The first step in our Human Practices work was to engage directly with people affected by B12 deficiency and Pernicious Anemia. This enabled us to better understand those who our project is aiming to help, as well as their needs and preferences. No literature review, however comprehensive, could provide the same level of insight, particularly in this field, where in-depth research on patient experiences with B12 malabsorption and its treatment remains limited. To this end, we have spoken with several individuals living with these conditions. Some chose to remain anonymous due to the sensitive nature of the information shared, while others agreed to have their stories published under their own names, as part of their advocacy efforts to improve the experiences of those living with B12 malabsorption. Across the five patient accounts, some clear similarities emerged in the lived experience of B12 malabsorption, alongside differences shaped by personal, medical, and systemic factors.

Reading about a problem and hearing directly from those with first-hand experience are two very different things. While we understood in theory that symptoms could be severe and that injections might be painful and inconvenient, we could not have anticipated the full extent of the challenges people face before, during, and after the diagnosis of B12 deficiency and malabsorption. Listening to these stories helped us move beyond the clinical view of B12 deficiency and better understand its everyday impact, from persistent fatigue and neurological symptoms to the psychological toll of being dismissed by doctors. These insights reinforced the importance of developing an alternative to injections that is scientifically robust and practical, accessible, and adaptable to different patient needs. It also pushed us to critically reflect on how we communicate about our project, ensuring that we acknowledge uncertainties and complexity rather than presenting B12 malabsorption as a single, uniform problem.

Patient 1 (Finland)

The interviewee explains that they have no other illnesses. The symptoms began in 2020, when they went for blood tests due to feeling weak. Several samples were taken over a couple of weeks, but no clear cause was found. Gradually, over the course of about a year and a half, their condition worsened. They also began experiencing eye problems, and vision in both eyes deteriorated.

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Patient 2 (UK)

This person’s journey with B12 deficiency began when, after years of being very active - working as a firefighter - they suddenly became extremely fatigued. They could not walk more than 200 meters without resting, experienced visual disturbances and severe nausea while driving, and often fell asleep after simple tasks like shopping. They also suffered from word-finding problems and mental fog. Despite these symptoms, doctors initially insisted that B12 deficiency was not the cause, and suspected a neurological condition.

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Patient 3 (India)

The interviewee is an iGEMer who came to us after we presented our project during an iGEM meetup, to tell us that they have B12 malabsorption. After a short conversation, they agreed to be interviewed as part of our Human Practices work.

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Katrina Burchell

Katrina Burchell’s symptoms began in her teenage years, when she experienced constant fatigue alongside gastric issues [1]. Her doctor dismissed these problems as irritable bowel syndrome and “normal tiredness.” Blood tests later showed low B12 and iron, but because her levels fell within the “normal” range, no treatment was offered. Over time, her symptoms expanded to include brain fog, pins and needles in her hands and feet, clumsiness, and memory lapses.

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Julie Wichlin

Julie Wichlin's experience with symptoms of Pernicious Anemia spans over 50 years, beginning in childhood with a variety of symptoms such as stomachaches, fatigue, recurrent infections, burning feet, headaches or irregular heart rhythms. Over the decades, she consulted numerous specialists across fields (gastroenterology, neurology, rheumatology, endocrinology, and hematology) undergoing multiple procedures without answers.

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Discussion

A first theme from those interviews is the long and difficult path to diagnosis. Both Katrina Burchell and Julie Wichlin described decades of symptoms being dismissed or misattributed, despite family histories of pernicious anaemia. Patient 2 also endured misdiagnoses, with his symptoms attributed to Parkinson’s or neurological disease, before he was able to prove to doctors that B12 deficiency was the cause. In contrast, Patient 1 and Patient 3 were diagnosed more quickly, though Patient 1’s diagnosis came almost by accident during unrelated surgery. Together, these stories highlight how inconsistencies in diagnostic practices, sometimes dependent on the initiative of patients themselves, create unnecessary struggle. Patients also consistently noted the burden of accessing and maintaining treatment. For some, injections were painful or inconvenient (Patient 3 stopped altogether, although this may not even be an option for people with more severe absorption issues), while for others, the challenge lay in healthcare logistics, finding someone to administer injections (Patient 1) or fighting for access to more frequent doses (Katrina Burchell, Patient 2). Both Katrina Burchell and Julie Wichlin emphasised how dismissive attitudes from healthcare professionals compounded these burdens, often leaving patients to advocate for themselves, self-inject, or seek alternative care. Finally, although all the interviewees’ symptoms improved once injections began, sometimes dramatically, it is noteworthy to point out that for some the relief was incomplete, and some damage was permanent.

Despite these shared struggles, experiences diverged in important ways. Patient 3, for example, described relatively mild symptoms and an ambivalent relationship with treatment, reflecting both uncertainty about the impact of deficiency and frustration with inconvenient injections. In contrast, Katrina Burchell and Julie Wichlin experienced profound, life-altering declines in health over decades, illustrating how severity and persistence vary dramatically between individuals. Cultural and systemic differences also played a role. Patient 2’s account revealed flaws in the UK healthcare system, where rigid treatment protocols and limited GP knowledge obstructed tailored care. Katrina Burchell’s experience echoed this systemic problem of misdiagnosis and under-treatment, while Julie Wichlin’s account illustrated the consequences of decades of struggles with U.S. healthcare services. By contrast, Patient 1, interviewed in Finland, seemed to have more consistent and easier access to injection-based care once diagnosed. It is important to note, however, that there are different kinds of absorption issues, so the easier experience of Patient 1 may not be due to the fact that the Finnish healthcare system is better than the others when it comes to B12 deficiency diagnosis and treatment, but that his need for B12 might be consistent with general guidelines (one injection every few months), unlike other patients whose bodies required more frequent injections. It is important to note that B12 absorption issues and need for treatment vary significantly between patients. The comparatively smoother experience of Patient 1 may therefore not necessarily reflect a superior Finnish healthcare system, but rather that their treatment needs align more closely with standard guidelines. By contrast, other patients require more frequent injections to manage their symptoms effectively, which places them in conflict with rigid protocols and limited flexibility in care.

