Human Practices

Professor, Critical Care Surgeon, and Co-Director of the UF Sepsis and Critical Illness Research Center

Dr. Frederick Moore is a professor and surgeon whose research specialties include translational research related to the body’s inflammatory response following trauma and multiple organ failure. Dr. Moore expanded the team’s understanding of the Sepsis and Critical Illness Research Center (SCIRC) and the key research objectives of the center. He described that the center focuses on taking observations from the clinical study and modeling them in murine models to strengthen the modeling systems for sepsis. Moore referred us to connect with Dr. Philip Efron to learn from his experience studying clinically relevant models of sepsis and discuss the relevance of an organoid model in understanding the human body’s response. Dr. Moore also emphasized that because sepsis is so heterogeneous, it is difficult to study, a challenge to be considered when studying human, animal, and organoid models.

Professor of Microbiology at the University of Florida

Dr. Abdolkarim Asghari is a senior lecturer at the University of Florida in the Department of Microbiology & Cell Science, who specializes in the instruction of general microbiology. Dr. Asghari provided his perspective as an undergraduate educator specializing in microbiology. He shared that the public's understanding of microbiology is limited and often negative due to its association with diseases. For example, GMOs are widely misunderstood due to public worry that engineered microbes may be harmful. He added that there is a need for more public health awareness, such as CDC campaigns or the distribution of brochures, to improve public understanding. This suggestion led to our team’s creation of a sepsis brochure for our educational work. Dr. Asghari encouraged our team to distribute the brochure to professors at UF to spread awareness of sepsis.

Dr. Asghari shared that the use of in vitro versus in vivo models has both benefits and downsides. It is difficult to create in vitro models that show the activity of microbes accurately, as microbial behavior varies depending on the environment, especially within the human body. Viral fitness is going to vary by host, which is a feature that is difficult to reproduce in vitro. Understanding human physiology is crucial to developing accurate models, but it is challenging to replicate real-life conditions outside the body. He added that the more you can understand an environment, the more you can reproduce the real environment, which is difficult to do outside of the body. Dr. Asghari presented a shortcoming of in vitro models and also highlighted a benefit of our model that is distinct from many other organoid models. As the bone marrow is difficult to study in sepsis patients, our in vitro model will help the scientific community understand the human body, consequentially enhancing our knowledge of human physiology.

ER Medical Director

Dr. Boaz Rosenblat is an emergency medicine doctor who provided valuable insight into the clinical aspects of sepsis and how furthering research on sepsis can be beneficial when put into effect. He described that the focus for clinicians is identifying if a patient fits into the spectrum of sepsis by evaluating symptoms and history. Infection signs can be obvious based on temperature and blood pressure or signs can be more obscure such as signs of confusion. While hospitals have implemented alert systems for patients showing signs of heart attack, this would be harder to implement for sepsis. For example, a young individual with strep throat may trigger the alert for sepsis due to their symptoms. This insight led the team to include infographics detailing the symptoms of sepsis on infographics distributed during Sepsis Awareness Month to promote public awareness of the signs of sepsis.

The goal of physicians is to do no harm. Dr. Rosenblat discussed the downsides of attempting to implement pre-hospital care for sepsis, such as giving patients antibiotics in the field prior to hospital care. He noted that antibiotic resistance has made sepsis treatment difficult, as hospital staff have to guess what treatment route is ideal until they have the test results back. Providers may not know if there is resistance to what they are trying to treat in real-time in an acute situation. Additionally, antibiotic resistance is a problem when considering aggressive sepsis treatment because antibiotics may be given to people who do not need it. The growing issue of antibiotic resistance emphasizes the need for an alternative means to treat sepsis.

Aditi Kumari, a medical student at the University of Miami and former member of our principal investigator's lab, Dr. Jing Pan, played a key role in helping us shape our approach to the project. Drawing on her experience with bone marrow organoids, she offered insightful mentorship that guided us in refining our own protocols. In June, Aditi walked us through the bone marrow organoid differentiation process, from iPSC culture to phase IV, demonstrating the techniques and helping us better understand how to adapt them for our specific needs. She also showed us her own results and images as an example and goal for us to attain. Aditi created a differentiation timeline that helped us prepare our reagents and guide our schedule. Additionally, she emphasized the importance of proper aseptic techniques in the lab, which were crucial for maintaining cell cultures and preventing contamination. Her hands-on instruction and support not only improved our technical skills but also boosted our confidence in conducting the experiments. Aditi's contributions were instrumental in refining our protocols and laying a strong foundation for our project, making her an essential part of our team.

