We’re On the Cusp of a Historic Epoch of Discovery

Scientists are undeterrable optimists, always on the cusp of game-changing discoveries that often prove elusive. But that hope is turning into a cavalcade of breakthroughs as revolutionary advances in both technology and ways to make those resources available to researchers to finally crack the code on a wide range of deadly and debilitating illnesses. News reports that long focused on promising new research are giving way to stories about effective new treatments for obesity, Respiratory Syncytial Virus (RSV) and Alzheimer’s disease. Then, of course, there was the use of mRNA technology to produce a COVID-19 vaccine, saving untold millions of lives around the world.

We are just at the start of a historic new epoch of discovery. Today, HIV, Hepatitis C, and various forms of cancer are no longer death sentences. I am confident that in the near future we will finally tame scourges – such as malaria, tuberculosis, multiple sclerosis, optic neuritis, amyotrophic lateral sclerosis (Lou Gehrig’s disease), and many illnesses that contribute to heart disease – that have long plagued humanity.

Our present moment feels different because while the velocity of consequential achievements can seem as sudden as they are stunning, they are rooted in decades of foundational research that are starting to pay off in wondrous ways.

The last few decades have witnessed the explosion in the knowledge of “omics” ‒ genomics, proteomics, metabolomics, metagenomics, phenomics, and transcriptomics ‒ that have enabled us, for the first time, to view biology from a sweepingly comprehensive standpoint. Two new technological approaches are especially critical to this effort:  1) Advanced imaging techniques including cryo-electron microscopy and light sheet microscopy, which are helping us understand how proteins and other structures interact in cells and 2) High-powered artificial intelligence and machine learning that are enabling scientists to create and analyze vast amounts of data and to develop new molecular entities to disrupt targeted diseases.

These tools are opening the window to interactions of proteins and other molecules in living cells and tissues. Although cryo-electron microscopy was first developed during the 1970s, its rapid improvement in recent years now allows scientists to understand the 3D structure of biomacromolecules in their native state in cells (without the need for crystallization). Light sheet microscopy, a complementary technology, illuminates molecules within cells and tissues without requiring perturbation with dyes or fixation. In one sense these two technologies allow discovery scientists who only had photographs to now watch motion pictures.

Advances in artificial intelligence and machine learning (AI/ML) are vastly increasing the pace of discovery research and the development of new treatments. Consider that just three decades ago, it took months or even years for advanced medicinal chemists to identify a small number of compounds they could modify and test. The emergence of in silico computer modeling a decade later allowed scientists to model hundreds of potential compounds in order to identify the most promising ones for testing. Just within the last year, AI/ML algorithms have been developed that can generate many millions of new structures in days or weeks. Using modeled interactions within cells, AI/ML algorithms can modify chemical structures to gain optimal properties such as high-life, toxicity, and on-target effect. None of this would be possible without the enormous advances in cloud-based computing and data storage.

Bringing together this computational power, new imaging technologies and top researchers will allow us to dramatically accelerate the identification of a new generation of potent and safe therapeutic targets. This approach will also empower us to facilitate the rapid discovery of approaches (chemical structures, humanized antibodies, RNA-derived therapies) that should enable us to target immunological contributions to neurologic diseases and do so while minimizing the risk of adverse risks to patients.

The possibilities are endless. Going forward, biomedical researchers will use these technologies to:

• Develop therapeutic advances that transform lethal diseases to treatable conditions. While this work will include the discovery of new drugs, it is also allowing researchers to find ways to direct the body’s immune system to combat disease and to overcome the evolutionary imperative of viruses to evade immunocompetent vaccines.
• Refine new gene editing techniques using CRISPR/Cas to correct genetic diseases in embryos and, at the bone marrow level, to correct genetic diseases in adults.
• Explore the nature/nurture feedback loop to understand how environmental factors spur or diminish the expression of genes that can lead to illness, under the rubric of epigenetics.
• Define the mechanisms/association of mental degeneration and aging that lead to Alzheimer’s, dementia.
• Identify root causes that underlie many health equities/inequities.
• Truly exciting innovation is also occurring in engineering, computer sciences, and many other disciplines.
• Expand the usefulness and reduce the cost of wearable and at-home technology to improve patient care and reduce the demand on hospital resources.

The impact of scientific breakthroughs is limited, however, if they can’t move swiftly from the lab to health care providers. Fortunately, another significant development is taking place that addresses this challenge: innovation hubs – pioneered by Silicon Valley entrepreneurs and now being embraced by engineers, the medical community, and other researchers across the country.

Instead of siloing investigators to their labs, innovation hubs make them part of a collaborative community where they have access to a vast network of resources – including access to a wide-range of expensive technologies and data sets – in close-knit communities that provide avenues for sharing and testing ideas with their colleagues, galvanizing creativity.

Innovation hubs are also designed to be entrepreneurial. They not only provide the facilities to make remarkable discoveries, but the guidance researchers need to usher their breakthroughs from the lab to the market. A number of universities and academic medical centers are working to create the same synergies. Each of us, including the University of Michigan which is now seriously considering an innovation hub, have unique ideas and challenges.

We enter a truly exciting era in medical research. We are not just on the cusp of a new era in human health, but we see how to get there.

Marschall S. Runge, former Executive Dean of the UNC School of Medicine, is Executive Vice President for Medical Affairs and Dean of the Medical School for the University of Michigan. His new techno-medical thriller is titled “Coded to Kill.”