Team:Duke/Human Practices

Overview

Throughout the iGEM design process, we deeply valued the broader ethical and social implications of our work. As such, we wanted to ensure that we actively engaged with individuals and groups outside of the research bubble to provide context to the work that we are doing. To this end, the team identified three major areas in which human practice engagement helped refine our project: Refining Project Scope and Execution, Ensuring Privacy and Diversity, and Considering the Human Factor. Additionally, to ensure that our approach to these considerations was meaningful, the team developed a novel four step human practice engagement cycle, coined the DUKE Cycle:

Figure 1. The human practices DUKE cycle

1. Discovering the problem: In this phase, the team begins to define topics of concern to address and gain a deeper understanding of.
2. Understanding the problem: In this phase, the team conducts stakeholder and expert interviews in order to learn more about current attitudes on the issues. The team also reflects upon information from the interviews, generates summaries, and creates connections between their project and the world.
3. Kickstarting positive action to address stakeholder concerns: In this phase, the team collected the concerns and issues raised by stakeholders. The team then incorporated these concerns into their project, undertaking various efforts to explore and address these issues.
4. Evaluating and Refining Project Plans: In this phase, the team evaluates the efforts that were undertaken and analyzes next steps that would allow for further engagement.

The DUKE cycle provides a simple four-step framework for considering how research impacts the world and how the world impacts research, allowing investigations to remain focused and contextualized while considering the perspectives of all key stakeholders. This cycle facilitates the incorporation of human practices work into actual lab research in an integrated manner by encouraging users to actively apply what they learn.

In Phase II of our project, we are planning to reiterate through the DUKE cycle to discover more considerations of our project, learn about relevant topics through stakeholder interviews, refine our project to integrate their feedback, and engage in community efforts. Specifically, we are planning to interview cell banks, physicians, researchers, and patients (if COVID restrictions permit) and host a series of education and outreach events for our community. We look to further tackle issues of patient privacy, diverse representation in clinical trials, and access to fair and economical care.

Refining Project Scope and Execution

1. Discovering the Problem

Despite being the most common malignant brain tumor, clinical treatment of glioma is severely limited by the lack of a scalable, physiologically-relevant model for testing therapeutics. To fully understand the implications of this problem, our team talked with researchers and individuals who work directly with patients to understand how our project scope should be refined to best address the needs of key stakeholders.

2. Understanding the Problem

What did we learn?

Lack of Treatments for Orphan Diseases

When there are more diseases than there are resources to develop therapeutics, pharmaceutical companies must allocate their resources in the most effective way possible. To determine which diseases to focus on, pharmaceutical companies consider factors such as expertise in disease, ability to execute research studies, and disease prevalence. Unfortunately, this causes rare diseases (conditions affecting fewer than 200,000 people) such as glioblastoma to become “orphaned” because of the complexities involved with funding research for these diseases. With the Orphan Drug Act in 1983, companies are incentivized to develop therapeutics for orphan diseases due to greater FDA flexibility, government funding, reduced taxes, and market exclusivity. Although a few therapies have been FDA-approved for treating high-grade gliomas, most have failed to reach the market (Lassen et al., 2014). Current treatment options in glioblastoma are sparse and the drug development pipeline is slow.

The FDA Approval Process: A Double-Edged Sword

The U.S. Food and Drug Administration (FDA) is responsible for ensuring the safety and effectiveness of drugs, vaccines, and medical devices used by humans. The complete research, development, approval, and market process for a therapeutic can take 12 to 15 years. Although the long drug approval process is necessary to ensure that new drugs are effective and safe, some stakeholders are frustrated that patients are suffering while waiting for a drug that already exists.

Mixed Perspectives on Organoids for in vitro Drug Screening

Organoids are 3D multicellular tissue constructs grown from stem cells that mimic an organ’s structure and function, making them better models compared to cells cultured in traditional 2D environments. Since stem cells can be reprogrammed from patient somatic cells, patient-derived organoids have the potential to be used in personalized medicine to determine the best treatment option for individual patients.

Some stakeholders are skeptical about making treatment decisions for patients solely based on the results of an organoid drug screening. They argue that organoids are an isolated system, and therefore disregard other biological factors such as immune response or effects of the drug on other organ systems; an organoid based system does not consider how the patient would respond holistically. However, organoid technologies can be useful for screening targeted therapies that target disease variants of specific mutations and as efficient drug testing tools in the preclinical phase.      

