Spotlight on Alexander Banks, PhD: Setting the Standard in Metabolic Research

Q&A with Metabolism Expert Alexander Banks

Alexander Banks, PhD, a leading metabolism expert at Beth Israel Deaconess Medical Center (BIDMC), studies the link the between obesity and insulin resistance. He also co-directs BIDMC’s Systemic Effects of Metabolic Disease Hub as well as directs the Energy Balance Core, a specialized facility that allows investigators to track animal models as they eat, move, burn energy, and manage body weight. Now sharing space with colleagues from Joslin Diabetes Center and Boston Children’s Hospital, he is also the newly appointed Assistant Director of the Boston Area Diabetes Endocrinology Research Center, working to foster greater collaboration across the Longwood Medical Area and beyond.

Banks recently led an international collaboration of 79 scientists to produce a landmark paper that establishes global standards for measuring and analyzing metabolism in animals, published in the journal Nature Metabolism. For more than a century, researchers have measured mammals’ oxygen consumption and carbon dioxide production to estimate energy expenditure, a process called indirect calorimetry. But inconsistent methods of analyses have made it difficult to compare results across studies.

The Nature Metabolism paper provides a unified framework that makes experiments more accurate, reproducible, and comparable. With new weight-loss medications rapidly advancing, these standards arrive at a critical moment, giving researchers worldwide a reliable measuring stick to better understand energy balance and body weight regulation, and to translate their findings into clinical applications.

We spoke with Banks about the landmark consensus paper he led aimed at solving this long-standing challenge and what it could mean for metabolism research going forward.

What is the problem your paper addresses, and why was now the right time to tackle it?

Banks: Our current paper establishes global consensus standards for analyzing and interpreting studies in metabolism research. It’s a milestone for our field, and particularly timely given advances in obesity therapeutics and new weight-loss medicines.

Mammals breathe in oxygen and produce carbon dioxide. We measure these gases with a technique called indirect calorimetry and it allows us to estimate rates of whole-body energy expenditure.

Scientists like me have been doing this for over 200 years, and in that time but people used different ways of analyzing and comparing the data. About a decade ago, an elegant series of papers showed the right way to analyze the data. All the experts agreed, but others carried on using an outdated system of analysis. It wasn’t that the old system was ever great; it was just inertia. 

This new paper says: as a field, we agree — there’s only one correct way to do it. Please don’t do it wrong. We’re all tired of correcting this mistake during peer review.

One thought we had was that people were unsure how to actually run the analysis. To make it easier, my team wrote a piece of software, called CalR. It pulls data from different systems that measure metabolic rates in experimental animals, and it analyzes the data the correct way, quickly and easily. We made it freely available worldwide. It is a web application that’s been used more than 85,000 times. Seeing how quickly it was adopted suggested that the field needed a little guidance. That was a big step forward toward this consensus paper.

How did you end up leading a collaboration of 79 scientists?

Banks: It is one of those things where I initially thought I was the only one noticing that the elegant standards papers from a decade ago weren’t catching on. And that I was seeing a lot of incorrect analyses. But it started with conversations among colleagues. This problem has been in the field for decades. Everyone has reached the boiling point of frustration because you don’t know what data you can trust — it depends on how the data were analyzed. A couple of papers pointed the problem out, but nothing changed.

So instead of writing another opinion piece, the idea was: let’s bring all the real experts together and say, as a field, “there’s a problem, it has to stop, and here’s how we’re going to change everything.” It started with conversations among colleagues, grew organically, and that’s how we wound up with 79 authors.

It’s really an international effort. We call it the International Indirect Calorimetry Consensus Committee. We have experts representing the U.S., Brazil, Chile, Canada, UK, France, Germany, Korea, China, Japan, and many more.

What kinds of research questions will this help answer more accurately?

Banks: One example is the GLP-1 receptor agonists, like semaglutide. Early studies, analyzed the wrong way, suggested they increased energy expenditure. Later, analyzed correctly, we saw the effect was really reduced food intake, not increased energy expenditure. That’s a huge distinction, and it clarifies confusion in the field.

Another example is brown fat and thermogenesis. When you lower the temperature, animals ramp up metabolic rate. Depending on your analysis, you can get exaggerated effects. The old way overstated the effect; the new way shows it more accurately.

What about older studies? Can their findings be converted, or are they no longer reliable?

Banks: Unfortunately, most can’t be reanalyzed, so we may have to reconsider some of their conclusions. We make the point in the paper: older studies used the methods of their time and it creates opportunities to re-evaluate old conclusions. They weren’t wrong for that era. But going forward, we need to use the new methods.

The measurements are the same; the difference is in the analysis. If you just look at total body weight without accounting for muscle versus fat, you get misleading comparisons. The new approach takes body composition into account.

Is there something you’d like colleagues at BIDMC or across BILH to know?

Banks: There’s still so much to learn about metabolism. Studying it in people is difficult. Whole-room indirect calorimetry chambers exist—subjects live in them for days but it is an artificial confinement, like jail. It measures metabolism under somewhat artificial conditions. Another method, doubly labeled water, allows individuals to live their lives normally but gives you only one data point over weeks. With rodents, we can get continuous, detailed data across many interventions. That’s why rodent studies are leading the way. There’s no substitute yet for whole-body physiology.

This publication has been a huge amount of work, but I think it will be a milestone for the field. I couldn’t be more excited.