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The Right Place and the Right Time: Incorporating Ethics into the Undergraduate Biochemistry Curriculum Meagan K. Mann* Department of Chemistry, Austin Peay State University, 601 College Street, Clarksville, Tennessee 37044, United States *E-mail: [email protected].

Ethics is a branch of philosophy that covers the morality of our actions. For scientists, this means the ethics associated with our research design, reporting of data, and the care taken when working with experimentation on humans and animals. Many chemistry students receive the bulk of their scientific ethics training, whether intentionally or unintentionally, from their chemistry professors over the years spanning their education. While any college education provides students with a knowledge of plagiarism, cheating, and other areas of academic misconduct, the study of ethics in chemistry as it pertains to research misconduct and bioethics is largely left untouched, covered briefly, or sometimes taught but not acknowledged outright as an area of ethics. Presented here is a course design that includes learning objectives, assessments, and a variety of course topics and case studies used to bring a comprehensive ethics training component to undergraduate students taking biochemistry.

The Importance of Teaching Ethics to Chemistry Students I would like to start this chapter on the informal side by asking a basic question: if you were asked to rank which professions you trust the most, what would be at the top of your list? Would you pick medical professionals over lawyers? Scientists over politicians? If you are the average American, you would be raising your hand for medical professionals and scientists, which generally © 2017 American Chemical Society Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


rank near the top of such lists (1). Perhaps it is an obvious statement then, that educating our students on how to maintain the trust of the public through ethically executed research is just as important as the chemistry that we teach them. The American Chemical Society reiterates this point by stating in the ACS Guidelines and Evaulation Procedures for Bachelor’s Degree Programs:

“Ethics should be an intentional part of the instruction in a chemistry program. Students should be trained in the responsible treatment of data, proper citation of others’ work, and the standards related to plagiarism and the publication of scientific results. The curriculum should expose students to the role of chemistry in contemporary societal and global issues, including areas such as sustainability and green chemistry. As role models, faculty should exemplify responsible conduct in their teaching, research, and all other professional activities (2).”

Unfortunately for our students, taking elective philosophy courses on ethics tends to fall low on their priority list. While many schools offer courses in philosophy as humanities electives, many students choose appreciation courses in music, art, or theater instead. For the chemistry students who do take a philosophy course, they may have difficulty applying abstract philosophical concepts directly to their work as scientists. Whatever the case may be for each student, the end result is the same: the ethics education a chemistry student receives falls largely on the shoulders of their chemistry professors. It is our job to educate them on acceptable research practices as well as other areas of ethics critical to a comprehensive chemistry education. While most of our students understand that issues such as plagiarism on a paper, fabricating yields in lab, or cheating on exams is unacceptable, the broader implications of this level of dishonesty outside of the classroom may not be as clear to them. They know that proper waste disposal is important but may not recognize intentional and reckless waste disposal as an issue of ethics. A solid foundation in research regulations, governing bodies, and historical and current case studies are critical in preparing our students to be well-educated ethical scientists and medical professionals. This chapter focuses on the methodology, learning objectives, assessments, background, and case studies used to bring an average of eight hours of ethics training to undergraduate students in a two-semester biochemistry sequence. For reference, this work was done at Austin Peay State University, an ethnically and racially diverse regional state university in Tennessee. The biochemistry courses have anywhere from 10-30 students and are roughly split equally between biology and chemistry majors. The vast majority are interested in pursuing professional school. To take biochemistry at Austin Peay, students must pass (with a letter grade of C or better) two semesters of general chemistry, two semesters of organic chemistry, precalculus, and one semester of general biology.

46 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

What is Ethics? Ethics is the branch of philosophy that covers the morality of our actions; essentially, it is the study of what is right and wrong. Of course, the world of philosophy stretches far from the reaches of science into many other fields such as political science, journalism, and military science. For the sake of this chapter, the study of “scientific” ethics will be divided into three categories: bioethics, academic ethics, and research ethics. An introduction to all three is essential for a comprehensive scientific ethics education.


Bioethics Bioethics covers the moral issues that arise with the use of biological samples: namely, animal and human research models, as well as certain other medical technologies using biological tissues. Students engaged in undergraduate research in this field may be familiar with the Institutional Animal Use and Care Committee (IACUC) that oversees animal experimentation or the Internal Review Board (IRB) that oversees human research, but they may not understand the history of why we have and need such approval processes. Many students have no background in historic cases of human and animal experimentation that have shaped our current regulations and guidelines, nor the repercussions of what can happen if these regulations are disregarded. While it is true that many chemists do not use any living models, many of our chemistry students will land in careers that do use them. Providing this education for our students is essential for when they reach professional school or start working in a lab that uses these biological models.

Academic Ethics This is likely the area that American students know the most about as it is reinforced at some point in their primary and secondary education. Academic misconduct covers any type of plagiarism, fabrication of data, and manipulation of data, facts, or other information. While chemistry students know that plagiarism is unacceptable, they may not understand that adding mass to their lab products to indicate a better yield is just as unethical. Students learning to recognize and avoid these areas of misconduct sets the stage for increased scientific integrity throughout their careers.

Research Ethics Research ethics involves the best practices for doing safe, effective, and environmentally responsible research whenever possible. For chemists, this is generally taught as a component of our lab courses and involves education on proper waste disposal and optimizing an experimental design to use safer 47 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

chemicals (or fewer very toxic ones). It is important to have students learn the consequences of unsafe handling of chemicals, illegal methods of disposal, and proper chemical hygiene. As professional scientists, they will work towards reducing the quantity of dangerous reagents used and waste products generated. While teaching these best practices to some degree is common in undergraduate chemistry labs, few lab books approach it from an ethics perspective or label it as a form of misconduct when scientists intentionally disregard these practices.


