Team:Virginia/ItP
Loading
#0269A4
Human Practices
“The potential for synthetic biology and biotechnology is vast; we all have an opportunity to create the future TOGETHER.” - Ryan Bethencourt
Human Practices
CHAPTER 2: IDENTIFY THE PROBLEM
1A) Exploring Biotechnology
Before beginning our wet-lab and modeling research, our first goal as the newly formed Virginia iGEM Team was to understand the problem that Manifold needed to be made for. Hence, we immediately met with the 2020 Virginia iGEM Team to understand the vision they set out for Manifold. As described by former member Eddie Micklovic, “Manifold is a versatile pharmaceutical manufacturing platform with the capabilities to revolutionize how drugs are made, from antimalarial drugs to dietary supplements. This synthetic biology project will bring an end to drug shortages and make medications more accessible to patients.” With such great expectations and promise for Manifold, these conversations with the 2020 Virginia iGEM Team directed our team to learn more about how last year’s work in synthetic biology related to current efforts to improve pharmaceutical manufacturing. Thus, we began interviewing experts involved with biotechnology research to contextualize the 2020 Virginia iGEM Team’s vision for Manifold. Contacting experts such as biotechnology professors, material scientists, synthetic biologists and pharmacologists, we started new conversations that explored current problems in biotechnology, why biosynthesis hasn’t become popular in manufacturing, the state of drug production, and how synthetic biology can uniquely solve these challenges. From the stories and guidance of former Virginia iGEM Team members, we began integrated human practices by meeting with Dr. Bryan Berger, a renowned synthetic biologists and successful biotech entrepreneur.
Associate Professor Bryan Berger
WHAT IS THE BIOTECH INDUSTRY?
Introduction: Dr. Bryan Berger is an associate professor at the University of Virginia, teaching hundreds of students each year about biotechnology. Besides his academic role, Dr. Berger has launched multiple biotech startups, including Lytos Technologies and Fiacre Enterprise. These companies have successfully developed synthetic biology solutions to optimize agricultural harvesting and have resulted in collaborations with the USDA. In his personal lab at the University of Virginia, Dr. Berger primarily researches new biomolecular technologies to improve chemical manufacturing and solve molecular structures. Hence, as a leading pioneer in biotechnology, experienced entrepreneur in synthetic biology and mentor, Dr. Berger was the first expert that the 2021 Virginia IGEM Team contacted.
Discussion: Our discussion with Dr. Berger was incredibly helpful in framing Manifold within the context of the biotechnology industry. We discovered that alongside the pharmaceutical industry, the chemical manufacturing industry at large faces several problems that stem from current manufacturing practices, including plant synthesis and chemical synthesis. These problems included supply shortages, poor product quality, low chemical yields, excess chemical waste, slow chemical discovery, or lengthy manufacturing steps to name a few. Because of the overwhelming amount of problems facing the entire chemical manufacturing industry, Dr. Berger shared that these problems were all a result of current manufacturing practices. Consequentially, the pharmaceutical industry, which uses the same practices like other industries in chemical manufacturing, face similar problems. However, Dr. Berger advised our team that we shouldn’t also just build a synthetic biology project that aimed to solve every problem in the chemical manufacturing industry. Instead, Dr. Berger shared that synthetic biology should only be used when other methods fail. “Synthetic biology must be targeted towards solving one problem extremely well, where other solutions cannot,” stated Dr. Berger. Before ending our interview, Dr. Berger recommended that the team seriously reflect on what problem synthetic biology needed to solve and understand precisely where Manifold could best help the chemical manufacturing industry.
Reflection: We knew we wanted to continue the vision that the 2020 Virginia iGEM Team set out and improve pharmaceutical manufacturing through Manifold. But, our conversation with Dr. Berger hinted a larger, more overarching problem that impacted all of chemical manufacturing. Current chemical manufacturing practices are inefficient which translates to industry wide inefficiencies in the pharmaceutical industry, agriculture industry, textile industry, basic and specially chemicals industry, etc. However, Dr. Berger also communicated the importance of building a responsible synthetic biology project, where we understood where Manifold could best help chemical manufacturing. Hence, Team Virginia needed to understand Manifold’s proper role in chemical manufacturing. Was Manifold supposed to increase the rate of chemical production? Was Manifold supposed to make drug manufacturing easier? Was Manifold supposed to fix the supply/demand issues among the industry? Was Manifold supposed to limit poor product quality? Was Manifold supposed to solve all these problems? We needed to find where our synthetic biology project could best help the chemical manufacturing industry. We needed to specify our project towards a single problem rather than applying synthetic biology to problems that do not call for it. After talking to Dr. Berger, we reflected on last year’s vision for Manifold, unanimously agreeing to repurpose their project through understanding where Manifold could best help the chemical manufacturing industry. This led us to Associate Professor Ann Meyer.
Associate Professor Ann Meyer
HOW DOES TECHONOLOGY LIKE MANIFOLD FIT IN?
Introduction: Dr. Ann Meyer is an Associate Professor at the University of Rochester, interested in reprogramming microorganisms to synthesize hierarchical and spatially controlled materials through new, engineered patterning approaches. What distinguishes Dr. Meyer’s work from other researcher in biotechnology is her 3D bacterial printer that can introduce novel properties, like high mechanical strength, high fracture toughness, or greater modularity, to naturally-occurring materials. As a result of her ingenuity, Dr. Meyer led the 2015 TU DELFT iGEM Team as their principle investigator and won grand prize through her project called Biolinker. With her knowledge in chemical manufacturing and experience in developing successful synthetic biology projects, Team Virginia met with Dr. Ann Meyer during the Mid-Atlantic Meetup at William and Mary.
Introduction: Dr. Ann Meyer is an Associate Professor at the University of Rochester, interested in reprogramming microorganisms to synthesize hierarchical and spatially controlled materials through new, engineered patterning approaches. What distinguishes Dr. Meyer’s work from other researcher in biotechnology is her 3D bacterial printer that can introduce novel properties, like high mechanical strength, high fracture toughness, or greater modularity, to naturally-occurring materials. As a result of her ingenuity, Dr. Meyer led the 2015 TU DELFT iGEM Team as their principle investigator and won grand prize through her project called Biolinker. With her knowledge in chemical manufacturing and experience in developing successful synthetic biology projects, Team Virginia met with Dr. Ann Meyer during the Mid-Atlantic Meetup at William and Mary.
