The Chimaeras of Nature and Their Promise to Grow Human Organs

Relevance: GS3, Chimaeras, Chimerism, Biotechnology, Biodiversity, Indigenization of Technology & Developing New Technology, Induced pluripotent stem cells (iPSCs) technology, Organ Transplant, Stem Cell Technology

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Why in the news?

• The article discusses the growing field of using chimeras—organisms with genetic material from more than one source—for medical purposes, particularly organ transplants.
• It emphasizes the severe shortage of organ donors worldwide, highlighting the potential of chimeras to address this issue.

Contextual Background

• There is a pressing issue of organ transplantation with severe disparity between the number of organ donors and recipients, particularly in India and globally.
• There have been instances where animals have historically bridged this gap, with examples like animal insulin and heart valves used in human surgeries.
• One of the significant advancements is induced pluripotent stem cells (iPSCs) technology, which has enabled attempts to grow human organs within animal bodies.
• This has led to the creation of chimeric animals, organisms composed of cells with different genotypes. While such research has shown promise, it also raises ethical and scientific controversies.
• Recently, in a groundbreaking study, scientists have successfully generated a live chimeric monkey using embryonic stem cells from macaques, marking a significant step towards using nonhuman primates to create models for biomedical applications.
• However, this also raises ethical concerns and limitations that need to be addressed.

What are Chimaeras?

• Chimaeras refer to organisms that have two or more different populations of genetically distinct cells originating from different zygotes.
• These cells can merge to form a single organism with different genetic makeups.
• Chimaeras are distinct from hybrids, which are the result of the mating of two different species and have a mix of genetic material from both parents evenly throughout their cells.
• In contrast, chimaeras have distinct cell populations with different genetic makeups coexisting within the same organism.

Different Types of Chimerism

1) Natural Chimaeras

• Random Genetic Changes: The genetic material in a cell can change, leading to a clonal population of cells different from the rest.
• Fusion of Fertilised Zygotes: Early in the embryonic stage, two fertilised zygotes can merge, resulting in a single individual with two genetic makeups.
• Twin or Multiple Pregnancies: Chimerism can occur from the fusion of twin or multiple pregnancies into a single fetus or from one twin fetus being absorbed by the other.
• Blood-Group Chimerism: This is relatively common in multiple births and is often detected during routine blood tests or organ transplant tests.
• Microchimerism: Traces of a fetus’s genetic material can remain in the mother’s tissues years after childbirth, resulting in two genetic materials in one person.
• Bone Marrow Transplants: Recipients of bone marrow transplants can have a different genetic makeup in their blood cells compared to their other tissues, leading to chimerism.
• Solid Organ Transplants: These also produce individuals with two unique genetic makeups due to the different genetic makeup of the donor’s organs.

2) Chimaeras in Laboratory Settings

• Animal Chimaeras: Experiments have created chimaeras in rats, mice, pigs, and cows to explore the possibility of growing human organs for transplant. However, these animals are evolutionarily distant from humans, posing challenges.

• Non-Human Primate Chimaeras: In a significant study, scientists successfully created a live chimaera in nonhuman primates, which are closer to humans evolutionarily. This was achieved by injecting modified embryonic stem cells into recipient embryos.

Chimaeras in Non-Human Primates – A Landmark Study Involving Cynomolgus Monkeys (Longtailed Macaques)

Before this study, chimeras had been induced in laboratory settings with combinations like rat-mouse, human-pig, and human-cow. These efforts were aimed at developing model systems for growing human organs suitable for transplant. However, these species are evolutionarily distant from humans, posing significant biological and technical challenges.

The Study with Non-Human Primates

• Objective: The research aimed to create chimeras using species closely related to humans, to potentially develop models for growing human organs.
• Method: Scientists extracted embryonic stem cells from one-week-old Cynomolgus monkey embryos. These cells were modified to include a green fluorescent protein (GFP), allowing them to be tracked.
• Procedure: The GFP-marked embryonic stem cells were injected into recipient monkey embryos. These embryos were then implanted into surrogate female monkeys.
• Outcome: The process resulted in six full-term offspring. The presence of GFP in the tissues indicated successful chimerism. However, the chimeric monkey had to be euthanized after ten days due to health reasons.
• Findings: Genome sequencing of the chimeric monkey revealed a high degree of chimerism in various tissues, including eyes, brain, heart, kidney, liver, and gonads.
• Significance: The success of this study marks a significant step forward in using non-human primates to create chimeras, potentially opening new doors for biomedical applications.
• Ethical Considerations: The research, however, is not without ethical considerations and limitations that need to be addressed, particularly regarding the implications of creating chimeric organisms and the potential for human biomedical applications.

