Passionate about learning about the human body, Marta Figueiredo, Ph.D, is a pharmacist, microbiologist, physiologist, and neuroscientist residing in Zurich, Switzerland. She has received her bachelor's and master's from two of Portugal’s most well-respected universities, Universidade de Coimbra and Universidade do Porto, and followed her educational journey by receiving her Ph.D in Integrative Molecular Medicine from the University of Zurich. She continued her work as a teaching/research assistant at the University of Zurich; and founded Science Xplore, a nonprofit dedicated to creative collaboration and education by scientists and artists alike. Currently, she works at the University of Zurich as a postdoctoral researcher, aiming to find the GABA neurotransmitter’s role in stroke.
We learned about her through our mentor, Vicky Makrides; and decided to interview her for her knowledge as a pharmacist. Thanks to her research background she was able to give informed insights about the heparin industry. This interview further improved our understanding of the pharmaceutical industry and how our project would be able to succeed through an entrepreneurial lens.
A few key points that she made were that (1) previous attempts at producing synthetic heparin were not very successful because of their price. In the heparin industry, synthetic heparin has to have a comparable price and quality to animal-sourced heparin to be preffered. Additionally, (2) she mentioned that figuring out a way of improving the pharmacology of heparin, say by making it easier to reverse its effects, etc., can give our product a competitive advantage. (3) The public should be informed about the sources of medications and alternatives to maintain the trust between the medical professionals and the public.
The most useful Q&A and the most critical pieces:
How do you think people would react to a synthetic heparin product?
People will be receptible to this type of synthetic heparin but there is a problem with the cost. Currently, I check that there are some synthetic heparin products in the US but the reason why they are not widely used is their price. If you get to produce it in a cheaper way people go with your synthetic option. It all comes to cost.
Do you think our project will have a disruptive impact on the porcine industry?I
don't think so. Long back jello that we all eat was produced using pigs and now most of it comes from vegetable sources. When you look back there wasn't a big impact on the pork industry. Initially, there won’t be a huge difference in diversity and pig population because the market diversifies and adapts as it happened in the past with the jello instance. So the trend is that you try the fix the problems with the supply chain and they will adapt. There will be initial complaints from producers but then they will adapt and there won’t be a huge disruption in the market.
You said that hospitals will adapt after the transition from the heparin now to synthetic heparin. Do you think the people are going to notice a big change or will that be mainly directed to hospitals?
So heparin is a drug mainly used in hospitals and hospitals purchase the drugs in bulk. The drug is purchased nationally in Europe and in America you probably do it state by state. Hospitals try to look for cheaper options especially in America since you guys have medicines that are quite expensive. For a drug to be approved by the FDA it needs to be ample and not have any toxicity. Once it is approved, hospitals only care about its price. They will go for the cheaper option. I don't think the patients will have the option to choose between different heparins because hospitals will only offer the cheaper version.
But you mentioned that currently, synthetic heparin is the more expensive version.
Yes, but once it gets cheaper everyone will prefer synthetic heparin because of its quality and reliability.
What makes a product competitive in the heparin market?
In the heparin market what gives you an edge is the product’s price and if it is pharmacologically interesting. This means that in the case of heparin, you need to be able to reverse the effects of heparin because you don't want someone to bleed to death. This is one of the aspects of the pharmacology of heparin. Also, you may want a heparin that acts right away. So it is a combination of economic and pharmacological aspects in this market. When it comes to drugs you need to evaluate all of these things. Think of ibuprofen and morphine. They are both painkillers with different prices but because of the difference in their pharmacological quality, there is a market for both of them.
What are the main challenges you think our project might face?
A potential concern is with the mass of the product. I did work with E. coli and you are probably going to get the product you want in grams but if you want to mass produce you need kilograms. That is why in our lab we always try to use yeast. You get to produce big amounts with yeast. But from my perspective when you manage to synthesize heparin with E. coli, it will probably be easy to scale it up.
“If more patients knew were heparin came from, more patients would be inclined to refuse Heparin.”
Dr.Angie Galletti is an accomplished pharmacist from Montana with extensive experience across various clinical settings. She earned her BA in Biochemistry from the University of Northern Colorado and later obtained her Doctor of Pharmacy (PharmD) from Midwestern University. Throughout her career, she has excelled as a researcher, leader, pharmacist, and clinical coordinator. Currently, she is a pharmacist at CVS Health, following over 15 years of experience with pharmaceutical companies like Albertsons and Walmart.