Discussion: During the Mid-Atlantic Meetup at William and Marry, Team Virginia had the unique opportunity to talk to Dr. Meyer about materials production and how upcoming synthetic biology platforms aimed at manufacturing industrial materials like the 2015 TU DELFT’s Project Biolinker could innovate the industry. To our surprise, we learned that the future of materials manufacturing wasn’t focused on improving current manufacturing practices, rather was focused around discovering new methods that introduced novel properties to existing material or entirely discovering new materials. But even more surprising, Dr. Meyer shared that this focus was similarly found in other industries across chemical manufacturing. Pharmaceutical companies are focused on discovering the next drug and vaccine to prevent a global pandemic. The specialty chemicals industry is focused on synthesizing new chemicals to improve existing adhesives or cleaning agents, and providing more complicated intermediates to assist with research. On the other hand, industries like the basic chemicals manufacturing industry have wholly accepted their inefficient manufacturing practices, choosing to repeat several chemical reaction and purification cycles when more efficient processes like biosynthesis exist. With these industries to name a few, their priorities explain why little research has been centered around improving chemical manufacturing practices.
Reflection: With greater context to the chemical manufacturing industry and their priorities, our conversations with Dr. Meyer left Team Virginia questioning, “Why?” Why can’t these multi-billion dollar industries focus on discovering new chemicals and optimizing their manufacturing practice? Why have some industries even accepted their inefficient processes, when better alternatives exist? This prompted Team Virginia to explore all sectors within biotechnology (e.g., pharmaceutical biotechnology, agriculture biotechnology and biofuel production, etc.) to understand where biosynthetic manufacturing has proven to work. After our conversation with Dr. Meyer, Team Virginia seriously questioned Manifold’s role within biotechnology.
Reflection: With greater context to the chemical manufacturing industry and their priorities, our conversations with Dr. Meyer left Team Virginia questioning, “Why?” Why can’t these multi-billion dollar industries focus on discovering new chemicals and optimizing their manufacturing practice? Why have some industries even accepted their inefficient processes, when better alternatives exist? This prompted Team Virginia to explore all sectors within biotechnology (e.g., pharmaceutical biotechnology, agriculture biotechnology and biofuel production, etc.) to understand where biosynthetic manufacturing has proven to work. After our conversation with Dr. Meyer, Team Virginia seriously questioned Manifold’s role within biotechnology.
Professor Mark Kester
WHAT IS MANIFOLD'S PROPER ROLE IN BIOTECH INDUSTRY?
Introduction: Dr. Mark Kester is the Director of the nanoSTAR Institute, co-author of the textbook Integrated Pharmacology, and a leading pharmacologist in liposome assisted drug delivery. Before working as a professor at the University of Virginia, Dr. Kester was previously the G. Thomas Passananti Professor of Pharmacology at Penn State Hershey College of Medicine and the inaugural Director of the Penn State Center for NanoMedicine and Materials. With such prestigious roles in pharmacology, Dr. Kester founded the Kester Lab and several biotech startups including the 2019 Virginia iGEM Team’s project Transfoam. Currently, Dr. Kester negotiates billion dollar deals with pharmaceutical companies like Pfizer to translate research at the Kester lab and start-ups to solving real-world problems. As a colleague and friend to our principle investigator Dr. Keith Kozminski, our journey of integrated human practices led us to Dr. Kester, because we wanted to understand how biosynthesis has proven effective in the pharmaceutical manufacturing industry.
Discussion: In our countless discussions with Dr. Kester, Team Virginia realized that the pharmaceutical manufacturing industry was split between maintaining current manufacturing practices like plant synthesis and chemical synthesis, while also trying to integrate new technologies like biosynthetic manufacturing. Overall, this dilemma stems from the start-up costs and opportunity costs of shifting towards new technologies. Although companies like Pfizer can afford the infrastructure to support biosynthetic manufacturing and even manufacture some drugs like insulin through biosynthesis, these companies cannot afford to momentarily halt drug production in their plants, when supplying the medical field with the correct amount of medications is truly a life or death situation. Instead, these companies invest in biotech startups to optimize biosynthesis until it becomes more affordable to implement industrially, while pharmaceutical plants continue to use current infrastructure to practice plant synthesis and chemical synthesis. On the other hand, simpler chemicals such as aspirin or ibuprofen are cheaply made through laboratory reactions, instead of dedicating millions of dollars to engineer a new microbe that produces those drugs and then investing in the infrastructure to maintain its biosynthesis. As a result, the pharmaceutical industry continues to be limited by 3 major issues: inefficient synthesis methods, lengthy reaction and purification steps which leads to global pollution, and high drug discovery and manufacturing costs. The culmination of these problems result in pharmaceutical companies unable to manufacture drugs at sustainable rates, resulting in routine nation-wide drug shortages. Before parting ways, Dr. Kester heavily advised Team Virginia to only build a project with the overarching purpose of helping the end user.
Reflection: From our routine conversations with Dr. Kester, Team Virginia realized that Manifold, a synthetic biology platform dedicated to optimizing biosynthesis for large-scale manufacturing, had the potential to solve all the problems created by inefficient chemical manufacturing. Manifold could end drug shortages, support the United Nation’s Sustainable Development Goals such as “Good Health and Well Being”, “Sustainable Cities and Communities”, and “Climate Action”, bring about an industry-wide movement towards adopting sustainable and environmentally friendly manufacturing practices. This was where Manifold could best help the chemical manufacturing industry, by replacing inefficient plant and chemical synthesis with large-scale biosynthesis. Besides our newfound understanding of Manifold’s proper role in society, Dr. Kester’s inspirational, altruistic and noble advice left our team even more motivated. Team Virginia adopted a document called “Team Values”, where we agreed to build Manifold for philanthropic purposes and truly understand the impact inefficient chemical manufacturing has on end-users.
