Donald C. Chang

Donald Choy Chang (traditional Chinese: 張東才; simplified Chinese: 张东才; 1942) is a founding professor of the Hong Kong University of Science and Technology (HKUST). He was also the founding President of the Biophysical Society of Hong Kong.[1] He is currently Professor Emeritus and Adjunct Professor in HKUST, and Council Member of Hong Kong Institute of Science (HKIS).[2] Chang has wide research interest: He was an experimental physicist by training; but his publication ranges from nuclear magnetic resonance,[3][4] biophysics[5][6] and quantum physics.[7][8]

Donald C. Chang
Occupationprofessor
Known forspin-echo NMR, electroporation and electrofusion
Academic background
Alma materRice University, National Taiwan University
Doctoral advisorHarold E. Rorschach Jr.
Academic work
InstitutionsRice University, Marine Biological Laboratory, Hong Kong University of Science & Technology

Detection of cancer using nuclear magnetic resonance (NMR)

Chang is an early pioneer in the study of the physical properties of water in cells using spin-echo nuclear magnetic resonance (NMR) techniques. When Donald Chang was working in the Physics Department at Rice University, he built a home-made NMR spectrometer to measure the relaxation times (T1 and T2) of water in normal cells/tissues, cancer cells and simply in free water samples.

His major collaborator at that time was the physiologist, C.F. Hazlewood, in the Baylor College of Medicine. Many publications related to this work were published with Hazlewood. Chang and his team gave the first time report that the relaxation time of cellular water (heart muscle cells in this case) is much shorter than the relaxation time of free water in 1971.[9] Also, their experiments suggested that such shortening of relaxation times in cellular water is not due to the diffusion limitation as was believed at that time.[3]

In 1972, they used the same technique to test the relaxation times for normal cells and cancer cells. They found that for breast tissue cells evolving from normal cells to pre-tumor cell (pre-neoplastic) and finally to tumor cells, their water relaxation times gradually increased.[4][10] This finding means it is possible to use NMR to detect pre-cancer cells and cancer cells. In 1973, Paul Lauterbur published a paper in Nature (1973) [11] suggesting that one can use a magnetic field gradient to differentiate water molecules in different location of a sample. This idea triggered the development of the MRI (magnetic resonance imaging) technique. And it is widely used today in detecting cancer/tumors. Later, Lauterbur was awarded the Nobel Prize in 2003 for this work.

Development of electroporation and electrofusion

In the early 1980s, researchers found that cell membranes can be transiently permeabilized using strong electrical pulses. During this “opening up”, many macro-molecules, including DNA, RNA and some proteins can enter the cells. After some time, the cell membrane will seal again. This is called “electroporation”.[12]

Chang invented a technique using a pulsed radio frequency electric field to achieve the electroporation, which is much more efficient in gene transfection and cell fusion.[13][14] (The “electrofusion” uses roughly the same technique as electroporation, the difference is that the electrofusion involves the fusion of two cells).

At 1980s, the concept of membrane "pore" was still a theory, but not visualized; the physical properties of the electroporation was not well understood. For example: What does the pore look like? What is the size of pores on the membrane? How long is the “opening up” time window? Chang and his collaborator T. S. Reese used a technique called “rapid freezing-fracture electron microscopy” to take the snapshots of this process. For the first time, he showed the structure of the pores induced by the external electric field.[15][16] This study provides the first structural evidence for the existence of the previously hypothesized "electropores" and was reported in the cover story of the July 1990 issue of the Biophysical Journal.

Works on biophotonics probes

Green fluorescent protein (GFP) and Fluorescent Resonance Energy Transfer (FRET) are two important optical probes/sensors discovered and developed in late 20th century. GFP was first isolated by Shimomura in 1962 in the Woods Hole Marine Biological Lab. After the GPF gene was cloned, it became a very handy tool for visualization of molecules in the cells. Chang collaborated with Roger Tsien's team and fused the GFP gene with calmodulin (CaM) gene, and injected this GFP-labelled CaM DNA into cells. After this fusion gene was expressed, the dynamic changes of the CaM-GFP protein can be recorded.[17]