Professor of BioSciences at Rice University

Dr. Jonathan Silberg is a Professor of Biosciences and Director of the Systems, Synthetic, and Physical Biology PhD Program at Rice University. As a synthetic biology educator and researcher, Dr. Silberg presented his perspective on the field.

Dr. Silberg emphasized that synthetic biology education is important for public stakeholders. We do not typically relate synthetic biology to a product, but the outputs of synthetic biology are an important aspect of the field and the team should think towards the future applications of our research.

Furthermore, he noted the importance of educating economic stakeholders in synthetic biology, as they are a powerful stakeholder subgroup and are critical to the scaling of a synthetic biology innovation. Dr. Silberg’s advice drove our team to analyze the future commercial applications of our organoid model, discussed in the 2024 Ethics Handbook. He also referred our team to the Engineering Biology Research Consortium (EBRC), which provides roadmaps to identify key societal challenges relevant to our device. For example, their research roadmap for engineering biology & materials highlights the societal challenges of sustainable production and scaling (EBRC, 2021). This led our team to consider the economic and environmental impacts of our device if it were to undergo the bench-to-market process. If Sepsynth were commercialized, the UFlorida team would need to design an efficient, environmentally friendly, and affordable manufacturing process to mass produce patient-specific organoid models in a sustainable manner.

Market Intelligence and Portfolio Manager, Center for Innovation in Diagnostics at Siemens Healthineers

Dr. Carpenter is currently on a research team at the Siemens Healthineers Center for Innovation in Diagnostics to develop a diagnostic tool for sepsis. Our conversation with Dr. Carpenter reinforced the lack of understanding surrounding sepsis progression as well as the importance in being able to understand sepsis detection and progression due to the severity of the diagnosis.

Dr. Carpenter noted that there are several bacteria that commonly lead to sepsis progression, and while the specific species are trade secrets, online literature reveals many of them. She advised that in our model, we should focus our pathogenic agents on the common sepsis-causing pathogens presented in literature.

Dr. Carpenter revealed the methodology used to test sepsis detection and presented a potential advantage to using an in-vitro model. The Siemens laboratory uses clinical samples of sepsis cultures obtained from patients with sepsis diagnosis. While this method provides a definitive sample to test whether their diagnostic tool is able to effectively diagnose active sepsis, these samples most likely do not replicate pre-septic progression which our model may be able to produce.

Dr. Carpenter provided insight into the regulatory processes of developing and converting a diagnostic tool from lab bench to market. While their diagnostic tool is currently in development, once it is ready for market it will have to undergo the FDA approval process, which will take at least 5 years before entering the market. Siemens Healthineers already has a large division dedicated to diagnostics which is how they are able to provide internal funding and resources to this project. Siemens Healthineers actively works with physicians and another diagnostics company to share resources and collaborate on this project together. This conversation contextualized the time, scale, and resources needed to develop sepsis diagnostic tools as well as insight into how our model would progress through the bench-to-market process.

Civic Science Postdoctoral Associate at the Rice University Baker Institute

Dr. Alicia Johnson is a civic science researcher at the Baker Institute Center for Health and Biosciences and the Science and Technology Policy Program. She studies synthetic biology in the context of social, ethical, and legal issues. Dr. Johnson emphasized the impact of regulations on the progression of science. Most scientists hope their science will be seen outside of the academic space, but often regulations can be the barriers preventing this. Regulations shape how the public gets the technologies, how soon, and how safe they are. Policy impacts what consumers get and what evidence is shared or studied.

This emphasis on policy led our team to research current policies regarding the development and commercialization of induced pluripotent stem cell-derived products. The UFlorida team included this research in our Organoid Commercialization Case Study in the 2024 Ethics Handbook the team created with Queens University, City University of Hong Kong, Arkansas State University, and Stanford. After researching current recommendations and regulations, our team described a bioethics-based company policy we would follow to limit their use of patient cells. This standard would limit the team’s use of patient cells if their Sepsynth model became commercialized to prioritize individuals’ informed consent and control over their cells’ use. The team asserted that the cells collected for the model should be used solely for that purpose to maintain the patient's privacy and trust.

