◆ Achievements and Contributions
I am currently a Distinguished Professor at the Institute of Environmental and Occupational Health Sciences at the National Taiwan University College of Public Health, and also a Distinguished Investigator and Director of the National Institute of Environmental Health Sciences at the National Health Research Institutes. My research has resulted in more than 400 scientific articles, and I have received the Outstanding Research Award from the Ministry of Science and Technology in Taiwan in 2015 and 2020, as well as the Outstanding Alumni Award from Kaohsiung Medical University in 2018, and have been recognized as one of the world’s top 2% scientists since 2019. I served as chair of the Scientific Committee on Reproductive Hazards in the Workplace (RHICOH) and the International Commission on Occupational Health (ICOH) from 2012-2018, and was the first chair of the Birth Cohort Consortium of Asia (BiCCA) from 2012-2014. I also served as an expert witness in the class action of the former workers of Taiwan RCA giving oral testimony in court for 7 days, totaling nearly 50 hours in 2013-2014. I was honored to receive the National Occupational Safety and Health Award - Personal Contribution Award from the Ministry of Labor in 2020. In addition, I served as President of the Taiwan Public Health Association from 2017-2022 and under my tenure, Taiwan became the first in Asia to pass the Public Health Specialists Act in 2020. I was also elected as a Fellow of the Collegium Ramazzini in 2023 and of the International Society of Environmental Epidemiology (ISEEF) in 2024. NTU Scholars, ORCID, PubMed, Google Scholar, YouTube
- Reproductive Hazards in the Workplace and Environment
“Silent Spring” by Rachel Carson in 1962 was a powerful and pressing warning about the dangers of manmade pesticides contaminating the natural world. “Our Stolen Future” by Theo Colborn et al in 1996, provided a detailed account of emerging scientific research on how various manmade chemicals disrupt delicate hormone systems, which play a critical role in everything from human sexual development to behavior, intelligence, and the functioning of the immune system. Occupational or environmental exposure to heavy metals, organic solvents, persistent organic pollutants, pesticides, endocrine disrupting chemicals, and radiation can harm reproduction and offspring, becoming important public health issues. I have been working in the field of reproductive and developmental epidemiology for several decades, conducting several occupational or environmental cohort studies, including lead-acid battery, semiconductor industry, and electronics worker cohorts, as well as a prospective pregnancy cohort in Taipei. Through these studies, I have made a significant and unique contribution to this field and played a leading role in Asia and the world. I am honored to have been a member of the executive board of the Scientific Committee on Reproductive Hazards in the Workplace, International Commission on Occupational Health (ICOH, the oldest scientific association in the field founded in 1906, with more than 2,000 members in 93 countries. ICOH is an NGO recognized by the United Nations and has a close working relationship with the International Labor Organization and World Health Organization) since 2007 and served as the chair of the committee from 2012-2018. We held the first International Symposium on Reproductive Hazards in the Workplace and Environment (RHICOH) in Taipei on April 20-21, 2010, and the symposia have continued to be held in Utrecht, The Netherlands on June 18-19, 2013, Barcelona, Spain on September 5-6, 2016, and Taipei, Taiwan on June 24-25, 2018 (our website).
- Children’s Environmental Health Based on Birth Cohort Studies
We have recently begun conducting a longitudinal birth cohort study to investigate the impact of the environment, genetics, and other factors on children’s health. Children’s environmental health is an increasingly recognized global public health concern. Despite our current knowledge, the exposure levels of environmental contaminants among reproductive-age individuals, infants, and children are not well understood, and the role of prenatal and postnatal exposure to environmental and genetic factors in the development of adverse child health outcomes remains unclear. In Taiwan, we have identified several pressing issues that require research, including: the prevalence of asthma, which has risen to over 10%; the rate of preterm delivery, which has risen to 9% in 2003; the high prevalence of neurodevelopmental disorders, which affect 8% of children under the age of four years; and a doubling of the prevalence of childhood obesity. In response, we started the Taiwan Birth Panel Study (TBPS) to investigate the impact of prenatal and postnatal factors on infant and early childhood health. This prospective birth cohort focuses on atopic diseases, child growth and development, and neurocognitive and language development. Factors studied include infection, herb use during pregnancy, breastfeeding, allergens, and pollutants such as environmental tobacco smoke, heavy metals, non-persistent pesticides, melamine, per- and polyfluoroalkyl substances (PFAS), phthalates, bisphenol-A, acrylamides, and psychosocial stress, all considered in relation to the interaction of the environment and genetics. A list of 61 publications can be found on our website.