Reflection: From our routine conversations with Dr. Kester, Team Virginia realized that Manifold, a synthetic biology platform dedicated to optimizing biosynthesis for large-scale manufacturing, had the potential to solve all the problems created by inefficient chemical manufacturing. Manifold could end drug shortages, support the United Nation’s Sustainable Development Goals such as “Good Health and Well Being”, “Sustainable Cities and Communities”, and “Climate Action”, bring about an industry-wide movement towards adopting sustainable and environmentally friendly manufacturing practices. This was where Manifold could best help the chemical manufacturing industry, by replacing inefficient plant and chemical synthesis with large-scale biosynthesis. Besides our newfound understanding of Manifold’s proper role in society, Dr. Kester’s inspirational, altruistic and noble advice left our team even more motivated. Team Virginia adopted a document called “Team Values”, where we agreed to build Manifold for philanthropic purposes and truly understand the impact inefficient chemical manufacturing has on end-users.
Associate Professor Keith Kozminski
WHERE IS BIOSYTNEHSIS RESEARCH TODAY?
Introduction: Dr. Keith Kozminski is the Associate Professor of Biology and Cell Biology at the University of Virginia. Currently, Dr. Kozminski leads the Kozminski Lab, where his research team explores the molecular mechanisms that regulate polarized cell growth using S. cerevisiae. Besides his strong reputation across cell biology research at the University of Virginia, Dr. Kozminski serves as the principle investigator for the 2021 Virginia iGEM Team. As an inspirational mentor and strong advocate for synthetic biology, we met with Dr. Kozminski to present our findings and a new question that troubled our team.
WHERE IS BIOSYTNEHSIS RESEARCH TODAY?
Introduction: Dr. Keith Kozminski is the Associate Professor of Biology and Cell Biology at the University of Virginia. Currently, Dr. Kozminski leads the Kozminski Lab, where his research team explores the molecular mechanisms that regulate polarized cell growth using S. cerevisiae. Besides his strong reputation across cell biology research at the University of Virginia, Dr. Kozminski serves as the principle investigator for the 2021 Virginia iGEM Team. As an inspirational mentor and strong advocate for synthetic biology, we met with Dr. Kozminski to present our findings and a new question that troubled our team.
Discussion: After defining Manifold for the purposes of replacing inefficient chemical manufacturing practices, Team Virginia began questioning, “If biosynthesis was better than current manufacturing practices, then why hasn’t large-scale biosynthesis been widely adopted by the pharmaceutical industry or specialty chemicals manufacturing industry? Currently, we only see biosynthesis being used to make simple metabolites and antibiotics, but we don’t see biosynthesis in manufacturing biologics or other complicated pharmaceuticals.” To answer our question, Dr. Kozminski shared that beneath the problems we see in industrial, large-scale biosynthesis, the real problem involved four cellular limitations to biosynthesis. These included flux imbalance, pathway competition, toxic intermediates, and loss of intermediates. By overcoming these four problems, Team Virginia would be the first group to make large-scale biosynthesis industrially viable.
Reflection: With new insight into biosynthesis, Team Virginia carefully began crafting a one-paragraph statement that dissected the global problem of chemical manufacturing into its underlying, specific problem and identified future contacts that could provide diverse insight into the chemical manufacturing industry. This allowed members of Team Virginia to precisely understand our purpose for making Manifold, while directing wet-lab and modeling research towards a common goal—replace current chemical manufacturing practices with a more sustainable approach. We knew that if were to introduce large-scale biosynthesis to the chemical manufacturing industry, we needed to solve these four biological limitations through synthetic biology. Here, we recognized how synthetic biology was the answer to the problems facing the chemical manufacturing industry.
Reflection: With new insight into biosynthesis, Team Virginia carefully began crafting a one-paragraph statement that dissected the global problem of chemical manufacturing into its underlying, specific problem and identified future contacts that could provide diverse insight into the chemical manufacturing industry. This allowed members of Team Virginia to precisely understand our purpose for making Manifold, while directing wet-lab and modeling research towards a common goal—replace current chemical manufacturing practices with a more sustainable approach. We knew that if were to introduce large-scale biosynthesis to the chemical manufacturing industry, we needed to solve these four biological limitations through synthetic biology. Here, we recognized how synthetic biology was the answer to the problems facing the chemical manufacturing industry.
What Did Our Conversations Discover?
1. Limited Biosynthesis used in Chemical and Pharmaceutical Manufacturing
With so many sectors to the chemical manufacturing industry, each having their own unique problems, the 2021 Virginia iGEM Team recognized why adopting new technologies was overshadowed by the priorities facing the industry. For instance, many of today’s rubbers are synthetically made, offering greater physical, mechanical and chemical properties compared to natural rubbers. Although introducing biosynthesis may optimize the manufacturing process of natural rubbers, the end-product will not possess the same desired properties as synthetic rubbers, making it less viable and important to make. Only currently, technologies like the TU Delft’s Biolinker have introduced biosynthetic methods to discovering new materials. However, the infrastructure isn’t present in the chemical manufacturing industry, because industrial biosynthesis hasn’t become viable (with the exception of some medications). This is greatly apparent in the pharmaceutical industry, where many of today’s drugs are better produced biosynthetically, yet remain manufactured through plant synthesis and chemical synthesis due to existing infrastructure. To remove the drawbacks of current synthesis methods (e.g., low yields, high impurities, excess resources, etc.), optimizing biosynthesis on an industrial scale could greatly enhance pharmaceutical production.
2. An Emerging Era of Manufacturing Synthetic biology platforms like the 2015 TU DELFT’s Biolinker have opened a new possibility to chemical manufacturing, where bacteria can artificially be arranged in 3D structures that introduce greater strength, greater resistances, greater flexibility, and other revolutionary properties to materials. For instance, cellulose-producing bacteria can be stacked and arranged in a t-shirt shape, where these bacteria naturally repair ripped parts. In the future, the fashion industry may adopt these materials, never requiring consumers to replace old clothes again. However, with such a new and exciting concept, more research is needed to develop this type of biosynthesis technology further.