Several unexpected or particularly striking points emerged. Some patients’ experience of empowerment through self-injection, despite a dislike of needles, stood out as a moment of agency in otherwise frustrating interactions with healthcare providers. Katrina Burchell and Julie Wichlin both illustrated the psychological toll of medical dismissal, with symptoms labelled as stress, anxiety, or lifestyle-related rather than investigated seriously. Julie Wichlin’s case also highlighted how reliance on serum B12 tests, without other types of investigation like antibody screening, can mask true deficiency, delaying diagnosis for decades. Several interviewees drew our attention to how their daily life was/is shaped by neuropathy, requiring adaptations such as assistive devices and memory techniques to manage basic tasks. Finally, Patient 3 raised concerns about the trustworthiness of new technologies, finding the idea of engineered intrinsic factor “scary,” which points to potential public hesitations about biotech-based solutions.

These findings are consistent with a study published in 2024 [2], that highlights the long and difficult journey many people face before being diagnosed with pernicious anemia. Alarmingly, it finds that 19% of participating patients were living with symptoms for at least five years before receiving a diagnosis, and around 14% waited for over a decade. One reason for that was misdiagnosis. Almost half of the patients were first told their symptoms were due to other conditions, most often anxiety, depression, chronic fatigue, or iron deficiency. Almost all participants (98%) experienced a wide range of neurological issues, including memory loss, poor concentration, clumsiness, pins and needles, dizziness, and balance problems. Cardio-respiratory symptoms such as shortness of breath and palpitations were also common, as were gastrointestinal problems like diarrhoea, indigestion, and stomach cramps. Emotional difficulties were frequently reported too, with irritability, mood swings, and even suicidal thoughts affecting many. Despite these severe and varied symptoms, diagnostic testing was often limited. The most common investigations were serum B12 and folate tests, but only a third of patients were tested for intrinsic factor antibodies.

Implementation

The patient interviews played a central role in shaping our project idea and our understanding of how it could fit into the real-world. They revealed not only the physical toll of B12 deficiency but also the emotional, financial, and time costs of relying on injections as the only effective treatment. Taken together, these accounts suggest that while B12 injections remain the dominant and most effective treatment for B12 malabsorption, they are embedded in systems that often fail to meet patient needs, whether due to diagnostic delays, inflexible treatment protocols, or lack of awareness among medical professionals. The interviews also underline the many similarities in patient experiences. While some patients eventually grew used to injections out of necessity, most described them as negative experiences, marked by inconvenience and struggle. Several interviewees shared how the lack of recognition from doctors pushed them to study the condition themselves, leaving them in the difficult position of having to convince medical professionals of their own needs. This often led to adversarial or at least unpleasant interactions, highlighting systemic barriers in treatment provision.

For our project, this highlights both the urgent demand for alternatives to injections and the importance of addressing not only the biomedical problem but also the social, systemic, and psychological dimensions of care. It made clear to us the importance of designing a treatment option that patients could access and manage independently, without repeatedly having to negotiate with healthcare systems or justify their symptoms. A supplement could offer a more practical, less contentious, and more easily accessible alternative, reducing unnecessary suffering. Beyond shaping our technical design, these conversations also gave meaning to our work: patients appreciated that we were trying to address their struggles, which reinforced our motivation and sense of responsibility.

When approaching a complex issue like pernicious anaemia and B12 malabsorption, speaking only to patients or clinicians would have given us a partial view. Advocacy and research groups operate at the intersection of science, medicine, and lived experience. They understand the biomedical challenges and the systemic gaps - in diagnosis, treatment, communication. They are also highly knowledgeable about the research landscape by being aware of past studies and actively following ongoing work. This meant that our conversations often felt like exchanges with expert collaborators rather than passive informants. Thus, by engaging with leaders of patient organisations, expert patients, researchers, and clinicians working across disciplines, we were able to situate our project within a broader landscape of ongoing struggles, unanswered research questions, and collective hopes for innovation. Their input also helped us reflect on how our project could meaningfully contribute, even if only in small ways, to this larger conversation.

Briefly about the Pernicious Anaemia Society

Briefly about Club-12

Katrina Burchell

Background

Katrina has worked as a solicitor and intellectual property lawyer and is currently the CEO of the Pernicious Anaemia Society. She herself has been diagnosed with pernicious anaemia, giving her both professional expertise and personal experience with the condition.

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Dr. Willemina Rietsema

Background

Dr. Willemina Rietsema is a General Practitioner in the UK and one of the founders of Club-12, a network of researchers, clinicians, and patient advocates dedicated to advancing knowledge on vitamin B12.

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Alfie Thain

Background

Alfie Thain is a PhD researcher and Registered Dietitian at the University of Surrey. His doctoral work, New Approaches to the Management of Pernicious Anaemia: An Overlooked, Lifelong Condition, focuses on better understanding and improving care for people with pernicious anaemia. He also collaborates closely with the Pernicious Anaemia Society, connecting academic research with patient advocacy.

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Julie Wilchin

Background

Julie Wilchin has lived with pernicious anaemia for several decades, during which she struggled to obtain a clear diagnosis. Over time, she has become an active advocate for people with B12 malabsorption, serving as a support group coordinator for the Pernicious Anaemia Society in the United States. She raises awareness by writing blogs and articles, guiding patients as they navigate complex medical systems, and sharing practical advice on symptom management and self-advocacy.

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Discussion

These interviews and meetings gave us a wealth of information about many aspects of B12 deficiency and pernicious anaemia. The following discussion highlights some of the most relevant insights for our project, while others, such as Medical Safety, will be discussed throughout the following sections.