Our research team has been investigating the health effects of per- and polyfluoroalkyl substances (PFAS), also known as forever chemicals and endocrine-disrupting chemicals (EDCs), since 2009. We have found that exposure to PFAS is linked to reduced fetal growth (PLoS ONE 2012) and childhood growth (Sci Total Environ 2017), disrupted thyroid function (Environ Pollut 2017), delayed neurodevelopment in children (Epidemiology 2013), increased symptoms of attention deficit/hyperactivity disorder (Chemosphere 2016), elevated IgE levels (Environ Res 2011), and reduced lung function development (Environ Res 2021). Additionally, our team has discovered associations between PFAS and increased risks of asthma (Environ Health Perspect 2013), reduced testosterone, increased estradiol levels (Environ Int 2016), and elevated uric acid concentrations (Environ Pollut 2016) in the Genetic and Biomarkers Study for Childhood Asthma (GBCA) study. Furthermore, our collaborative studies have revealed that PFAS can interfere with reproductive hormones (Int J Hyg Environ Health 2015), increase carotid intima-media thickness (Environ Int 2016), and raise the risk of metabolic syndrome (Int J Hyg Environ Health 2020) and diabetes (Environ Int 2016) in adults and premenopausal breast cancer in women (Environ Int 2020). To date, we have published 36 articles in international journals and have become a leading research team studying the human health effects of PFAS globally. The Taiwan Semiconductor Industry Association (TSIA) announced the complete withdrawal of PFOS in 2017, and Taiwan Semiconductor Manufacturing Company Limited (TSMC) also announced a replacement timetable for PFOA and related chemicals. PFHxS has been listed as a toxic chemical substance, and will be completely banned except for research, experimentation, and educational purposes in the end of 2023. The Executive Yuan approved the Action Plan for the Management of Per- and Polyfluoroalkyl Substances (PFAS) in 2024.
Other environmental contaminants that are also common endocrine-disrupting chemicals (EDCs) include phthalates and phenolic compounds such as bisphenol-A (BPA), nonylphenol (NP), octylphenol (OP), and parabens, a group of substances commonly employed as antimicrobial preservatives. Our research has found that prenatal exposure to phenolic compounds can negatively impact neurobehavioral development in early childhood (Sci Total Environ 2017); prenatal exposure to phthalates can raise IgE levels and the risk of atopic dermatitis (Environ Int 2014); and postnatal exposure to phthalates can interfere with childhood thyroid function and reduce lung function development (Sci Total Environ 2018) in the Taiwan Birth Panel Study (TBPS). Our research team also revealed that exposure to phthalates (Environ Int 2016) increased carotid intima-media thickness by increasing DNA and lipid oxidative stress, decreased testosterone levels, and raised insulin resistance (Environ Pollut 2017) in the Young Taiwanese Cardiovascular Cohort (YTCC) study. Furthermore, exposure to phenolic compounds increased carotid intima-media thickness (Environ Pollut 2019) in adolescents and young adults. Recent findings have also revealed a sex-specific association between parabens and children's attention performance (Environ Int 2024).
Our research team has been investigating the health effects of per- and polyfluoroalkyl substances (PFAS), also known as forever chemicals and endocrine-disrupting chemicals (EDCs), since 2009. We have found that exposure to PFAS is linked to reduced fetal growth (PLoS ONE 2012) and childhood growth (Sci Total Environ 2017), disrupted thyroid function (Environ Pollut 2017), delayed neurodevelopment in children (Epidemiology 2013), increased symptoms of attention deficit/hyperactivity disorder (Chemosphere 2016), elevated IgE levels (Environ Res 2011), and reduced lung function development (Environ Res 2021). Additionally, our team has discovered associations between PFAS and increased risks of asthma (Environ Health Perspect 2013), reduced testosterone, increased estradiol levels (Environ Int 2016), and elevated uric acid concentrations (Environ Pollut 2016) in the Genetic and Biomarkers Study for Childhood Asthma (GBCA) study. Furthermore, our collaborative studies have revealed that PFAS can interfere with reproductive hormones (Int J Hyg Environ Health 2015), increase carotid intima-media thickness (Environ Int 2016), and raise the risk of metabolic syndrome (Int J Hyg Environ Health 2020) and diabetes (Environ Int 2016) in adults and premenopausal breast cancer in women (Environ Int 2020). To date, we have published 36 articles in international journals and have become a leading research team studying the human health effects of PFAS globally. The Taiwan Semiconductor Industry Association (TSIA) announced the complete withdrawal of PFOS in 2017, and Taiwan Semiconductor Manufacturing Company Limited (TSMC) also announced a replacement timetable for PFOA and related chemicals. PFHxS has been listed as a toxic chemical substance, and will be completely banned except for research, experimentation, and educational purposes in the end of 2023. The Executive Yuan approved the Action Plan for the Management of Per- and Polyfluoroalkyl Substances (PFAS) in 2024.
