The Fight Against Addiction: How Dr. Ben Brown is Using AI to Develop Nonaddictive Painkillers

Stuti Jain | February 29th, 2024

In the field of medical science, the pursuit of precise targeting of illness and relieving human suffering while avoiding unintended negative consequences presents a sophisticated and commendable challenge. At the forefront of this challenge is Dr. Ben Brown, a Research Assistant Professor at the Vanderbilt Ingram Cancer Center, who has been awarded $2.375 million by the National Institute on Drug Abuse to help support his development of nonaddictive painkillers using artificial intelligence (AI). 

Dr. Brown is an MD/PhD graduate from Vanderbilt University, but over the course of his degree, he learned that he did not want to be a clinical provider. Rather, he wanted to build on the interest and passion for scientific research he had discovered as a freshman in college. Despite deciding against practicing medicine, Dr. Brown sees the value in having his clinical knowledge base. In our interview, Dr. Brown explained that his prior training as a physician continues to inform his research. With this foundation, he “knows a lot more about [practicing medicine] than the average PhD, and so, [he] can bridge this gap between physicians and scientists” (2).   

At first, the idea of using computers instead of benchtop science for drug design may seem far-fetched. However, computer modeling seems to be the future of effective drug design. Dr. Brown explained that the structure and motion of proteins are what give rise to their function. In order to modify or cure any given disease, one may have to change the way that a certain protein works. When asked how he uses computers to design a drug, Dr. Brown noted that “when we’re looking at how a potential drug interacts with a protein, we want to be able to not just account for some static structure, but understand how that engagement with a small molecule changes the rest of its motion.” To develop the most effective treatment possible, a holistic perspective of how a drug will interact with other proteins is vital, and Dr. Brown’s models enable just this type of understanding. Essentially, often when drugs are being designed, only the static structure of these proteins is considered, but to increase a drug’s efficacy, one has to understand how this drug would interact with those proteins (2). 

One of the focuses of Dr. Brown’s lab is the Mu receptor, which is a protein receptor (2) that primarily binds opioids (1). Mu receptors are the target for treating severe pain because they bind to compounds such as morphine. However, repeated activation of these receptors can result in severe side effects such as sedation and dependence, also known as addiction (3). Molecules that bind to and activate protein receptors are called agonists. However, drugs can also act as a partial agonist. Partial agonists do not create a full activating effect, like strong drugs (i.e., oxycontin or percocet) with the Mu receptor (2). This attenuated outcome could reduce likelihood of dependence long-term. Dr. Brown hopes to design a drug that acts as a partial agonist of the Mu receptor such that it can “control the level of efficacy for things like pain management without getting the negative effects.” 

Dr. Brown’s motivation as a scientist is to contribute to science in a way that is useful to everyone. He described that he would be “a very happy person, if [he can] discover a piece of information or build something that other people can actually use.” His current step in this journey is aiding the fight against addiction by producing nonaddictive painkillers, a key step in realizing his vision of making a practical impact through scientific endeavors.

References 

1. Herman TF, Cascella M, Muzio MR. Mu Receptors. [Updated 2023 Jul 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551554/
2. Jain, Stuti. “Dr. Ben Brown Interview .” 9 Feb. 2024. 
3. Richard Morphy, Zoran Rankovic,Chapter 19 – Multitarget Drugs: Strategies and Challenges for Medicinal Chemists, Editor(s): Camille Georges Wermuth, David Aldous, Pierre Raboisson, Didier Rognan,The Practice of Medicinal Chemistry (Fourth Edition),Academic Press,2008,Pages 449-472,ISBN 9780124172050, https://doi.org/10.1016/B978-0-12-417205-0.00019-5.