Firstly, challenges in diagnoses were discussed, specifically the fact that the testing of serum B12 is not sufficient to diagnose B12 sufficiency. In cases of functional B12 deficiency, patients may have B12 in their body that is not absorbed but still detected by those tests. Moreover, even experienced clinicians and patients may struggle to recognise when symptoms stem from low B12 levels or from other conditions, which further complicates diagnosis. This leads many patients through multiple specialists before receiving a correct diagnosis. The uncertainty and delay not only prolong suffering but can also worsen mental health, since B12 deficiency itself may contribute to anxiety and mood disturbances.

Another shared conclusion across the interviews was that treatment for B12 deficiency should be tailored to individual needs rather than following rigid guidelines, as patients’ respond in unique ways to both deficiency and treatment. However, current medical regulations are stricter, typically recommending one injection every three months, which fails to reflect the diversity of patient needs. Even when patients clearly communicate that their current treatment is inadequate, they often face obstacles in accessing additional care. These include reluctance from doctors or fear of damaging the doctor-patient relationship. This power imbalance appeared repeatedly across interviews. Many patients reported becoming highly knowledgeable about their condition, staying up to date with research and guidelines and sometimes having to educate their healthcare providers to receive adequate treatment. One solution could be to say that general practitioners need to be educated about the nuances relating to B12 deficiency. However, several interviewees explained that general doctors cannot have in-depth knowledge of every condition because their medical practice is based on knowing a little about many things. Thus, even if this limited understanding often results in patient suffering, this "simple" solution would not be realistic, we cannot expect them to specialise in every rare condition. At the same time, the clinical guidelines they follow could be expanded to include greater nuance [3]. However, if made too detailed, they would become impractical for everyday use. More research is needed to explore how to balance precision and usability in these protocols.

Further, one of our initial questions concerned the effectiveness of different B12 treatments. We found little consistent and reliable information about alternatives to injections as literature (scientific or otherwise) was limited. The only clearly supported conclusion was that injections remain the most effective and widely used method. However, we wanted to understand whether sprays, high-dose oral supplements, or animal-based B12–IF supplements were truly ineffective or simply under-researched. We discussed these questions with several experts and learned that sprays and sublingual supplements can work for some patients, although they are usually effective only to some extent and often used incorrectly. Animal-based B12–IF supplements, while occasionally beneficial, are rarely prescribed, and their effectiveness tends to decline over time. Injections, despite their inconvenience and associated challenges, continue to be the most reliable and medically supported option.

Interviewees confirmed that a significant gap remains in vitamin B12 and pernicious anaemia research. Research into intrinsic factor has largely declined since B12 injections became the standard treatment, yet some experts suggested that this area may deserve renewed attention, particularly for patients who have undergone gastric surgery but still retain an intact ileum, where binding to cubam receptors occurs. For such patients, IF-based supplements could offer a valuable alternative. One research gap concerns the prevalence of people who have B12 deficiency, or pernicious anaemia. Current imprecise prevalence estimates suggest that about 0.1% of the general population and 2–3% of older adults have pernicious anaemia, but these numbers are most likely underestimated. Many cases go undiagnosed, and most data come from outdated, small-scale studies. New research, currently under review, indicates that the true prevalence could be closer to 0.8%.

Finally, while pernicious anaemia is a key cause of B12 malabsorption, deficiency can arise from many other factors beyond autoimmune attacks on intrinsic factor. With age, parietal cells in the stomach may gradually deteriorate, reducing intrinsic factor production even in the absence of antibodies. A striking point raised in several meetings was that B12 deficiency can mimic signs of ageing (difficulty walking, incontinence, or cognitive decline) yet their specific cause often goes uninvestigated. As a result, some individuals may be misdiagnosed with conditions like dementia and placed in long-term care facilities, when in reality, their symptoms could be significantly improved through B12 supplementation. This highlights a deeply troubling gap in awareness and diagnosis, where treatable conditions are mistaken for irreversible decline.

Implementation

The insights gained from our conversations with advocacy and research groups were very valuable in understanding the complexities of B12 deficiency on many levels. First, they reinforced our understanding of the importance of personalisation in treatment. Since patients experience B12 deficiency and respond to therapies differently, we aimed to design a solution that could potentially be a viable option for some of them. However, at this stage, it is challenging to know which groups would benefit from this kind of supplements. By exploring multiple IF species, we hope to identify versions that could improve absorption across more patient groups.

The interviews also highlighted the need for renewed scientific attention to intrinsic factor and the mechanisms of B12 absorption. Recognising that much of the existing research dates back several decades, and that many questions remain unanswered, we shaped our project to contribute to this neglected research area. Our experimental plan and documentation were therefore designed to test our specific hypotheses and to serve as a foundation for future studies, offering other researchers a clearer starting point in this underexplored field.

Discussions about diagnostic challenges and clinical misunderstandings around B12 deficiency further informed our communication and outreach activities. Hence, we decided to pursue education and awareness activities in our work. We also became more attentive to how complex medical information should be communicated to non-specialist audiences, including general practitioners and patients themselves.

Finally, the recurring theme of misdiagnosis and avoidable suffering, especially among older adults, strengthened our sense of responsibility to ensure that AbsorBuddy, if developed further, remains both scientifically sound, ethically grounded and more accessible than injections currently are. It also encouraged us to consider accessibility in a broader sense, not only improving convenience and comfort compared to injections, but also potentially helping populations who are currently underserved or misdiagnosed.

Overall, these interviews helped us understand how our work could align with real-world needs.

Engaging with Finnish medical professionals was an essential part of our Human Practices work. While B12 malabsorption is a global challenge, its prevalence is particularly high in Northern Europe. Thus, local doctors, dieticians, and specialists hold unique insights into how B12 deficiency is experienced and treated in practice. It also allowed us to compare their perspectives with patients’ accounts, helping us identify where experiences align, where their perspectives diverge, and how these differences shape the overall challenges of B12 deficiency. By speaking directly with them, we were able to understand the day-to-day realities of diagnosis, treatment protocols, and patient care in Finland. Their perspectives highlighted both the strengths and the limitations of the current practices, from the accessibility and cost of injections to the strain that they pose on the healthcare system. These conversations also grounded our project in the needs of our immediate community, ensuring that our work did not remain an abstract exercise but was connected to the people and healthcare systems around us. For us as an iGEM team, this local engagement was particularly important. It allowed us to investigate whether our proposed solution could realistically integrate into existing medical practices, identify barriers we had not considered, and explore how a new treatment might reduce strain on healthcare providers while improving patients’ quality of life.