Other environmental contaminants that are also common endocrine-disrupting chemicals (EDCs) include phthalates and phenolic compounds such as bisphenol-A (BPA), nonylphenol (NP), octylphenol (OP), and parabens, a group of substances commonly employed as antimicrobial preservatives. Our research has found that prenatal exposure to phenolic compounds can negatively impact neurobehavioral development in early childhood (Sci Total Environ 2017); prenatal exposure to phthalates can raise IgE levels and the risk of atopic dermatitis (Environ Int 2014); and postnatal exposure to phthalates can interfere with childhood thyroid function and reduce lung function development (Sci Total Environ 2018) in the Taiwan Birth Panel Study (TBPS). Our research team also revealed that exposure to phthalates (Environ Int 2016) increased carotid intima-media thickness by increasing DNA and lipid oxidative stress, decreased testosterone levels, and raised insulin resistance (Environ Pollut 2017) in the Young Taiwanese Cardiovascular Cohort (YTCC) study. Furthermore, exposure to phenolic compounds increased carotid intima-media thickness (Environ Pollut 2019) in adolescents and young adults. Recent findings have also revealed a sex-specific association between parabens and children's attention performance (Environ Int 2024).
We have been actively involved in the Taiwan Birth Cohort Study (TBCS) project, investigating various factors such as breastfeeding, vaccinations, dietary supplements, Chinese herbal medicine, exposure to environmental tobacco smoke, parental stress and employment, and air pollution in relation to maternal and children's health. Our findings have been published on our website, with a list of 35 publications available for viewing. Recently, we were the first to report that exposure to household incense burning (Environ Int 2018) and maternal shift work (Int J Epidemiol 2019) were associated with delays in motor neurodevelopmental milestones. Our research bridges knowledge gaps and addresses unsolved issues related to low-level, prenatal or postnatal, multiple exposures, and genetic effect modification in the initiation and progression of environmentally-related childhood diseases. We also actively participate in education, research, and services in the field of pediatric environmental health by integrating multiple disciplines. To provide clinical services, exposure assessments, and risk communication, we established the Environmental Medicine Coordination Center at the National Taiwan University Hospital in 2014. We have also continuously held the International Symposium of Precision Environmental Medicine (ISPEM), participated in solving the issue of lead water pipes inTaipei in 2015, and took part in the banning of incense burning at the 281-year-old Longshan Temple from 2017-2019. Additionally, we have recently published “Understanding Toxics in Your Daily Life (毒懂您的生活)” and “Respiratory Protection Handbook in the Air Pollution Era (空汙世代的肺部養護全書)” for the general public.
- Birth Cohort Consortium of Asia (BiCCA)
In 2000, the United Nations Millennium Declaration established the importance of child health and environmental sustainability through the Millennium Developmental Goals (MDGs). According to the World Health Organization (WHO), over 40% of the global burden of disease caused by environmental factors affects children under five years old, despite them making up only about 10% of the world’s population. To address this, birth cohort studies have been established in Asia to investigate the effects of different environmental risks on child health. The Birth Cohort Consortium of Asia (BiCCA) was established by the principal investigators of three birth cohorts in Asia, including the Taiwan Birth Panel Study (TBPS), the Mothers and Children’s Environmental Health Study (MOCEH) and the Hokkaido Study on Environment and Children’s Health (Hokkaido Study). I had the privilege of leading the first meeting for the Birth Cohort Consortium of Asia (BiCCA) in 2012-2014, where we aimed to investigate the impact of the environment, genetics, and children’s health issues in Asia. Through the BiCCA, 33 birth cohorts have been established across 17 Asian countries, with a total of approximately 90,000 study subjects. Our research has provided valuable insights into the study framework, environmental exposure and health outcomes, as well as maternal and infant characteristics of the participating cohorts (Epidemiology 2017). The BiCCA serves as a unique and reliable source of birth cohort information in Asian countries, and our team continues to work together to identify specific regional environmental threats and improve the health of children in Asia (Sci Total Environ 2017; Environ Res 2019). For more information, please visit our website.