Dr. Johnson provided her insight into science communication, which informed how the Human Practices team engaged in our outreach. She stated that we need to be able to understand what synthetic biology is and articulate our plans for it well. As we communicate, make sure we’re managing expectations and distinguishing our wants from what is currently developed. Dr. Johnson also noted that there is difficulty defining synthetic biology, as various definitions exist. She is working on a publication to consolidate what the definition of synthetic biology is. Dr. Johnson and her colleagues found a consensus, compiled from U.S. government agency definitions and the top 100 Google Search results, that people mention the terms interdisciplinary, biology, and engineering, and the research involves systems.

We discussed the schism between “soft” and “hard” sciences (social sciences and hard sciences), and Dr. Johnson emphasized the importance of social sciences. Scientists cannot just sit on the sidelines and hope that people understand what we are doing. This sentiment further motivated the Human Practices team to continue our work connecting our hard science with our outreach and work to effectively communicate our work in forms accessible to a broad range of audiences. Our conversation with Dr. Johnson sparked our team’s interest in communication ethics. We formally described proper communication practices in the 2024 Ethics Handbook our team jointly prepared and enhanced our team’s mindfulness as we designed our educational tools.

Dr. Johnson stated that community engagement in synthetic biology research has been very extractive in the past, referred to as “helicopter science,” where one goes to an area and does what they need to do instead of what the community needs. This practice can be very exploitative. She provided the example of creating synthetic biology solutions to target Environmental Protection Agency (EPA) superfund sites, which are sites the EPA designates as special sites in need of cleanup. These areas often overlap with marginalized communities, and there is historical context for why certain communities feel a certain way about science. When designing solutions, the community piece is key.

Overall, the team’s conversation with Dr. Johnson contextualized the complex relationship between synthetic biology researchers, policymakers, and the general public. This expansion of the team’s perspective informed our approach to public engagement and project design. The team sought out more stakeholder perspectives to affirm and pinpoint the societal need for our model.

Director of Sepsis And Critical Illness Research Center at the University of Florida

Dr. Philip Efron is a professor of surgery, director of the UF Health Shands Hospital Surgical Intensive Care Units, and director of the Sepsis And Critical Illness Research Center (SCIRC) at the University of Florida. His leadership in the SCIRC and research work studying inflammation and immunology resulting from serious injury and infection expanded the UFlorida team’s understanding of sepsis and its study at the University of Florida.

The perspective of a physician-scientist added context on our team’s understanding of the severity of sepsis. He commented how only recently people have started understanding the importance of sepsis and the large scale of lives impacted. Many people understand what a stroke is and can recognize the signs. However, sepsis is not commonly understood despite the higher probability of experiencing sepsis than a stroke. Notably, one’s parents and grandparents are much more likely to suffer from sepsis than a stroke.

Dr. Efron described how increased awareness of sepsis and standardizing initial care has changed sepsis progression in the hospital setting. The UF Health Shands Hospital now has very good early identification and hospital awareness. Additionally, initial clinical care is now standardized, which allows researchers at UF to work on the next stage of sepsis research. The government and WHO have realized the importance of sepsis recently, and the US Centers for Medicare and Medicaid Services now have penalties for not treating sepsis properly.

Dr. Efron emphasized the importance of intentional efforts in awareness campaigns. He listed the effective strategies the SCIRC executed to spread awareness, including the promotion of sepsis awareness month on cups in a local coffee shop,, signs, tabling, and overall many of the same strategies used to promote cancer screening at the hospital. He commented that sepsis promotion and awareness are especially important for populations with increased risk such as cancer and Alzheimer’s patients. Dr. Efron’s perspective emphasized the societal impact of sepsis and its impacts on our local community.