One reason for our interview was her significant contribution as a Wellness Screener & Lead Driver with Marketing Werks, where she traveled to low-income neighborhoods across the country. Her role involved training temporary staff, honing her skills in effective communication, adaptability, and meticulous record-keeping. As a researcher, she focused on drug design, synthesis, and DNA analysis at the University of Colorado, where she developed critical thinking, technical writing, laboratory techniques, communication, teaching, and problem-solving skills.
Our team values diverse perspectives, and this interview provided valuable insights into patient care as well as broader issues in drug manufacturing and the pharmaceutical industry. We gained a deeper understanding of anticoagulants, particularly Heparin, which is frequently used in both everyday and acute cases, especially in emergency and invasive surgeries. However, Heparin also carries a risk of contamination. There are two main types of Heparin, each with its own advantages and disadvantages. Oral anticoagulants offer variety, cost-effectiveness, and are suitable for long-term patient management, although some newer options are not covered by insurance. On the other hand, parenteral anticoagulants, such as injectable Heparin and Lovenox (which is emerging as a potential alternative), are typically cheaper and preferred in emergency situations or as a preventative measure.
The feedback we received suggested that alternatives to traditional Heparin could be safer and more reliable if manufactured domestically. However, challenges include cost, ensuring non-pathogenic production, and managing patient risks. We were advised to consult with members of the Pharmacy and Therapeutics committee of a large healthcare system to further evaluate the safety, benefits, and costs of synthetic Heparin. We have incorporated this advice into our project and plan to interview a pharmaceutical company with expertise in drug manufacturing, which will be reflected in our next conversation.
Three most useful Q&A and the most critical pieces:
Faria: Most of the heparin used in the U.S. is sourced from China and is derived from pig intestines. This process has contamination risks. Our project aims to biosynthesize heparin in a more economically efficient, environmentally friendly manner within the U.S. to ensure better quality control.
Faria: How many types of anticoagulants do hospitals typically have access to, and what are the preferences?
Dr. G: Anticoagulants fall into two main categories: oral and parenteral (injected). For parenteral use, we mainly use Heparin and Lovenox. For oral anticoagulants, newer agents like Xarelto and Eliquis are common, though Warfarin is still widely used due to cost.
Michael: Are there alternatives to Heparin that are as effective and similarly priced?
Dr. G: Lovenox is a close alternative but is more expensive, costing about $5-$10 for daily doses compared to Heparin’s $0.75-$3.00 per day. Despite the cost, Heparin remains the more affordable option, particularly for large institutions.
Faria: Do lower-income hospitals have limited access to medications like Heparin?
Dr. G: As a critical access hospital, we generally don’t face severe restrictions on medications. However, during drug shortages, we may experience allocation limits from distributors, restricting how much we can order.
Erin: Does the safety and effectiveness of Heparin depend on a patient’s health condition?
Dr. G: Yes, certain risk factors, such as a history of clotting disorders or Heparin-induced thrombocytopenia (HIT), increase the risks associated with Heparin. Females are also at higher risk for HIT.Dr. G: What are the potential benefits of your proposed solution for heparin biosynthesis?
Faria: Our solution involves using an E. coli strain to biosynthesize heparin, which would be cheaper, more purified, and less prone to contamination compared to current methods. Given these benefits, do you think your solution is a better alternative?
Dr. G: Even if slightly more expensive, domestically produced heparin could reduce supply chain disruptions and improve safety, especially considering recent international disturbances and drug shortages.
Erin: How often is Heparin used in non-emergency versus emergency surgeries?
Dr. G: We use Heparin daily for DVT prophylaxis and occasionally for acute situations. It is more commonly used in emergency surgeries at large cardiac centers.
Michael: Does your hospital differentiate between low molecular weight heparin and regular Heparin?
Dr. G: Yes, low molecular weight heparin (like Lovenox) is often preferred due to convenience and cost, but regular Heparin is used for patients with poor renal function or when immediate cessation of anticoagulation is needed.
Faria: Are there concerns about the quality of Heparin or developing a new manufacturing process?
Dr. G: There are concerns about the current sources of Heparin, especially regarding contamination and the ethics of using animal-derived products. For any new process, ensuring it does not introduce pathogenic risks is critical.
Faria: What are the ethical considerations surrounding Heparin?
Dr. G: Many patients might refuse Heparin if they knew it was derived from pigs, especially those with religious objections. Moving away from animal-sourced products is a preferable option.
Erin: How does the safety of Heparin compare to other anticoagulants?
Dr. G: Heparin is considered safe, particularly for patients with renal issues or those at risk of HIT, as it can be closely monitored with lab tests.
Michael: Have you seen many complications with Heparin use?