Significance of Chimaeras

• Addressing Organ Transplant Shortages: The global shortage of organ donors versus the high demand for organ transplants is a critical issue.
• Chimeras, particularly those created through the integration of human cells into animal hosts, offer a potential solution.
• By using animals as hosts to grow human-compatible organs, this approach could significantly alleviate the shortage.
• Advancements in Stem Cell Technology: The use of induced pluripotent stem cells (iPSCs) technology has been instrumental in these advancements. By injecting human iPSCs into animal embryos, researchers have been experimenting with growing human organs inside animals.
• Natural Chimerism: In humans, chimerism can occur due to various reasons, including the fusion of two fertilized zygotes or during multiple pregnancies. This natural phenomenon has been crucial in understanding and developing artificial chimeric models.
• Medical and Scientific Implications: The presence of chimerism in humans, whether naturally occurring or due to medical interventions like bone marrow transplants, reveals the complexities and possibilities of having more than one distinct genotype within a single organism. This understanding is pivotal for various medical applications, including organ transplants and treatment of genetic disorders.
• Recent Breakthroughs in Non-Human Primates: A recent landmark study involving the creation of a live chimeric monkey, is significant as monkeys are evolutionarily closer to humans compared to other animals like pigs or cows.
• This advancement opens new possibilities for creating more accurate and ethically acceptable models for human organ growth and biomedical research.

Ethical Concerns Regarding Chimaeras

• Human-Animal Boundary Crossing: The creation of chimeras, especially those involving human cells in animal embryos, challenges the conventional boundaries between species. This blurs the lines of what constitutes a human or an animal, raising philosophical and ethical questions about the nature of these beings.
• Animal Welfare: The use of animals in creating chimeras for medical research or organ transplantation raises concerns about the welfare of these animals.
• Consent and Identity Issues: In cases where human cells are used, questions arise about consent (especially if the cells are derived from embryos) and the identity of the resulting chimeric organism. This is particularly relevant if the chimera exhibits human-like characteristics or intelligence.
• Unintended Consequences: There could be unintended consequences of introducing such organisms into the environment or the impact they might have on natural ecosystems.
• Ethical Use of Technology: There is a need to balance the potential medical benefits (like organ transplantation) against the ethical implications and the respect for the integrity of living beings.
• Regulatory and Legal Challenges: Current laws may not adequately cover the unique situations created by chimeras, leading to a legal grey area regarding their status, rights, and treatment.
• Societal and Cultural Implications: The concept of chimeras may be at odds with certain cultural, religious, or personal beliefs, leading to societal resistance or ethical dilemmas for individuals and communities.

Conclusion

The study represents a major advancement in chimeric research, bridging the gap between animals and humans in organ transplant technology. Despite the potential, ethical questions and limitations remain, necessitating careful consideration before applying these findings to human biomedical applications.

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FAQs

MCQs

Q.) In the context of the developments in Bioinformatics, the term ‘transcriptome’, sometimes seen in the news, refers to (UPSC 2016)

(a) a range of enzymes used in genome editing

(b) the full range of mRNA molecules expressed by an organism

(c) the description of the mechanism of gene expression

(d) a mechanism of genetic mutation taking place in cells

Q.) What is the application of Somatic Cell Nuclear Transfer Technology? (UPSC 2017)

(a) Production of bio-larvicides

(b) Manufacture of biodegradable plastics

(c) Reproductive cloning of animals

(d) Production of organisms free of diseases

Q.) Which of the following is a natural example of a chimera?

1. a) Liger
2. b) Mule
3. c) Halfsider budgerigar
4. d) Lab mouse