3. Ideating and Implementing Stakeholder Concerns

How did we implement our findings?

        Validating Need to Address Glioma and Drug Screening

We talked to our stakeholders to verify the need for a glioma drug screening platform. After learning about the long process of bringing drugs from research labs to patients, our team confirmed that we wanted to dedicate our project to drug screening for glioma. A drug screening platform may be useful as a tool at the patient level to determine the best drug for each patient or in the preclinical phase to eliminate drugs that are harmful or ineffective before they enter clinical trials. Based on what we learned about the FDA approval process from Dr. Musella, our team began to ask other stakeholders (i.e. physicians, researchers, and patients) about their opinion of the drug development process.  

        Pivoting to a Preclinical Trial Drug Screening Tool

Although we decided to focus our project on developing a glioma drug screening platform, we were undecided whether we should develop it to assess drug efficacy and toxicity during preclinical testing or to inform doctors of what the best therapeutic option is for individual patients. After talking with Dr. Peter Fecci and Dr. Henry Friedman, we learned that there were concerns that patient-specific in vitro drug screening platforms do not consider a patient’s holistic drug response and do not adequately predict how a patient would respond to a drug. Therefore, we decided to focus our efforts on creating a preclinical drug screening platform to make the drug development pipeline more efficient.

Shifting to a Mutation-specific Reporter System

We initially wanted to create a drug screening platform for all variants of glioma. After learning about the concerns some stakeholders had about trusting a generalized organoid-drug screening platform, we decided to shift our project to target a specific glioma mutation. In our conversations with Dr. Henry Friedman and Dr. Katherine Peters, we learned that the methylation of the MGMT promoter (O(6)-Methylguanine-DNA methyltransferase) and mutations of the IDH1 and IDH2 genes (isocitrate dehydrogenase 1 and 2) are strong biomarkers in glioma. After learning that approximately 70% to 80% of secondary glioma have a mutation in the IDH1 gene, our team began to investigate how our drug screening platform can be used to assess IDH1 drug response.

Raising Organoid Awareness on Social Media (Dr. Ashley)

Based on our interviews, we discovered that some physicians and researchers have a positive view towards the potential of organoids because their collaborators have worked with them before. Since the average person is unfamiliar with topics like stem cells and organoids, we created social media posts on Instagram and Twitter to educate the general public about the potential uses of brain organoids.

 

Figure 3. Raising awareness on social media

4. Evaluating and Refining Future Plans

As a two phase project, our team plans on executing more design-build-test cycles and human practice problem cycles. After we construct our mutation-specific glioma drug screening system for preclinical testing, we plan to interview more physicians and researchers for their expert opinions and iterate our project based on their feedback. In order to better understand physician attitudes on organoids, we hope to interview doctors across a wider range of specialities and cultural contexts in the future. Furthermore, by simply interviewing a wider range of physicians, we hope to gain perspective on other design considerations that should be addressed.

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Ensuring Privacy and Diversity

1. Discovering the Problem

When utilizing tissue samples derived from patients, special measures must be taken to ensure that patient privacy is maintained through the research process, given concerns related to patient autonomy, informed consent, and genetic discrimination. However, at the same time, total anonymization of tissue samples can be equally problematic. To learn more about these issues and the careful balance that must be reached, our team reached out to relevant stakeholders and interviewed them.

2. Understanding the Problem

Stakeholder Interviews

Figure 4. Ensuring privacy and diversity

Click here to read the summaries of each interview (www.LinkToTheIntegratedHumanSummariesAtEndOfThisDocOrAsaPopUpwouldbeNice.com) ^[b]

What did we learn?

Gender Differences in GBM

Through our interview with Dr. Peters, the team learned that glioma treatment can often be significantly affected by the sex of the patient. This results from the fact that the signaling pathways that are affected in glioma can vary between male and female patients; as such, the treatment options that a physician pursues must be cognizant of these differences.