Why Put Ethics in Biochemistry? The idea of bringing ethics discussions to undergraduate science students is not new. Undoubtedly, if you have surveyed enough textbooks you have seen special sections dedicated to a case study or other ethics topic. At the lower level, these discussions can help lend relevance to introductory non-major science courses aimed at humanities students. At the higher level, ethics discussions provide a critical component of the humanities to a chemistry student’s education. While useful, these small sections found in textbooks are far from replete and beg for additional information. A summary of representative literature available on this subject is presented in Table 1, including two possible textbooks aimed specifically at teaching ethics to science students. While a survey of the literature does show that there are instructors working to incorporate ethics into their classes, there is significantly less research available on ways to integrate more than a single ethics lesson into the standard undergraduate curriculum without designing an entirely new ethics course. While it is ideal to spread ethics training throughout a student’s education, a case can be made to incorporate a significant ethics component in the biochemistry courses. As biochemistry is typically a course for juniors or seniors, students in the course are likely committed to, and qualified for, a career where a proficiency in scientific ethics is necessary. One semester of biochemistry is a requirement for all students receiving ACS accreditation with their chemistry degree and is highly encouraged (or required) by many medical, dental, pharmacy, and veterinary schools. This means that biochemistry courses reach many, if not all, chemistry, biology, and pre-professional students towards the end of their undergraduate studies. Additionally, many relevant and interesting issues related to scientific misconduct are in the field of bioethics. These topics overlap with the biochemistry curriculum significantly when compared to the other branches of chemistry. Bringing these topics to biochemistry is thus a logical starting point for increasing student exposure to the study of ethics as it relates to the sciences.


Table 1. A Summary of Ethics Research in the Science Classroom Topic


Title Scientific Ethics (1991) (3)

Bringing a case study to lab

Scientific Ethics in Chemical Education (1996) (4)

Bringing a case study to lecture

Ethics in Science for Undergraduate Students (1999) (5)

An ethics course for science students

The Ethical Chemist: Professionalism and Ethics in Science (2004) (6)

A textbook on science ethics

Preparing the Senior or Graduating Student for Graduate Research (2005) (7)

An ethics course for science students

Who is Responsible for a Fraud: An Exercise Examining Research Misconduct and the Obligations of Authorship Through Case Studies (2005) (8)


Education Resources for Guiding Discussions of Ethics in Science (2007) (9)

Instructor resources for ethics

Using “Ethics Labs” to Set a Framework for Ethical Discussion in an Undergraduate Science Course (2007) (10)


Why and How to Teach Ethics in Chemical Education (2009) (11)

Instructor resources for ethics

Ethics, Chemistry, and Education for Sustainability (2011) (12)

The importance of teaching ethics

Ethics in Science: Ethical Misconduct in Scientific Research (2012) (13)

A textbook on science ethics

Course Design: Making Room in the Curriculum A burden on any instructor is finding enough time to cover all the material they want included in their syllabus. At some point a decision must be made to prioritize certain topics over others. Unlike other branches of chemistry, there is far less consistency in the topics taught in biochemistry and the methods through which they are delivered. This is likely due to three reasons: •

•

The interdisciplinary nature of biochemistry. Instructors often have primary training in fields that intersect with biochemistry but not biochemistry itself such as molecular and cell biology, biophysics, organic chemistry, chemical biology, medicinal chemistry, pharmacology, physiology, and toxicology. Where biochemistry is taught. Because the content of biochemistry is so interdisciplinary, courses may be found in biochemistry, biology, or chemistry departments. Cross-listing biochemistry courses in multiple departments is also common. 49 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


•

The number of possible topics. There are many more topics included in a standard biochemistry text than can reasonably be included during a two-semester sequence, as well as a lot of topic variability between textbooks.

This inherent variability means that comparing any two courses will have a significant amount of deviation between topics covered. Some instructors may focus more on mechanistic and experimental biochemistry, while others focus on the areas that intersect more with the molecular biosciences. Some may cover fewer pathways in more detail, and others may cover more pathways in less detail. All are common and acceptable ways of teaching biochemistry, as is any method that falls between. It is largely dependent on the instructor’s background, the department the class is housed under, and the student body’s needs. In essence, a biochemistry instructor that prioritizes an education in ethics the same way they do glycolysis and amino acids can find room in their schedule to incorporate these ethics lessons by modifying their content in reasonable and acceptable ways common in the field. As shown in Table 1, there are various possibilities for giving chemistry students ethics training. Making an entirely new course for ethics has obvious advantages but requires more room to be made in an already-full curriculum, and, if listed as an elective, many students will not take it. Using existing lab courses to present case studies, assigned readings, and take-home assignments requires the sacrifice of at least one of the precious few days available for lab during a semester. This leaves spreading out the ethics discussions in the lecture course as the logical choice to fit in multiple case studies throughout the term. This seemed less intimidating than other methods and was the model used from 2009-2016 for this project. This allowed for a dedicated hour, four times a term, for lecture and discussions of history, regulations, and ethics case studies without straying away for weeks at a time from the biochemistry curriculum. Choosing which days to use for the discussions was simple; the lecture on the day preceding an exam always seems awkward from a teaching and learning standpoint. Generally, if new material covered that day will be on the exam, the students have very little time to work problems and study it in as much detail as they can the other exam topics. If new material is covered that is not going to be on the exam, students may not study it when it is fresh in their minds after a lecture, favoring the upcoming exam material, thus having more difficulty with the material when they do get to study it. The ethics lessons were designed to require no supplemental time outside of class and exam questions were based solely on the principles covered in the discussion. This allowed students to perform well on ethics-based questions derived from the previous day’s discussion without having to sacrifice any of their study time away from the core biochemistry content. With four hourly exams per semester as a model, each student, provided they were present in class that day, received 4 hours of in-person ethics training for each semester of biochemistry (students who were absent could ask for a supplementary reading of the case study covered to read before the exam).



Students were aware of the ethics days beforehand and were told that they would have an exam question related to the material discussed. Students were also asked to spend their time in the class participating in the open dialogue rather than taking formal notes so they would pay closer attention to the conversation around them. The discussion was open to stories, anecdotes, thoughts, religious beliefs, and any other facet of a student’s life that influenced their thoughts regarding morality. While more detailed information about case studies is provided in the “Course Content” section of this chapter, the following was the general outline for the ethics lectures:

•

Lecture 1: The first lecture was a standard digital presentation covering the basics of bioethics. This included the history of animal and human testing regulations (or the lack thereof), the modern regulations that we follow, including IACUC and IRB approval for research, and a brief overview of several notable historical case studies. The focus of the first lecture was to convey why we need to learn about ethics, and what types of ethical misconduct helped shape our current laws and regulations.

