Bioethics with Biotechnology, Bioengineering, and Genetic Engineering

Biotechnology and bioengineering are advancing at an unprecedented pace. Through genetic engineering, possibilities once considered unthinkable are now within reach. While it is widely accepted—both morally and ethically—to use genetic engineering for treating diseases and addressing organ transplant shortages, its application for human enhancement remains highly controversial.

Recently, I watched a YouTube video titled "Rewriting Genomes to Eradicate Disease and Aging" featuring Dr. George Church. In the discussion, Dr. Church covered topics like synthetic genomics, germline editing, and more. When speaking about xenotransplantation, he stated:

“…to have something that’s enhanced is immunologically superior—that is less rejected, resistant to pathogens, resistant to cancerous senescence, and capable of cryopreservation. All of these things have been demonstrated in animals, and now we want to either get them into humans via cell or organ transplants.”

This statement highlights the transformative potential of genetic engineering in medicine, particularly in creating organs that are less prone to rejection and more resilient to diseases. However, it also raises important ethical questions about how far these advancements should be pursued.

I am a fan of the Harvard philosopher Michael Sandel. I thoroughly enjoyed watching his online course, "Justice: What's the Right Thing to Do?" and reading his book, "What Money Can't Buy: The Moral Limits of Markets." Sandel has also weighed in on the ethical issues surrounding genetic engineering.

In a lecture held in the Netherlands, Sandel engaged with the audience to explore these ethical dilemmas in depth. I have included the video below for those interested.

The Perfect Human Being

In the video, Michael Sandel posed several thought-provoking questions to the audience:

• Should biotechnology aim to create the "perfect" human being? And perhaps an even harder question—what would "perfection" mean?
• Should parents be able to choose the sex of their child? This is already possible through embryo screening and other methods. Imagining yourself as a parent, would you find it morally permissible or objectionable to select whether to have a boy or a girl?
• What about selecting a child’s sexual orientation? If technology existed to predetermine whether a child would be straight or gay, should parents have the freedom to make that choice?
• What about enhancing traits like intelligence, appearance, or talents? Suppose it became possible (and safe) to select for a smarter, more attractive, athletically gifted, or musically talented child. Would parents have a responsibility to use these technologies to give their children the best possible advantages?
• Should genetic engineering be used for self-enhancement? For instance, could interventions—genetic, pharmacological, or surgical—be morally justified if they were used to make oneself smarter, improve memory, or enhance cognition? Should individuals have the freedom to do whatever they want with their own brains?
• If biotechnology enabled us to live far longer—perhaps even forever—would that be desirable? How many people would want to live to 1,000 years old, for example?
• Should humanity evolve without limits? What would be the implications of such limitless evolution? Could it lead to a genetic arms race?

Sandel ended by encouraging the audience to reflect on these questions: What would the world look like if everyone could use biotechnology to become the smartest or if people no longer died?

Sandel wrote a book "The Case against Perfection: Ethics in the Age of Genetic Engineering" to explore the ethical implications of genetic engineering and other forms of human enhancement. Sandel argues that the pursuit of perfection through biotechnology undermines core human values and raises profound moral concerns.

• Ethical Limits of Enhancement

Sandel critiques the drive to enhance human traits—such as intelligence, physical abilities, or appearance—through genetic engineering. He contends that this pursuit reflects a problematic desire for mastery over life, rather than an acceptance of human imperfections.

• The Giftedness of Life

A central argument is the importance of appreciating the "giftedness" of human life. Sandel suggests that genetic enhancement erodes this appreciation, replacing humility with hubris and diminishing our capacity to accept the unbidden aspects of existence.

• Moral and Social Implications

Genetic engineering risks exacerbating social inequalities by creating a divide between the "enhanced" and the "unenhanced." Sandel also highlights how it could lead to a commodification of human traits, treating them as products to be optimized.

• Parenthood and the Drive for Perfection

The book explores how the desire for "designer babies" transforms the relationship between parents and children, shifting the focus from unconditional acceptance to a mindset of control and customization.

• The Ethical Boundary

While Sandel acknowledges the benefits of genetic engineering for therapeutic purposes (e.g., curing diseases), he argues that enhancement for non-medical reasons crosses a crucial ethical boundary.

Sandel urges society to resist the temptation to pursue perfection through biotechnology and instead embrace the inherent imperfections that define humanity. He advocates for humility and a respect for the natural limits of human life, warning that unchecked enhancement technologies could compromise the moral fabric of society.

Known knowns and Unknown Unknowns

On several occasions during scientific presentations, I have come across citations of Donald Rumsfeld's statement. Donald Rumsfeld was one of the most famous US Secretary of Defense.

"There are known knowns; there are things we know that we know. 

There are known unknowns; that is to say, there are things we now know we don't know.

But there are also unknown unknowns - there are things we do not know we don't know."

Wikipedia includes an entry on the phrase 'there are unknown unknowns,' a term popularized by Donald Rumsfeld. He famously used it in response to a question about the absence of evidence linking the Iraqi government to the supply of weapons of mass destruction to terrorist groups.

With respect to awareness and understanding, unknown unknowns can be compared to other types of problems in the following matrix:

In clinical trials, comparing an experimental therapy to a control group is often complicated by confounding factors—both known and unknown. Randomization is a key method for addressing these challenges, as it helps balance these factors across treatment groups. By randomly assigning participants to different groups, randomization ensures that potential confounders are evenly distributed, enabling a more accurate comparison of treatment effects.

For known confounding factors, stratified randomization can be employed. This approach involves dividing participants into strata based on specific factors and then randomizing them within each stratum, ensuring an equal probability of assignment to either treatment group within each category. For unknown known or unknown unknown confounding factors, the only way to minimize the impact is to utilize the randomization. 

Randomization is regarded as the cornerstone of causal inference in randomized controlled trials (RCTs). It enables researchers to attribute differences in outcomes between groups to the treatment under investigation, rather than to pre-existing differences among participants, thereby strengthening the validity of the findings.

The awareness-understanding matrix, which includes concepts like 'known unknowns' and 'unknown unknowns,' can be applied to scenarios such as xenotransplantation—for instance, the transplantation of porcine organs into humans. In the context of xenotransplantation, there is always a potential risk of zoonotic infections, where pathogens may be transmitted from animals to humans. There are known pathogens (viruses) and there are unknown pathogens. As Dr Jay Fisherman discussed the issue in his paper "Xenotransplantation-associated infectious risk: a WHO consultation":

"In xenotransplantation, there is the unique potential risk for the transmission of both known and unknown zoonotic infectious agents of animal origin into human recipients and into the wider human population."

"Xenotransplantation will necessitate the development of surveillance programs to detect known infectious agents as well as previously unknown or unexpected pathogens in the absence of recognizable clinical syndromes. This may include assays for known infectious agents, probes for classes of infectious agents (e.g., common genes or antigens of herpesviruses), and assays for unknown pathogens in a variety of tissues."

 "Unknown pathogens: Organisms not known to be human pathogens, not known to be present in the source animals, or for which clinical syndromes and microbiologic assays are poorly described or unknown"

The awareness-understanding matrix is dynamic. With advancements in science, today's unknown unknowns may eventually evolve into known unknowns or even known knowns.