Genetics and stem cells

Glowing monkeys 'milestone'

“The world's first ‘glow in the dark’ monkeys could help in cure for diseases such as Parkinson's,” The Daily Telegraph has reported.

The news comes from Japanese research into genetically modifying marmosets, a type of monkey that breeds rapidly. Monkey embryos were injected with a jellyfish gene that makes animals glow green under ultra-violet light, allowing scientists to tell easily whether the foreign gene successfully combined with the monkey DNA. A number of these embryos grew into monkeys that glowed under UV light, and these, in turn, were bred with regular monkeys. These offspring also carried the fluorescent gene. Theoretically, scientists could create and breed monkeys with genes for incurable human illnesses such as Parkinson’s disease. These monkeys could then be used in experiments as animal models of human disease.

This research is an early step towards monkey models of human disease. While this is an exciting prospect, it is also controversial, and will need public and scientific debate. At present, there are ethical, legal and regulatory guidelines regarding use of animals in research, and review of these will doubtlessly be needed as this technology advances.

Where did the story come from?

This research was conducted by Dr Erika Sasaki and colleagues from the Central Institute for Experimental Animals, Kawasaki, in Japan. The study was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology along with other organisations in Japan. The study was published in the peer-reviewed scientific journal Nature.

What kind of scientific study was this?

This was a laboratory study looking at whether it was possible to genetically engineer marmoset monkeys to carry a DNA from a foreign species, and then use these marmosets to breed healthy offspring that also carried this DNA. If they proved this was possible, this technique might one day be used to introduce a gene for human disease into marmoset DNA and then breed a number of marmosets with the gene for use in medical research.

The creation of these genetically modified animals is useful in medical research as animal models of human diseases can be created, and new drugs and treatments can be tested in these models. Creating models using genetically modified mice is currently the preferred technique in many areas of medical research. However, the authors of this study say that, in many cases, the research results obtained in mice models cannot be directly applied to humans because of the many differences between mice and humans. Primates more closely resemble humans in function and anatomy and are, therefore, more likely to provide relevant research results as experimental animals.

Animals engineered in the laboratory to carry genetic material (DNA) from another species are known as transgenic. The researchers explain that, although several attempts have been made to produce non-human transgenic primates, it has not been conclusively shown that these transplanted genes are expressed in live infant primates.

In this study, the researchers introduced a jellyfish gene coding for a green fluorescent protein (GFP) into the DNA of marmoset monkey embryos. They did this by injecting a virus that then carried the genetic material into the cell. The GFP gene was used because under UV light the protein it produces in the body glows an intense fluorescent green. Simply by exposing transgenic monkeys to UV light the researchers could verify that the transgene was present in the monkeys, meaning that the experiment had worked.

The fertilised embryos with the introduced gene were grown in the laboratory for a few days, and the researchers only selected those fertilised embryos which expressed GFP, that is, they glowed under UV light. These selected embryos were implanted into the wombs of fifty surrogate mothers. After birth they checked whether the monkeys were expressing the transgene by shining UV light at their skin, for example on the soles of the feet, to see if they glowed green.

On reaching maturity, the sperm and eggs of the transgenic animals were examined. The researchers then fertilised ordinary eggs, in vitro , with this transgenic sperm, and allowed the female transgenic monkey to mate naturally with a normal monkey. They then checked whether the embryos generated expressed the GFP gene. A sample of embryos that did express GFP was implanted into a surrogate mother, and the offspring were also checked for the GFP gene after birth.

What were the results of the study?

The researchers found that, of the monkeys implanted with transgenic embryos, seven became pregnant. Three monkeys miscarried and four gave birth to five transgenic offspring whose skin glowed green in UV light.

Two of these transgenic monkeys (one male and one female) reached sexual maturity during the study. The male monkey’s sperm was successfully used to fertilise normal eggs, and the female marmoset was impregnated naturally. Both of these matings produced embryos carrying the GFP gene. Some of these embryos were implanted into a surrogate mother, who delivered a baby that carried the GFP gene in its skin.

What interpretations did the researchers draw from these results?

The researchers say that they successfully fertilised ordinary eggs with the transgenic sperm and that the resulting healthy offspring also expressed the green, fluorescent protein. This shows that the foreign gene was expressed in both the somatic cells (body cells) and germline (reproductive) cells of these transgenic marmosets.

The researchers say that, to their knowledge, their report was both the first successfully to introduce a gene to primates and to have this gene successfully inherited by their next generation of offspring. This expression occurred not only in somatic tissues, but they also confirmed germline transmission of the transgene with normal embryo development.

What does the NHS Knowledge Service make of this study?

This work represents an exciting development in medical research, which could greatly expand the applications of using animal models to fight human disease. The teams behind this research have also achieved two important goals, both fully integrating a foreign gene into the DNA of monkeys and then successfully breeding these monkeys to produce healthy offspring that also carried this foreign gene.

This shows there is the potential to engineer and breed a number of marmosets that carry a defective gene that causes human diseases such as muscular dystrophy or Parkinson’s disease. This would allow medical research to be performed using an animal model that is genetically and physically closer to human beings than the genetically modified mice that are currently used in much medical research.

Ultimately, this work might accelerate the translation of discoveries from animal research to patients who have few treatment options. However, it should be noted that the marmosets produced in this research were not intended to be models for a human disease, and that this is only the first step towards such a goal.

While there are a number of potential benefits, there are some issues, both technical and ethical, that should be considered regarding this matter:

  • Marmosets have limitations as research models. They are what is known as “new world primates”, and are less closely related to humans than are “old world primates”, such as rhesus macaques and baboons. Because of biological differences, diseases such as HIV/AIDS, macular degeneration and tuberculosis can be studied only in these old world primates.
  • There are bioethical concerns. One of these is the prospect of applying transgenic technologies to human sperm, eggs and embryos for reproductive purposes. The Nature editorial claims any use of the technology in humans would be unwarranted and unwise, as transgenic technologies are still primitive and inefficient, with unknown risks for animals, let alone people.
  • There are considerations that researchers need to take into account before establishing colonies of primate disease models, such as isolating primate colonies to prevent contamination with other research colonies and ensuring that the disease under study cannot be modelled in transgenic mice or other non-primates.
  • At present, there is a limit to the amount of genetic material that can be inserted into the marmosets’ DNA. This may mean that this technique could only be used to create models of genetic conditions involving a single, small gene but not those conditions involving multiple genes or larger genes.

Both genetic engineering and animal experimentation are controversial issues, and the implications of this work will need to be considered openly through rational public debate of the strengths and limitations of these technologies. Such debate may need to address potential benefits, adherence to principles of animal welfare and discuss where pursuing this research might ultimately lead.

NHS Attribution