Dinesh Bojja: Chimeras—Taming the Modern Medical Monster
The Chimera. Feared in Greek Mythology as a terrifying monster, an amalgamation of various animals: the head of a lion, the body of a goat, the end of a dragon, and with fire-breathing abilities to boot. Though chimeras are a myth of ancient times, scientists in the 21st century have begun to revere them again—now as a vessel for accelerating research. Other members of the scientific community, on the other hand, fear that chimeras may be harnessed wrongfully, compromising ethics for the sake of healthcare and the sciences.
Chimeras, broadly speaking, are organisms that contain cells from two distinct genotypes—not necessarily from two different species. The first reported chimeras, dating from the mid-to-late 20th century, were humans with two sets of DNA; through blood testing, individuals found that they contained cells with different DNA in various parts of their body, usually from a fraternal twin they absorbed in the womb.[1] This was revolutionary, as it marked the potential for individuals to contain DNA from two different human genotypes, and also sparked scientists’ interest: could interspecies chimeras exist?
In January 2017, two independent research groups confirmed that these interspecies creatures could be created. These labs—one from the Salk Institute in California, another led by Professor Hiromitsu Nakauchi at the University of Tokyo in Japan—grew animal cells from one species of mammal into another. Nakauchi’s group grew mouse-derived pancreases in a rat-mouse chimera and transplanted them into mice with diabetes, restoring their blood sugar regulation without excessive immune response.[2],[3] The Salk Institute group, however, took it a step further, implanting human stem cells into a pig blastocyst (a group of precursory developmental cells that later form embryos) and transferring the hybrid blastocyst to an adult sow; after some time, the stem cells grew into their own human cell lines in the developed pig embryos.[4]
In 2019, the Salk Institute expanded their research, culturing an embryo composed of both human and monkey cells for 20 days. The 20-day timeframe is crucial, as it allows scientists to observe the developmental stages of chimeras—including replication and differentiation into important tissues and organs at the embryonic stage.[5]
With the growing potential to create viable human-animal chimeras, the scientific world has become more divided on the ethics of such research. On one hand, the potential to grow organs and conduct life-saving research on “humanoid” chimeras could revolutionize the healthcare industry; however, this miracle raises inherent moral questions about testing on part-human beings and brings a risk that chimeras may be mistreated.
A World of Infinite Test Subjects and Donors…
From January to September 2022, an astounding 30,000 Americans received an organ transplant; regardless, over 100,000 people remain on the waitlist for a life-saving transplant. Most organ donors do not die in a way such that their organs can be safely used for a transplant, perpetuating the problem; PennMedicine found that although 170 million people are registered to be organ donors, only 3 in 1,000 people can have their organs used after their passing.[6],[7] It is seemingly impossible to satisfy the ever-growing need for organ transplants in the United States through conventional means.
Pig chimeras, however, may provide a solution. By adding human cells to a developing animal embryo, one could feasibly grow human organs within the animal and harvest them for transplantation. The most natural animal to choose for this transplant is pigs; since they have organs similar in size to those of humans and a fast development rate (four months compared to the regular nine of a human), pig chimeras can be grown quick enough to match the transplant demand.[8]
The techniques required to do such inter-species transplantations have been rapidly advancing as well. In 2022, scientists began testing the transplant of pig kidneys and hearts into the bodies of humans pronounced brain dead. This meant that though the patient was irreversibly dead due to insufficient brain function, some functions of the body were still active, allowing for the efficacy of transplantation to be monitored. Some transplants were successful—one person was even able to survive for two months with a pig heart, more than any human has survived with animal organs in the past.[9]
The implications of using chimeras for organ transplantation are revolutionary. People would no longer have to sit on the waitlist for a transplant for years, unsure of whether they will ever receive a necessary organ; instead, they can order a personalized organ to be harvested from a chimera that matches their blood-type and immune system, decreasing the risk of organ rejection. Millions of people across the world could have their lifespans extended with the use of such “farmable organs.”