3. Inefficient Drug Production and Drug Discovery Firstly, current pharmaceutical manufacturing practices (e.g., chemical synthesis and plant synthesis) regularly result in low yields and high impurities, leading to frequent drug shortages across the medical field. As a result, many patients pay unnaturally high prices for drugs, while others suffer from drug inaccessibility. Ultimately, the current problems facing the pharmaceutical industry stem from the fact that drug manufacturing costs and drug discovery costs are extremely expensive, negatively affect the quality and economics of patient care.
4) A Common Solution: Biosynthesis Many of the crowning achievements of biotechnology have involved the engineering of organisms to produce chemicals of industrial value. This includes the production of anti-malarial drugs by yeast, enzymes that replace pesticides in strawberries, intermediates like 1,4- butanol in Escherichia coli, or even engineered cells to produce synthetic products like nylon. These fields offer exciting possibilities to circumvent the large chemical waste, large impurities, low chemical yields and high costs associated with plant-based or chemical production methods, However, many limitations exist which prevent the implementation of biosynthetic manufacturing to a wider array of chemicals.
2. An Emerging Era of Manufacturing Synthetic biology platforms like the 2015 TU DELFT’s Biolinker have opened a new possibility to chemical manufacturing, where bacteria can artificially be arranged in 3D structures that introduce greater strength, greater resistances, greater flexibility, and other revolutionary properties to materials. For instance, cellulose-producing bacteria can be stacked and arranged in a t-shirt shape, where these bacteria naturally repair ripped parts. In the future, the fashion industry may adopt these materials, never requiring consumers to replace old clothes again. However, with such a new and exciting concept, more research is needed to develop this type of biosynthesis technology further.
3. Inefficient Drug Production and Drug Discovery Firstly, current pharmaceutical manufacturing practices (e.g., chemical synthesis and plant synthesis) regularly result in low yields and high impurities, leading to frequent drug shortages across the medical field. As a result, many patients pay unnaturally high prices for drugs, while others suffer from drug inaccessibility. Ultimately, the current problems facing the pharmaceutical industry stem from the fact that drug manufacturing costs and drug discovery costs are extremely expensive, negatively affect the quality and economics of patient care.
4) A Common Solution: Biosynthesis Many of the crowning achievements of biotechnology have involved the engineering of organisms to produce chemicals of industrial value. This includes the production of anti-malarial drugs by yeast, enzymes that replace pesticides in strawberries, intermediates like 1,4- butanol in Escherichia coli, or even engineered cells to produce synthetic products like nylon. These fields offer exciting possibilities to circumvent the large chemical waste, large impurities, low chemical yields and high costs associated with plant-based or chemical production methods, However, many limitations exist which prevent the implementation of biosynthetic manufacturing to a wider array of chemicals.
Where Did We Go From Here?
Our conversations with biotechnology experts gave Team Virginia an overview of all the problems facing the chemical manufacturing industry. As a result, our discussions led our team to reevaluate the 2020 Virginia iGEM Team’s vision for Manifold, which involved designing Manifold to end drug shortages. But through our integrated human practices, we realized a common problem existed across several industries in chemical manufacturing—inefficient chemical manufacturing practices. This was the reason why drug shortages are so prevalent across modern medicine or why chemical manufacturing contributes to a majority of carbon emissions or why so much chemical waste ends up in oceans, landfills and natural habitats. Ultimately, our team specified the problem towards replacing the current, inefficient chemical manufacturing practices of plant synthesis and chemical synthesis, while supporting the UN’s Sustainable Development Goals.
By introducing large-scale biosynthesis to the pharmaceutical industry, Manifold ensures the consistent production of life-saving drugs, bringing an end to Drug Shortages and promoting greater Quality of Life through modern medicine.
Manifold replaces the wasteful and inefficient process of plant synthesis and chemical synthesis with a sustainable version of biosynthesis that supports large-scale manufacturing. Instead of having rows of plants growing chemicals or lots of chemists dedicated to running reactions and isolation procedures, special bacteria are placed in bioreactors, where the temperature, pH, growth medium are controlled to optimally synthesize our product to meet the demands of society.
With plastics manufacturing contributing to 15% of the global annual carbon emissions, 7 the textile industry producing one-fifth’s of the world’s water pollution,4 and pesticides making entire ecosystems inhabitable, 8 Manifold provides the solution through biosynthesis. Cells can produce biodegradable plastics that entirely remove burning fossil fuels in their manufacturing process. Cells can produce synthetic textiles like nylon, while sequestering cellular waste from the environment through bioreactors. Cells can synthesize environmentally friendly enzymes that substitute harmful, chemical pesticides. Manifold makes these possibilities a reality by making biosynthesis economically and industrially viable.
1B) Empathize with Patients
Responsible Patient Interviews
Following the guidance of Dr. Kester, Team Virginia unanimously signed into effect our “Team Values” document, affirming our commitment towards philanthropy and improving patient-care. Here, Team Virginia agreed that before starting wet-lab research, we needed to understand drug shortages from the end-user perspective. We needed to design a synthetic biology project that effectively ends problems created by inefficient chemical manufacturing practices like drug shortages, while keeping people as our central focus. As a result, our team met with the representatives from the University of Virginia’s Internal Review Board for Social and Behavioral Sciences to understand how our team could approach patient interviews in a responsible manner. We learned that we needed our purpose to be transparent with the participant. We needed to ask for patient consent to conduct the interview and show integrity and confidentiality when presenting our findings. However, upon submitting a provisional application for this study to be reviewed, our team was informed that it could take several months for our study to be approved. With little time to waste before the Giant Jamboree, we instead opted for a different approach as recommended by the Internal Review Board. If we were to conduct a successful interview that didn’t require the internal review board application, we would have to report our findings in a general manner, keep all participant information (even the location where we conducted these interviews) anonymous, and treat these interviews as simply a conversation. With the new parameters established by the Internal Review Board, we were ready to meet with patients.
What Problems Did We Discover?
