Exploring chemistry's frontiers:

Interdisciplinary pioneer Joseph Ackerman applies technology to image chemical processes

Not many scientists have the opportunity to experience firsthand one of their own experiments. After all, they can't swab themselves on a petri dish, dissect a part of their body or alter their genetic makeup. But Joseph J. H. Ackerman, Ph.D., professor and chair of the Department of Chemistry in Arts and Sciences, knows exactly what it feels like to lie inside a powerful nuclear magnetic resonance (NMR) machine.

"A number of years ago, I had some imaging techniques I wanted to try out," Ackerman said. "I got into a high-field NMR imaging machine at the National Institutes of Health in Bethesda and laid in it for about four hours while they did experiment after experiment. It was a lot of fun. I understood the physics taking place, and I could hear the machine's field gradient coils pulsing. I came away even more convinced that NMR would be a dominant technology well into the 21st century."

NMR imaging, also known as magnetic resonance imaging (MRI) in medical parlance, involves placing the subject in a strong magnetic field. The instrument detects nuclear-spin resonance within the magnetic field as radio signals. The signals are processed in computers and turned into a spatial image similar to an X-ray image but containing far more information. In a related field, NMR spectroscopy, the signals are processed to reveal information about molecular structure and dynamics.

Part of the reason that Ackerman enjoys research involving NMR imaging and spectroscopy is that it allows scientists to look at the bodily chemical processes of an intact living specimen without being invasive or destructive.

"With NMR, you can put a laboratory animal such as a transgenic mouse in the machine, take your images or acquire spectra, then return it to its cage unharmed," he said. "You can look at that same animal the next day and the day after that and so on. You can, for example, follow treatment of a given animal over time or do a longitudinal study with an entire sample population over time. That gives you much, much stronger statistical data."

Pioneering experiments

"I was trained as a physical chemist and became very interested at the end of my Ph.D. studies and during my post-doctoral studies in the application of physical chemistry -- I was doing NMR -- to biological systems, in particular living systems such as cultured cells, perfused organs and laboratory research animals," he said. "Magnetic resonance, which is my specialty, has the valuable attribute of being nondestructive and noninvasive in principle. In practice it can be difficult to apply, but in principle one gets the sample back undisturbed -- which is a really good thing if the sample is you!"

Ackerman came to Washington University as an assistant professor in 1979. He was promoted to associate professor in 1985 and to full professor in 1988. Not long after that, he accepted the position and responsibilities of department chair.

That day when Ackerman was lying in the NMR machine, if it had been possible to make an image of his motivation and interests, it would show a man deeply committed to his research as well as to the University's chemistry department. On the surface, it may seem these two commitments are at odds, but Ackerman is drawn equally to both. That's because he is the kind of man who likes to look deeply into things and investigate the relationship of one process to another, whether inside the brain of a laboratory mouse or within his department.

A great team

One of the people Ackerman hired was Andre d'Avignon, director of the University's High Resolution Nuclear Magnetic Resonance Facility.

"Andre has run one of our key instrumental -- or equipment -- centers in the chemistry department," he said. "It is very important to chemists of all types. Not only has Andre's facility been a model for other centers in the department, but other centers in the University have studied it to see how he has managed resources and operation."

D'Avignon pays equally high compliments back to his chair. "When I came here 14 years ago, the main reason I came was because of Joe. He was known as a 'rising star' in NMR," he said.

Ackerman is known internationally for his contributions to and development of NMR techniques for the study of intact living systems. In recognition of his contributions to the field of NMR, Ackerman has received the Gold Medal from the international Society of Magnetic Resonance in Medicine (the society's highest and most-esteemed award); the William Simpson Award for Excellence in Experimental Oncology from Wayne State University; the St. Louis Award from the American Chemical Society's St. Louis Section; and he was recently made a Fellow of the International Society for Magnetic Resonance in Medicine.

"He's also created an environment within the department in which the faculty can learn and grow," d'Avignon said. "He's a real motivator, particularly for people willing to take on a challenge."

During his tenure as chair, the chemistry department increasingly is embracing the interface between disciplines. Ackerman believes in providing undergraduate students with a solid core of training in the fundamentals of chemistry, as well as an appreciation for the application of chemistry at its interfaces with biology, physics and medicine.

"One of the things our faculty has been very much involved in is integrating chemistry experiments that have a strong life sciences flavor into the lower division undergraduate laboratory curriculum," he said. "The 21st century will continue to experience a revolution in biological sciences. For our students, it is important that they take courses that not only present fundamental, core concepts of chemistry but that also show the direct application of that chemistry to medicine, biology or the life sciences."

His belief in and support of an interdisciplinary approach fits neatly into Ackerman's own experience. In addition to his position in Arts and Sciences, Ackerman holds joint appointments at the School of Medicine as research professor of chemistry in medicine and professor of radiology.

An exciting time

Another Ackerman project that is just getting started involves developing high-resolution NMR imaging techniques that are suitable for use on transgenic mice -- mice whose genome, or DNA pattern, has been altered in some way.

"It is becoming clear that the dominant experimental laboratory animal in the 21st century is probably going to be the transgenic mouse," he said. "These mice can be expensive to produce and maintain, making them excellent subjects for non-invasive, non-destructive NMR techniques. What we need are higher resolution images of them, and that's the direction our team is now heading."

The third area of research that Ackerman and his associates are investigating is defining biophysical events associated with cell injury. In particular, the team is beginning what may be a long journey toward helping physicians distinguish between salvageable cells and irreversibly damaged cells at the site of a stroke in the brain.

"I enjoy moving into new research areas," he said. "Advances in magnetic resonance technology now allow experiments barely dreamed of a decade ago. New discoveries and methods are coming at an astonishing rate. I can't imagine a more exciting time to be pursuing NMR experiments in the life sciences."