Works on fundamental physics

Since the last decade, many of Chang’s work are focusing on some fundamental questions in physics. One of his works examined the physical meaning of the Planck’s constant based on the Maxwell theory.[18] The Planck’s constant h is one of the most important universal constants. But the physical nature of h is not well understood. The Planck’s relation was originally derived based on phenomenological considerations rather than from first principles.[19] Chang’s paper showed that by modeling the photon as a wave packet of electromagnetic radiation, the energy and momentum can be calculated directly based on the Maxwell’s theory. Using the assumption that the emission and transmission of a photon follows the principle of all-or-none, he found that the energy of the wave packet is proportional to its oscillation frequency. Follow this work, the Planck’s constant is derived explicitly. It suggests that the Planck’s constant is closely related to the physical properties of the vacuum.[18]

Another major work of Chang is a proposed experimental testing of whether there is a resting frame in the universe by measuring the particle masses.[20] There is an unsolved conflict between the postulate of relativity and the quantum theories used in cosmology and particle physics today: The former assumes the universe does not have a resting frame, but the latter implies a resting frame exists. The famous Michelson–Morley experiment tested that for light, all inertial frames are equivalent, i.e., there seems to be no resting frame for light propagation. However, it has never been tested whether the massive charged particles follow the same law. Chang's proposal is to precisely measure the particles' mass of two electrons moving in opposite directions. If a difference in mass of the two electrons is detected, it means not all inertial frames are the same for massive particles; if no difference is detected, it means all inertial frames are also the same for massive particles.[21][22]

Books & book chapters

Structure and function in excitable cells. Chang, Donald C., Tasaki, Adelman, W.J., Jr., and Leuchtag, H.R. (Eds). New York: Plenum Press. 1983. ISBN 0306413388. OCLC 9830807.

Chang D.C. (1989) Cell Fusion and Cell Poration by Pulsed Radio-Frequency Electric Fields. In: Neumann E., Sowers A.E., Jordan C.A. (eds) Electroporation and Electrofusion in Cell Biology. Springer, Boston, MA

Guide to electroporation and electrofusion. Chang, Donald C., Sowers, A.E., Chassy, B. and Saunders, J.A. (Eds). San Diego: Academic Press. 1992. ISBN 1299193528. OCLC 817706277.

Chang D.C. (1997) Experimental Strategies in Efficient Transfection of Mammalian Cells. In: Tuan R.S. (eds) Recombinant Gene Expression Protocols. Methods in Molecular Biology, vol 62. Humana Press, doi: 10.1385/0-89603-480-1:307, ISBN 978-1-59259-548-8

Chang D.C. (1998) "Chapter 88: Electroporation and Electrofusion", Spector, D. L., Goldman, R. D., Leinwand, L. A. (eds) Cells: A Laboratory Manual. Cold Spring Harbor Laboratory Press. ISBN 9780879695224, pp. 88.1-88.11.

Chang, Donald C. (2006-09-15), "Electroporation and Electrofusion", Meyers, Robert A., ed., Encyclopedia of Molecular Cell Biology and Molecular Medicine, Wiley, doi:10.1002/3527600906.mcb.200300026, ISBN 9783527600908

Chang D.C., Zhou L., Luo K.Q. (2005) Using GFP and FRET Technologies for Studying Signaling Mechanisms of Apoptosis in a Single Living Cell. In: Shen X., Van Wijk R. (eds) Biophotonics-Optical Science & Engineering for 21st Century. Springer, Boston, MA, doi:10.1007/0-387-24996-6_3,ISBN 9780387249964