Team Virginia met with patients to ask one question, “What are your greatest concerns when your prescription drug isn’t available at your local pharmacy?” These one-on-one conversations shined light on the true impact that drug shortages have on patients, while exploring the real reason why Manifold needed to be made. After sitting down with several patients at a local free clinic in Charlottesville, VA, our one-on-one conversations uncovered three heartbreaking effects that drug shortages have on patients.
1. Unnecessarily High Drug Prices The high cost of prescription drugs poses a serious problem towards the availability of medications. Besides drug shortages limiting the supply of medications across local pharmacies, patients must now pay more out-of-pocket costs for their prescription medication, because of its scarcity. Coupling these problems together makes drug accessibility nearly impossible, especially in poorer communities where patients cannot afford life-saving medication without financial assistance.
2. Lack of Access to Local Pharmacies that Supply Desired Medication In poorer communities that don’t maintain local pharmacies or remote cities that are isolated from modern medicine, drug shortages entirely prevent these populations from acquiring their desired medication. As a result, these patients must resort to alternative forms of medicine that haven’t been fully documented as effective. For patients whose lives depend on acquiring their prescription drug, their lives become endangered from drug shortages. Overall, the current lack of access to pharmacies in poorer and isolated communities coupled with drug shortages creates greater barriers towards patients receiving quality care.
3. Different Side Effects, Dosages and Schedules when Prescribed Substitute Medication When drug shortages occur, pharmacies may not store all the medications that modern medicine demands. As a result, patients that are prescribed one medication may be refused service by the pharmacy if their prescription drug isn’t present. This causes patients to return to their doctors, until an alternative medication can be prescribed. With an alternative medication, the doctor must also reidentify the dosage and consumption schedule, while balancing the risks of side effects with the disease. The overall effect is that drug shortages prompts logistical problems that prevent patients from obtaining their desired drugs, while introducing several challenges to finding an alternative medication.
1. Unnecessarily High Drug Prices The high cost of prescription drugs poses a serious problem towards the availability of medications. Besides drug shortages limiting the supply of medications across local pharmacies, patients must now pay more out-of-pocket costs for their prescription medication, because of its scarcity. Coupling these problems together makes drug accessibility nearly impossible, especially in poorer communities where patients cannot afford life-saving medication without financial assistance.
2. Lack of Access to Local Pharmacies that Supply Desired Medication In poorer communities that don’t maintain local pharmacies or remote cities that are isolated from modern medicine, drug shortages entirely prevent these populations from acquiring their desired medication. As a result, these patients must resort to alternative forms of medicine that haven’t been fully documented as effective. For patients whose lives depend on acquiring their prescription drug, their lives become endangered from drug shortages. Overall, the current lack of access to pharmacies in poorer and isolated communities coupled with drug shortages creates greater barriers towards patients receiving quality care.
3. Different Side Effects, Dosages and Schedules when Prescribed Substitute Medication When drug shortages occur, pharmacies may not store all the medications that modern medicine demands. As a result, patients that are prescribed one medication may be refused service by the pharmacy if their prescription drug isn’t present. This causes patients to return to their doctors, until an alternative medication can be prescribed. With an alternative medication, the doctor must also reidentify the dosage and consumption schedule, while balancing the risks of side effects with the disease. The overall effect is that drug shortages prompts logistical problems that prevent patients from obtaining their desired drugs, while introducing several challenges to finding an alternative medication.
Where Did We Go From Here?
After having this opportunity to meet with local community members, our conversations left a huge impression on Team Virginia. We realized that drug shortages affected everyone, that drug shortages creates many health-care problems for patients, that if drug shortages were to end, equal access to health care could become possible. Our conversations with community members exposed the real problems that affected patients, reminding Team Virginia our real purpose for building Manifold—to help end-users. With our immense empathy for all patients that suffer day-to-day from drug inaccessibility, Team Virginia adjusted our framework to include the same people-centered focus as the University of Florida College of Medicine’s curriculum. As a result, Team Virginia sought the creation of Manifold with hopes of ending drug shortages and most importantly, their negative effects on patients.
1C) Engage with Stakeholders
From our candid discussions with biotechnology experts and disadvantaged patients, our team acquired greater perspective on Manifold. We needed to build Manifold to help end-users directly affected by inefficient chemical manufacturing. We could help these end users by solving the four problems to biosynthesis, which includes flux imbalance, intermediate loss, pathway competition and toxic intermediates. But, we did not entirely understand how these biological problems lead to practical problems during chemical manufacturing. We needed to understand how Manifold should be implemented to help chemical manufacturers during production and consequentially, end-users. Hence, we wanted to understand the final perspective—stakeholders. Before proceeding to Step 2 of the I4A Framework “Imagine Solutions”, understanding the stakeholder perspective was key to building a realistic solution. A common problem amongst the biotech startups involved ideating a useful solution to a global problem, but failing to implement and scale their solution to meet the demands of society. Here, Team Virginia contacted chemical manufacturing companies around Charlottesville, VA that were involved in different sectors of the chemical manufacturing industry. These companies included the production of pharmaceuticals, the synthesis of specialty chemicals, and the manufacturing of plastic products, respectively. By identifying these distinct companies, we wanted to see if common problems existed across different sectors of the chemical manufacturing industry. But more importantly, we wanted to understand each company’s situation, their respective visions for a sustainable solution, and any guidance on implementing Manifold.
AMPAC FINE CHEMICALS
SYNTHESIZING THE ACTIVE PHARMACEUTICAL INGREDIENT
AMPAC Fine Chemicals is a manufacturer of active pharmaceutical ingredients (APIs) for customers in the pharmaceutical industry. This company produces APIs in large reactors, where raw materials undergo several chemical reactions to become different intermediates before entering its final API form and being distributed to commercial drug manufacturers. These lengthy processes involve as many as 10 intermediates, where rigorous purification is needed throughout each step. For this particular part in the pharmaceutical manufacturing process, our team was informed that the major contributor to drug shortages was the complicated and extensive purification steps. When APIs are distributed to commercial drug manufacturers, their products must be of high purity or they risk contaminating patients that ingest the medication. Because of current chemical synthesis practices, generating unwanted side products is highly likely, requiring extensive purification which are costly and time-consuming.