Clinical Trial Initiatives/Diversity

One common concern highlighted throughout the interviews was the need to utilize a biologically diverse range of samples in our testing platform. This ensures that our system is able to identify compounds that are effective and safe for individuals, regardless of any genotypic or phenotypic differences. On the other hand, utilizing a diverse sample would allow us to identify how drug responses might vary across different groups, allowing therapeutics to be designed and applied in a more targeted manner. In a similar manner, stakeholders also emphasized the importance of diverse research samples within clinical trials themselves, given the ethical need to maintain justice within the medical process. Many noted how this currently remains an issue, as individuals with more resources are more likely to participate in clinical trials and reap their benefits.

Patient privacy and ownership of samples

Another common concern voiced by different stakeholders, particularly Professor Katsanis, was the issue of consent in tissue use. Given general medical ethics concerns, the stakeholders highlighted the clear need to de-identify patient data in a way that made samples untraceable. However, at the same time, the point was made that phenotypic and demographic data can be useful to researchers, as they provide vital pieces of information about a patient’s general condition. Thus, the team began to understand the importance of differentiating between de-identification and anonymization of samples. In the former, identifying information is removed without eliminating access to medically relevant information. In the latter, all information about the source of the tissue sample is removed.

Another point mentioned was the issue of ownership for tissue samples. Generally, it appears that sample ownership can be a grey area in some cases, which can make it hard for a patient to retract consent for use of their samples in research. This can be a particularly large issue for pediatric patients, who may have samples donated before they can be involved in the consent process. When they come of age, it can be a complicated process for them to practice patient autonomy and withdraw sample use consent if they want. Furthermore, this concern interfaces with the aforementioned de-identification issue, as patients may have a hard time tracing back their samples for removal if they have been stripped of any identification information.

3. Ideating and Implementing Stakeholder Concerns

How did we implement our findings?

BTS Speaker Series: Dr. Defne Bayik

In order to learn more about the gender differences that affect brain cancer progression and treatment, we attended a talk organized by the Duke Brain Tumor Center which was related to this issue. The speaker was Dr. Defne Bayik, who spoke on utilizing sex-based differences in glioblastoma for the optimization of therapies. In the talk, Dr. Bayik discussed some of the biological reasons behind sex differences in brain cancer, mainly related to the contrasting behavior of different myeloid-derived suppressor cells (MDSC) subpopulations in the two genders. Dr. Bayik talked about the ability to leverage the differences in cell behavior between the two sexes in order to increase treatment efficacy.

Refining Lab Protocols

Due to the emphasis the interviewed stakeholders placed on maintaining the privacy of patients, the team made a new commitment to maintaining sample deidentification. Given that our glioma samples were sourced from labs, rather than directly from patients, we hope that the “second-line nature” of our tissue use will eliminate any possibility of tracing our samples back to the individual who provided them. In addition, we will actively avoid looking into this information; when phenotypic data could be useful and is obtainable, we will only utilize it in a manner that eliminates any possibility of patient identification.

4. Evaluating and Refining Future Plans

As a two phase project, our team intends to continue engaging with relevant literature in order to better understand the bioethical concerns of patient privacy. Next year, we would like to work in the area of public awareness, which might mean producing pamphlets and educational materials meant to inform the public of privacy considerations that must be made in biological research. Furthermore, we would like to interview a cell bank, as we hope this will give us information on how the concerns we have heard about are addressed in real practice. Additionally, we expect to begin working with more patient-derived tissue samples in the lab, as this will allow us to verify that our platform works for a variety of primary lines; throughout this process, we will continue to refine and implement our privacy protocols in order to ensure that patient information is protected.

Considering the Human Factor

1. Discovering the Problem

Glioma is a deadly disease that greatly affects both patients and their loved ones from the moment of diagnosis. Families grieve over the loss of a normal life, and patients are forced to adjust to a new reality. Even for long-term survivors, many societal factors can make it difficult to return to their previous lifestyle, pre-diagnosis. After learning about the emotional impacts of these diseases, our team was motivated to connect with key stakeholders to hear about their experiences with patients and their loved ones, and determine how to best raise awareness of this disease.

2. Understanding the Problem

Stakeholder Interviews

Figure 6. Considering the human factor

Click here to read the summaries of each interview (www.LinkToTheIntegratedHumanSummariesAtEndOfThisDocOrAsaPopUpwouldbeNice.com) ^[c]

What did we learn?