•

Lectures 2-8: The remaining seven lectures focused on a single case study per class. Roughly 5-10 minutes of background, delivered from the researcher’s perspective, would be delivered orally to describe what they were trying to accomplish through their research. This was followed by a short discussion about what, if any, the students knew about that specific area of research. Another 5-10 minutes was used to detail the ethical issues related to the case study. The remaining class time was dedicated to general discussion of the case, with “what do you think about…” style questions from the instructor to lead and guide as necessary. The goal of these lectures was to focus on who or what was harmed because of the research. Was there a better way to do the research? Was there any way to make it ethical? Was the knowledge obtained worth the cost? The case studies used varied depending on the year, and were chosen in response to current events and the collective classroom’s interests. Interestingly, the discussion would oftentimes end up in the same conclusions term after term when reusing case studies.

To add an anecdotal note, students responded positively to this model and the topic of ethics in general. Our “ethics days” were something they looked forward to learning, and I heard a few reports back from students who used their knowledge of ethics to help answer questions in professional school interviews. Furthermore, it allows for the inclusion of, and elaboration on, very specific information about a student’s ethics training in their letters of recommendation—this is something many professional schools like included in a letter.



Learning Objectives and Course Assessments The learning objectives were straightforward and are presented in Table 2. More time was spent focusing on bioethics and academic ethics than on research ethics, as research ethics tends to receive significant coverage in all lab courses. Additionally, bioethics tends to be more interesting to the predominantly preprofessional student population in the biochemistry courses at Austin Peay. The formative assessments (ungraded assessments used to help monitor student learning) utilized during the discussions were informal variations on commonly used classroom assessment techniques; these proved helpful in guiding the instructor-student dialogue during the class time. As students did not have reading materials beforehand, background knowledge probing, whereby the students were orally asked general questions about that day’s topic at the start of class, were useful in guiding the introductory materials presented. After the collective classroom background was established, focused listing, where the instructor would ask students to list what they knew about a specific topic related to that day’s case study, often showed students had very little preexisting knowledge regarding any of the bioethics topics and also indicated very little background in research ethics. Misconception/preconception checks, where students were asked leading questions to determine if they had misconceptions or preconceptions regarding the case studies, were done orally throughout class discussion to find areas where students were making false comparisons.

Table 2. Learning Objectives for Ethics in Biochemistry Students should be able to think critically about:

Students should have a working understanding of:

Use of humans in research

Belmont Report

Use of animals in research

Vulnerable populations

Vulnerable populations

Institutional Review Boards (IRB)

Social and scientific consequences of fabricated data

Institutional Animal Care and Use Committees (IACUC)

Historical and cultural differences in ethical behavior

Peer review process

Environmental consequences of poor chemical hygiene

Superfund Sites

As far as summative assessments (high-stakes graded materials used to evaluate what students gained from the lectures), standard short essay test questions regarding the content covered in the previous lecture were used. These were generally one question per exam. Each essay question was written to help evaluate the understanding of the learning objectives in Table 2. For example, students were given a fake research study and asked to explain what areas of 52 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


ethics needed to be considered for implementation of the research plan. As another example, students were asked about vulnerable populations in a study. A third example was using a case study we covered to discuss a certain area of ethics. These exam questions were worth 5-10% of each exam grade, and contributed roughly 7% to the final grade. A representative rubric assigned 50% of a question’s point value to being able to describe the ethical issue in general terms (something all students present for the lecture should be able to easily do), 25% was assigned for appropriate use of key words (or descriptions of concepts) that were introduced in the discussion, and the last 25% of the value assigned was for showing a deeper understanding of the ethical issue and its lasting societal implications. These were scaled so that a student who was present in class and who participated in discussion should be able to get 75% of the question’s point value, corresponding to an average grade in the class grading scale. A 100% value was generally given to students who understood the material, participated in the discussion, and who were able to draw conclusions and parallels from the case study covered to the question on the exam.

It is understandable that a chemistry professor may not be as comfortable writing and evaluating this type of exam question. It is not a common way of testing in chemistry courses, and it was, admittedly, more difficult for me to know how to grade these questions. This is where being in contact with a philosophy instructor is instrumental, as they can help guide you in developing questions and an adequate grading rubric. For the first few years of this work, I consulted frequently with Dr. Jordy Rocheleau, a philosophy professor at Austin Peay, for his expertise in developing and grading exam questions on ethics.

Course Content Listed here are some representative examples of background lessons and case studies presented to my classes. These topics could be covered alone during a full lecture block as I did, combined with each other to hit multiple topics per lecture to fit the instructor’s needs (as I did with the introductory bioethics lecture), or even covered briefly during downtime in lab. The way each topic is approached could easily vary by instructor preferences. The introductory lecture on bioethics history included the terms in Table 3. The following sections provide a brief background on certain case studies, with references available to allow for more in-depth study by both the instructor and student, as well as some of the discussion points I have used in the past to facilitate a two-way exchange with the students. It would be impossible to fit all known case studies into this chapter, but in the attached Appendix to this chapter you can find a summary of a few additional case studies in ethics that I have used throughout the years. I realize websites often change: rest assured, an internet search of those cases is generally sufficient to find ample trust-worthy background. 53 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

Table 3. Bioethics Terminology


Term

Definition

Vivisection

Operating on a living animal or human

Dissection

Dismembering a deceased biological specimen

Autopsies

Determining the cause of death in a human

Necropsies

Determining the cause of death in an animal

Institutional Animal Use and Care Committee (IACUC)

Reviews research to be done on animal subjects

Internal Review Board (IRB)

Reviews research to be done on human subjects

Bioethics History: Animal Experimentation The written history of animal vivisection begins as far back as the time of Aristotle in ancient Greece (14). Ibn Zuhr, a twelfth century physician, practiced and perfected surgical procedures on animals before bringing those surgeries to humans (15). The Age of Enlightenment led to more vivisection as more people were literate and doing scientific research; this is largely when debates on vivisection ethics began (14). Early vivisection would be widely considered horrific by modern standards: vertebrate animals would be immobilized by being strapped to a table and cut into with no anesthetic, as there was none available at the time. The animals would generally die a painful death being tortured under the knife. There were several thoughts about the ethics of vivisection during the 1700’s that ran from one extreme of advocacy to the other extreme of opposition. Common thoughts from advocates at the time included (15, 16): • •

Animals could not feel pain because they had no soul; therefore, testing on them was fine. Animals could feel pain, but researchers felt the information acquired from these studies was valuable enough to weigh the risk to the animals with the benefit to humanity.