Dr. Efron shared the progress UF has made in sepsis research and current research foci. The work of the SCIRC was impacted by the realization that sepsis is such a systemic effect and requires precision medicine for treatment. The goal of sepsis treatment is to restore homeostasis which varies on multiple factors such as sex, age, ethnicity, race, and type of infection. Understanding the role these factors play in sepsis determines proper therapeutics. The organ, individual, infecting organisms, and patient care will all determine a patient’s treatment. There is potential for organoid models to be patient-specific, derived from an individual’s iPSCs. Future applications of our model could study the state of the bone marrow at the individual level.

Dr. Efron reported that for surgical sepsis at Shands, one-third of critical outcomes result in post-ICU syndrome. Those patients are the population in the most dire need of effective treatments. Acute morality is disappearing in patients and is being replaced by individuals who survive but survive poorly. Furthermore, sepsis is the most deadly and expensive condition in the hospital. This provided context for our background information and reasserted the importance of sepsis research.

Our team asked whether the SCIRC had considered using organoid models, but Dr. Efron shared that mice are the most feasible model for the center currently because they are affordable. Cost is a limiting factor, as sheep or pigs would be a more effective model, but research is limited by affordability. He added that sepsis research requires a multipronged approach, so organoids will likely be important in the future. When we shared that we are working on a bone marrow organoid model, he stated that it would provide valuable insight in the present, as changes in bone marrow stem cells are so critical in sepsis. The center currently does stem cell research, but without cellular interaction with other elements in the bone marrow that would affect the response, the results are not comprehensive.

Dr. Efron noted that most organoids are too simplistic to provide valuable insight into sepsis, such as a lung or heart organoid. He commented that researchers should not create something just to create it. There has to be meaning behind the project. He affirmed that our bone marrow model would provide relevant new insight into sepsis and expand the capacity of testing for therapeutics. This supported the relevance and value of our model, as the insights it can provide will be good for the world.

Dr. Efron added that a good bone marrow organoid is relevant for studying many diseases affected by white blood cells, such as pancreatitis, burns, and trauma, as these conditions alter the white cells and the products they produce. Additionally, one could target the bone marrow specifically with drugs if you know what is going on, utilizing the organoid to provide that insight.Dr. Efron’s insights highlighted potential future applications of our model, both for sepsis therapeutic development and additional disease studies.

Fellow of Science and Policy at the Rice University Baker Institute

Dr. Kristen Matthews is the director of the Baker Institute Science and Technology Policy Program and the Center for Health and Biosciences’ Biomedical Research Program, and lecturer for the Department of BioSciences at Rice University. Dr. Matthews contextualized some of the key ethical considerations regarding the use of iPSCs. She noted that embryonic stem cells have greater controversy surrounding their use in research, but researchers should be aware and informed of bioethical issues related to iPSCs. Although iPSCs do not have an embryonic form, the consent model with donations is still critical. Cells induced to pluripotency will be immortal and the genetics of those cell lines would be readily available to those working with the cells. Therefore, donors should be thoroughly informed of what would happen to their cells if they were donated or provided for a patient-specific model to be made.

The team also discussed how U.S. policies and public attitudes influence animal testing. Dr. Matthews noted that there has been a push to limit and justify the number of animals used. However, the American public has not been largely bothered by animal testing, so there is not an influential push for any policy changes. Our team’s bioethical focus seeks to reduce animal use in research but through the provision of an improved means to study the bone marrow in the context of sepsis. Our conversation with Dr. Matthews also stressed the importance of how to frame our interests, as it would be unproductive to stir public dissent over animal testing when the standard is still often the most effective model in biomedicine given our current resources as researchers.

Dr. Matthews also referred our team to two resources to expand our bioethical basis. The International Society for Stem Cell Research provides guidelines on how to use cells ethically. However, Dr. Matthews noted that this resource is written by scientists, so the document reflects scientists regulating themselves, which may influence the rationale behind some recommendations. Dr. Matthews also recommended that our team look into the International Society for Cellular Gene Therapies’ physician papers published in their journal Cytotherapy. Our team used these recommended resources in our contribution to the 2024 Ethics Handbook.