SYNTHESIZING THE ACTIVE PHARMACEUTICAL INGREDIENT
AMPAC Fine Chemicals is a manufacturer of active pharmaceutical ingredients (APIs) for customers in the pharmaceutical industry. This company produces APIs in large reactors, where raw materials undergo several chemical reactions to become different intermediates before entering its final API form and being distributed to commercial drug manufacturers. These lengthy processes involve as many as 10 intermediates, where rigorous purification is needed throughout each step. For this particular part in the pharmaceutical manufacturing process, our team was informed that the major contributor to drug shortages was the complicated and extensive purification steps. When APIs are distributed to commercial drug manufacturers, their products must be of high purity or they risk contaminating patients that ingest the medication. Because of current chemical synthesis practices, generating unwanted side products is highly likely, requiring extensive purification which are costly and time-consuming.
AFTON SCIENTIFIC
DRUG COMMERCIAL PRODUCTION
Afton Scientific operates a cGMP aseptic drug manufacturing facility in Charlottesville, Virginia that offers Grade A/Class 100 processing. This company produces commercialized drugs for globally renowned pharmaceutical manufacturing companies like Pfizer and GE Healthcare. From our conversations with Afton Scientific, Team Virginia was surprised by how production rates prevent pharmaceutical companies from adopting other practices that are more cost-efficient and yield higher product. Currently, pharmaceutical companies are constantly manufacturing drugs to supply enough medications to support modern medicine. As a result, pharmaceutical companies do not adopt more cost-efficient and higher yielding processes like biosynthesis, because current biomanufacturing suffers from slow production rates. This results in pharmaceutical companies maintaining current chemical synthesis practices that require extensive purification steps, which serve as bottlenecks for downstream operations if the drug is not properly isolated. This sentiment was similarly shared by Dr. Mark Kester in our early conversations, indicating that pharmaceutical production rate matters significantly in drug manufacturing.
DRUG COMMERCIAL PRODUCTION
Afton Scientific operates a cGMP aseptic drug manufacturing facility in Charlottesville, Virginia that offers Grade A/Class 100 processing. This company produces commercialized drugs for globally renowned pharmaceutical manufacturing companies like Pfizer and GE Healthcare. From our conversations with Afton Scientific, Team Virginia was surprised by how production rates prevent pharmaceutical companies from adopting other practices that are more cost-efficient and yield higher product. Currently, pharmaceutical companies are constantly manufacturing drugs to supply enough medications to support modern medicine. As a result, pharmaceutical companies do not adopt more cost-efficient and higher yielding processes like biosynthesis, because current biomanufacturing suffers from slow production rates. This results in pharmaceutical companies maintaining current chemical synthesis practices that require extensive purification steps, which serve as bottlenecks for downstream operations if the drug is not properly isolated. This sentiment was similarly shared by Dr. Mark Kester in our early conversations, indicating that pharmaceutical production rate matters significantly in drug manufacturing.
ADIAL PHARMACEUTICALS
DRUG DISCOVERY
Adial Pharmaceuticals is a clinical-stage biopharmaceutical company focused on drug discovery with respect to treating and preventing addictions. Their new drug product, AD04, is currently in Phase 3 development as a genetically targeted therapeutic agent for the treatment of Alcohol Use Disorder (AUD). After discussing drug shortages with workers at Adial Pharmaceuticals, Team Virginia recognized that clinical testing of drugs requires hundreds of millions to billions of dollars, which could be used in the actual drug manufacturing process. As a result, drug manufacturing companies like Afton Scientific and AMPAC Fine Chemicals do not have enough capital to support the latest technology in drug manufacturing, resulting in these companies continuing to use existing practices that are cost-inefficient and time-consuming.
Additionally, workers at Adial Pharmaceuticals discussed that the major reason drug discovery costs so much money involves the immense risk of discovering a new drug. The increasing complexity of advanced medicines and investment into treatments often do not end in success. This results in rising cost for prescription drugs, while making drug discovery a highly expensive and risky endeavor.
DRUG DISCOVERY
Adial Pharmaceuticals is a clinical-stage biopharmaceutical company focused on drug discovery with respect to treating and preventing addictions. Their new drug product, AD04, is currently in Phase 3 development as a genetically targeted therapeutic agent for the treatment of Alcohol Use Disorder (AUD). After discussing drug shortages with workers at Adial Pharmaceuticals, Team Virginia recognized that clinical testing of drugs requires hundreds of millions to billions of dollars, which could be used in the actual drug manufacturing process. As a result, drug manufacturing companies like Afton Scientific and AMPAC Fine Chemicals do not have enough capital to support the latest technology in drug manufacturing, resulting in these companies continuing to use existing practices that are cost-inefficient and time-consuming.
Additionally, workers at Adial Pharmaceuticals discussed that the major reason drug discovery costs so much money involves the immense risk of discovering a new drug. The increasing complexity of advanced medicines and investment into treatments often do not end in success. This results in rising cost for prescription drugs, while making drug discovery a highly expensive and risky endeavor.
BARRIER PLASTICS
RECYLABLE PLASTICS
Barrier Plastics is a chemical manufacturing company involved in the production of plastic products for containing hazardous liquids, including acetone, adhesives, methanol, flammable solvents, and carcinogens. These containers provide an alternative to metal containers and fluorinated high-density polyethylene containers that require extensive resource mining and burning of fossil fuels to manufacture. Instead, Barrier Plastics uses a green proprietary production process centered around optimizing system conditions to generate the plastic of interest through chemical synthesis. Thus, materials like polyamide can be stretched into modular polyethylene matrixes that are easily molded and layered to build highly resilient plastic products. From our initial conversations with Barrier Plastics, our team was surprised to see how chemical synthesis has become more efficient and environmentally conscious. Instead of simply meeting the demand of consumers through any means necessary, Barrier Plastics seriously focuses around making chemical synthesis less wasteful and manufacturing products that are biodegradable. By methodically changing the system conditions during every step of chemical synthesis, Barrier Plastics skips many of the intermediary reactions and purification steps that other companies employ. This results in a plastic product with unique properties like modularity, recyclability, plastic matrices, while reducing chemical waste. The overall effect is that consumers can now purchase more resilient plastics at more affordable prices, while significantly cutting the carbon emissions and wasted products in bodies of water that come from normal plastics manufacturing. The problem, however, involves the immense amount of energy needed to heat their systems at incredibly high temperatures. So although combustion reactions aren’t needed to produce these plastics, the immense energy usage still requires other electric companies to burn fossil fuels.