Pr. Ursula Schwab

Clinical Nutritionist at the University of Eastern Finland and North Savo Wellbeing County Hospital. Association of Clinical and Public Health Nutritionists in Finland

Interview summary

Experience with B12 Deficiency

Ursula teaches and works clinically with patients who have Pernicious Anaemia (PA), gastrectomy, or loss of terminal ileum. The main groups needing B12 supplementation are gastrectomy patients, those with lost terminal ileum, and older adults on metformin for diabetes. It is hard to estimate the prevalence of different causes of B12 deficiency and malabsorption from her experience, as the hospital where she works mainly treats the most complex cases, which may skew her perspective.

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Dr. Pauliina Molander

Chief Physician in Internal Medicine and Gastroenterology at HUS Stomach Center

Interview summary

Diagnosis

In the interview, it was noted that there is very little prevalence data on pernicious anaemia in Finland, though hereditary cases are considered rare. Current estimates suggest that around 5,000 people in the country live with the condition. Because the disease is seldom encountered, diagnoses are often incidental, for example when changes in the stomach lining are noticed during a gastroscopy carried out for other reasons. Most cases are discovered in non-urgent contexts, and only rarely through specialized healthcare.

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Dr. Markku Nissinen

Chief specialist officer in gastroenterology at Terveystalo

Interview summary

B12 deficiency in general and in Finland

The conversation with Dr. Nissinen began with an overview of the causes of B12 deficiency and the current treatment practices. He emphasised that lifelong B12 injections remain the only consistently effective therapy, as the vitamin is delivered directly into the muscle. In Finland, the costs are relatively low, and in some cases the social security service Kela reimburses part of the expense. Diagnosis has also improved significantly compared to the 1980s: today, blood tests are easily performed when anaemia is suspected, and if a B12 deficiency is detected, the underlying cause is investigated. Pernicious anaemia is no longer as difficult to diagnose as in earlier decades, with modern methods including gastroscopy and microscopic biopsy examinations, as well as gastropanel tests that measure stomach bacteria and enzyme levels.

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Dr. Robert Bergholm

Chief Medical officer at Pihlajalinna

Interview summary

Experience with B12 deficiency

Dr. Robert Bergholm, senior physician and head of internal medicine at Pihlajalinna, has extensive experience with B12 deficiency through both clinical practice and research. He was unfamiliar with the concept of combining intrinsic factor with B12 in a supplement but found the idea intriguing as a potential alternative to injections, which remain the standard treatment. In Finland, injections are usually administered every two to three months, though some patients require them more frequently at the beginning or if levels are very low. While effective, injections are painful, sometimes leave soreness at the injection site, and create issues with patient compliance. According to Dr. Bergholm, he has not seen patients self-administer injections, and many would likely prefer a less unpleasant option if one were available. When asked about the possibility of overdose, he explained that B12 is stored in the liver and that while levels rise sharply after injections, they never reach concentrations that would cause toxicity. He has never encountered a case of B12 poisoning.

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Discussion

Our conversations with Finnish medical professionals revealed both shared understandings and differing perspectives on B12 deficiency and its treatment. All experts agreed that injections remain the gold standard, but they also highlighted certain limitations and burdens associated with this approach. Particularly the strain on healthcare systems, and accessibility problems for patients with reduced mobility or living far away from health centers. For instance, it was mentioned that in the Finnish region Lapland, some people need to travel more than 150km to receive treatment. In many cases, nurses themselves need to travel to provide treatment. Interestingly, while some doctors considered injections simple and cost-effective for most patients, others noted additional hidden burdens such as time and indirect financial strain, and compliance issues with some patients failing to attend appointments or maintain treatment schedules. Finally, some interviewees mentioned diagnostic uncertainty. While Finland has improved testing procedures in recent decades, intrinsic factor antibody tests are rarely used, and full diagnostic workups are not always carried out. This leaves many patients without a clear explanation for their deficiency. The difficulty of diagnosis also feeds into treatment debates, as B12 deficiency is sometimes masked by other conditions or mistaken for age-related decline, mental health issues, or dementia. Thus, any new treatment would need to fit into a healthcare context where awareness and diagnostic practices remain uneven.

When comparing the perspectives of medical professionals with those of patients we interviewed, several contrasts and overlaps became clear. Both groups acknowledged that injections are effective, but their framing of the experience differed: while several interviewed doctors described them as relatively unproblematic, individuals living with B12 deficiency frequently portrayed them as painful, emotionally draining, inconvenient, and even a source of conflict with healthcare providers. Patients also emphasized the time, cost, and self-advocacy required to secure adequate treatment, while professionals tended to focus more on clinical efficiency and compliance. This contrast highlights a gap between how treatment is perceived by those who provide it and those who receive it. At the same time, both groups expressed openness to alternatives, provided that safety and efficacy could be proven. Taken together, these interviews illustrate the importance of designing new solutions that not only meet medical standards but also alleviate the systemic and personal burdens patients repeatedly encounter.

The idea of a B12+IF supplement was met with cautious interest. Medical professionals acknowledged its potential to reduce strain on healthcare systems, improve accessibility, and provide a less invasive alternative for patients. However, they also raised several caveats. First, patient compliance with daily pills cannot be taken for granted, particularly since some patients find injections easier than remembering regular supplements. Second, safety and efficacy would need to be demonstrated through robust clinical data, especially considering the complexity of absorption and the possible role of antibodies. Third, cost emerged as a critical factor: while some saw patients as willing to pay more for easier treatment, others questioned whether an oral supplement could compete with cheap, widely available injections.