Emotional Impacts of Glioma

Through our interviews with relevant stakeholders, the team gained a more thorough and thoughtful perspective on the impacts that brain cancer has on patients and their loved ones. Brain tumor patients often experience significant cognitive and psychological changes, which can impact them in profound ways. Diagnoses of brain cancer are life-changing events, and patients are forced to quickly adjust to new realities in the treatment period. This can manifest in feelings of stress and uncertainty, which can further impact a patient’s health. Even for long-term survivors, there are still persistent financial burdens for them and their families from ongoing medical care. Our interview with Kathy Riley was particularly insightful, as she was able to provide specific information regarding the emotional weight of a cancer diagnosis and the ways that her organization helped families navigate treatment and recovery.

Patient Advocacy and Education

Through our interviews with organizations like the American Brain Tumor Association (ABTA) and Pediatric Brain Tumor Foundation (PBTF), the team learned more about the vital role that patient advocacy organizations play in supporting patients through the overall treatment process. These organizations not only support research efforts and therapeutic development, but they also support patients with information, financial resources, and peer groups. For example, the PBTF offers the Starfolio to patients, which provides relevant information on issues related to treatment and care for pediatric brain tumor patients. On the other hand, the ABTA provides access to support networks and one-on-one peer mentoring, which allows patients to get support and guidance from others who have gone through similar treatment processes. Overall, these services play a vital role in encouraging a holistic approach to patient treatment.

3. Ideating and Implementing Stakeholder Concerns

        How did we implement our findings?

        Teaching at Triangle Math and Science Academy

To increase awareness of glioma and the impact that it has on patients, the team organized a teaching day at the Triangle Math and Science, where we taught high school biology students about brain cancer and synthetic biology.

        Attending Patient Panel at American Brain Tumor Association Conference

On September 11, 2021, we attended the “Living with a Brain Tumor: Patient and Caregiver Panel” hosted by the American Brain Tumor Association. The ABTA conference provided us with insight into the impact brain cancer has had on both the survivors and their loved ones.

Running at the Angels Among Us 5K

A couple members of our team also attended the 2021 Angels Among Us 5K run. This historic run has been raising funding for the Preston Robert Tisch Brain Tumor Center since 1994, and provided our team an opportunity to speak directly with brain cancer survivors like Tom O’Donnell. Through these conversations, we were able to get a first hand account of the continuing impacts of treatment for survivors, as well as learn about the significance of a strong patient-physician relationship.

For more information about the outreach and education efforts we undertook to address stakeholder concerns, please consult the Communication and Education.

4. Evaluating and Refining Future Plans

In the future, our team aims to continue our education outreach by teaching at other schools in the Durham area. Through these efforts, we hope to continue expanding scientific literacy; furthermore, we hope to showcase the incredible world of synthetic biology and increase awareness of this field. We are also planning to raise public awareness for glioma through tabling and hosting other activities on brain-cancer-related days throughout the year. Next year, we would like to reach out to more GBM patients and their families to gain a better understanding of the diverse issues these individuals face, ranging from healthcare costs to clinical trial participation.

Integrated Stakeholder Interview Summaries

Refining Project Scope and Execution

Jim Albright

Mr. Albright’s interview provided a great deal of insight into the role that pharmaceutical companies play in the patient treatment process, as well as information on the considerations that these companies make in designing therapeutics.

One point that was mentioned throughout the interview was the fact that there are many more diseases to treat than there are resources to develop therapeutics, which leads to a situation where drug companies must allocate their resources in the most effective way possible. Often, these resource considerations can be quite complicated for orphan diseases like glioblastoma, which affect fewer than 200,000 people in the US. Currently, incentives, like rolling submission and extended patents, exist for pharmaceutical companies to work on drug development for orphan diseases. Furthermore, many companies have research and development wings that are specifically dedicated to designing therapeutics for orphan conditions. Overall, it appeared that continuing to facilitate the development of therapeutics for orphan diseases would require more communication and collaboration between regulators and drug developers, in order to 7attempt to minimize some of the hurdles that companies continue to face. This issue is tightly related to the broader topic of the FDA regulatory process, which affects the pharmaceutical development process in many ways. Overall, the FDA was characterized as having a close working relationship with pharmaceutical companies, due to the nature of the oversight that they provide. Firms are often required to provide a great deal of data indicating safety and efficacy even before beginning the clinical trial process.

