Bioprinting Ethics and Regulation — Part I, The Good

(“This was originally posted on 3dheals.com”) Jenny Chen, M.D.

Pushing the technological boundaries has been the focus and motivation behind increasing interests in bioprinting and regenerative medicine from both the public and private domains. [1] Behind the scene, there are fierce competitions, drawing resources, talents, and media attention. However, “bioethics” is often dismissed as good dinner topics that are not worth considering when building serious projects and companies.

I think not.

This discussion is especially in light of the ongoing coronavirus pandemic, global warming, and increasing class and racial divides.

I have done my limited research in this area. While the subject is involved, it is worth diving deep into as its evolution will impact both the future of companies and humanity, two inseparable entities.

Assumption

One primary assumption making discussions around bioprinting ethics relevant is that bioprinting (or broader concept of regenerative medicine) will work and will work soon (next five years). While it is hard to precisely predict when and what the first bioprinting product shows both technical and market success, the increasing research activities and investment inflow are good indicators that accelerated advancements in the field are in progress. [1]

Why should Bioethics be seriously discussed?

From a practical perspective, bioethical issues will directly impact the functions and policies of existing regulatory bodies and future policies. The Healthcare industry is highly regulated, resulting from intrinsic complexity of life, high potential for abuses, and grave consequences if not managed carefully. The possibility to fabricate living tissues for research and therapeutic endpoints, including tissue repair, replacement, and augmentation, brings up many new ethical questions and challenges with no clear established regulatory pathways.

Of course, even if there are existing regulatory processes, bad things will still happen. A few people will always break the law and regulations using emerging technologies. Some salient recent examples include 3D Printing firearms [3] and gene editing unborn children without proper consent [2]. Therefore, another good reason to discuss bioethics is to answer the question:

How can we pick the right problems to solve to avoid future abuses of new technologies that could lead to humanity’s downfall?

With these in mind, in this three-part series, I will discuss:

1. The Good: Ethical benefits of bioprinting
2. The Bad: Ethical challenges of bioprinting
3. The Unknown: Evolving regulatory landscape and policies relevant to bioprinting

I also don’t believe these blogs will cover all aspects of the discussion and welcome others to engage in online or offline conversations.

Part I The Good: Ethical Benefits of Bioprinting

When it comes to discussing the ethical problems related to emerging technology, one must not omit the fact that, without the technology, humanity continues to face a set of dilemmas and hard choices in life. The benefits of new technology like bio-printing not only solve healthcare problems but also solve ethical issues that the healthcare community fails to address with existing medical options. Although there is nothing wrong with being a critique, it is worthwhile first to understand the potential ethical benefits of new technology.

A. Solving transplant shortage crisis

Perhaps the most attractive future for bio-printing is solving the current transplant shortage crisis [4]. According to the American Transplant Foundation [5], “around 114,000 people in the United States are currently on the waiting list for a lifesaving organ transplant.” When living donor transplantation cannot occur, the first apparent dilemma is that for one person to receive a transplant, another person must die first. Although most of these organs benefit from salvaging deceased patients who died of natural causes, illegal human organ trades and abuses are thorny issues that are quite livid in the transplant industry worldwide. [6] These include issues arising from unlawful organ harvesting and businesses to unfair distribution of available organs. For example, in the recent Netflix series “House of Cards,” the president was able to (illegally) jump the line to receive a liver transplant.

Ironically, the deficit worsens as the transplant technology improves, allowing a more extensive range of organs to be transplanted and hence more organs needed [6].

B. Cost reduction for an organ transplant

The cost of an existing organ transplant option is expensive. One can consider the total price include pre-transplant care (after officially listed as a potential recipient), organ harvesting procedure, organ transplantation, post-transplant recovery, and long-term immunotherapy and follow-up care. The availability of bio-printed organs from the patient’s own stem cells allows for an autologous organ transplant. Autologous transplantation will reduce the cost of pre-transplant care (i.e. dialysis, etc.) because the patient will no longer be required to be on a long list waiting for a donor organ. Autologous transplantation will also obviate the steps for organ harvesting and post-transplant immunotherapy, which itself carries a significant risk for complication and related costs.

C. Reducing animal testing and animal products in medicine

Photo Credit: Allevi3D

Bio-printing allows for the creation of disease models using human cells (e.g., induced pluripotent stem cells), potentially reducing or even eliminating animal testing. It is predicted that, as the technology progresses, large scale human-specific organ systems can be developed in the laboratory for industrial level research and development, ranging from pharmaceutics discovery and testing to manufacturing personalized medical treatment for individual patients. [6] This is especially favorable in light of the momentum behind new laws against animal testing. For example, in 2013, E.U. banned all cosmetics with animal testing ingredients, one step further its 2004 ban on all animal testing of finished cosmetics [7].

