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Chimeras in Medicine and Organ Transplants


Why is it in the news?

  • Organ transplantation is a critical medical procedure with a significant shortage of organ donors worldwide. In India alone, over 3 lakh people are waiting for organ transplants, and this issue is even more pronounced globally.
  • Animals have been instrumental in addressing this gap. For example, animal insulin and animal heart valves have been successfully used in human surgeries, saving lives. These medical interventions have demonstrated the potential of leveraging animals to overcome organ scarcity.
  • Researchers have been exploring cutting-edge technologies like induced pluripotent stem cells (iPSCs) to grow full human organs inside the bodies of animals. The goal is to develop a renewable source of organs for transplantation.
路聽聽聽聽聽聽 Chimeras are organisms that are made up of the cells of two distinct species, for instance, humans and monkeys. If this hybrid embryo was placed in the womb of a monkey, it could possibly grow into a new kind of an animal.

路聽聽聽聽聽聽 induced pluripotent stem cells (iPSCs) are created by reprogramming skin or blood cells, returning them to a pluripotent state similar to embryonic cells. This transformation allows for the generation of a virtually unlimited supply of various human cell types for therapeutic applications.

 

Natural Chimeras in Nature

  • Chimeras exist in nature, and they refer to organisms composed of cells with distinct genotypes (genetic makeups). These can be found in various forms across the animal kingdom.
  • Examples include the half-sider budgerigar, a type of common parakeet that displays different colours on either side of its body due to chimerism. The anglerfish exhibits extreme symbiotic chimerism, where the male fish fuses with and is absorbed into the female fish, resulting in a single animal with mixed genetic material. Marine sponges may have up to four distinct genotypes in a single organism.
  • Humans can also experience natural chimerism. This occurs when genetic material in one cell changes, giving rise to a clonal population of cells with a different genetic makeup from the rest of the cells in the body. Chimerism can also result from the fusion of two fertilized zygotes early in the embryonic stage or from the absorption of a twin foetus into a singleton.
  • Blood-group chimerism during multiple births is relatively common, and pregnant women can harbour the genetic material of their foetuses in their bloodstream during pregnancy. Such foetal DNA can be used for genetic screening.
  • Micro-chimerism is another phenomenon where traces of a foetus’s genetic material are found in a mother’s tissues many years after childbirth, resulting in two different genetic materials within a single individual.
  • Medical procedures like bone marrow transplants and solid organ transplants can result in chimerism. In these cases, the transplanted cells have a different genetic makeup from the recipient’s other tissues, leading to chimeric individuals.

 

Chimeras in Medical Research

  • In the realm of medical research, scientists have conducted experiments to induce chimeras in laboratory settings. These experiments have involved creating chimeras between different species, such as rat-mouse, human-pig, and human-cow chimeras. The goal was to develop model systems that could potentially generate human organs of suitable size, anatomy, and physiology for transplantation.
  • However, these experiments have faced limitations, particularly when using species that are evolutionarily distant from humans, such as rats, mice, pigs, and cows. These differences pose biological and technical challenges when attempting to grow human organs within these animals.

Recent Breakthrough with Non-Human Primates

  • A recent milestone in this field was the successful generation of a live chimeric monkey, a non-human primate species that is evolutionarily close to humans. Researchers extracted embryonic stem cells from one-week-old embryos, modified the DNA, and injected these cells into recipient embryos. These embryos were then implanted into surrogate female monkeys, resulting in six full-term offspring.
  • Genome-sequencing investigations of the chimeric monkey revealed a high degree of chimerism in various tissues, including the eyes, fingernails, brain, heart, kidney, liver, gonads, and placenta.

 

(In a recent landmark study, scientists have reported successfully producing a live infant chimeric monkey of the species Macaca fascicularis)

Ethical Considerations:

  • While this research holds promise for biomedical applications, it also raises important ethical and practical questions. The creation of chimeras involving humans and non-human primates has sparked ethical debates about the boundaries of research and the potential consequences.
  • Ethical considerations include concerns about animal welfare, the moral implications of creating creatures with mixed genetic material, and the necessity of robust oversight and regulation in this field.
  • Addressing these ethical and practical challenges will be crucial before considering the use of chimeras in human biomedical applications, including organ transplantation. Researchers and policymakers will need to balance the potential benefits with ethical responsibilities and societal concerns.

Conclusion

  • Genetic modification, including chimera studies, remains a highly debated topic, with ethical concerns at the forefront.
  • India has prohibited the production of hybrid animals since 1985, reflecting the cautious stance on genetic manipulation.
  • Genetically modified crops are contentious in developing countries like India, adding to the complexity of the genetic modification debate.
  • Human genetic modification is even more controversial, given its potential long-term impact on future generations.
  • To navigate these ethical challenges, governments should establish comprehensive policies that prioritize animal welfare, human dignity, and societal values before approving such research endeavours.

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