References
  1. Zhu, Guang (2019). "The Biophysical Society of Hong Kong (BPHK): past, present, and future". Biophysical Reviews. 11 (3): 259–261. doi:10.1007/s12551-019-00525-2. ISSN 1867-2450. PMC 6557936. PMID 31055758.
  2. "Hong Kong Institution of Science". Hong Kong Institution of Science. Retrieved 11 April 2019.
  3. Chang, D. C.; Hazlewood, C. F.; Nichols, B. L.; Rorschach, H. E. (1972). "Spin-echo studies on cellular water". Nature. 235 (5334): 170–171. arXiv:1412.6003. Bibcode:1972Natur.235..170C. doi:10.1038/235170a0. PMID 4551228. S2CID 4167213.
  4. "Nuclear Physics Seen Aiding In Breast Cancer Detection". Atlantic City Press. March 1972.
  5. Chang, Chassy, Saunders and Sowers (1992). Guide to Electroporation and Electrofusion. San Diego: Academic Press. ISBN 978-0-12-168040-4.CS1 maint: multiple names: authors list (link)
  6. Donald, Chang; Meng, C. (1995). "A localized elevation of cytosolic free calcium is associated with cytokinesis in zebrafish embryo". J. Cell Biol. 131 (6): 1539–1545. doi:10.1083/jcb.131.6.1539. PMC 2120692. PMID 8522610.
  7. Chang, Donald (Aug 2018). "A quantum mechanical interpretation of gravitational redshift of electromagnetic wave". Optik. 174: 636–641. Bibcode:2018Optik.174..636C. doi:10.1016/j.ijleo.2018.08.127.
  8. Chang, Donald C. (2020). "A quantum interpretation of the physical basis of mass–energy equivalence". Modern Physics Letters B. 34 (18): 203002. doi:10.1142/S0217984920300021.
  9. Hazlewood, C. F.; Chang, D. C.; Nichols, B. L.; Rorschach, H. E. (1971). "Interaction of water molecules with macromolecular structures in cardiac muscle". Journal of Molecular and Cellular Cardiology. 2 (1): 51–53. doi:10.1016/0022-2828(71)90078-2. ISSN 0022-2828. PMID 5110317.
  10. Hazelwood, C. F.; Chang, D. C.; Medina, D.; Cleveland, G.; Nichols, B. L. (1972). "Distinction between the preneoplastic and neoplastic state of murine mammary glands". Proceedings of the National Academy of Sciences of the United States of America. 69 (6): 1478–1480. arXiv:1403.0914. Bibcode:1972PNAS...69.1478H. doi:10.1073/pnas.69.6.1478. ISSN 0027-8424. PMC 426730. PMID 4504364.
  11. Lauterbur, P. C. (1973). "Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance". Nature. 242 (5394): 190–191. Bibcode:1973Natur.242..190L. doi:10.1038/242190a0. ISSN 0028-0836. S2CID 4176060.
  12. Chang, Donald C. (2006-09-15), "Electroporation and Electrofusion", in Meyers, Robert A. (ed.), Encyclopedia of Molecular Cell Biology and Molecular Medicine, Wiley-VCH Verlag GmbH & Co. KGaA, doi:10.1002/3527600906.mcb.200300026, ISBN 9783527600908
  13. Gallagher, Sean (April 1989). "RF pulses change mammal cells in novel experiments". Genetic Engineering and Biotechnology News. 9 (4).
  14. "Method of and apparatus for cell poration and cell fusion using radio frequency electrical pulses". United States Patent and Trademark Office database. Retrieved 12 April 2019.
  15. Chang, D. C.; Reese, T. S. (1990). "Changes in membrane structure induced by electroporation as revealed by rapid-freezing electron microscopy". Biophysical Journal. 58 (1): 1–12. Bibcode:1990BpJ....58....1C. doi:10.1016/S0006-3495(90)82348-1. ISSN 0006-3495. PMC 1280935. PMID 2383626.
  16. S. Roberts, "Electroporation: galvanizing cells into action," ''J. NIH Res.,'' vol. 2, pp. 93-94, 1990.
  17. Li, C. J.; Heim, R.; Lu, P.; Pu, Y.; Tsien, R. Y.; Chang, D. C. (1999). "Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique". Journal of Cell Science. 112 ( Pt 10): 1567–1577. ISSN 0021-9533. PMID 10212150.
  18. Chang, Donald C (2017). "Physical interpretation of Planck's constant based on the Maxwell theory". Chinese Physics B. 26 (4): 040301. arXiv:1706.04475. Bibcode:2017ChPhB..26d0301C. doi:10.1088/1674-1056/26/4/040301. ISSN 1674-1056. S2CID 119415586.
  19. Slater, John Clarke (1969). Concepts and development of quantum physics. Dover. ISBN 0486622657. OCLC 833138434.
  20. Chang, Donald C. (2017). "Is there a resting frame in the universe? A proposed experimental test based on a precise measurement of particle mass". The European Physical Journal Plus. 132 (3): 140. arXiv:1706.05252. Bibcode:2017EPJP..132..140C. doi:10.1140/epjp/i2017-11402-4. ISSN 2190-5444. S2CID 118966045.
  21. "Is There a Resting Frame in Universe? | Physics | Sci-News.com". Breaking Science News | Sci-News.com. Retrieved 2019-05-02.
  22. "Does the universe have a rest frame?". EurekAlert!. Retrieved 2019-05-02.
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