Surprisingly, some of the early opponents were not particularly concerned with animal welfare but rather the validity of data acquired from animals. Their thoughts included (15): • •

Animals under duress would have altered physiology that would not be reliably transferrable to human physiology. Humans were a special organism different than all others; thus, knowledge derived from research on other animals could not be transferred to humans.


We now know that vertebrate animals can feel pain, that they often prove a good model for human physiology, and that a very stressed animal does have differences in some aspects of their physiology but not in others. Of course, it was through the work of early vivisection that we know this information.


Discussion Points Over time, it became hard to deny a few truths. 1) The type of testing being done on animals was inhumane, and 2) vivisection was instrumental in providing meaningful data that could advance the understanding of human physiology. This led to a simple conclusion which parallels the current Western beliefs: animal research is incredibly useful, but we need to do it in a way that minimizes the suffering of animals. This enlightenment coincided with the time that anesthetics became commonplace, the mid-1800’s, giving an obvious way to continue doing vivisection in a way that reduced animal suffering and was generally considered more humane than in previous generations. Bioethics History: Regulations on Animals in the Research Lab Generally, as public support grows for animal welfare, so does the push for government oversight into vivisection. The first known law passed on animal welfare was in the United Kingdom in 1822 with the “Act to Prevent the Cruel and Improper Treatment of Cattle”. This act stated that if any person “shall wantonly and cruelly beat, abuse, or ill-treat any horse, mare, gelding, mule, ass, ox, cow, heifer, steer, sheep, or other cattle” they would be imposed a fine (16). Shortly after, in 1824, the Royal Society for the Prevention of Cruelty to Animals (RSPCA) was founded and in the latter part of the 19th century, anti-vivisection societies organized to oppose vivisection in the UK (15). The UK is still considered one of the leaders in animal welfare protection laws and pushes for the “3Rs”: Reduce the number of animals used in testing, Refine experiments that use them to reduce their suffering, and Replace animal models when possible. In the US, the history of animal welfare laws started much later with the passing of the Animal Welfare Act (AWA) in 1966. Enforced by the United Stated Department of Agriculture (USDA), the AWA has seen significant revisions in 1970, 1976, 1985, 1990, 2002, 2007, and 2008 (17). The 1985 revision included language to mandate an Institutional Animal Use and Care Committee, which must include at least three people, one of which must be a veterinarian, to act as an advocate to the animals and encourage finding alternatives to animal models for the research. The AWA covers issues of handling, housing, space, feeding, sanitation, veterinary care, and handling of animals in transit.

Discussion Points A study of the AWA and its amendments will bring to light a few issues regarding the consistency of the law as it pertains to all animals (18): The 1970 55 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


amendment included a definition for animals that they must be warm-blooded but excluded all farm animals. While there are policies in place for farm animals, they are much more relaxed than those for animals used for research purposes. The 2002 revision redefined “animal” to exclude mice, rats, and birds bred for laboratory work (95% of all animals used in labs). This still stands as a significant issue for vivisection opponents. Since the AWA only covers warm-blooded vertebrates, fish, reptiles, and amphibians are left completely unprotected. In 2005, the USDA released a regional report regarding hundreds of violations to the AWA with very few cases of legal action taken against the offending researchers/institutions (19). This indicates that there are still plenty of experiments being done on animals in the US that the public at large would deem as unethical from an animal rights perspective, with apparently very little oversight into the enforcement of the laws in place to protect those animals. Bioethics History: Human Experimentation While in the 21st century the term vivisection is generally used to refer to animal experimentation, there is a written history of human vivisection that dates from ancient Greece to modern day reports out of North Korea. In ancient Greece, Herophilus and Erasistratus were both active in dissecting people but were also reported to have done vivisection on criminals who had been condemned (20). Generally these cases of human vivisection happen when one group of people has power over others: the disenfranchised people make for easy targets, and with few rights, they can be exploited experimentally with a socially accepted justification. Most students are familiar with the history of human experimentation done on the Jews in Nazi Germany, but are often unfamiliar with the physician, Josef Mengele, who was responsible for the infamous atrocities in Auschwitz. Fewer students are familiar with Unit 731; the department of Japanese doctors during the Second Sino-Japanese war who were responsible for, arguably, worse atrocities than the Nazis. Unit 731 would actively cut into living people, cut off body parts, submerge them in ice hypothermia studies, and justified this as the subjects were Chinese, not Japanese (21). It has been reported from people who have escaped the camps in North Korea that prisoners are being experimented on there as well. While there is less physical evidence of this happening, it is an important point to note that large-scale human vivisection is likely still happening in 2017 (22).

