Hard Lessons Learned: Bioethics Then and Now

Research

By Brianna Gutierrez
Illustration by Paolo Paramio
Published 2020 October 5

Science will always favor discovery. It allows us to understand how the universe works, to uncover the secrets of our surroundings. Adding to the current knowledge pool is, at face value, a service done for the greater good, especially if it has to do with advancing the human race. However, the ends don’t always justify the means. Everything needs to have limitations—even science. No matter how well-intended, researchers are obligated to make choices grounded in “moral imperatives” [2] (or simply the pull to do what is right) in order to protect the rights—and possibly even the lives—of all parties involved. The discipline concerned with understanding this obligation, the factors that influence it, and the implications of deviating from it, is called ethics [11]. 

Most people develop their ethical counsel in their childhood, but not everyone experiences similar upbringings [11]. Different groups divided by differing cultural norms or values often end up in disagreements over what is ethically acceptable. Various fields of study are wrought with such disagreements and scientific research is not an exception to this. If ethics weren’t seriously considered, the number of potential discoveries would practically be limitless—however, this would be at the expense of the lives of the subjects involved, which can render even the most valid research studies void [4]. This calls for a set of standards based on ethical imperatives by which researchers can be guided when conducting their studies. This is especially important in medical research, in which human participants may be involved. Their rights and safety must be considered before they can contribute to research, no matter how relevant or groundbreaking the topic of the study may be.

Unfortunately, the path to this conclusion is laden with controversy. In the past, there had been no set ethical principles to adhere to, and as a result, there were no laws or guidelines that served to protect the human subjects medical researchers involved in their studies. For example, one of the most heinous acts of cruelty done with the goal of furthering clinical research was carried out by Nazi physicians who experimented on unwilling convicts from the concentration camps during the time of World War II [2,7]. In response to these atrocities, the Nuremberg Code, or essentially ten (10) ethical guidelines for research, was finally developed in 1947. The Code outlined the importance of voluntary consent and participation; the protection of human subjects; the utmost avoidance of suffering, whether physical or mental; and the relevance of the study to the greater good, among others. It was the first international set of ethical guidelines that researchers could refer to when making important choices concerning the participants they involve in their studies. 

Before this historical turning point, however, researchers all over the world did not have a set of rules to mark the line separating ethical from unethical. This became an issue that spread even to developing and underdeveloped countries (including the Philippines), in which medical research was becoming increasingly prevalent [2]. An article by two Atenean alumni, Patricia Ana Vic H. Arcega and Chiara Louise P. Cabantac, as well as Ateneo Biology Professor Ronald Allan L. Cruz, outlines the trends in medical research ethics in the Philippines during the American Colonial Period [1]. The researchers collected 288 clinical research studies that were conducted in the Philippines within the years 1898 and 1946 and tracked the trends of bioethics throughout the period. It was found that not many studies outwardly observed any ethical protocol, even including review. In fact, the first study in the Philippines that mentioned the adherence to any kind of ethical protocol was conducted in 1926, in which dengue patients from the Sternberg General Hospital in Manila participated. It is unsurprising, therefore, to discover that very few studies practiced the informed consent process on their subjects. The informed consent process is an important step to any project concerning human participants. In this process, each participant must sign a document that states their agreement to their voluntary participation in the study, as well as the fact that they are fully aware of the risks, benefits, and other similar details that participating would entail [14]. 

During the American Colonial Period, some researchers chose to acquire consent verbally in lieu of formally signed documents [1]. Some discerned not to get consent at all. This is alarming because out of nearly 300 studies, it was found that 60.8% made use of vulnerable persons as subjects for their research. The article specified children, prisoners (from Bilibid Prison), and men enlisted in the army as vulnerable persons. Others include pregnant women, indigenous people, students, workers, and those with “sensitive health conditions” [2]. Judging by the results of the research, as well as other circumstances that may have rendered vulnerable participants ignorant of the “gravity” of the experimentation being conducted on them, it would seem that many of them became participants without understanding exactly what they were taking part in [1]. One study, for example, conducted in 1906, involved the performing of autopsies on infants and children fed with different types of milk/food—all without the consent of the parents. It was only in 1923, with a study conducted on lepers from the Culion Leper Colony, that researchers began to discuss how the research was conducted with the participants. 

Compared to the number of studies that mentioned the practice of informed consent, the number of those which identified inclusion and exclusion criteria for their participants is slightly greater [1]. Inclusion criteria are understood to be the characteristics of an ideal participant, or features of a population that can be used to answer the research question [9]. Exclusion criteria are the opposite: characteristics of a participant that may interfere with the outcome of the study. These parameters must be defined not only to increase the study’s validity but also to inform possibly vulnerable subjects of the risks that they may be exposed to upon participating [5]. For example, in a 1910 study conducted on prisoners from Bilibid aiming to find the cause of beriberi, two of the subjects were recovering from surgery, and the changes in diet required as a participant in the study may have interfered with their recovery. In conclusion, the identification of inclusion and exclusion criteria can serve as a layer of protection for the potentially vulnerable, and it is a lesson researchers must learn from history.