Dr. G: Complications with Heparin are not significantly different from those with other blood thinners. During the COVID-19 pandemic, we saw complications across all anticoagulants due to the higher risks of both bleeding and clotting.
Faria: Do you have any final recommendations for your project?
Dr. G: It might be valuable to consult with someone from the Pharmacy and Therapeutics committee at a larger healthcare system, as they specialize in evaluating the risk-benefit profile of medications, including cost and safety aspects.
Dr. Panagiotis Fakitsas is the Senior Quality Product Lead at Roche in Basel, Switzerland. With an extensive and intensive history in the Small and Large Molecule world, Dr. Fakitsas is in charge of quality oversight and quality control strategy development. His work with Roche gives him a unique perspective on the transfer and launch of products from the lab to the market.
Our team interviewed him to understand the safety precautions involved in the research and development process. While Dr. Fakitsas is primarily involved in the development of medical devices, his adept understanding of quality control processes gave our team valuable insight to the safety standards and priorities that we should consider in drug synthesis. When dealing with devices and drugs aimed toward improving the quality of life of patients and healthcare workers, safety, he says, is the number one priority. His role in research and development is one that focuses intently on upholding such standards and ensuring each customer receives a functional, safe product.
In order to create good quality products, we require a detailed understanding of the protocols used to insure our intended effect
Rabbi Benjamin Flax is a local rabbi in the greater Boston area. He is originally from the other side of the United States and grew up around and proudly serves for the Air Force Chaplain. Rabbi Flax received his BA in 2014 at the University of Alabama in Religious Studies and History. At Harvard in 2018, he got his Masters of Liberal Arts. In 2022 at the Wurtzweiler School of Social Work of Yeshiva University, Rabbi Flax earned a Graduate Certificate in Gerontology and Palliative Care. His rabbinic ordination is from Yeshivat Pirchei Shoshanim. He currently proudly serves for the Massachusetts Army National Guard in the Chaplains Corps.
One reason for our interview was his notable standing in the Jewish community and respect within the greater Boston area. In the past ten years, he has worked with fundraising and advancing education, Jewish life, and political campaigning. Currently, he serves as a rabbi of Tifereth Israel of Winthrop.
Our team values diverse perspectives and this interview provided the viewpoint of kosher following/Jewish communities. Rabbi Flax discussed different laws and exceptions such as the value of saving life trumping other kosher laws. These laws are based on a widespread belief of trying to not disrupt the natural order of the world. For example, mixing animals or fruits, or even GMOs. In some cases, GMO products can become kosher certified and it is becoming more widely accepted within the community, specifically the Orthodox union, the largest governing body for certifying which products are kosher in the United States. The Rabbi told us about his part of pastoral work of meeting with families to talk about options and answering questions.
During our discussion with Rabbi Flax, we learned much about the community and the various positions within it. Our team gained insights on what the tenets of Judaism are and what is based on religious text. We took away the diverse schools of thoughts within the Jewish community, the different laws that are followed, the overall strong belief of the value of life, as well as the reactions of the community to previous synthetic products such as insulin. We have noted the information learned during this conversation and incorporated it into our project.
Q&A:
Nico: Thank you. Our first question is about the most common anticoagulant: Heparin. Heparin is produced from pork products. And even though there are alternatives to Heparin, they are less effective. According to the Jewish beliefs and opinions, what should a person who needs this type of medicine do?
Rabbi Flax: Leviticus chapter 11 verse 7 to 8, it says that the swine is unclean to you their flesh, you shall not eat and their carcass you shall not touch…The thing was when it is a, a fresh carcass, a rotting piece, something that can, what in Jewish laws is saying, transmitting Tuma, this impurity that makes you ritually unfit… We are not told that we cannot utilize elements of a pig. We're told we cannot eat of the flesh. And so porcine by-product when you're looking in that way, and insulin is a great example. Prior to synthetic insulin becoming viable, the two options were either porcine derived pork derived insulin or one from that was a human derived compound that was made from deceased individuals. That one is more problematic. We are not allowed to benefit in any way from the use of a dead body.
Nico: Ok, thank you. So just so that I can make sure I understand. If there is another option, that's what should be done. And that's why without it being life threatening at the moment, correct?
Rabbi Flax: If there is a viable, sustainable and usable option, so if you need something every single day and the question is I can get a synthetic thing but it takes a lot longer to get or it's not as reliable of a source, but I need this every day and changing insulins or changing other types of medications are going to be problematic. You should go for the one that is rapidly available to benefit your life and save your life…So within anything, there is no such thing as a universal belief…What I will say is that I am following what is, what is a middle ground that will be generally accepted by most people.
