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Biophysicist in Profile

Donald C. Chang

Donald C. Chang

October 2024 // 232

Donald C. Chang was born in a small town in southern China, now part of the city of Shenzhen, near the border with Hong Kong. His father was a rice merchant and his mother a home­maker. He faced adversity from a young age, however, and did not grow up with his parents. He explains, “When I was a primary school student, my family was persecuted during the land-reform movement. I was forced to escape to Hong Kong. Fortunately, with the help of a relative there, I was accepted by a refugee school. Although Hong Kong was a booming city, the refugee school was in an isolated suburban area by the sea. The living conditions and my childhood life were very simple. I had to face challenges just on my own; it was tough. Fortunately, I had a good education.”

Chang became interested in science as a child studying at the refugee school. He shares, “As a child refugee, I did not have the benefit of growing up with my parents. So, my start in science was purely by interest. When I was a high school student, I loved to read popular science publications, including reports in newspapers and popular science books. Also, I was strongly influenced by two high school teachers; one taught me biology in the 7th grade, and another taught me physics in the 9th grade. They were very inspiring. I decided to study sci­ence because I was highly curious about how nature works.”

Chang was an exceptionally good student and was given the opportunity—and scholarships—to study physics at the National Taiwan University in Taipei. He states, “After getting a bachelor’s degree in physics, I was fortunate to receive a fellowship to come to the United States to study at Rice University in Houston, Texas. I spent five years there and ob­tained a master’s and a PhD degree, both in physics. The one who helped me to start in the area of biophysics was my PhD advisor, Professor H.E. Rorschach. He was a physics professor at Rice University and was very kind to me.”

He continues, “When I decided to move into the field of biophysics, there was no biophysics study at Rice Univer­sity. We had to develop everything from scratch. Professor Rorschach supported me wholeheartedly during this process. He generously offered me lab space and equipment so that I could start my research work. I converted a spin-echo NMR spectrometer I built for studying quantum physics to study biological cells. I collaborated with a young physiologist, Pro­fessor C.F. Hazlewood at Baylor College of Medicine.”

After the completion of Chang’s PhD, he pursued postdoc­toral work, primarily at Baylor College of Medicine and Rice University. He explains, “After I finished my PhD degree, I used my expertise in physics to start doing biophysics work. This work involved faculty in the Physiology Department of Baylor College of Medicine and the Physics Department of Rice Uni­versity. I also spent some summers at the Marine Biological Laboratory at Woods Hole, Massachusetts. I took two special courses there, one on neurobiology, another on embryology.”

In the early 1990s, he moved to a new university, the Hong Kong University of Science and Technology (HKUST), where he was a founding professor, and later a professor chair. He now serves as a professor emeritus at HKUST, due to age restric­tions for researchers in Hong Kong. His current work is mainly in theoretical biophysics, quantum physics, and quantum biology.

Chang has made several important contributions to the field of biophysics. The first was helping to establish the physical basis of using NMR for cancer detection. Magnetic resonance imaging is a powerful technique for detecting cancer, based on the discovery that the NMR relaxation times of water pro­tons are closely related to the physiological and pathological state of the tissue. Chang is a major contributor in this work; he was among the earliest investigators in using spin-echo NMR to study the physical properties of water inside biologi­cal cells.

He is also a major contributor in the development of elec­troporation technology, an important tool for the develop­ment of gene therapy, which has the potential to cure many diseases, including cancer. He was a pioneer in applying the pulsed electric field to permeabilize the cell membrane so that exogenous molecules can be injected into the living cell. It was discovered in the 1980s that the cell membrane can be transiently permeabilized by using an intense electric pulse. Various types of molecules, including DNA, RNA, and proteins, can be introduced into living cells by using this method. How­ever, it was not clear at first what the physical mechanism involved in this process is. Chang was an early investigator in this field and made major contributions in delineating the physical mechanism involved in electroporation.

He explains, “In the 1990s, a powerful bio-photonic technique using green fluorescent protein (GFP) emerged. The gene of GFP can be edited and fused with targeted proteins and then expressed in a living cell. Using such fluorescently labeled molecules, it becomes possible to use optical methods to investigate the signaling pathways in vivo. By using genetic engineering methods, GFP can be modified to develop novel biosensors to rapidly screen new drugs for cancer or neuro­degenerative diseases (such as Alzheimer’s disease).”

Using a fluorescent probe and confocal laser microscopy, he was the first to demonstrate that a localized Ca2+ signal is involved in regulating cell division in embryonic cells. This signal was absent in the domestic cells. “In collaboration with Professor Roger Y. Tsien of the University of California San Diego—2008 Nobel Laureate in Chemistry—I used GFP-based bio-photonics to show that the mammalian cells use the Ca2+ signal receptor (calmodulin), instead of the Ca2+ ions, as the key signaling regulator for controlling the cytokinesis process,” Chang details.

He notes, “Biophysics is a truly interdisciplinary field. It covers a very wide area in the study of nature. So, there is a lot of room for innovative research. One is only limited by his or her own imagination. That is great! Also, biophysics is pretty down to earth. Unlike some other fancy studies such as parti­cle physics or cosmology, the major hypotheses in biophysics usually can be tested in experiments.”

Asked about where he thinks the field of biophysics will go in the future, Chang postulates, “I think in the future, biophys­ics will continue to be a booming field. There will be many opportunities in this discipline. I foresee the need to use more quantum physics in this field. Most of the biophysics studies today use classical physics and traditional chemistry. This may not be enough. Living systems are built on atoms, molecules, and macromolecules; cellular structures are really nanostructures. Their operational principles should be under­stood at a quantum physics level. Now, with the advancement of technology, we can do new modeling and have new under­standings. That is also what I plan to work on. I will collabo­rate with physicists, neuroscientists, and quantum chemists to contribute to this field.”

In his free time, Chang serves as a BPS Ambassador repre­senting China. Outside of science, he enjoys sports, reading history, and watching news. He played tennis regularly for many years and was also a table tennis champion during his time at Rice University.