Additionally, there is exciting potential for streamlined drug testing on chimeras, allowing for prospective life-saving drugs to be tested without putting anyone at risk. In 2013, it was discovered that human-mouse chimeras could have a “humanized liver” grown in them, and the efficacy of drugs could be tested on the organ. If implemented on a large scale, this would have allowed scientists to measure the effects of the drug on a human liver without risking any human lives.[10]
Such chimeras could replace the need for drawn-out human clinical trials to receive FDA approval; in the status quo, it can take over ten years to approve a single drug, which can jeopardize the lives of those who could have used the potentially life-saving treatment earlier. In a chimera model, by testing if a drug can target the right organs or the right cell types in a humanized organ, it becomes far easier to measure the localized effects of a drug and allows for more efficient drug market entry.[11]
…And a World of Factory Farming and Abuse
Opponents of chimera-based research argue that chimeras could be exposed to —all of which should never be morally permissible, not only to protect the welfare of all animals and hybrids but also because these chimeras are part-human, which complicates the debate.
One school of thought is that the development of human-animal chimeras would lead to the development of “factory farms” for organs, with chimeras being bred and grown only to be slaughtered later in their lifetimes to harvest the human organs that were injected and grown inside their bodies without their consent. If chimeras have human-level cognition, they may be able to autonomously make their own decisions, making harvest organs from them akin to harvesting organs from a healthy human being.[12] Considering factory farms for animals as food is already something controversial in modern society for its ethical implications, it may be hard to establish similar institutions for creatures that are now half-human.
Beyond the issues of consent, it may be physically detrimental to chimeras to harvest organs from them. While it can be possible to make space for these human organs inside the bodies of pigs, it would lead to decreased development for the other organs of the hybrid, as there is less space in the chimera’s body for the development of its own organs. Thus, even though the chimeras may survive after human organ removal, it would have severe developmental defects.
Furthermore, there is no guarantee the animals will be fairly treated after the organs are harvested. What is to become of the pig chimera after the organs are removed? After growing hundreds of thousands of chimeras for the sole purpose of harvesting human organs from them, there is no sustainable way to keep all of the pigs alive. It is impractical to keep the pig chimeras in enclosures, as it wastes excessive resources and space, while leading to more clutter and health risks for the chimeras. Releasing them into the wild would put them at a natural disadvantage against predators and other wildlife, as they have lost an organ and are not accustomed to a non-domesticized lifestyle. Using the chimeras for food would be even more harrowing, as any human consumers would be eating pig meat with human DNA in it—something that would violate all sorts of natural laws.
The biggest consideration in all of this, however, is whether the chimeras would be conscious in the same way as a normal human. While many recognize animals as having their own moral status, it is almost universal to put the moral status of human life and consciousness over that of an animal. However, once human DNA is injected into the chimera, there is potential for the chimera to generate some level of human-like consciousness, self-awareness, and perception; indeed, adding enough human immune progenitor cells to a chimeral mouse was able to increase its intelligence, memory, and conditioning ability significantly, suggesting that it was able to affect the core neural pathways and potentially increase the conscious awareness of the mouse.[13]
If an animal can perceive the world in a manner nearing that of a normal human, then it seems much more morally unjust to test on and harvest organs from them. Obviously, doing this to a human being is grossly impermissible, but the lines of right and wrong start to blur much more when it comes to non-human, yet slightly human, chimeras. At which point is it morally wrong to use chimeras for our needs? How can that threshold be established or measured? The further down these questions go, the more morally concerning the situation becomes.
Current Restrictions on Chimera Research
Considering the arguments for and against chimera research, science agencies across the globe have each created their own regulations. The first of these restrictions came in December 2006 by the United Kingdom, which banned the creation of all chimera embryos, even for research purposes. Scientists in the UK fought back vehemently, arguing that precious experimental potential and time to innovate in developmental biology was lost because of the ban.[14] In 2008, however, the law was amended to allow for the insertion of human cells into predominantly animal embryos strictly for research purposes.[15] Japan similarly lifted their ban on human-animal chimera embryo creation in March 2019, allowing for scientists to transition from using animal-animal chimeras to human-animal embryo hybrids.[16]
Many scientists on both sides of the debate strongly believe that governing bodies should not have a hand in regulating chimera research, instead pushing for regulation by purely scientific administrations. Dr. Stephen Minger, former director of the Stem Cell Biology Laboratory at the King’s College in London, argued that “…it's not very practical for parliamentarians to regulate science… The science moves too quickly.”[17] Countless research groups argue that lawmakers and politicians do not have the expertise to understand the needs of the scientific industry and that having to adhere to the whims of the national legislature will only decelerate true scientific growth.