Another topic that was mentioned was that of ethics and guiding principles in conducting clinical trials. Many companies have patient financial assistance programs, which are intended to help those who might not have insurance or those who might not otherwise be able to afford the drugs that they need. Additionally, companies have made an effort to ensure that their clinical trials involve samples that are representative of the population in as many ways as possible, including socioeconomic factors and other demographics.

Dr. Henry Friedman        

Dr. Henry Friedman is a pediatric neuro-oncologist who, in conjunction with Dr. David Ashley, leads the Duke Preston Tisch Brain Tumor Center. He is actively involved in researching treatment efficacy and management of glioblastoma. Dr. Friedman believes that it is difficult to create an in vitro system that can truly predict drug efficacy in humans, and it is necessary for drugs to be tested in immunosuppressed animals before human clinical trials. An organoid-based drug screening system may help support animal testing results, but he would not trust any evidence derived only from an in vitro drug screening. Dr. Friedman thinks that an in vitro screening may potentially be useful for targeted screening of a specific glioblastoma mutation for a treatment targeting that mutation. When asked about his opinion on the FDA approval process for drugs, Dr. Friedman states that “The FDA has an impossible task: under-resourced, understaffed” and embodies the philosophy in which a drug that has no merit or produces toxic effects should be eliminated. The FDA can prevent drug disasters and he is a huge fan of the FDA bearing in mind the lack of support and resources given to them. The people who criticize FDA may not have enough experience interacting with the FDA or truly understand the purpose of the organization.

Before talking with Dr. Friedman, our team has only received positive or neutral feedback for using an in vitro drug screening system for aiding drug development and testing. In this interview, we learned about the concerns some stakeholders may have with trusting drug screening. Our drug screening platform is an isolated system that does not consider how the patient would respond holistically (e.g. immune response or effects from other organ systems). Based on Dr. Friedman’s feedback, we decided to shift our project to target a specific glioblastoma mutation. In our conversation with Dr. Katherine Peters, we learned that the methylation of the MGMT promoter (O(6)-Methylguanine-DNA methyltransferase) and mutations of the IDH1 and IDH2 genes (isocitrate dehydrogenase 1 and 2) are strong biomarkers in glioblastoma. After learning that approximately 70% to 80% of secondary glioblastomas have a mutation in the IDH1 gene (Chen), our team began to investigate how our drug screening platform can be used to assess IDH1 drug response.

Dr. David Ashley        

Dr. David Ashley is a professor at the Duke University School of Medicine whose work focuses on the investigation of immunotherapy as a treatment for cancers of the central nervous system. Through this interview, the team learned a great deal about the technical aspects of brain tumors, as well as the ethical considerations involved in the clinical trial process. Dr. Ashley stressed to the team that due to the unique features of the brain, including general sensitivity and delivery challenges, there have been very few recent advances in the treatment of brain tumors like GBM. However, given the aggressive nature of certain tumors, like glioblastoma, such advances are sorely needed. As part of his role as a researcher, Dr. Ashley was able to provide information to the team about his experience with clinical trials; he highlighted the many safeguards present to protect patients throughout the process, and explained the specific additional measures that are taken when conducting clinical trials with children. Furthermore, he discussed some of the ways in which clinical trials begin; overall, regardless of the funding source, these trials all emphasize the importance of the “bench to bedside” aspect of clinical and translational research. When asked about the FDA regulatory process, Dr. Ashley expressed a relatively positive opinion. Even though he highlighted some of the ways that regulations could be modified to better help patients, he acknowledged the difficult task of the FDA and commended their ability to protect consumers while promoting scientific innovation. Finally, Dr. Ashley expressed a positive view regarding the potential of organoids as a tool for scientific discovery, mentioning the fact that collaborators had used them before. However, he did outline some of the limitations that still exist with these systems, like lack of immune or blood-brain barrier elements.