When comparing the perspectives of medical professionals with those of patients we interviewed, several contrasts and overlaps became clear. Both groups acknowledged that injections are effective, but their framing of the experience differed: while several interviewed doctors described them as relatively unproblematic, individuals living with B12 deficiency frequently portrayed them as painful, emotionally draining, inconvenient, and even a source of conflict with healthcare providers. Patients also emphasized the time, cost, and self-advocacy required to secure adequate treatment, while professionals tended to focus more on clinical efficiency and compliance. This contrast highlights a gap between how treatment is perceived by those who provide it and those who receive it. At the same time, both groups expressed openness to alternatives, provided that safety and efficacy could be proven. Taken together, these interviews illustrate the importance of designing new solutions that not only meet medical standards but also alleviate the systemic and personal burdens patients repeatedly encounter.

Implementation

These interviews gave weight to the importance of engaging with local healthcare professionals. Since B12 deficiency is relatively prevalent in Northern Europe, their insights ensured that our project remained grounded in the realities of the Finnish healthcare system, while also speaking to global concerns. This strengthened our conviction that patient-centered, system-aware innovation is not only necessary if new treatments are to gain trust and adoption. Thus, any alternative to injections must be more than scientifically plausible, it must also be practical, cost-effective, and adaptable to varied patient circumstances.

These conversations, in addition to those with patients and advocacy and research groups, pushed us to think critically about the potential advantages of our solution beyond efficacy, such as reducing hidden costs, lowering environmental waste from injections, and saving healthcare resources. Furthermore, the repeated emphasis on compliance highlighted the need to design a treatment that patients will realistically use. Additionally, hearing about diagnostic limitations and clinical uncertainty helped us recognise that our project does not exist in isolation. It interacts with wider systemic issues of awareness, testing, and medical culture. By acknowledging these factors, we reframed our work not as a “replacement” for injections, but as a possible complementary option that could expand patient choice and reduce barriers in certain contexts. Furthermore, we realised that a B12+IF supplement could help more people than those with Pernicious Anaemia and IF-related malabsorption, for instance, those who have undergone gastric bypass surgery. All these considerations, and the ones related to safety, are further discussed in the later chapters of this page.

As the goal of our team was to create an alternative for injections, it was important for us to understand what had already been studied and build on previous work. Therefore we dove deeper into understanding the potential of our idea by researching different treatment options. We used three different strategies for achieving this: 1) Learning from other iGEM teams, 2) Contacting companies with commercial IF-B12 supplements and 3) Researching treatments based on IFs. This work ultimately finalized our project plan: to produce recombinant IF proteins from human, porcine, rat, bovine and platypus to find the optimal versions for an oral IF supplement.

Learning from Other iGEM Teams

Contacting companies with commercial IF-B12 supplements

Researching treatments based on IFs

From the beginning, we recognised that safety is a central concern in the conception and development of an oral supplement, given that it is intended for human consumption. This concern was also reflected in the questions raised and discussed during our stakeholder interviews.

Learning points from expert interviews

Host System: <i>pichia pastoris</i> (Komagataella phaffii)

Stability of Intrinsic Factor in the Gut

Immunogenicity and Allergenicity Risks

Toxicity and General Safety Profile of Intrinsic Factor

Throughout our lab work it was important for us to consult the scientific community to ensure that what we are doing in practice makes sense. When starting the lab work we had two main goals: 1) designing a safe, scalable system for recombinant IF production and 2) choosing reliable, stakeholder-informed methods to analyze and compare IF function. With the help of many interviews and collaboration with the community, we were able to adjust our design to fit these goals. The meetings helped us create a scalable IF expression system using Komagataella phaffii and ensure that our analyses methods provide us accurate information about IF function. Additionally, our dialogue with the scientific community taught us the potential and importance of dry lab work, which led us to thoughtfully integrating it into our project.

Dr. Kristiina Hildén

Kristiina Hildén is a Docent in Microbial Biotechnology and a Senior University Lecturer at the University of Helsinki.

She is the principal investigator in the Fungal Genetics and Biotechnology group, which studies plant biomass modifying enzymes from fungi and bacteria. The research focuses on various aspects of fungal molecular biology and enzymology.

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Nicholas Farrell Wijaya

Nicholas Farrell Wijaya is a fresh graduate from Indonesia. He completed the Master’s Programme in Genetics and Molecular Biosciences at the University of Helsinki, specializing in Biochemistry and Structural Biology. He was also part of the iGEM 2024 team.

During his studies, Nicholas gained broad experience in molecular biology techniques, including CRISPR knockout library design and construction, multiplex plasmid assembly, size exclusion chromatography, membrane protein expression and purification, mammalian cell culture and transfection, and X-ray crystallography. His master’s thesis focused on structural biology, where he successfully solved the first crystal structure of exopolyphosphatase from a kinetoplastid parasite.

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Dr. Leonardo de Almeida-Souza

Dr. Leonardo (Leo) de Almeida-Souza is an Assistant Professor in Cell Biology at the Helsinki Institute of Life Science (HiLIFE) at the University of Helsinki.

He leads a research group at the Institute of Biotechnology, focusing on the interplay between clathrin structures, the actin cytoskeleton, and cellular adhesions. His multidisciplinary work combines cell biology, biochemistry, and structural biology to better understand disease processes and identify new therapeutic targets, especially for cancer.

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Nordic iGEM Conference 2025

The Nordic iGEM Conference (Nic) is an international synthetic biology conference. The conference is held each year in a different Nordic city and gathers iGEM teams annually across Northern Europe.

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Dr. Nilgün Yakuboğulları Özefe

Nilgün Yakuboğulları Özefe is a post-doctoral researcher at Izmir Institute of Technology, Department of Bioengineering

Her current research lies at the intersection of tissue engineering, regenerative medicine and immunoengineering, with a particular emphasis on hydrogel and biocomposite scaffolds; from her MSc and PhD work in natural product-based drug discovery she has developed strong expertise in immunity and immunomodulation (especially dendritic cell activation and T cell responses), along with hands-on skills in assays such as flow cytometry and ELISA.