- Preventive Actions of Banning Herbal Medicine Containing Aristolochic Acid
The consumption of Chinese herbs containing aristolochic acid has been linked to a higher risk of urothelial carcinoma. In 2002, the International Agency for Research on Cancer classified plants containing aristolochic acid as carcinogenic to humans (Group 1), and in 2012, it classified aristolochic acid itself as carcinogenic to humans (Group 1). Studies have also reported increased risks of chronic kidney disease, kidney failure, and urinary tract cancers in Taiwan as a result of consuming Chinese herbs containing aristolochic acid. Furthermore, Chinese herbalists have also been found to have an increased risk of kidney failure and urinary tract cancers. Additionally, a study by Chen et al. found that 93 out of 152 patients with upper urinary tract urothelial carcinoma had been exposed to aristolochic acid, based on the presence of aristolactam-DNA adducts and an AA-mutational signature in the renal cortex. Finally, aristolactam-DNA adducts were also detected in 76% of clear cell renal cell carcinoma (ccRCC) and an AA-mutational signature was evident in 6 out of 10 sequenced ccRCC exomes from Taiwanese patients (Cancer Epidemiol Biomarkers Prev 2016). Due to our early studies, we were able to convince the government to take preventive actions and ban Chinese herbs containing aristolochic acid in November 2003. As a result, there has been a gradual reduction in the incidence of bladder cancer and carcinomas of the renal pelvis and other urinary organs since 2011. More recently, our research has shown that there is a significant linear dose-response relationship between aristolochic acid consumption and hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients. This suggests that aristolochic acid, which may be associated with HBV infection, plays a significant role in HCC development, and those infected with HBV or HCV who have taken these herbs should be closely monitored (Int J Cancer 2018; Cancer Epidemiol Biomarkers Prev 2019). Our studies also suggest that aristolochic acid exposure may increase the risk of kidney, bladder, pelvis, ureter, liver, and colorectal cancer in all patients, prostate cancer in men, andextrahepatic bile duct cancer in women (Phytomedicine 2022).
- Cancer Chemoprevention Based on Health Informatics Research
Preventing illness is more effective than treating it once it occurs. Cancer risk reduction using medication is an appealing modern preventive approach. Statins have been shown to have potential protective effects against cancer, but previous research has not focused on patients with chronic hepatitis B or C virus (HBV or HCV) infection. This study aimed to investigate the association between the use of statins in HBV- or HCV-infected patients and the risk of hepatocellular carcinoma (HCC). Our team conducted a population-based cohort study using data from the Taiwan National Health Insurance Research Database. We found that statin use may reduce the risk of HCC in HBV- or HCV-infected patients in a dose-dependent manner. Similar findings have been reported in several other countries, including Denmark (N Engl J Med 2012), Sweden (Pharmacoepidemiol Drug Saf 2014; Ann Intern Med 2019), the United States (Cancer Epidemiol 2014; Hepatology 2015; Clin Gastroenterol Hepatol 2019; J Clin Gastroenterol 2020; Am J Gastroenterol 2021; J Clin Gastroenterol 2022; Clin Gastroenterol Hepatol 2023), the United Kingdom (JNCI 2015; Int J Cancer 2020; Cancer Epidemiology 2020; JAMA Netw Open 2023), Hong-Kong (J Hepatol 2015), and Korea (J Hepatol 2017; Hepatology 2020; BMC Gastroenterology 2023), and have been cited by UpToDate@. We have published two original articles in the Journal of Clinical Oncology that have been recognized as “Highly Cited Paper and Research Front Core Paper” by ISI Essential Science Indicators. We have also reported that statin use is associated with a reduced risk of cirrhosis development among patients with HCV infection in a dose-dependent manner (J Hepatol 2015) and a reduced risk of pancreatic cancer in type 2 diabetic patients (Int J Cancer 2016). Another cancer-preventing agent, acarbose, an α-glucosidase inhibitor, has been shown to reduce the risk of colorectal cancer in patients with diabetes in a dose-dependent manner (Diabetes Care 2015). I was invited to speak at the 2017 International Congress of Epidemiology to share our knowledge and experience in health informatics research. I also published an invited article that has been recognized as “Highly Cited Paper” by ISI Essential Science Indicators,which was co-authored with Professor Liam Smeeth, Director of the London School of Hygiene of Tropical Medicine.