Discussion Points Vulnerable populations are specific demographics that have historically been exploited during human vivisection. The Greeks, Nazis, Japanese, and (likely) North Koreans did their experiments on imprisoned people such as criminals, prisoners of war, and political prisoners. Other populations that are considered atrisk would include soldiers, pregnant women, fetuses, children, the impoverished, the uneducated, the terminally ill, refugees, ethnic or religious minorities, or the physically or mentally handicapped. A great point to consider is why these groups would be considered at-risk for exploitation. 56 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Bioethics History: Regulations on Human Research Subjects After the concentration camps were liberated during World War II, it became apparent that there needed to be worldwide rules in place to prevent similar atrocities. The first set of ethical human research regulations came during the Nuremberg Trials. The Nuremberg Code (1947) was a list of 10 ethics principles that were intended to guide any research done with humans to ensure it was done ethically (23). Around that same time, the Declaration of Geneva (1948) from the World Medical Association updated the Hippocratic Oath. The Declaration of Helsinki (1964) from the World Medical Association was the first attempt from the worldwide medical community to codify ethics principles regarding human research and built upon the Declaration of Geneva and the Nuremburg Code. It relaxed some of the rules in the Nuremburg Code as well as included language for scientists who were not physicians doing research. These codes, while not legally binding in many countries, are the basis for the Belmont Report (1978). The Belmont Report is the list of three federal regulations regarding the ethical use of human test subjects in the United States. The three tenants of the Belmont Report state (24): 1) Respect for persons: Individuals must be able to give informed consent, must not be lied to or coerced into an experiment by the researcher, and can leave the experiment at any time for any reason. 2) Beneficence: Researchers must do no harm. If anything in a study indicates the subjects will be harmed, the study must stop. No research can be done that will inherently harm the subjects. 3) Justice: Care must be taken to not exploit vulnerable populations, and a fair selection process must be used in determining who will participate in an experiment. The Belmont Report is the basis for the modern Institutional Review Board used to oversee experiments involving human subjects in the United States.

Discussion Points While the rules of the Belmont Report seem obvious, it is important to have students realize that we have these principles in place because there were researchers who were being exploitative and were not acting in the best interest of their subjects. After studying the different ethics codes for human experimentation, it is worthwhile to continue a discussion about vulnerable populations, and giving example scenarios for the type of research that can be done that is classified as “human experimentation.” Most students do not know that even doing surveys in class as part of a research project constitute human experimentation and need IRB approval, and have never considered whether recruiting research subjects for higher risk experiments exclusively from an unemployment office is ethical. Bioethics Case Study: Tuskegee Syphilis Study (25) In 1932 a group of 600 poor, male, black sharecroppers were recruited to participate in a study on syphilis. The name of the study was “Tuskegee Study of Untreated Syphilis in the Negro Male” and was intended to gain data needed 57 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


to justify the enforcement of syphilis treatment programs for African Americans. Important to this case study is the fact that long term health effects of untreated syphilis were not well understood, and thus the research had a noble goal in helping better understand the progression of syphilis. Unfortunately, the men recruited were told that they were receiving free medical care to treat “bad blood”, when in reality they were being observed and given no treatment for syphilis. In 1945, penicillin was accepted as the treatment for syphilis, but the men in the study were still not given antibiotic treatment. Their disease was allowed to progress with no medical intervention with the full understanding that they could spread it to others. Finally, in 1972, 40 years after the study started and 27 years after penicillin, the Tuskegee Syphilis Study was ended after Peter Buxtun came forward to the public about the study with serious concerns about its ethics. His whistle blowing effectively ended the study and directly led to the writing of the Belmont Report in 1978.

Discussion Points In the 40 years of the Tuskegee Syphilis Study, men belonging to a vulnerable population were lied to, misled by medical researchers, and experimented on without any sense of informed consent. Of that 40 years, 27 of them included the intentional withholding of life-saving medication with the full intent of following the progression of the disease in the men until they died. At the beginning of the study, the Nuremburg Trials had not yet happened, thus the Nuremburg Code did not exist. This is an interesting case study in reminding us that just because something is legal does not make it ethical. An important question to ask is: Are the principles in the Belmont Report sufficient from keeping this from happening again, and is it possible that it could happen with less scrupulous researchers in other countries?

Bioethics Case Study: Guatemala STD Study (26) In 1946 a group of American researchers supported with federal funds carried out a series of experiments on 1,500 prisoners, sex workers, mental health patients, and soldiers in Guatemala. The study, the “1946-1948 U.S. Public Health Service Sexually Transmitted Diseases (STDs) Inoculation Study”, had a worthwhile goal: to find new ways to prevent STDs like gonorrhea and syphilis. Unfortunately, the experimental design involved infecting sex workers with these STDs and then having them have unprotected sex with the recruited men. When the researchers observed that very few men contracted the diseases, they were infected through inoculating directly into the urethra, exposing skin to infection, or in some cases, directly injecting the infection into the men under their skin or into their spinal cord. The study ended after two years due to the increased use of penicillin to treat these infections, making prevention less of a concern than in pre-antibiotic years. 58 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Discussion Points Like the Tuskegee Syphilis Study, the men and women in the chosen population were members of highly vulnerable populations so a similar discussion regarding vulnerable populations is in order. The research was never published and was not actually “discovered” until many years later when the ethics of the Tuskegee Syphilis Study was under review, but it is important to note that this was also done prior to the Nuremburg Code. None of the subjects gave informed consent, and there was clear deception in place that prevented the subjects from knowing what was happening. It is not clear in the historical records if all (or even some) subjects were eventually given penicillin, which was very expensive at the time, but it is believed that not all patients were given treatment for the infections they incurred during the study. Also worth noting is that the study only ended because of the discovery of penicillin, not because the researchers thought what they were doing was wrong. In essence, American researchers funded with US federal monies, gave unsuspecting Guatemalans highly contagious, deadly infections that they likely did not have the money or resources to treat after the study ended, and were likely not given treatment by the people responsible for their disease.