Faria: So how do you think that religious leaders and organizations can help educate the community about new alternative medications?
Rabbi Flax: With new medical technologies, you get polarization, polarization and politicization, and that is one area that I personally believe clergy should not be getting too involved in when you're looking at emerging technologies and abilities to get synthetic sources until it is a viable piece where education can be performed. It really, I think should be case by case if people are going into hospitals and are looking at treatments that are necessary. Look, if you're saying your options are you can, you know, have a slight headache and, or, or you can eat a pork laced gelatin capsule that'll help your headache go away, maybe have a little bit of headache and drink some water because it's not debilitating. The most important thing is that you, can, can ask for forgiveness later too.
What are the pros and cons of synthetic biology and biotechnology?This is a very broad question that I suspect will be difficult to get a clear answer to. The pros and cons of synthetic vanillin vs. gene drives, while both biotechnologies, don't strike me as terribly similar― and the benefits and costs of the technology will be different depending on the context where it is used (e.g. gene drives might be more vital in a context like
What are the ethics behind manufacturing a traditionally animal-produced medicine, such as heparin?
I don't have an immediate answer to this, but I'd suggest looking into other synthetic alternatives to animal production, including the Revive & Restore Horseshoe Crab Blood project and maybe some things on monoclonal antibody or vaccine manufacturing? Has anyone done previous work on replacing animal-produced medicine or heparin specifically? I'd also point you towards this old iGEM blog post: https://blog.igem.org/blog/2020/7/8/how-to-find-insights-from-social-science-research-related-to-your-project.
Do you have any helpful tips and methods for analyzing a medicine to decide if it is ethical and safe?Ethical and safe feel like they will demand very different methods of analysis! For safety, you could look into Good Manufacturing Practice (GMP) and CLIA Certification (kind of throwing keywords related to pharma manufacturing at you) as well as the design of Phase I trials. For ethics, you might want to look at https://responsibility.igem.org/guidance/responsible-design and https://www.globalcodeofconduct.org/
Dr. Quincey Fish is a veterinary pathologist specializing in drug evaluation and safety, with a focus on molecular pathology for target cancer drug discovery. Currently working in the field of veterinary pharmaceuticals, Dr. Fish applies her expertise in both animal health and drug development, making her a valuable resource for us to understand its regulatory requirements.
We connected with Dr. Fish through Rayan, one of our team members. We decided to interview her because of her extensive background in drug development and regulatory standards that newly developed drugs must adhere to. Dr. Fish's knowledge of veterinary and pharmaceutical sectors provided valuable insights into animal ethics and drug safety.
In the interview, Dr. Fish emphasized that our synthetic heparin must consistently achieve 95% purity to meet regulatory approval. We were advised to check the FDA website to get a more thorough understanding of the regulations enforced in the heparin industry. She also remarked that sticking to a standard plasmid generation approach would be advantageous as it would allow us to avoid complications in getting approval for our manufacturing method. Additionally, she recommended familiarizing ourselves with the clotting cascade and understanding the historical failures in developing new heparin sources to avoid costly mistakes.
Faria: Do you have concerns over the heparin quality?
Quincy: When you manufacture something new, like synthetic heparin, you will need to meet modern FDA standards. Most drugs are fairly strictly regulated; obviously there are some big exceptions but most drugs have a requirement of having 95% purity. And if your manufacturing process can’t reliably generate a 95% pure batch, generally the FDA will not be able to give you approval. You might want to look up the ICH (International Council for Harmonisation) guidelines on drug development, which are likely to provide more detailed information about what the FDA requires for purity and manufacturing requirements. You can find a lot of useful information on the FDA’s website too.
Faria: Is there something that would be better if changed in our manufacturing process?
Quincy: I think the plasma generation approach is pretty standard. To be honest with you, I think it is a great idea. Given that you are trying to fast-track this into the clinic, I don't think I would try something too fancy just yet because it then gets a lot harder to get into the IND filing. So you can get away with just generating plasmids.
Faria: Do you have any suggestions on ethical considerations we should highlight for this project?
Quincy: Anything that is going to take the excessive use of animals off the table is going to be something that I am going to like. There are a whole host of ethical questions about animal usage in countries outside of the United States like pretty egregious ethical violations. So anything that is going to make us not support that industry that obviously exploits animals is going to be something that I would highlight about the project. From an environmental perspective, moving away from livestock production will reduce carbon emissions and methane gas. Also, removing reliance on animals, especially in a global market where diseases like avian influenza can impact pig populations, makes your solution more sustainable.