- Expert Witnesses for the RCA Corporation Employees Caring Association
The civil lawsuit against Taiwan’s Radio Corporation of America (RCA) is one of the most scientifically-backed cases in Taiwan’s judicial history. In 1994, a hazardous waste site polluted by the dumping of solvents from a former electronics factory was discovered in Taoyuan, Taiwan. This case subsequently emerged as a severe contamination case involving chlorinated hydrocarbons, with suspected occupational cancer. Studies found that female workers exposed to trichloroethylene (TCE) and a mixture of solvents may have an increased risk of breast cancer. Female workers with potential exposure to organic solvents during the periconception period might increase the risk of childhood cancers, particularly leukemia. Male workers also had an increased risk of infant mortality and deaths due to congenital malformations in their offspring. The first witness testified in court in November 2009. The final argument was made on December 12, 2014, and the verdict was announced on April 17, 2015. The court found that RCA did expose the former workers at the RCA Plant to mixtures of contaminants, including TCE, tetrachloroethylene, trichloroethane, and methylene chloride, and that the routes of exposure included drinking groundwater contaminated with those organic solvents. Based on the expert testimony of Professors Pau-Chung Chen (陳保中) and Jung-Der Wang (王榮德), the court found that exposure to a mixture of organic solvents such as TCE, TCA, and their derivatives can cause more severe harm to the human body than exposure to any single chemical within the mixture. RCA and its parent companies were aware of the health risks of these chemical substances, but failed to fulfill their environmental maintenance and pollution control responsibilities, resulting in many workers being exposed to carcinogenic chemicals such as trichloroethylene and tetrachloroethylene and suffering from various diseases. At least 133 people involved in the litigation have passed away, and many more are still living and suffering from significant injuries. Another group of 1,163 injured laborers and their families filed a lawsuit in the Supreme Court of Taiwan upheld the liability of RCA and its parent companies, General Electric, Thomson Electronics, and Technicolor, on August 16, 2018, and ordered them to pay NT$ 564 million (around US$ 18 million) in compensation to 262 plaintiffs. On March 11, 2022, the Supreme Court, upon further review, ruled that an additional 24 individuals were collectively awarded over NT$ 54.7 million (around US$ 1.8 million) in compensation. The Taipei District Court also awarded NT$ 2.3 billion (around US$ 77.5 million) in compensation to the second batch of 1,115 former employees of RCA, Taiwan, on December 27, 2019. These related cancers have also been recognized by the Bureau of Labor Insurance as occupational cancers. The RCA lawsuits are ongoing, but they have gained international recognition as the most successful case of collaboration between public health and law.
- Taiwan Passes Public Health Specialists Act
We proposed the first draft of the Public Health Specialists Act in 2000 when I served as Secretary General of the Taiwan Public Health Association. Past presidents and I have continuously advocated for the act for 20 years. The final reading of the Public Health Specialists Act passed the Legislature on May 15, 2020, highlighting the government’s ongoing commitment to improving the well-being of local residents. The act, which comprises 40 articles, defines the qualifications, rights, obligations and scope of operation of a public health specialist. The responsibilities of public health specialists include conducting environmental health risk assessments, epidemiological investigations, disease prevention, health surveys, health promotion, food safety inspections, and other tasks outlined by the Ministry of Health and Welfare in communities and public spaces. National Taiwan University established the country’s first department of public health in 1972, and since then, Taiwan's tertiary institutions have trained thousands of public health professionals. For more than four decades, these individuals have played a crucial role in shaping the Country’s public health landscape by participating in policy making, providing health education to communities, and conducting epidemiological research. Given the country’s economic and social development, the Public Health Specialists Act will greatly enhance the ability of Taiwan’s public health system to manage challenges such as the COVID-19 pandemic. President Ing-wen Tsai praised the legislation as evidence of the government’s belief in valuing expertise. Taiwan’s success in containing the coronavirus is due in part to the dedication of the country's frontline medical staff and public health specialists. The Public Health Specialists Act certificate can be used to identify professional talents, establish the professional image of Public Health Specialists, enhance competitiveness in the workplace, and sustain the professional value of public health. In the future, we will continue to advocate for more refined public health career planning, the integration of professional teaching, examination, and application, and further solidifying the importance of public health professionals. In 2023, co-edited the forum monograph “Professional Development and Manpower Planning of Public Health Specialists in Taiwan” with Professor Yue-Chune Lee, and also co-edited the “Contemporary Public Health Series” with six volumes along with Professors Wei J. Chen and Yue-Chune Lee, continuously promoting the professional development of the public health.