Bioethics Case Study: Henrietta Lacks and HeLa Cells (27) Along with the polio vaccine, research in cancer, HIV/AIDS, radiation poisoning, biochemistry, toxicology, genetics, drug testing, in vitro fertilization technology, and cloning all have something in common: a mutant cell line found in the 1950’s called HeLa cells were used for a significant component of the research. In fact, to the date of this writing, HeLa cells are featured in close to 100,000 published research studies on PubMed, have been cultured to the tune of over 50,000,000 metric tons, and have been instrumental in the research that has led to five Nobel Prizes. These mutant cells were a major medical breakthrough, as normal cells cannot be used in cell culture. If provided the necessary nutrients, normal, healthy cells will grow in a petri dish until they bump into each other, creating a single continuous layer of cells (density-dependent inhibition of cell division). These cells have a limited number of replication cycles before they die, normally within a few days. These attributes make culturing typical cells impossible and is where HeLa cells, the first “immortal cell line”, become useful: they do not die. They will continue replicating regardless of cell density and cell age, essentially until they run out of nutrients. They double at a rate much higher than typical cells and are so prolific that they can lead to major contamination issues of other cell cultures in a lab. There are quite a few immortal cell lines now that are commonly worked with in research labs, including 32 derivatives of the original HeLa line. Without much other information, it would be very hard to see HeLa cells as anything other than a medical marvel that have significantly benefited society. In fact, until you hear the term “human negroid cervical carcinoma”, you may not even realize they came from a human at all. 59 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

Henrietta Lacks was a poor, black, illiterate woman who grew up in a racially segregated America. She spent her life working tobacco fields and was married to her first cousin. In 1951 at the age of 31, Henrietta travelled to Johns Hopkins Hospital for abdominal pain; at the time, Johns Hopkins was the only hospital around her that would even see black patients. She was admitted to the “free ward for colored women” and was diagnosed with cervical cancer. At the time of admission, she signed a form stating,


“I hereby give consent to the staff of the Johns Hopkins Hospital to perform any operative procedures and under any anesthetic, either local or general, that they may deem necessary in the proper surgical care and treatment of ___.” During her treatment, Henrietta had biopsies taken from her for both the pathology of her disease and for research. At the time, a Johns Hopkins physician named Dr. George Otto Gey was trying to find cancer cells that would grow in culture. Cancer cells lack the signals and triggers that tell them to stop growing, making them an obvious choice for creating an immortal cell line. Henrietta’s cells, HeLa cells, worked wonderfully. They would double at a rate of once every 48 hours and would grow, essentially uncontrolled, in culture. Henrietta died not too long after her cervical cells started being shipped all over the world to research labs.

Discussion Points Henrietta was illiterate and was therefore unable to read the forms she signed at Johns Hopkins. She came to the minority ward of a hospital for treatment and was told she had to sign those forms for that treatment. While George Gey never received money from his HeLa cell line (he gave them away, all over the world without a second thought), they quickly became a goldmine for many companies, even today. Henrietta’s family did not know about HeLa cells for over 20 years after her death, and in 1976 a group of researchers tracked them down for additional genetic testing. The family was under the mistaken impression (perhaps through a misunderstanding between them and the researchers) that they were being tested for the disease that killed Henrietta, when in reality they were research subjects, not patients, being used in the same way Henrietta was. There are obvious issues here of informed consent and the fact that she was a part of a vulnerable population. The fact that her genetic material has made massive amounts of money for people other than her family, who are still poor and have no health insurance, is an interesting ethics point to ponder with a class. Her children have been outspoken with very negative feelings about what they see as unethical and exploitative research done on their mother without her knowledge or consent. Is there any sort of reparation that would make this okay? Who would be responsible for it? Johns Hopkins where the procedure was done did not capitalize on her cells, nor did the scientist that first cultured them. The companies that capitalized on them never even met her. In 2013 a research group 60 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

published the genome of HeLa cells without considering the issue of privacy of her living relatives who share those genes. Since that time, the NIH has given some level of control to the family over who can see and use the genome; does that adequately protect her living descendants? Further information on this case study includes the cited book at the top of this section, The Immortal Life of Henrietta Lacks (2010), as well as an HBO film (2017) of the same title.


Academic Ethics Case Study: The Wakefield Debacle (28) A topic that many students have some familiarity with is that of the ongoing controversy of the safety of vaccines. They often do not know about the research of Dr. Andrew Wakefield. In 1998 Wakefield published a research article in The Lancet drawing a link between the Measles-Mumps-Rubella vaccine (MMR) and autism spectrum disorder. His results were speculative, his research design faulty, and his sample size far too small for statistically significant results (n=12). That said, his paper received widespread publicity, and the rates of vaccines in young children continue to drop. Numerous studies have been done that refute the Wakefield paper, and in 2004, 10 of the 12 authors involved in the original paper put a partial retraction on the interpretation of results in the paper to show no causal link between MMR and autism. In 2010, the entire paper was retracted as an investigation by The Lancet showed that there were significant flaws in the study and some serious ethical violations on the part of the researchers who published it. That said, there are still significant numbers of parents who are refusing to vaccinate their children. Measles and mumps have seen a resurgence in the past few years as has whooping cough and other easily preventable, deadly infections.

Discussion Points One important point to note is that Andrew Wakefield failed to disclose that his research was funded by lawyers who represented parents involved in suing vaccine makers. His research involved intentional scientific misrepresentation of data to push inaccurate results, and it is likely that this fraud was for undisclosed financial gain. Additionally, there were other bioethics violations in this case, as the children’s parents used in the study were not given the necessary information for informed consent. While a single case study could be made about the bioethics issues of the Wakefield case, it is a fantastic example of the far-reaching implications of dishonest research reporting. While there is no link known to any issue with autism and vaccines, the Wakefield paper was enough to put a question into the thoughts of the public on whether vaccination of their child was worth the risk. If they are from the United States, parents of small children right now have never lived in an area where measles is a deadly childhood disease and may underestimate the severity of it. The Center for Disease Control shows over 600 measles diagnoses in the United States in 2014, the highest number of measles cases since 1994. The mortality from measles is usually around one or two from 1000 reported cases, making this a dangerous and preventable childhood infection (29). 61 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Academic Ethics Case Study: Guilty by Association (30) Dr. Elizabeth Goodwin was a tenured professor of genetics at the University of Wisconsin-Madison (UW-Madison) campus. In 2005, a graduate student named Chantal Ly came to Goodwin with concerns about her research: it seemed she had hit a significant roadblock in her progress and was unable to replicate previous data generated from the lab. Goodwin decided to give Ly three pages from a recent NIH grant proposal to look over with the understanding that if she was interested, she could join another graduate student, Garett Padilla, on the project. At first glance, Ly found a significant error in the grant proposal; results reported as unpublished had been published a few years earlier by the lab. When she brought this to the attention of Padilla, he found a slew of other inaccuracies in the grant proposal: 1) there was a reference to a study that had never been done, 2) several figures had been visibly manipulated, 3) at least two images were presented as unpublished but were published, and were from different experiments than were indicated in the proposal; all from only three pages. When Padilla approached Goodwin on the topic, she repeatedly said that she messed up and then blamed the issue on a computer file mix-up. Unfortunately, a single computer file mix-up did not explain the numerous issues found in the grant proposal, and eventually, Padilla called a meeting with the seven members of the lab to discuss the findings of the grant proposal written by Goodwin. It was decided over multiple meetings with the graduate students that Padilla and Ly would take their findings and concerns to the department chair. The chair quickly referred the issue to the university administration for an informal investigation, which led to a formal investigation of academic misconduct. The formal investigation indicated that there was evidence of deliberate falsification in three of her grant applications with $1.8 million in federal funds and led to questions regarding several published articles that had come out of the Goodwin lab in previous years.