Overall, this interview provided our team insight into the great potential of organoids as a tool for biomedical innovation. At the same time, Dr. Ashley’s own experience working with organoid-involved labs showed us the importance of increasing general awareness of organoids as a tool for research. Thus, our team has focused on conducting social media outreach related to organoid awareness by writing posts on organoids and their uses in research.

Musella Foundation

The Musella Foundation is a nonprofit organization focused on patient emotional and financial support, treatment combination identification, and advocacy for novel therapy development. As part of this goal, they have a system connecting patients to clinical trials, a patient registry tracking how certain treatment combinations perform, and expanded access programs for patients to access drugs that might otherwise be too hard or expensive to obtain. During our interview with Musella Foundation President and retired podiatrist Dr. Al Musella, we learned about the ethical implications of clinical testing and the federal approval process of new therapies. Dr. Musella and many others are dismayed that bureaucratic considerations such as FDA approval often hinder the rate of innovation and public access to treatments. The approval timeline is very long and, unfortunately, “thousands of patients die waiting.” He finds it frustrating that, even if more effective treatments exist, patients are not able to access these drug combinations that could have led to better health outcomes. Although placebo controlled experiments confirm drug efficacy, Dr. Musella is concerned about giving patients placebo drugs. Patients in the placebo group are given drugs that are either much less effective than the experimental drug or have no effect at all. Delaying patients' access to these drugs may lead to worsening health outcomes when better options are available.

Meeting with Dr. Musella allowed our team to realize that the FDA is a double-edged sword. Although the long drug approval process is necessary to ensure that new drugs are effective and safe, patients are suffering while waiting for a drug that already exists. After learning about the long process of bringing drugs from research labs to patients, our team confirmed that we wanted to dedicate our project to drug screening for glioblastoma. A drug screening platform may be useful as a tool to determine the best drug for each patient or in the preclinical phase to eliminate drugs that are harmful or ineffective before they enter clinical trials. Moving forward, our team wanted to learn how other stakeholders (i.e. physicians, researchers, and patients) viewed the drug development process.  

Dr. Peter Fecci        

Dr. Fecci is a practicing neurosurgeon at Duke and is studying immune dysfunction and tumors in inbred mice. Regarding our project, he is optimistic towards using brain organoids as a high-throughput screening system that is chapter and faster than in vivo methods. At the same time, he doesn’t think that the in vivo infrastructure in an in vitro setting is going to replace in vivo methods. It can also be helpful in personalized medicine as specific patient derived organoids that can allow testing for multiple drugs to determine the best drug for the patient. Another method he advocates for is the use of immunocompromised mice with human tumors implanted in them to serve as petri dishes for drug screening. He thinks that the FDA approval process can be illogical and inefficient but has deep respect for the agency in relation to their safety first philosophy, stating “you need that kind of watchdog”. He brings in the new perspective that patients often see clinical trials and new treatments as a big opportunity to advance medicine and do not see themselves as test subjects. They are more interested in the treatments themselves than the process of clinical trials.

Dr. Fecci reassured the team that our research in using brain organoids has the potential to serve as a high throughput drug screening system that can advance the treatment of glioblastoma. He thinks it is a good technology to advance the realm of personalized medicine which again brought up the ethical issues of using patient derived tumor samples similar to Dr. Katsanis. His opinion on the patient perspective when entering a clinical trial provided us the new perspective that the public may not necessarily care about the nitty gritty details of the research, but rather the potential treatments of glioblastoma and how effective they are. This again ties into our education outreach and public awareness events in the sense that we have to create pamphlets and posters that simplify the research and scientific processes for the intended audience.

Ensuring Privacy and Diversity

Brain Tumor Project        

The Brain Tumor Project is part of a nonprofit organization led by Broad Institute called Count Me In that focuses on analyzing genetic differences in tumor tissues to identify potential genetic therapeutic targets, collecting patient reported data to optimize treatment, and making information broadly accessible to accelerate and facilitate brain tumor discoveries. Throughout the interview, the team learned about the privacy and ethical concerns in patient tissue sample collection and the importance of patient partnership.

 

First, it was emphasized that there’s a big difference between a patient-partnered study and a patient-centered study where patients are never engaged. “We are trying to change the mold of how we are including these people who are living with the diseases and undergoing the side effects. We are really trying to change the future of cancer and make sure they are a part of the conversation – not someone you talk around.”

