Joel Dudley and What Happens When You Let Data—Not Hypotheses—Drive Discovery

In June 2018, a paper published in the journal Neuronhad the media buzzing. From NPR [1] to The New York Times [2], Joel Dudley, Associate Professor at the Mount Sinai School of Medicine and Director for the Institute for Next-Generation Healthcare and his team’s discovery of Herpes viruses found in the brains of people who had Alzheimer’s disease brought fervent debate about what causes Alzheimer’s disease and how we might treat or prevent it. The viruses the researchers found are quite common—they are often the cause of a relatively mild early childhood illness called roseola, which causes a pinkish rash and a fever. Although roseola predominately affects children younger than 5 years old, it can lay dormant in the body for decades, reactivating in adults during times of stress or illness. In the brains of people who had Alzheimer’s disease, the scientists found evidence of these viruses.

Part of what makes this discovery so groundbreaking is that the scientists weren’t even looking for the viruses in the first place. For years, researchers and pharmaceutical companies have been looking for drug targets that could stop the devastating neurological disease in its tracks, with little success. Most of these attempts had focused on two proteins that have been found to accumulate in the brain of people who had Alzheimer’s: β-amyloid and tau. But nearly every promising agent has failed in clinical trials and the current FDA approved drugs target symptom control only [3-5], leaving scientists to search for new options. This is what Dudley and his team of researchers set out to accomplish. As Dudley stated in his New York Timesinterview, ‘“I went looking for drugs, and all I found were these stupid viruses”’ [2].

So, how did Joel Dudley’s team find this link between Alzheimer’s disease and the human herpesvirus? Using a supercomputer, the scientists used software to compare the brains of patients with Alzheimer’s disease and patients without, who had other neurological disorders. The differences found between the two could point to biological pathways that might be specific to Alzheimer’s and open the door to research into new therapeutic targets. The software that many scientists use today for these types of genomic studies use algorithms to reduce the massive amounts of data to something more manageable. In many genomic studies looking at human disease, this includes removing any signs of bacterial or viral species, which are considered to be contaminants. For many studies, this makes a lot of sense—but it comes at a price.

In my latest MoneyBall Medicinepodcast episode, I talk with Joel Dudley about his breakthrough study and how an innovative mindset and hypothesis-agnostic approach drive his research and his work as Director of the Institute for Next-Generation Healthcare at Mount Sinai in New York. We discuss the evolving healthcare landscape and what it takes to rethink and implement how we deliver healthcare today. Join me for this episode of the MoneyBall Medicinepodcast!

References:

  1. Hamilton, J. 2018. Researchers Find Herpes Viruses In Brains Marked By Alzheimer’s Disease. NPR Shots. https://www.npr.org/sections/health-shots/2018/06/21/621908340/researchers-find-herpes-viruses-in-brains-marked-by-alzheimers-disease
  2. Belluck, P. 2018 A Common Virus May Play Role in Alzheimer’s Disease, Study Finds.https://www.nytimes.com/2018/06/21/health/alzheimers-virus-herpes.html
  3. National Institute on Aging. 2018 Treatment of Alzheimer’s Disease | How Is Alzheimer’s Disease Treated?https://www.nia.nih.gov/health/how-alzheimers-disease-treated
  4. Mehta, D., Jackson, R., Paul, G., Shi, J. and Sabbagh, M. 2017. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert opinion on investigational drugs 26 (6):735-9.
  5. Egan, M. F., Kost, J., Tariot, P. N., Aisen, P. S., Cummings, J. L., Vellas, B., Sur, C., Mukai, Y., Voss, T., Furtek, C., Mahoney, E., Harper Mozley, L., Vandenberghe, R., Mo, Y. and Michelson, D. 2018. Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer’s Disease. New England Journal of Medicine 378 (18):1691-703.