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Enrique de Dios Mateos

Enrique de Dios Mateos is a PhD student at Aalto University, in the Biochemistry group led by Silvan Scheller

His project thesis involves fundamental research, genetic engineering and metabolic engineering of Methanococcus maripaludis, a model organism among methanogenic archaea. His ultimate goal is to gain insight on key metabolic processes carried out by this organism, how these are regulated inside the cell and how to tailor M. maripaludis for the production of high-value chemicals.

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From the beginning, we recognised that developing a recombinant B12–intrinsic factor supplement was an ethical challenge in addition to being a technical one. Synthetic biology projects inherently raise questions about safety, responsibility, and societal impact, and we wanted to ensure that these dimensions were considered along with our laboratory work. To do so, we engaged with experts in bioethics and synthetic biology, whose perspectives helped us reflect critically on the broader implications of our project. These conversations encouraged us to look beyond regulations and compliance, and to ask deeper questions about how our work should be framed, communicated, and used in practice. They pushed us to think about risks such as misuse or inequitable access, and about the philosophical and societal implications of modifying life forms for human benefit. By integrating these reflections into our planning, we aimed to make our project more transparent, responsible, and aligned with the principles of responsible innovation.

Leonardo de Almeida-Souza (Leo)

Background

Dr. Leonardo de Almeida-Souza is an Assistant Professor at the University of Helsinki’s HiLIFE Institute. He leads a research group at the Institute of Biotechnology, focusing on the interplay between clathrin structures, the actin cytoskeleton, and cellular adhesions. We contacted him for his expertise in cell biology, biochemistry, and structural biology, as well as his interest in the ethical dimensions of synthetic biology.

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Tero Ijäs

Background

Tero Ijäs is a doctoral researcher at the University of Helsinki's Department of Political and Economic Studies at the University of Helsinki, focusing on the philosophy of science and biology, with publications on synthetic biology. He is also affiliated with the Helsinki Institute of Sustainability Science (HELSUS) and TINT, the Centre for the Philosophy of Social Science.

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Discussion

Our conversations with Leonardo de Almeida-Souza and Tero Ijäs brought forward the importance of embedding ethical and societal reflection into our project alongside technical development. Both emphasised that regulations alone are not enough: while they provide a baseline, they do not capture the full spectrum of ethical responsibility. Instead, researchers must go further, asking critical questions about long-term consequences, accessibility, and communication. Leo challenged us to think about the blurred lines between supplements and medicines, noting that this distinction is not just regulatory but also tied to patient safety and public perception. He also raised philosophical questions about using living organisms for human benefit, reminding us that ethical science involves more than technical success, it also requires awareness of environmental costs, and the possibility of a supplement being overused, or used by people who don’t need it. Tero complemented this by framing ethical reflection in three categories: ontological (creating and modifying life), methodological (misuse and unintended consequences), and social justice (equity and access). He highlighted practical risks such as off-label use, forgery, and inequitable access, but also pointed out that the likely benefits of our project outweigh these risks if handled responsibly. His perspective helped us situate our work within broader societal debates, including issues of resource use, responsibility, and fairness in global distribution. Taken together, these discussions reinforced the idea that our project is not only a scientific challenge but also a societal one. Thinking critically about what we are doing, why, and how it may be used or misused ensures that our approach is more robust and aligned with responsible innovation.

Implementation

These conversations shaped our human practices in concrete ways. First, we integrated ethical reflection into our project framing, explicitly considering not only technical feasibility but also regulatory pathways, public communication, and societal impact. We also began mapping potential risks and unintended consequences more systematically and considered potential safeguards that could mitigate them. In terms of project framing, Leonardo de Almeida-Souza’s point about not needing to solve every ethical dilemma but raising and acknowledging them inspired us to document ethical questions directly on our wiki. This transparency reflects our awareness of both the benefits and the limitations of our work. Meanwhile, Tero’s emphasis on access and equity led us to reflect on scalability and global availability, questions that informed our broader discussions on how such a supplement might realistically be deployed in different healthcare contexts. In short, these meetings pushed us to go beyond the lab and integrate responsibility into our decision-making and ensured that our project is not just scientifically rigorous, but also socially aware and ethically grounded.

Public perception plays a decisive role in shaping how new biotechnologies are received, regulated, and ultimately adopted. In the case of a recombinant B12–intrinsic factor supplement, societal acceptance is just as important as technical feasibility, since opinions on GMOs and novel health products can influence trust, market uptake, and even policy decisions. To better understand these perspectives, we conducted a survey of the general public, focusing on knowledge and attitudes towards B12 deficiency, intrinsic factor, and the use of genetic engineering in supplements. By examining responses across different demographic groups, we aimed to capture levels of awareness and the factors that may shape acceptance or resistance to such innovations.

Aim of the survey

The survey was designed to gather data from the general public to assess their knowledge of, and attitudes towards topics such as GMOs, IF protein, and B12 deficiency, and to examine how this knowledge varies across different demographic groups.

Methods and procedure

The survey was conducted as an online questionnaire via Google Forms and posted on r/Suomi thread on Reddit. R/Suomi was chosen as the survey channel because its user base consists of a diverse audience consisting of users of different ages and sexes from various parts of Finland. In this study, participants are asked to complete a survey about their knowledge of synthetic biology, the IF protein, and the factors that may influence their opinions on GMOs and synthetically produced IF supplements. They were briefly explained the issue of B12 deficiency and injections and animal-based B12+IF supplements as the existing treatments, and that we were working on creating an alternative to those that would not be animal-based.

The survey was made completely anonymous and in compliance of the GDPR guidelines. The data collected in this survey was kept confidential and only in the use of our team’s analysis purposes. No information was gathered that could be traced back to the person answering the questionnaire. To ensure that the person answering the survey was aware of everything related to the handling of the data, they were provided our privacy policy, and they needed to explicitly confirm that they had read and consented. For questions about gender or diet, participants were given the option to skip answering, providing them with a safe and comfortable space to respond. Most of the answers from people aged 60 and over were gathered via street interviews (with exactly the same questions as in the online survey) in the Helsinki area to compensate for the lack of answers in the online survey. In total 229 individuals participated.