From a manufacturing perspective, many animal products currently used in medicine can be replaced with bio-printing technology. [8] Bio-printing can be a new way of manufacturing ingredients for medications using functioning autologous human cells instead of animal products.

Animal testing and animal products have been perceived as a necessary evil for years in medicine, but with the availability of bio-printing, this dilemma may soon come to an end.

D. Avoiding xenotransplantation

Photo Credit: Prellis Biologic

Xenotransplantation, also known as “cross-species transplantation,” is another experimental but promising technology aiming to solve the human organ and tissue shortage crisis [6,10,12]. This is a procedure that involves, “the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs” [10]. With progress made in genetic engineering and genome editing, including CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), this technology has made significant progress in the last decade [9, 12] However, xenotransplantation remains experimental. One major technical concern is the worry of cross-species infection with known and unknown viruses (e.g. PERV), which poses an uncertain but potentially grave risk to humans [9,10]. In light of the current coronavirus pandemic, this fear is well and alive.

Aside from the technical challenges, xenotransplantation involves animal testing and sacrifice. It also has a high “yuck factor”, also known as the “wisdom of repugnance” [6,11]. The “yuck factor” is the belief that an emotional intuitively negative response to an idea, a thing, or a practice (without rationalization) should be considered as “evidence” of the existence of intrinsically harmful or evil. Xenotransplantation is often used as an example of such a concept with high “yuck factor”. The idea of “wisdom repugnance” itself is not without criticism, but if bioprinting can become a successful technology as an alternative donor organ source, xenotransplantation will not be necessary [6]

E. Solving the “youth” problem

Photo Credit: Volumetric Bio

Organs for young adults and children have always been difficult to procure for all the reasons stated above and have to come from a young donor. Some applications of 3D printing may in the future be primarily directed at a young age cohort given young people’s suitability to receive a bioprinted replacement organ as their bodies can grow around with the organs [6] Equally, more youthful individuals who suffer from heart valve disease can have issues relating to using bioprosthetic heart tissue valves. Such valves from porcine sources only last as long as the pig donor would have done; approximately 10–15 years, and therefore, the tendency is to use them with older patients. MHVs last longer but with the side effects of a lifetime on anticoagulants for younger recipients. The ‘appeal’ then of 3D bioprinting, or of ‘here is one made earlier,’ is a much more attractive option than a lifetime on medication.

References:

1. 3D Bioprinting Industry Worth $1.95 Billion by 2025 — Increasing Investments in Healthcare Applications, such as Model and Organ Prototyping & Production
2. Chinese scientist who produced genetically altered babies sentenced to 3 years in jail
3. A Loaded Issue 3D Printed Guns — The Current Situation
4. Richard Adhikari Bioprinting, Part 2 — The Ethical Conundrum https://www.technewsworld.com/story/80205.html
5. American Transplant Foundation [5] https://www.americantransplantfoundation.org/about-transplant/facts-and-myths/
6. Vermeulen N, Haddow G, Seymour T, et al. 3D bioprint me: a socioethical view of bioprinting human organs and tissues Journal of Medical Ethics 2017;43:618–624. http://jme.bmj.com/content/43/9/618
7. E.U. Bans Cosmetics With Animal-Tested Ingredients
8. Medicines or pharmaceuticals of animal origin — Queensland Health https://www.health.qld.gov.au/__data/assets/pdf_file/0024/147507/qh-gdl-954.pdf
9. Kelly Servick, CRISPR slices virus genes out of pigs, but will it make organ transplants to humans safer? http://www.sciencemag.org/news/2017/08/crispr-slices-virus-genes-out-pigs-will-it-make-organ-transplants-humans-safer Aug. 10, 2017
10. FDA: Xenotransplantation (2019) https://www.fda.gov/BiologicsBloodVaccines/Xenotransplantation
11. Wisdom of repugnance https://en.wikipedia.org/wiki/Wisdom_of_repugnance
12. Aseda Tena. Xenotransplantation: Can pigs save human lives? http://sitn.hms.harvard.edu/flash/2015/xenotransplantation-can-pigs-save-human-lives/

Relevant Contents:

1. Relevant Recordings from 3DHEALS2020 including Legal and Regulatory Landscape for Healthcare 3D Printing, Bioprinting for Organogenesis, and Biofabrication Ecosystem. Recordings are on sale until September 2020.
2. The Yellow Brick Road of 3D Bioprinting (Part 2): Soft Is Hard
3. BIOPRINTING — An Introduction
4. 3D Bioprinting in Space?