Ethics in research have greatly evolved since then, though disagreements still happen once in a while. Fortunately, since the establishment of the Nuremberg Code in 1947, as well as the passing of various laws and bills for the protection of the rights of vulnerable parties, researchers are more likely to respect and adhere to ethical guidelines as provided by their respective ethics review committees or institutional boards [8,12,13]. In 2011, the World Health Organization drafted a digital booklet, Standards and Operational Guidance for Ethics Review of Health-Related Research with Human Participants, to serve as an international guide to which ethical protocols for research may be patterned [15]. Meanwhile, the Philippine Health Research Ethics Board (PHREB) published a revision of our National Ethical Guidelines for Health and Health-Related Research in 2017, outlining all general and special guidelines for clinical research studies [10]. 

With all these newly set protocols, one might think that controversy and conflicts of interest have become less frequent over the years. Unfortunately, ethical choices still need to be made in today’s period of medical research. Especially now, when the world as we know it is overrun by the COVID-19 pandemic, ethics must be considered at a time when anyone could be at risk. For example, conducting research within quarantine requires ethical considerations [3]. One ethical issue posed by quarantine is that its issuance may have been a result of the government’s failed response to the pandemic, which deems all those confined as “victims of injustice.” Furthermore, some instances of quarantine can even exacerbate the transmission of the disease. These factors would make the origins of scientific research based in quarantine questionable. Another COVID-19-related ethical issue being debated on is the execution of human challenge studies, or studies in which human participants are intentionally infected by the virus in order to “accelerate…vaccine development” [6]. This is clearly controversial as death may be a risk to consider as a potential participant. Some scientists, however, continue to argue its acceptability, so long as various factors are controlled and the benefits of the study outweigh the ethical considerations.

The evolution of research ethics is a fascinating picture, one in which controversy and tragedy have led to hard lessons learned. Even now, the lessons history has made us learn remains to be essential; from high school science projects to groundbreaking research to cure the world of COVID-19, ethics must play an important part in research for knowledge to be validated. The current state of health ethics is certainly nowhere close to perfect, however, with the current set of protocols laid out by official committees and institutional boards, the line separating the acceptable from the unacceptable has surely become much clearer. Although the unacceptable makes science virtually limitless, the ethically acceptable keeps everyone safe in the process—and at the end of the day, that’s the right thing to do.

References

1. Arcega PAVH, Cabantac CLP, Cruz RAL. Trends in health research ethics in the Philippines during the American Colonial Period (1898‐1946). Developing World Bioethics. 2019;19(3):180–5.
2. Avasthi A, Ghosh A, Sarkar S, Grover S. Ethics in medical research: General principles with special reference to psychiatry research. Indian Journal of Psychiatry [Internet]. 2013 [cited 2020Sep30];55(1):86. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574464/
3. Evans NG. Covid-19: the ethics of clinical research in quarantine. Bmj [Internet]. 2020 [cited 2020Sep30];:m2060. Available from: https://www.bmj.com/content/369/bmj.m2060
4. Explorable.com. Scientific Misconduct [Internet]. Ethical Violations in Research. 2009 [cited 2020Sep30]. Available from: https://explorable.com/scientific-misconduct
5. Inclusion and Exclusion criteria in research [Internet]. reviewingresearch.com. [cited 2020Sep30]. Available from: http://www.reviewingresearch.com/inclusion-and-exclusion-criteria-in-research/
6. Jamrozik E, Selgelid MJ. COVID-19 human challenge studies: ethical issues. The Lancet Infectious Diseases [Internet]. 2020 [cited 2020Sep30];20(8). Available from: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30438-2/fulltext
7. Jarmusik N. The Nuremberg Code And Its Impact On Clinical Research [Internet]. Top Medical Device CRO Company. 2019 [cited 2020Sep30]. Available from: https://www.imarcresearch.com/blog/bid/359393/nuremberg-code-1947
8. Page SA, Nyeboer J. Improving the process of research ethics review. Research Integrity and Peer Review [Internet]. 2017 [cited 2020Sep30];2(1). Available from: https://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-017-0038-7
9. Patino CM, Ferreira JC. Inclusion and exclusion criteria in research studies: definitions and why they matter. Jornal Brasileiro de Pneumologia [Internet]. 2018 [cited 2020Sep30];44(2):84–. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044655/
10. Philippine Health Research Ethics Board. National Ethical Guidelines for Health and Health-related Research. Taguig: Department of Science and Technology – Philippine Council for Health Research and Development; 2017.
11. Resnik DB. What Is Ethics in Research & Why Is It Important? [Internet]. National Institute of Environmental Health Sciences. U.S. Department of Health and Human Services; 2015 [cited 2020Sep30]. Available from: https://www.niehs.nih.gov/research/resources/bioethics/whatis/index.cfm
12. Ruyter KW. The history of research ethics [Internet]. Forskningsetikk. 2019 [cited 2020Sep30]. Available from: https://www.forskningsetikk.no/en/resources/the-research-ethics-library/systhematic-and-historical-perspectives/the-history-of-research-ethics/
13. UNLV. History of Research Ethics [Internet]. History of Research Ethics | Research and Economic Development | University of Nevada, Las Vegas. [cited 2020Sep30]. Available from: https://www.unlv.edu/research/ORI-HSR/history-ethics
14. Why Is Informed Consent in Clinical Trials Essential?: Avail Clinical Research [Internet]. Accel Research Sites. 2018 [cited 2020Sep30]. Available from: https://accelresearchsites.com/why-is-there-informed-consent-in-clinical-trials/
15. World Health Organization. Standards and Operational Guidance for Ethics Review of Health-Related Research with Human Participants. Geneva: WHO Documentation Production Services; 2011.