Results

Discussion

The survey results offer interesting insights into public knowledge and attitudes toward genetically modified supplements. A notable, but unsurprising, finding is the generally low public awareness of IF protein and its crucial role in preventing B12 deficiency, as most participants had never heard of IF prior to the survey. This highlights a knowledge gap that could limit informed decision-making regarding supplementation options, and corroborates the account of the nutritionist that we interviewed, who mentioned that - due to a lack of knowledge - people who need supplements often don’t take them, while those who need them, often don’t. Despite limited prior knowledge, participants expressed relatively high levels of comfort and trust toward GMO-produced IF, with most rating it as neutral or trustworthy and showing a preference for GMO-derived IF over animal-sourced alternatives. This suggests that initial unfamiliarity does not necessarily translate into rejection, particularly when ethical concerns — such as animal welfare, are taken into account. Safety and effectiveness emerged as the primary considerations influencing attitudes, surpassing concerns about naturality or environmental impact. The data indicate that trust in science and medical professionals plays a key role in acceptance, as participants reported that a doctor’s recommendation and additional scientific evidence would most strongly influence their willingness to use GMO IF. This aligns with broader trends in public health, where professional endorsement and robust research are critical to adoption of novel technologies. Interestingly, curiosity and fascination toward GMO IF were more common than toward animal-based IF, suggesting a cautious openness to innovation. Several qualitative comments further illustrate the diversity of perspectives. While some expressed interest in GMO IF as a plant-based alternative compatible with ethical dietary choices, others raised concerns about long-term safety and the reputation of genetic modification. The demographic skew toward younger age groups, likely due to the online survey method, means the results may not fully represent older populations, though supplementary street interviews helped mitigate this. Importantly, age did not appear to significantly influence attitudes, suggesting that acceptance is shaped more by trust and perceived safety than by generational differences.

Conclusion

This survey found that public attitudes toward GMO-produced intrinsic factor supplements are generally positive, even among individuals with little prior knowledge of IF or B12-related malabsorption. Across demographics, safety and proof of efficacy were the most important factors influencing acceptance, with ethical concerns also playing a role. Trust in science, medicine, and professional recommendations emerged as a decisive influence on willingness to adopt such products. Although unfamiliarity with IF protein is widespread, the openness to GMO IF suggests that informed communication, backed by scientific evidence and healthcare professional endorsement, could facilitate public acceptance. Future efforts should focus on increasing public awareness of IF’s role in B12 absorption, specifically for at-risk groups (the elderly, Northern Europe), addressing concerns about long-term safety, and providing clear, evidence-based comparisons between a GMO B12+IF supplement and other treatment methods. Overall, the findings point to a cautiously optimistic public attitude toward biotechnology in supplementation, contingent on transparency, safety assurance, and trusted guidance.

Several of the stakeholders we interviewed highlighted the environmental burden of regular, lifelong injections, like the ones used in the case of B12 malabsorption, because they generate a lot of packaging waste and sharp waste. This prompted us to hypothesise that our proposed supplement could represent a more environmentally friendly alternative, in addition to being more patient-friendly. While we expected that a pill-based supplement would reduce certain types of waste, we also recognised that lower impact in one area does not necessarily translate into overall sustainability. Moreover, estimating the environmental footprint of a product that has not yet been scaled up, and for which many parameters remain unknown, presents a real challenge. To address these uncertainties and explore how the environmental impact of AbsorBuddy could be assessed, we consulted Dr. Donya Kamravamanesh.

Dr. Donya Kamravamanesh

Background

Donya Kamravamanesh is a University Lecturer at Aalto University in Finland, specializing in bioprocess engineering, sustainable technologies, and chemical engineering, with research focusing on topics like carbon dioxide utilisation. Her work contributes to UN Sustainable Development Goals (SDGs) and involves developing new infrastructure for bioprocess education, such as a Future Pilot Hall for bioreactor systems.

Our initial idea was to create a theoretical Life-Cycle Analysis (LCA) for AbsorBuddy by imagining its potential large-scale production. However, our discussion with Dr. Kamravamanesh revealed that this approach was not feasible. Too many aspects of the final product remain unknown, and reliable data on the ecological footprint of existing treatments are scarce and imprecise. Attempting a comparative study between AbsorBuddy, injections, or animal-based B12+IF supplements would therefore be highly challenging and time-consuming with our resources, while still producing results that would be largely speculative. Instead, she advised us to focus on investigating the environmental impact of the work carried out in our own lab, as this would provide more reliable and practically useful results. Following this advice, we estimated that such an approach could also serve as a foundation for future assessments and discussions about the scalability and environmental footprint of supplements like AbsorBuddy. More broadly, we believe that it is desirable that incorporating this kind of analysis becomes standard practice, since recognising the environmental impact of a process is often the first step toward reducing it.

1. Raw Material Sourcing

2. Energy Intensive Processes

3. Reagent Use & Chemical Waste

4. Plastic Waste

5. Life Cycle Assessment Challenges and Future Pathways

While our project made significant progress in exploring the potential of recombinant intrinsic factor variants as part of a next-generation B12 supplement, several limitations shaped both the scope and the outcomes of our work.

One limitation we encountered throughout our project was the challenge of communicating such a complex and uncertain topic as vitamin B12 deficiency and pernicious anaemia. There are still many unknowns, for instance, the true global prevalence of B12 deficiency or how many of those affected actually have pernicious anaemia, or the mechanisms at play in certain types of malabsorption. Explaining this complexity clearly and concisely, without oversimplifying or distorting important nuances, proved difficult. At times, we felt that simplifying the topic risked being misleading, while excessive detail made it confusing. However, through feedback from our presentations (visit our Engagement page) and stakeholder meetings, we gradually refined our communication. We learned which explanations resonated best, how to frame uncertainty transparently, and how to use our slides and visuals to make complex information more accessible and impactful.

