Spotlight: J. James Frost, radiologist and molecular imaging pioneer
Rapamycin Press recently interviewed Dr. J. James Frost, M.D., Ph.D., M.B.A. to discuss his collaborative research paper “Symmetry and Symmetry Breaking in Cancer: A Foundational Approach to the Cancer Problem.”
Frost is currently an adjunct professor and professor emeritus with the Department of Radiology at The Johns Hopkins University School of Medicine, Department of Radiology. Frost received his M.D. and Ph.D. degrees from Washington University; his Ph.D. degree is in nuclear and radiochemistry. Frost also obtained an M.B.A. degree from John Hopkins University.
Frost’s research with Johns Hopkins School of Medicine collaborators Kenneth Pienta and Donald Coffey focuses on symmetry and symmetry breaking concepts from physics and biology as applied to the problem of cancer.
Cancer remains unsolved despite centuries of research and accumulated knowledge about its molecular biology, biochemistry, pharmacology application and physics. Because cancer is a complex system highly adaptable to environmental changes, a new approach to the problem is needed.
According to the authors, “Therefore, it is not surprising that cancer biology remains at an impasse as it confronts a problem that involves a practicably uncountable number of interacting cell agents. In the three-body or multi-body problems of physics, major simplification is introduced by consideration of symmetry, resulting in new solutions that can be classified based on their symmetry features.”
The new cancer symmetry concepts are relevant to cancer’s origin, spread, treatment and resistance. Symmetry and symmetry breaking could provide a new way of thinking and a pathway to a solution of the cancer problem.
Origins of a new approach
A very early origin of the work was from the time when Frost was an undergraduate chemistry and physics major, in which symmetry concepts permeated many aspects of his education. His graduate work in a nuclear and radiochemistry further cemented these fundamental concepts, but they had lain dormant until recently. A few years ago Frost was invited by Ken Pienta, M.D., of the James Buchanan Brady Urological Institute at Johns Hopkins, into his lab, which sparked a collaboration with Pienta on all aspects of research and thinking about cancer.
“That experience sparked the link to symmetry and symmetry breaking, and stimulated me to think about whether cancer could be viewed at a system level as a state of broken symmetry beyond that of normal biology,” said Frost.
Their research article, “Symmetry and Symmetry Breaking in Cancer: A Foundational Approach to the Cancer Problem,” presents an analysis that makes a strong case for this idea of broken symmetry, and the need for more theoretical and empirical investigation to translate this research into meaningful therapeutic approaches for patients.
A fascination with symmetry
The stimulus for Frost’s recent work is two-fold. Said Frost, “it derived from many wide-ranging conversations I had with the late Johns Hopkins cancer pioneer Don Coffey about the fundamental nature and fascination of symmetry, including its exceedingly important role in the foundations of physics, mathematics, chemistry and cosmology.” These conversations also included concepts of biology and life as a state between perfect order and chaos. That is, life is a condition of partially, but not completely broken symmetry.
Another stimulus for Frost’s work derived from Pienta. “The interactions with him and his research group on cancer mechanisms and how improved understanding can be translated to new treatments for cancer patients,” said Frost.
Challenges of applying symmetry to cancer
Learning and relearning the fundamentals of symmetry across the physical and mathematical sciences is a challenge for any scientist. It also retains a mysterious aspect of space and time that Coffey and Frost marveled at over and over when they were together. At last count, the bibliography for the project there were over 200 articles and books that Frost had read and studied; hard work, but rewarding.
Another challenge was uncovering the possible links to cancer within the symmetry and cancer literature. Early on Frost codified the goal of not merely calling cancer phenomena instances of broken symmetry, but showing how the new approach could eventually help patients. “That search involved a series of rewarding ‘ah ha’ moments that formed the basis for the article,” said Frost. A notable one was the link between the symmetry of a network, or more generally a graph, and its stability and tolerance to attack at different nodes or subsystems. The complexity of this network is akin to the electrical grid and the world wide web.
When extended to cancer, Frost and others lay out the argument that therapies directed to destroying cancer at a system level – rather than at the level of a single molecular target – could be directed at points in the cancer network where symmetry is maximally broken and the system is most vulnerable. “Conversely, could points of broken symmetry be targeted for repair in order to restore the normal homeostasis of the cell?” asked Frost. “That’s a much more futuristic aspect of the research.”
What are the future implications of this research?
The article is a purely conceptual piece from the standpoint of cancer, because no one has previously examined in this detail the question of symmetry breaking in cancer. “We think that just as symmetry considerations for all the physical sciences and mathematics have provided foundational insights and otherwise greatly simplified our thinking about complex phenomena, the same can happen for cancer,” said Frost. In the article, Frost and others erect many signposts for more in-depth theoretical research and empirical investigation, which they hope cancer biologists and even clinical oncologists will take up.
As for Frost’s team, the possibilities for this direction of research comprise a rich area. Given the cross-disciplinary nature of the project, the impact of this research will depend on the strength of the collaborations that can be developed at Johns Hopkins, as well as with scientists in other institutions. “As cancer is a phenomenon of practically unlimited possibility space, we think that will also be the case for future research in this area,” said Frost.
Dr. J. James Frost, M.D., Ph.D., M.B.A., is the President of BioMolecular Imaging, LLC, a molecular imaging strategic planning and advisory group around the use of molecular imaging in new drug and diagnostics development.
Frost is also an adjunct professor at the Johns Hopkins University School of Medicine where he was a full-time Professor of Radiology for over 30 years and an originator of molecular imaging and its clinical applications.
Johns Hopkins is known for its major strengths in medicine, biomedical research, physics and engineering. Frost has a background in physics, math and chemistry, which forms the infrastructure for his current conceptual work dedicated to stimulating new collaborative, cross-disciplinary theoretical and empirical research within the wider John Hopkins community.