RECYLABLE PLASTICS
Barrier Plastics is a chemical manufacturing company involved in the production of plastic products for containing hazardous liquids, including acetone, adhesives, methanol, flammable solvents, and carcinogens. These containers provide an alternative to metal containers and fluorinated high-density polyethylene containers that require extensive resource mining and burning of fossil fuels to manufacture. Instead, Barrier Plastics uses a green proprietary production process centered around optimizing system conditions to generate the plastic of interest through chemical synthesis. Thus, materials like polyamide can be stretched into modular polyethylene matrixes that are easily molded and layered to build highly resilient plastic products. From our initial conversations with Barrier Plastics, our team was surprised to see how chemical synthesis has become more efficient and environmentally conscious. Instead of simply meeting the demand of consumers through any means necessary, Barrier Plastics seriously focuses around making chemical synthesis less wasteful and manufacturing products that are biodegradable. By methodically changing the system conditions during every step of chemical synthesis, Barrier Plastics skips many of the intermediary reactions and purification steps that other companies employ. This results in a plastic product with unique properties like modularity, recyclability, plastic matrices, while reducing chemical waste. The overall effect is that consumers can now purchase more resilient plastics at more affordable prices, while significantly cutting the carbon emissions and wasted products in bodies of water that come from normal plastics manufacturing. The problem, however, involves the immense amount of energy needed to heat their systems at incredibly high temperatures. So although combustion reactions aren’t needed to produce these plastics, the immense energy usage still requires other electric companies to burn fossil fuels.
AFFINITY CHEMICAL
SPECIALTY CHEMICALS
Affinity Chemical is a leading manufacturer in sulfate chemicals that are purchased by other chemical manufacturing companies and used as intermediaries to produce their products of interest. For example, one of Affinity Chemical’s crowning chemicals is aluminum sulfate, which allows waste treatment centers or bottled water companies to purify drinking water. From our conversation with Affinity Chemical, their manufacturing process heavily involved making specialty chemicals sustainably and at competitively low prices, which surprised many of the team. In specialty chemicals manufacturing, verifying that the correct product is chemically synthesized poses a serious financial and economic challenge as many of these products require dozens of reaction-purification cycles and produce tons of additional waste products, As a result, when our team first learned that Affinity Chemical engineered a way to make aluminum sulfate in one continuously stirred tank reactor with steam as the only waste product and excess aluminum constantly recycled back into the reaction, we were surprised by the broad optimization and simplicity of their manufacturing process. Simply, trihydrate powder is mixed with water in a batch reactor, left for nine hours to stir and the product is then tested for identity, quality and yields. In the meanwhile, excess aluminum added in earlier batches is vented back into the reaction and steam is produced. However, this sustainable process unfortunately isn’t the same in other specialty chemical plants. With synthesis of aluminum sulfate being a one step reaction that produces water as a side product, Affinity Chemical could design a process around this naturally occurring reaction. However, for chemicals like ethanol or steroids, chemical synthesis of these products remains wasteful as different chemical reactions and different reactor setups are needed which produce waste products that pollute the environment. The biggest issue identified by Affinity Chemical was the lack of standardization in manufacturing processes that limit environmental impact while promoting high production.
SPECIALTY CHEMICALS
Affinity Chemical is a leading manufacturer in sulfate chemicals that are purchased by other chemical manufacturing companies and used as intermediaries to produce their products of interest. For example, one of Affinity Chemical’s crowning chemicals is aluminum sulfate, which allows waste treatment centers or bottled water companies to purify drinking water. From our conversation with Affinity Chemical, their manufacturing process heavily involved making specialty chemicals sustainably and at competitively low prices, which surprised many of the team. In specialty chemicals manufacturing, verifying that the correct product is chemically synthesized poses a serious financial and economic challenge as many of these products require dozens of reaction-purification cycles and produce tons of additional waste products, As a result, when our team first learned that Affinity Chemical engineered a way to make aluminum sulfate in one continuously stirred tank reactor with steam as the only waste product and excess aluminum constantly recycled back into the reaction, we were surprised by the broad optimization and simplicity of their manufacturing process. Simply, trihydrate powder is mixed with water in a batch reactor, left for nine hours to stir and the product is then tested for identity, quality and yields. In the meanwhile, excess aluminum added in earlier batches is vented back into the reaction and steam is produced. However, this sustainable process unfortunately isn’t the same in other specialty chemical plants. With synthesis of aluminum sulfate being a one step reaction that produces water as a side product, Affinity Chemical could design a process around this naturally occurring reaction. However, for chemicals like ethanol or steroids, chemical synthesis of these products remains wasteful as different chemical reactions and different reactor setups are needed which produce waste products that pollute the environment. The biggest issue identified by Affinity Chemical was the lack of standardization in manufacturing processes that limit environmental impact while promoting high production.
WHAT DID WE DISCOVER FROM STAKEHOLDERS?
1. Pharmaceutical Manufacturing Requires Lengthy and Costly Purification Steps
With a majority of the pharmaceutical manufacturing industry relying on plant synthesis and chemical synthesis, lengthy reaction schemes and purification steps are needed to turn a naturally-occurring chemical into an industrial medicine. Although many pharmaceutical plants possess the infrastructure to support these lengthy procedures, they remain costly as growing plants require extensive amounts of resources and running reaction-purification cycles repeatedly demands large quantities of chemicals and constant oversight. These problems justify the high costs for most medications, even though some medications like insulin can be produced cheaply through biosynthesis.