The United States, however, has taken a different approach to restricting chimera research. Rather than outright banning human-animal hybrid embryos to be made, the National Institute of Health opted in 2015 to withhold all federal funding for chimera research. In 2016, they considered lifting their moratorium to allow federal funding. Although this never materialized, scientists working on chimera research in the United States can still conduct their experiments, albeit through purely private funding.[18]
Chimeras: Saving Grace or Unnatural Abomination?
Chimeras are undoubtedly some of the most disputed issues in the modern medical industry, with their potential applications and downsides equally pressing. On one hand, millions of lives could be improved or even saved through chimera research, organ growth, and drug testing. However, do those benefits outweigh the ethical implications of farming organs or testing on a semi-conscious creature?
Using the Five Pillars of Bioethics can help provide a framework to evaluate the benefits and the harms of chimera research. However, the relative importance of the framework is up to interpretation, and these metrics only act as a guiding point for analysis:
Autonomy, or free will: Chimeras, by design, do not have the autonomy to consent for research or to have their organs harvested, assuming they do have the consciousness and awareness to make informed decisions.
Beneficence, or benefit to others: Using chimera research could save the lives of millions of humans across the world by providing organs or hastening the research for life-saving drugs or innovative techniques.
Nonmaleficence, or preventing harm: Testing on chimeras or harvesting organs from them inherently harms them, which means that the chimeras are intentionally put in harm’s way.
Utility, or quantitative cost-benefit: The sacrifice of some chimeras for research or organ donations could save countless more lives down the line, which would have benefits that outweigh the costs of chimera research. However, it would cost many lives of chimeras to make such research happen, so researchers need to weigh the importance of a human life to a chimera life.
Justice, or fairness: This can be disputed, as one could consider it fair to harvest organs from a chimera specifically created to donate organs, while others may consider it impermissible as it has a right to its own life.
Evidently, the arguments are very split, and the moral permissibility of human-animal chimeras needs to be carefully analyzed. A joint effort, from leaders in biology and philosophy, would provide the necessary input to make an informed decision to restrict certain practices with chimeras while allowing their potential benefits to manifest. Chimeras may have been feared as monsters in the past, but now we cannot allow ourselves to become the true monsters after harnessing them.
Dinesh Bojja is a first year at Yale University in Morse College
Citations
[1]https://www.sciencedirect.com/science/article/pii/S1769721220302895
[2]https://www.nature.com/articles/nature21070
[3]https://bioethics.hms.harvard.edu/journal/chimera-transplantation
[4]http://www.cell.com/cell/fulltext/S0092-8674(16)31752-4
[5]https://time.com/5954818/first-human-monkey-chimera-embryo/
[6]https://unos.org/data/
[7]https://www.pennmedicine.org/updates/blogs/transplant-update/2022/march/6-quick-facts-about-organ-donation
[8]https://www.bbc.com/news/health-38717930
[9]https://www.aamc.org/news-insights/how-pig-organs-made-their-way-humans-slow-advance-transplant-kidneys-and-hearts
[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558826/
[11]https://www.nationwidechildrens.org/family-resources-education/700childrens/2018/03/what-does-it-take-to-get-a-drug-approved-through-the-fda
[12]https://academic.oup.com/jlb/article/6/1/37/5489867
[13]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700554/
[14]https://www.nature.com/news/2007/070903/full/070903-12.html
[15]https://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0345-9/tables/1
[16]https://www.nature.com/articles/d41586-019-02275-3
[17]https://www.nature.com/articles/nm0807-890b
[18]https://www.cell.com/stem-cell-reports/pdf/S2213-6711(20)30374-X.pdf