We also discussed the most pressing synthetic biology ethical and policy issues. Dr. Matthews described that broadly there are issues about how to regulate and which U.S. agency will regulate synthetic biology innovations. She stated that there needs to be more consistency in the definitions within these agencies so they know how to define what they may be regulating. She also noted that the Supreme Court’s overturning of Chevron U.S.A. v. Natural Resources Defense Council means that federal agencies can no longer define ambiguous aspects of a statute and courts can now engage in this process. As judges do not have a biological background and it is difficult even for individuals with a science background to approach synthetic biology regulations, this decision will likely lead to greater hurdles and slower approvals in the process of approving synthetic biology projects to reach the market.

Dr. Matthews also stated that scientists need to be aware of how development would be received. Two-way conversations with the public are needed to address concerns, be aware of how it would be used, and gain public approval. This advice further motivated the Human Practices team to engage with stakeholders who would be affected by our project.

We consulted the Center for Cellular Reprogramming (CCR) at UF College of Medicine when our Wet Lab team had difficulty with aggregate formation. In August, we provided a summary of our challenges with aggregate formation and images of our underdeveloped cell clumps for guidance on protocol changes.

As a result, we were able to obtain a starter iPSC plate containing wells of various passage numbers. This allowed us to attempt aggregate formation with a new cell line to determine if our current cell line was the source of our culture difficulties. The aggregates formed from the new cell line were much larger and healthier, confirming that our previous iPSC line was not optimal for aggregate formation, likely due to storage conditions of some cryovials at -80°C. Some members of our lab also benefited from official iPSC training at the CCR, enhancing our expertise. The training explained how to culture and maintain iPSCs, as well as thawing and passaging techniques. The CCR’s guidance and resources greatly enriched our capabilities and understanding of iPSC culture, enhancing the efficiency of our Wet Lab team’s iPSC culture and informing our team’s development of the iPSC Cell Culture Guide.

The Center for Cellular Reprogramming (CCR) at UF College of Medicine significantly supported our project by providing essential services, resources, and training in iPSC techniques, including differentiation and derivation.

Visiting Postdoctoral Scholar at the Rice University Baker Institute

Dr. George is a policy researcher who specializes in science policy and social dimensions regarding synthetic biology. His experience working both in the wet laboratory and science policy research settings framed his insights shared with the UFlorida iGEM Team. When the team asked what drew Dr. George to synthetic biology policy, he described how unprepared the United States is regarding current regulations and understanding what is being governed. He stressed the importance of having practical conversations regarding synthetic biology policy to understand the best uses of biotechnology in society.

He described the importance of public opinion and engagement, noting that scientists have improved in communication as the inherent resistance to biotechnology in the early 1990s to mid-2000s has reduced. Dr. George referenced a publication by Dr. Claire Marris which termed “synbiophobia-phobia,” which describes scientists’ false belief that the public would likely become fearful of synthetic biology and resultantly impede the progress of the field. Dr. George emphasized that movement away from synbiophobia-phobia has led to greater collaboration between academic and industry communities working more with public groups to understand values, wants, and needs.

Furthermore, he discussed the fallacy of the deficit model, which assumes that the public does not know about synthetic biology, and if a researcher tells them the science, they will understand and adopt the researcher’s values. He stressed that synthetic biology education should engage with the public in an exchange, not a one-sided lecture, to learn their perspectives. The UFlorida iGEM Team integrated this perspective into our educational initiatives and education section of the 2024 Ethics Handbook. In the latter resource, the UFlorida team wrote a communication ethics section emphasizing the value of engaging with the greater community and valuing their perspectives, rather than avoiding conversations.

Dr. George noted that when individuals in synthetic biology research understand public opinion regarding their inventions, they can work and tailor business models to align more with public values. Usually, public values are in the right place, and public support can be a great catalyst for change. In speaking with medical practitioners, the UFlorida team has learned the community's need for improved sepsis research. Dr. George’s commentary motivated the UFlorida team to engage in conversations with the wider community through interactive educational presentations and promote sepsis awareness further to garner public support. He noted that there is significant space between what happens in knowledge production at universities and public life. Therefore, the UFlorida team resolved to bridge the gap between synthetic biology research targeting sepsis and public awareness. In the fall semester, the Human Practices team targeted multiple routes of educational awareness to help remedy this disconnect.

• Industrial Biotechnology | EBRC Research Roadmap. (2021). https://roadmap.ebrc.org/2021-roadmap-materials/application-sectors-materials/industrial-biotechnology/