Discussion Points The outcome of this case study was typical for such misconduct: Elizabeth Goodwin was forced to resign from her position, and her students were left suffering the consequences. Of her six graduate students, only two stayed at UW-Madison to finish their degree. One transferred schools to start all over in a new doctoral program, one abandoned their studies to become a lab technician, and two others abandoned science entirely. These students suffered the most significant consequences of Goodwin’s misconduct. An important point to make with students here is that there are actual legal ramifications for fabricating data. While the journal articles in question were shown to be valid and not retracted, two funded grant proposals were found to be fraudulent. She was barred from getting any other federal funding for three years, and was ordered to pay $50,000 back to the government and another $50,000 to UW-Madison, and she was eventually sentenced to two years of probation for the offense (31). Interestingly, when asked what my students would do in a similar situation, there is a lot of 62 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

discussion on whether they would blow the whistle. Quite a few have said they would not, hoping to preserve their own careers by staying complacent in the misconduct. Others realize, like the Goodwin lab did, that eventually this type of misconduct will be discovered, and anyone associated with the unethical scientist could be viewed by the scientific community as guilty by association.


Academic Ethics Case Study: Cultural Differences in Academic Ethics (32) Perhaps not a case study in the traditional sense, the news article, “Plagiarism Plague Hinders China’s Scientific Ambition” was published by NPR in 2011 and does a great job of detailing the cultural differences in accepted academic conduct between China and the United States. The article focuses on the work of Helen Zhang, a journal director for a Chinese publication called the Journal of Zhejiang University-Science, as she tries to push Chinese scientists into accepting international publication standards (largely based on current Western practices). The Journal of Zhejiang University-Science was the first in China to use text analysis software to spot plagiarism in submissions. Her first few years were discouraging as she found upwards of over 30% of the submissions had unacceptable levels of copying and plagiarism (only counting life science and computer science, the figure rose to 40%). While this level of plagiarism would be considered unethical in Western journals, it is often commonplace in Chinese journals. Zhang attributes a large part of the issue to cultural factors in the education system in China. In China, rote memorization and repetition of an instructor’s work is considered a good way of learning and is generally encouraged. Confucian ideas of respecting those who provide knowledge as well as not challenging or criticizing are the norm. This inherently leads to copying of work, which at that point is considered acceptable—Confucian education shows that knowledge is knowledge and that no single individual “owns” that knowledge. While Chinese standards could easily stay Chinese standards, the problem lies with the fact that scientists exist largely outside of the bubble of their nationality, but on a global stage of other scientists. Zhang and many others are pushing for Chinese academics to accept more internationally accepted Western standards for publications.

Discussion Points It is important that care be taken in this topic to avoid overt condemnation of an entire culture, but the fact is, cultural differences in how scientists view ethics is a very important subject that needs to be addressed in our increasingly global society. Is there a right and wrong when it comes to an entire culture’s standards? Are they wrong, or just different? Perhaps it is a little bit of both? Another topic brought forth in the article is that of money. Chinese academics receive extra financial compensation depending on how much they publish, and in such scenarios, the numbers are all that matter, not the originality of the research. This means that many Chinese scientists have a history of submitting the same research to multiple journals for publication, even though that is widely considered 63 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

unethical internationally. One example of this is from the international journal Acta Crystallographica Section E. The article highlighted that between 2009 and 2011, 120 papers had to be retracted (70 of those were from Jinggangshan University) due to plagiarism. This is not just an issue of the educational system in China: thousands of Chinese students come to the United States to study in our colleges and universities (33). How does this background impact their academic success? This proved to be an interesting point of discussion that international students, in particular, were very interested in discussing.


Research Ethics Case Study: A Background in Superfund Sites In 1980, the Comprehensive Environmental Response, Compensation, and Liability Act was passed, which allowed the United States Environmental Protection Agency (EPA) to designate areas with significant toxic waste issues, and to put money towards the long-term cleanup of those areas. These “superfund sites” are put on a National Priorities List, which currently numbers nearly 1,400 locations across all states and US territories (34). These locations are considered so hazardous to human health that immediate removal of people from the area is often recommended, leaving at the least a mandate to not eat local fish, and at worst, leaving behind an entire ghost town. A great example of this is Pitcher, OK, which has been contaminated with lead over decades of local mining. The town has been largely evacuated, with only a handful of residents intentionally remaining after a federal buyout helped relocate the majority. There is a wonderful documentary, “Tar Creek”, about the environmental issues in Pitcher, the federal response, the buyout, and the long-term implications that I show sections of in class. As most students do not live in these areas, they are largely unaware that they exist and are generally horrified to know that 1,400 of these places exist all around us.