 

In addition, it was stressed that “informed consent is pivotal in order to be a proper research study.” The Brain Tumor Project has very specific guidelines for tissue sample collection to ensure that 1) the tissue is large enough for them to take a small portion for sequencing and 2) that the tissue is not needed for clinical care. Accessibility of information is also very important. “We are adamant about sharing information… if we put all this information in a publicly available database, there’s a lot of other people out there that can dive in and potentially make new discoveries that we don’t have the time to make.” However, publicly available information can become a double-edged sword. All participant information is de-identified to ensure that publicly available information is not linked back to specific individuals.

Professor Sara Katsanis        

Professor Katsanis is a Research Assistant Professor of Pediatrics in Northwestern Feinberg School of Medicine and focuses on the ethics of genetic technologies for testing purposes. When considering personalized medicine, the focus should be on the access and control of genetic data. Great care should be taken to handle and process the data. Ethics is especially prominent in the area of pediatric testing as young children often lack the mental capacity to make informed consent and the responsibility should transfer over to the caretakers. As children grow older and begin to understand their situations, then they can make an informed consent decision. In the area of tissue banks, the donors should be informed and control the use and continued access of their tissues. It is important that bands should deidentify but not anonymize the data of the patients. Another aspect that Professor Katsanis talks about is inequality and discrmination in the arena of personalized medicine. Most clinical trials recruit only a specific subgroup of a population and there are a lot of undefined genetic differences within diverse populations, and data is sometimes wrongfully combined. This can even lead to misinformation which can cause stigmatization and misuse, bringing overall harm rather than benefit for a specific population. She is a big fan of collective phenotypic data as it is key to understanding the connection between genotypes and disease states.

Overall, this interview was impactful on our team and our project as we learned about the ethics of genome research. Our project involves synthesizing plasmids and inserting them into patient derived tumor cell lines, and many ethical questions can result from the use of these cell lines such as how this research can benefit the patient and how the team can obtain more information on the cell line to learn about the phenotypes of the patient. If the research ends up being successful, how can the donor patient be properly compensated? Also, where do we draw the line between deidentification for confidentiality and reidentification for the purpose of understanding the relationship between genes and phenotypes? Our team continues to ponder about ethical dilemmas that can arise from using patient derived samples and how to best avoid potential ethical issues.

 

Dr. Katerine Peters, MD PhD FAAN, is an associate professor of neurology and neurosurgery at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. Her research centers around patient care and the cognitive and physical function of brain cancer patients, focusing on the improvement of the quality of life and cognition of those afflicted with brain cancer. When asked about the typical prognosis of glioblastoma (GBM) patients, Dr. Peters shared that there are several factors that can predict prognosis, including patient ability to carry out daily tasks, the resectability of the tumor, key biomarkers (i.e. MGMT, IDH1, IDH2), and patient sex. “Women tend to do better...it’s the biology of the tumor” (1:42) The differences in signalling pathways between males and females can affect the success rate. Dr. Peters also provided insight into the concerns that might surround the acceptance and utility of an organoid-based system like the one proposed by our team. Generally, she mentioned that such an organoid tool would have utility in therapeutic testing, rather than in diagnostic applications. Also, she mentioned the fact that the sourcing of tissue used in such a model would also be an important consideration. Different samples will respond to environmental stimuli in a wide variety of ways, based on differences in demographic factors, like gender; if tissues are only derived from individuals with similar demographic characteristics, the system may not be able to accurately encapture disease aspects for all patients, which would limit the applicability of an organoid-based screening platform.

One of the biggest takeaways from our conversation with Dr. Peters is the importance of considering the sociodemographic factors that may lead to different glioblastoma outcomes. Testing with tissue samples from only one demographic of people may cause researchers to overlook other factors, such as differences in signaling pathways between males and females, that may affect how a disease progresses or how effective a drug is.

