] is doing here by bringing in writers and artists. That’s what universities can do really well.

Mayookh Barua: I’d like to return to something I was going to ask earlier, but we went in another direction. From what I understand, the work in your lab on antimicrobial resistance moves closely with work in the field and the public domain. You’re invested in policy making, which strikes me as really important. Could you speak about those collaborations, between the lab, field, and policy, and why they’re important? Is that a trend, and if not, is it a model you’d like to see in other global health labs? It’s so essential for academia to stand afoot with policymaking, which we see especially with the pandemic.

Muhammad H Zaman: I believe that people should focus on what they feel strongly about. There are some labs that feel strongly about policy issues—ours is one of them—and I think they should engage with policymaking. The core interest of other labs is discovery. If policymaking were thrust upon those labs, they wouldn’t find it very engaging. And if everybody does policy, that’s also a problem, because you need people who are dedicated to discovery, to figuring out the intricacies of science.

We need an open door and encouragement. I’ve been on the faculty for fifteen, sixteen years now. If I were starting my career today, I would tell the ‘young me’ not to pursue policy work, because it wouldn’t help my tenure. My book would have little influence on my promotion or professional development if I was a young faculty in a STEM discipline. What gets you promoted in research active universities, in a STEM discipline are research papers, grants, recognition by your peers, and discovery. In science and engineering departments, that’s the culture. And I would hate to give that advice to a junior faculty member, because I do want people to engage with the public and write, but it would be the right advice for their professional development. 

I consider myself fortunate, because my science was going well. I did most of the policy work once I was tenured and a full professor. I’d been thinking about it for a long time, but I held back because it wasn’t part of the success formula. In some departments, for example public policy or government, policy work is expected and appreciated. But in the sciences and engineering, it’s not. The expectation is that you will be working in the lab, or on your computational model, or your research. Only once you have established yourself it is less risky to to spend time on policy.

Maya Afilalo: Do you think that the culture of these departments needs to change in order to effectively combat antimicrobial resistance in the future?

Muhammad H Zaman: Yes, I think it does need to change. I think we need to encourage people to spend part of their time on policy engagement if they want to. But in order for that to be possible, we need to change how we measure “excellence.”

A single person or dean isn’t responsible for setting the rules—it’s the culture of the field. When you’re up for tenure or promotion, the department looks at your record of scholarship, research dissemination, funding, evaluations from peers at your institution and experts at other institutions. And when they ask the leading experts to evaluate you, it’s on your research and discoveries—there’s no section for policy engagement.

Adding a policy engagement section to an evaluation is also problematic. What do you do if someone doesn’t focus on policy? Should everyone have to do policy work? Of course not. But for the person who wants to, how do you account for that in professional development and evaluation? Policy work can be very fast, or super slow—sometimes it takes decades—how do you accommodate that? We need to rethink the culture. I think it’s important to recognize that excellence in scholarship is not a monolith. Ultimately, the goal is broader impact. That happens through discovery, development of new tools and technology, but it also happens through engagement. 

If my younger colleagues are interested in policy, I advise them to carve out a limited amount of time for it. Say five, ten, fifteen percent. That’s what I did. I ensured the things critical for success and tenure were in place before pursuing policy work. And I tell my junior colleagues they should spend one fifth or one sixth of their time on high risk work, anyway. Even in science. Policy work could be one of those high risk projects. If it works out, great. If it doesn’t work out, it doesn’t bring everything down.

Mayookh Barua: What do you think the future looks like in terms of how science engages with the public domain? We know from COVID that there’s so much misinformation in mass media, and we’re seeing this with the recent monkeypox outbreak, too. There are reports saying that only gay and bisexual men can be transmitters, which we know isn’t true. Do you think the future looks grim, or will things change in terms of how scientists, biologists, and academics communicate with the public?

Muhammad H Zaman: I think among the very few silver linings of the difficult couple of years it’s been with COVID, one is public engagement. And even that is a little problematic, because the accuracy of information on social media, even from scientists, needs to be rigorously analyzed. On one hand, COVID has brought people into the conversation who would have kept quiet or not had a platform otherwise. On the other hand, it has also increased the likelihood that you hear something—even from someone you trust—that’s grossly inaccurate. 

Some questions get settled with time. For example, the question of whether schools should be closed is still up in the air. It’s a public health question with implications beyond COVID. At the core of that question is risk mitigation. How do you manage risk? There’s the Chinese policy of zero COVID, which is manifesting in complex ways that impact tens of millions of people. Then there’s the Swedish model of reaching herd immunity. I think scientists have a tremendous role to play, but they also need tremendous humility, to recognize they may get it wrong, and they often do. And that’s okay, to recognize that you may not always get things right.

Overall, I think there is more public engagement, which is a good thing. On the other hand, public engagement doesn’t change the culture of research. Having an active Twitter feed doesn’t mean anything. When you start your job as a researcher at a university, you need to understand what is expected of you. Are you hired to be an advocate for something and develop public understanding, or are you hired for discovery and excellent research?

I think that’s the key question here. And my solution is that you need to hire all kinds of people. You need to hire people who are active in the lab, people like myself who think about policy, and people like yourself [Maya and Mayookh] who can communicate with the public effectively and rigorously. When somebody reads your piece, they know it’s not impulsive or reactive, but thoughtful and well-researched. I also think there will be scientists who find their voice outside of academia. They’ll choose to engage through other avenues, like think tanks, public office, NGOs, writing. If scientists can bring their skills there, not only to the lab, and there are productive and meaningful career options available to them, I think that’s a good thing.

Mayookh Barua: Can I say, therefore, that you are optimistic about the future?

Muhammad Zaman: Yes.

Mayookh Barua: That’s great.

Find more of The Long View interviews here: https://cals.ncsu.edu/applied-ecology/news/category/the-long-view/