Discussion Points While many superfund sites are the result of non-chemists, there are quite a few of them that are. The EPA has only existed since 1970; before that, there were very few regulations regarding pollutants entering the environment. In fact, it wasn’t until the public outcry that resulted from Rachael Carson’s Silent Spring in 1962 that the public was even concerned with environmental pollutants at all. Many consider Silent Spring to be the spark that ignited the environmental movement in the 1960’s and 1970’s, which resulted directly to the formation of the EPA. Many of the superfund sites stand as a testament to the possible outcome from reckless waste disposal at the hands of people working with industrial-scale toxic chemicals. A few examples can be found in Table 4. While not all superfund sites are directly related to the work of chemists, it is important for us as instructors to make our students aware of these areas and to encourage them to always be ethical in their waste disposal and experimental design efforts and to always try to do chemistry with the environment and disposal of chemicals in mind. Something 64 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

as simple as washing chromium down the sink or evaporating certain chemicals through a hood can have significant implications to our environment and health.

Table 4. Selected Superfund Sites on the National Priorities List (35)


Location

Cause

Responsible Party

Fernald, OH

US DOE Feed Materials Production Center

Release of dust emissions containing radioactive uranium from 1951-1989 during cold-war ammunition manufacturing

Toone, TN

Velsicol Chemical Corp.

Large-scale chemical contamination from 1964-1973 of surface and ground water, soil, and air from the plant’s landfill

La Salle, IL

Matthiessen and Hegeler Zinc Co.

From 1858-1978 the smelting and rolling of zinc ore led to major heavy metal contamination of cadmium, chromium, copper, lead, and zinc

Ashland, MA

Nyanza Chemical Inc.

A chemical waste landfill that contaminated soil and groundwater with acids, organics, and mercury from 1917-1978

Denver, CO

Chemical Sales Co.

Poor waste disposal practices lead to groundwater contamination with volatile organic chemicals from 1976-1991

Conclusions To my students, much of our discussions revolve around what likely seems ancient history, sometimes done in faraway lands. The reality is that the United States has an extensive history of intentionally exposing people to diseases, radiation, and chemicals, all without their consent. We have done permanent damage to the lives and health of prisoners, soldiers, slaves, pregnant women, children, and mentally handicapped people, all through unethical human experimentation (see the attached Appendix for further examples). We have lied about research findings, fabricated results, and done unethical things to get the research results we want and to secure funding that our research does not warrant. We have intentionally thrown toxic waste into our rivers, soil, and sky, contaminating our communities, sometimes irreparably. We have covered up things we should not have done, hoping nobody will find out. We, as a community of scientists, are not “above” practicing poor scientific ethics; this has unfortunately been shown repeatedly. What is important is that, individually, we can and should push ourselves to the highest level of ethics, pursuing our research interests with utmost care, honesty, and integrity. 65 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


This chapter has covered the importance of why ethics needs to be taught to undergraduate students, and provides a model for doing so in a way that pushes for an interactive, continuing education in the demographic of students that will most likely need that education. Hopefully, this chapter can serve as a model for other institutions to help prepare future scientists for fully preparing their students for careers in science and medicine. There are many more ethical scientists than there are unethical ones, and if we continue to teach our students to be ethical in their work, our community will continue to be society’s truth-bearers, holders of knowledge, and people that the general population can trust to work in the best interests of mankind.

Appendix: Additional Case Studies Testing Medical Procedures on Slaves (36) In the mid-1800’s a doctor named J. Marion Sims performed vivisection of a gynecologic nature on about 10 slaves without anesthesia. He developed a surgery still used for correcting fistulas in developing countries. Studying Malaria on Prisoners (37) In the 1940’s a group of researchers infected around 500 inmates with malaria at the Stateville Penitentiary in Stateville, IL. The disease was studied as well as experimental medications. Psychologically Abusing Orphans To Make Them Stutter (38) In 1939, Dr. Wendell Johnson used extreme psychological abuse to show children who were tortured in this way could develop a speech stutter. A speech pathologist, Johnson used children in a local orphanage to do his experiments. The study became nicknamed the “Monster Study”. His research showed that, indeed, you could give children a lifelong speech impediment through extreme emotional stress. Giving Radioactive Iron to Pregnant Woman (39) In the 1940’s, researchers at Vanderbilt University gave over 800 pregnant women “vitamin drinks”. These women were poor, and came to the clinic for free prenatal care. The effects of radiation exposure were not well understood at the time, but the result was a higher rate of the women and their children were diagnosed with cancer later in their lives. Developing the Smallpox Vaccine on Children (40) Edward Jenner was a physician in the late 18th century who is responsible for saving countless lives through the invention of the smallpox vaccine. Indeed, this 66 Kloepper and Crawford; Liberal Arts Strategies for the Chemistry Classroom ACS Symposium Series; American Chemical Society: Washington, DC, 2017.

is a wonderful feat of science, which has been perpetuated into many vaccines for countless diseases. Jenner’s main research subject was the 8-year old son of his gardener. After exposing the young boy to cowpox lesions, he deliberately infected the boy with smallpox to see if he would acquire the deadly disease. Fortunately, he did not.


Testing on Children in Mental Institutions (41) In the mid-1900’s, children who had been committed to the Sonoma State Hospital for being mentally handicapped were given extremely painful treatments involving pushing air into their spines. This research had no direct medical benefit for the children and was done for basic research to learn about cerebral palsy. There were at least 1,400 patients of the hospital who died while there, and any child with cerebral palsy had their brain removed and dissected without parental consent. Data Manipulation Using Photo Editing in Nano Letters (42) In 2013 a publication in Nano Letters was full of fabricated images of “chopstick nanorods”. These images included obvious doctored photos of multiple images pasted together. In 2015 the paper was retracted due to the obvious misconduct. Self-Plagiarism from the Elite (43) In 2012 Ronald Breslow was found to have plagiarized whole sections of one paper with paragraphs from previously published papers. What makes this story interesting is that Breslow is considered a very well-known and respected chemist. He was the president of the American Chemical Society at one point, works at the prestigious Columbia University, and is the recipient of several notable awards such as the National Medal of Science and the Priestly Medal. A Multifaceted Case Study Spanning Academic, Research, and Bioethics (44) In 2005 Hwang Woo-Suk received wide-spread fame in South Korea after he published success in making human stem cell lines. It was found a short time after that he fabricated much of his data. Further investigation showed that he used women’s eggs that he purchased on the black market or received from his female graduate students. He also misled the egg donors regarding the fate of their eggs, and he was charged with embezzling his research grants.


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