Alice Chien Chang

The native form of this personal name is Chien Chia-yun. This article uses Western name order when mentioning individuals.
Alice Chien Chang
錢嘉韻
Born
Chien Chia-yun

(1950-03-14)March 14, 1950
Taiwan
DiedMarch 2, 2026(2026-03-02) (aged 75)
Taipei, Taiwan
CitizenshipTaiwanese
Alma materFu Jen Catholic University
University of Cincinnati
Iowa State University
Scientific career
FieldsMolecular biology, Neuroscience
InstitutionsEast Carolina University
National Yang-Ming Medical College
National Yang-Ming University
National Yang Ming Chiao Tung University
Academic advisorsHorst Dieter Dellmann

Alice Chien Chang (March 14, 1950 – March 2, 2026) was a Taiwanese molecular biologist and neuroscientist. She taught at National Yang-Ming Medical College, National Yang-Ming University, and National Yang Ming Chiao Tung University. In 1976, she and her collaborators published research on the purification of a DNA polymerase from the extreme thermophile Thermus aquaticus; this work was later regarded as one of the key technical foundations that enabled the high-temperature cycling, automation, and commercialization of the polymerase chain reaction (PCR).[1][2]

Background

Chien graduated from the Department of Biology at Fu Jen Catholic University in 1972. She later pursued graduate studies in the United States, earning a master's degree in cell biology from the University of Cincinnati and a Ph.D. in molecular, cellular, and developmental biology from Iowa State University. She subsequently conducted postdoctoral research in microbiology at the East Carolina University School of Medicine. After returning to Taiwan in 1982, she joined National Yang-Ming Medical College, where she engaged in teaching and research in neuroscience for many years.

During her tenure within the Yang-Ming academic system, she served as director of the Institute of Neuroscience, director of the Neuroscience Research Center, and university librarian, before retiring in 2013.[3][4]

Alice Chien was married to Chang Nan-chi.[5][6] She died on March 2, 2026, at the age of 75.[7]

Contributions to PCR

In 1976, under the name Alice Chien, Chien co-authored the paper "Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus" with David B. Edgar and John M. Trela in the Journal of Bacteriology. The study reported the purification of a stable DNA polymerase from Thermus aquaticus, a thermophilic bacterium, and found that the enzyme had an optimal reaction temperature of approximately 80 °C.[1]

When the polymerase chain reaction (PCR) was first developed in the mid-1980s, it still relied on the Klenow fragment of Escherichia coli DNA polymerase I, which was not thermostable. Because each cycle required high-temperature denaturation, the polymerase would become inactivated and had to be replenished after every round, making the procedure cumbersome and prone to error. In his 1993 Nobel Prize lecture, Kary Mullis recalled that one of the major difficulties of early PCR was the need to add fresh heat-sensitive polymerase after each cycle of temperature change.[8][9][10]

In 1988, Randall K. Saiki and colleagues introduced the thermostable DNA polymerase from T. aquaticus into PCR, noting that this change "greatly simplified" the procedure. Because the reaction could be carried out at higher temperatures, it also significantly improved specificity, yield, sensitivity, and the length of DNA fragments that could be amplified. Later review literature likewise noted that the introduction of thermostable polymerase eliminated the need to add fresh enzyme in every cycle and made automated PCR on thermal cyclers possible, thereby constituting a crucial step in the transformation of PCR from a conceptual method into a widely applied technology.[11][12][10]

In 1993, the Nobel Prize in Chemistry was awarded to Kary Mullis for the invention of the polymerase chain reaction (PCR) method. However, the official prize citation did not address the contributors involved in the earlier isolation and purification of Taq DNA polymerase. In terms of the technology's developmental trajectory, Chien's 1976 study was directly connected to the 1988 introduction of thermostable polymerase into PCR, and it has therefore often been regarded in later historical reviews of PCR as an important part of the prehistory that made the technique practically viable.[13][10]

In patent litigation concerning Taq polymerase during the 1990s and early 2000s, court documents also identified the 1976 paper by Chien and her co-authors as relevant prior art, further underscoring the study's early and foundational place in the history of Taq technology.[14]

Selected publications

  • Chien, Alice; Edgar, David B.; Trela, John M. (September 1976). "Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus". Journal of Bacteriology. 127 (3): 1550–1557. doi:10.1128/jb.127.3.1550-1557.1976. PMC 232952. PMID 8432.

See also

References

  1. ^ a b Chien, Alice; Edgar, David B.; Trela, John M. (September 1976). "Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus". Journal of Bacteriology. 127 (3): 1550–1557. doi:10.1128/jb.127.3.1550-1557.1976. PMC 232952. PMID 8432.
  2. ^ "她的研究促成PCR成功商業化，但她什麼都沒得到". 科學棋談 (in Traditional Chinese). 2023-06-09. Retrieved 2026-03-07.
  3. ^ "壹、歷史沿革貳、現況" (PDF). 國立陽明交通大學神經科學研究所 (in Traditional Chinese). Retrieved 2026-03-07.
  4. ^ "113年1月26日下午三點至四點於圖資大樓5樓512會議室生科院專訪錢嘉韻退休教授". Flickr（國立陽明交通大學生命科學院） (in Traditional Chinese). Retrieved 2026-03-07.
  5. ^ 呂, 翔禾 (March 9, 2026). "促PCR商業化 神經學家錢嘉韻辭世". 台灣醒報. Retrieved March 11, 2026.
  6. ^ 李, 容珍 (March 9, 2026). "諾貝爾獎PCR技術背後的關鍵研究者 台灣女科學家錢嘉韻教授安息 師生追念她忠心事主的一生". 論壇報 (in Chinese). Retrieved March 11, 2026.
  7. ^ "奠基PCR商用化，關鍵推手錢嘉韻教授安息主懷上帝引領的精采人生". 基督教今日报 (in Traditional Chinese). 2026-03-05. Retrieved 2026-03-07.
  8. ^ Saiki, R. K.; Scharf, S.; Faloona, F.; Mullis, K. B.; Horn, G. T.; Erlich, H. A. (1985-12-20). "Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia". Science. 230 (4732): 1350–1354. doi:10.1126/science.2999980. PMID 2999980.
  9. ^ "Kary B. Mullis – Nobel Lecture: The Polymerase Chain Reaction". NobelPrize.org. 1993-12-08. Retrieved 2026-03-07.
  10. ^ a b c Neuzil, Pavel; Zhang, Chaoyong James; Pipper, Jiri; Oh, Shing Ho; Zhuo, Liang (July 2020). "PCR past, present and future". BioTechniques. 69 (4): 317–325. doi:10.2144/btn-2020-0057. PMC 7439763. PMID 32815744.
  11. ^ Saiki, R. K.; Gelfand, D. H.; Stoffel, S.; Scharf, S. J.; Higuchi, R.; Horn, G. T.; Mullis, K. B.; Erlich, H. A. (1988-01-29). "Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase". Science. 239 (4839): 487–491. doi:10.1126/science.2448875. PMID 2448875.
  12. ^ Erlich, H. A.; Gelfand, D. H.; Saiki, R. K. (February 1988). "Specific DNA amplification". Nature. 331 (6155): 461–462. doi:10.1038/331461a0.
  13. ^ "The Nobel Prize in Chemistry 1993". NobelPrize.org. Retrieved 2026-03-07.
  14. ^ "Hoffmann-La Roche, Inc. v. Promega Corp., 323 F.3d 1354 (Fed. Cir. 2003)". Justia. Retrieved 2026-03-07.


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