2. Production Rates Primarily Determine Manufacturing Practices of Pharmaceutical Plants Because of western medicine and its introduction of drugs to treat disease, societies across the world have adopted a dependence for these medications. As a result of the high prevalence of disease, doctors look towards the pharmaceutical industry to constantly supply the correct amounts of medicine to ultimately save patient lives. However, because of this constant demand for medication, halting pharmaceutical companies from producing drugs creates shortages that leave patients at risk. This causes pharmaceutical companies to continue practicing inefficient manufacturing practices, even though more sustainable technology has emerged.
3. Drug Discovery is Expensive Pharmaceutical companies invest billions of dollars each year into discovering new medications to support greater quality of life and prevent future pandemics like COVID-19. As a result of the immense amount of resources dedicated to drug discovery, pharmaceutical companies deprive resources that could be used in other parts of pharmaceutical manufacturing like optimizing the pharmaceutical manufacturing process. In lieu of this, pharmaceutical companies invest and partner with biotech startups to support the development of new technologies to use in pharmaceutical manufacturing. But, these start-ups are risky and costly, causing pharmaceutical companies to mark up all drug prices, even those that determine if a person lives or dies.
4. Green Chemical Synthesis Demands Extensive Amounts of Energy to Maintain Reactors For over 200 hundred years, chemical synthesis has provided consumers with valuable chemicals through industrialization. However, much of the world’s pollution stems from the carbon emissions, water pollution and product waste generated through chemical synthesis. With greater focus on sustainability and climate action, chemical manufacturers are figuring out new solutions that are more environmentally friendly, while producing higher chemical yields with newer properties through the careful manipulation of reactor conditions during chemical synthesis. Although a significant portion of the chemical manufacturing industry’s pollution has been cut, chemical synthesis remains a key contributor to global pollution. Although some chemical plants advertise zero carbon emissions or zero waste streams, the extensive energy needed to run green chemical synthesis in reactors involves the burning of fossil fuels by offsite companies. Nevertheless, the optimization of reactors shows great promise, but its energy consumption must be reduced.
5. Standardization in Chemical Manufacturing Practices Regulates Pollution Because chemical products necessitate different chemical reactions and different plant setups, the chemical manufacturing industry lacks standardization that can adequately regulate the amount of pollution being made. However, the problem of standardization doesn’t end with pollution. Different manufacturing practices yield varying qualities, amount of chemicals, purification, etc. The overall effect is that the lack of standardization necessitates different manufacturing processes that generate drastically different product qualities and pollution.
2. Production Rates Primarily Determine Manufacturing Practices of Pharmaceutical Plants Because of western medicine and its introduction of drugs to treat disease, societies across the world have adopted a dependence for these medications. As a result of the high prevalence of disease, doctors look towards the pharmaceutical industry to constantly supply the correct amounts of medicine to ultimately save patient lives. However, because of this constant demand for medication, halting pharmaceutical companies from producing drugs creates shortages that leave patients at risk. This causes pharmaceutical companies to continue practicing inefficient manufacturing practices, even though more sustainable technology has emerged.
3. Drug Discovery is Expensive Pharmaceutical companies invest billions of dollars each year into discovering new medications to support greater quality of life and prevent future pandemics like COVID-19. As a result of the immense amount of resources dedicated to drug discovery, pharmaceutical companies deprive resources that could be used in other parts of pharmaceutical manufacturing like optimizing the pharmaceutical manufacturing process. In lieu of this, pharmaceutical companies invest and partner with biotech startups to support the development of new technologies to use in pharmaceutical manufacturing. But, these start-ups are risky and costly, causing pharmaceutical companies to mark up all drug prices, even those that determine if a person lives or dies.
4. Green Chemical Synthesis Demands Extensive Amounts of Energy to Maintain Reactors For over 200 hundred years, chemical synthesis has provided consumers with valuable chemicals through industrialization. However, much of the world’s pollution stems from the carbon emissions, water pollution and product waste generated through chemical synthesis. With greater focus on sustainability and climate action, chemical manufacturers are figuring out new solutions that are more environmentally friendly, while producing higher chemical yields with newer properties through the careful manipulation of reactor conditions during chemical synthesis. Although a significant portion of the chemical manufacturing industry’s pollution has been cut, chemical synthesis remains a key contributor to global pollution. Although some chemical plants advertise zero carbon emissions or zero waste streams, the extensive energy needed to run green chemical synthesis in reactors involves the burning of fossil fuels by offsite companies. Nevertheless, the optimization of reactors shows great promise, but its energy consumption must be reduced.
5. Standardization in Chemical Manufacturing Practices Regulates Pollution Because chemical products necessitate different chemical reactions and different plant setups, the chemical manufacturing industry lacks standardization that can adequately regulate the amount of pollution being made. However, the problem of standardization doesn’t end with pollution. Different manufacturing practices yield varying qualities, amount of chemicals, purification, etc. The overall effect is that the lack of standardization necessitates different manufacturing processes that generate drastically different product qualities and pollution.
WHERE DID WE GO FROM HERE?
From our conversations with stakeholders, Team Virginia confirmed our notion (from the scientific perspective) that inefficient chemical manufacturing practices have created many of the problems we face today, including climate change, drug shortages, chemical waste, and high prices for chemical products. Although we were pleasantly surprised to learn some chemical manufacturers have successfully made chemical synthesis more environmentally friendly, the broader chemical manufacturing industry has largely accepted the environmental harm and inconsistencies of chemical synthesis. This choice stems from the fact that chemical synthesis is currently the only industrially viable solution to supply many of the chemical products that society demands today. This concern prompted immense team discussion over the direction Manifold would take. In particular, we questioned, “How can we Manifold more industrially viable, such that biosynthesis can replace current chemical manufacturing practices?” From here, Team Virginia needed to imagine solutions.
Home
Project
Parts
Outreach
Team
Awards
Resources
Chemistry Building
485 McCormick Rd
CHARLOTTESVILLE, VA 22903
485 McCormick Rd
CHARLOTTESVILLE, VA 22903