Considering the Human Factor

Dr. Margaret Johnson        

Dr. Margaret Johnson is a neuro-oncologist at Duke specializing in palliative care issues, and through this interview,we learned about the emotional and spiritual needs of the patients affected by brain diseases such as GBM. Dr. Johnson, like many other doctors, made clear that many protective measures are put in place to ensure autonomy and informed consent throughout the clinical trial process whether it is the FDA requiring a great deal of time and effort to design and reviewing proposals to clinical trials subject to IRB and a separate evaluation committee. Her opinion of using the brain organoid as a diagnostic tool and therapeutic development is that it is a unique niche that involves features such as immune privilege and the BBB, creating challenges not available in non-brain tumors. She mentioned a key aspect of the clinical trials was to explain complex scientific concepts to patients who come from a diverse background of understanding. Because she is involved in palliative care, she often deals with the emotional and spiritual impacts of the disease. Caring for the patients is truly the work of a team ranging from nurses to volunteers, and each member plays a unique role in making the end of life care optimal for the patients. She reminds the patients that there are long term survivors of the disease, giving patients hope and a desire to fight through the disease.

Overall, this interview provided our team a brand new perspective on the role of the doctor in treating a terminating disease such as GBM. By breaking down complex scientific concepts and communicating the process of clinical trials to patients in a simple manner, patients are able to be better informed and are able to make the best decisions for themselves. Simarlily, our educational outreach project aims to break down complex scientific concepts and explain them to third graders in local Durham schools. We know that many of our outreach events would involve a diverse set of audiences with differing levels of understanding, and it is important to convey our project in a simple and meaningful way.

Kathy Riley (PBTF)        

Kathy Riley is the Vice President of Family Support at the Pediatric Brain Tumor Foundation and the parent of a long term pediatric brain tumor survivor. Our interview with her provided insight into the emotional and social impacts of a brain tumor diagnosis on pediatric patients and their families. She emphasized that these diseases affect patients in a profound way. Even if they recover from a brain tumor, they are often left with long-term cognitive impacts after treatment, which can make care complex. Furthermore, she also stressed that the impacts of brain tumors also deeply affect family members. For many of them, a brain tumor diagnosis forces them to reconsider the dreams and hopes that they had for their children; with brain tumor patients and survivors facing many barriers to independent living and social integration, the burden of care placed on parents and loved ones is often immense. Given the increasing number of pediatric brain tumor survivors, the need to address quality of life and equitable opportunity concerns for these individuals has become increasingly urgent.

Overall, this interview was incredibly impactful for our team and our project. In contrast to many of the previous individuals we had interviewed, who provided a more technical look at GBM and related diseases, Mrs. Riley drew from personal experience as a parent and patient advocacy leader to shed light on the emotional, human-focused aspects of these diseases. After learning more about the profound human impact of these diseases, our team was motivated to further connect with patients in order to hear about their experiences living with brain tumors. Thus, we attended the ABTA National Conference on September 11th, where we listened in on a panel of brain cancer patients. These individuals were able to share their experiences with brain cancer, like their initial reactions upon being diagnosed or their management of cancer symptoms.  

ABTA

The ABTA has been in existence for almost half of a century, and it remains one of the most well-recognized brain cancer organizations. Its mission is to advance understanding and treatment of brain tumors in order to improve/extend/one day save the lives of those with brain tumor diagnoses. Its major areas of focus include advancing research, supporting patients/families, providing education/support services, and public policy/advocacy work. It also covers all facets of brain tumors (primary or secondary, across all ages and walks of life).

The key takeaway from our talk with the ABTA is that it is a patient advocacy organization, which is very different from some other organizations we’ve spoken with, such as the Musella Foundation. It doesn’t give medical advice, and doesn’t directly match patients to clinical trials. Instead, its overarching goal is to provide information, and sees its main role in education and support for patients who are going through treatments (information about treatments, how to manage side effects, etc.) It also organizes large conferences to raise awareness.

References

Lassen, U., Mau-Soerensen, M., & Poulsen, H. S. (2014). Orphan Drugs in glioblastoma multiforme: A Review. Orphan Drugs: Research and Reviews, 83. https://doi.org/10.2147/odrr.s46018

Chen, Jun-Rui MD; Yao, Yu MD; Xu, Hong-Zhi MD; Qin, Zhi-Yong MD, PhD Isocitrate Dehydrogenase (IDH)1/2 Mutations as Prognostic Markers in Patients With Glioblastomas, Medicine: March 2016 - Volume 95 - Issue 9 - p e2583. doi: 10.1097/MD.0000000000002583

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