Ryan: Do you have any final suggestions on what we should focus on to improve our project?
Quincy: If I were you I would familiarize myself with the clotting cascade and the exact mechanism of how the heparin molecule interacts with antithrombin. Like what are the prices and downstream effects of that reaction? I would also educate myself on every attempt there has been made in the past to create a new heparin source and why they failed. Researching the past 20 years of drug development is pretty easy to do. You can just Google it and see who else is in the game. For me when I am investigating a new target for oncology, I familiarize myself with why that molecule target is important in the body and how it works in the cancer cells.
At Tufts University, professor Blanchette teaches a wide range of classes on environmentalism, capitalism, labor politics, value beyond work, interspecies relations, food production, political economy, ethnography, and the rural United States. His research is concerned with the politics of industrial labor and life in the post-industrial United States and he’s published an ethnography of work within some of the world's largest meat corporations, one that follows the making of the modern pig across every facet of its existence from genetics to 1,100 post-death commodities.
Do you think the public should be informed about the product they are using (GMO or porcine-derived Heparin)?
I do not see why the public should not be informed of the source of something, especially if there are safe alternatives available. I have not paid much attention to the battles over GMO labeling. Though I understand (?) there is some controversy in that labeling can nudge people to believe that there is a problem with genetically modified goods, which others refute. It seems to me that labeling animal derived goods is a different matter from the GMO debates. In that case it is not a matter of questionable disputes over health and safety (it’s not a debate over fact), but a simple matter of values. There are many people, for religious or ethical reasons, who would prefer not to consume porcine-derived goods if given a choice. If I needed heparin, I’d prefer yours.
How do you envision the political landscape changing thinking of the climate surrounding international vs domestic manufacturing of products?
I honestly do not really think of this often. I would assume the potential issue is not so much one of domestic vs international production, per se, but rather depending on a single source country with whom the U.S. may have strained relations. You would know more of this than me, but my quick search indicates that most heparin comes from China. I have no opinions on the geopolitics there. But, as a general principle, it certainly seems problematic to have the production of a medically-vital ingredient made in any one global location given the fragility of industrial animal agriculture (including the US). I am attaching a recent interesting academic paper with some mention of heparin and the particular circumstances that led to near-shortages during COVID (COVID itself plus bouts of African Swine Fever in hogs). I imagine this paper will give you some things to think about.
How can we evaluate the impact of switching to synthetic pharmaceutical options from porcine sources? Will switching really have much of an impact given the prevalence of animal product usage?
The biggest question is where is the raw material, the organs, coming from for heparin manufacture? Is it that they’re coming all out of Chinese slaughterhouses, or is it that slaughterhouses around the world are shipping their organs to China for processing? If it’s the latter, it’d obviously decrease profitability somewhat, but I’m not sure if it would have a large impact on the quantity of pigs killed. The trouble is just that there’s too many things coming from pigs for any one substance to change a market. This certainly wouldn’t be a new story – there are long histories of synthetic materials replacing ‘natural’ ones.
If all heparin is coming from China, I think it’s more complicated still because we can’t assume that this is just a matter of simplistic economics 101 whereby less demand for parts of pigs bodies might reduce supply. In the case of China we know that this is not just a matter of profits/losses. As my colleague Mindi Schneider at Brown has written about extensively, Chinese pork production is very much a state project that has also become a symbol of ‘modernization.’ Which is all just to say that I’m not sure pig production would decrease even if it was slightly less profitable, as there are many other forces and considerations driving its explosion.
Alternatively, if they are all sourced in China – what slaughterhouses are they sourcing from? Any/all packers? Or are there specialized (often smaller) facilities that specialize in the derivation of biomedically useful substances. From what I’ve seen online, anecdotally, it would appear that certain animal-derived drugs like surfactant operate in this manner. Perhaps, then, it would at least impact some marginal quantity of animals raised and killed.
I also imagine you’d have to think about global political economy. What will your product cost versus porcine-derived heparin? Is it possible that we’d get a situation where your product circulates in higher income countries, while the porcine-derived drug begins circulating more, for cheaper, in lower-income countries? So would your product actually ‘end’ animal derived heparin, or instead change its circulation. Are there heparin shortages in the broader world that might be alleviated by this split in the market? I don’t know, but that seems like one way to think about impact – for better, or worse.
The impact might have qualitative or symbolic effects that are important. Perhaps replacing animal-derived medicines with GE bacteria-derived ones will act as a step or minor catalyst towards making people comfortable with lab-based animal or meat replacements. That is all speculative, of course.