Then, the experimental limitations inherent to a student-led project constrained our ability to complete all stages of validation. Time and equipment access restricted how far we could progress and developing an oral supplement is habitually a several year long endeavour. Thus, while AbsorBuddy was originally envisioned as an accessible oral alternative to injections, it remains at an early research stage. Key aspects of formulation, stability, and delivery within the gastrointestinal environment remain speculative. Without full-scale production or clinical data, we cannot yet predict effectiveness, safety, or immunogenicity in humans. Long-term effects and effectiveness are also essential future research priorities. These uncertainties make direct comparison to existing treatments, such as injections or oral supplements, largely conceptual at this stage, though we have attempted it (Table 4).

Table 4. AbsorBuddy and existing B12 supplementation options

On the human practices side, our research relied primarily on qualitative insights gathered through interviews and surveys. While these provided valuable and diverse perspectives, the sample sizes were relatively small, and responses may have been influenced by selection bias, particularly among patients already active in advocacy or support communities. We took steps to minimise this bias when conducting certain activities, such as avoiding the distribution of our survey through personal social media or university networks, yet it is unlikely that our survey sample represents the full diversity of the Finnish population.

Our ethical and environmental analyses were similarly exploratory. Despite engaging with a wide range of ethical perspectives, many questions remain open. Neither we nor our stakeholders identified clear pathways for the misuse of our research, given its specificity, yet the possibility cannot be ruled out entirely. Questions of accessibility also remain speculative, as the scalability of such a product would directly determine who (across regions and socioeconomic groups) could realistically access it. This uncertainty is compounded by the broader research gaps surrounding B12 malabsorption. Without more precise data, it is difficult to determine which patient groups would benefit most from our proposed solution. The lack of routine diagnostic practices for identifying the causes of malabsorption further complicates this issue. Similarly, limited data availability prevented us from performing a full life-cycle assessment or any quantitative evaluation of ecological impact. Consequently, while AbsorBuddy may represent a theoretically more environmentally friendly alternative to existing treatments, this remains an assumption rather than a verified outcome.

Finally, a major limitation lies in the complexity of translating scientific innovation into real-world impact. While our project focuses on developing a biological solution to improve vitamin B12 malabsorption, this alone cannot address the broader social, medical, and systemic issues surrounding B12 deficiency and pernicious anaemia. The challenges faced by patients (such as misdiagnosis and inconsistent care, unequal access and medical stigma) are rooted in institutional, educational, and societal structures that cannot be solved through synthetic biology alone. Even if a scientifically robust and safe supplement were to be developed, its success would depend on effective communication with healthcare professionals, regulatory approval, patient trust, and equitable distribution. These human and systemic factors introduce uncertainties that no laboratory experiment can fully capture. Our project, therefore, represents only one piece of a much larger puzzle.

The next steps for AbsorBuddy and the broader research it represents lie in building upon and deepening the foundations established during this project. From both scientific and societal standpoints, several avenues have emerged.

From the scientific perspective, future work should focus on expanding and refining experimental validation to confirm the most potential IF variants. Moreover, optimising protein expression is essential for scaling up the production and paving the way toward pre-formulation studies for oral delivery. To read more on the next steps of our wet lab work, visit the project description and proof of concept sections. Once the most promising variants have been identified, laboratory-scale in vitro and in vivo studies should be conducted, followed by extensive clinical studies, to assess the absorption efficacy and safety profiles of the candidates. While some interviewed stakeholders mentioned cases, where previous animal-based B12+IF treatments were reported as less effective in the long-term than vitamin B-12 injections, we have not found studies confirming this. It is hypothesised that this reduced long-term effectiveness in certain patient groups results from the development of new antibody responses, mirroring challenges seen with early insulin therapies. Some of these limitations could potentially be addressed by exploring alternative delivery strategies, such as cycling between different IF variants or combining them. However, long-term studies are needed to investigate these possibilities and to confirm the suitability of recombinant IFs as a safe and effective treatment option.

On the ethical and human practices side, our findings underscore the need for continued dialogue between researchers, clinicians, and patients. Future iGEM teams or research groups could collaborate with medical institutions to study how IF-based supplements might fit into current care protocols and regulatory pathways. Co-designing solutions with patients, especially those with pernicious anaemia or other malabsorption disorders, could ensure that treatments address real needs and concerns, particularly regarding accessibility and trust.

After further laboratory research and expression optimisation is conducted, environmental impact assessment would be another valuable direction of work. Future studies could quantify the ecological footprint of recombinant IF+B12 supplement production compared to injection-based treatments, including waste reduction potential, energy use, and scalability.

We recognise that developing AbsorBuddy or similar biomedical innovations requires collaboration with medical regulatory bodies and industry partners. Engagement with medical regulators is particularly important to clarify how recombinant IF–based supplements would be classified, as medication, or dietary supplement, since this distinction determines testing, approval, and accessibility. Working with regulators early could also help identify potential safety and quality standards for recombinant IF production, while allowing for dialogue about dosage, labeling, and monitoring protocols tailored to B12 malabsorption. In parallel, industry engagement will be key to assess the real-world feasibility of large-scale production and distribution. Industrial partners can provide expertise in manufacturing, cost analysis, and product stability, which are vital in ensuring that a supplement like AbsorBuddy remains both affordable and environmentally responsible. Collaboration with the biotechnology and pharmaceutical sectors would also help bridge the gap between laboratory-scale innovation and healthcare application.

Ultimately, AbsorBuddy is a first step toward bridging biomedical innovation and human wellbeing. The project’s greatest legacy may be the foundation it lays for collaborative, responsible innovation, where synthetic biology research, ethical reflection, and lived experience inform one another to create sustainable and patient-centred healthcare solutions.

In the broader research landscape of B12 deficiency and pernicious anaemia, the Pernicious Anaemia Society has worked with the James Lind Alliance to establish the top ten research priorities in these fields (one of them being better treatment options). These priorities represent key areas of unmet need and should be carefully considered in any future research or development efforts.

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