Science in Society Archive

Green Fluorescent Monkey Not a Glowing Success

Researchers in Oregon Health Sciences University created the first transgenic primate, a rhesus monkey carrying a gene for green fluorescent protein GFP originating from a jelly fish, raising public alarm as a step down the slippery slope to human germline gene therapy. It is by no means a glowing success and serious questions remain over the ethical justifications for the experiment and safety aspects.

The GFP under the control of cytomegalovirus early promoter, or the human elongation factor-1 alpha promoter, was spliced into a vector made from a disarmed moloney retrovirus. The viral vectors carrying the GFP were injected into the space between the egg and its protective vitelline membrane. The eggs were then fertilised and allowed to develop. A total of 224 eggs were injected, 126 developed into embryos, and 40 were implanted into 20 surrogate mothers. Five became pregnant, one carrying twins. Three fetuses were lost, and three were carried to term, among them the twins, which died at birth. The remaining live birth was found to carry the transgene, but did not express it, ie, failed to glow. The two dead twins however, were found to express the green fluorescent protein.

This is the first experiment to create a transgenic primate, and the retroviral method used appears to gives a high survival rate of eggs to embryos, 126 out of 224 or 56%. The first question to be raised is why the experiment was done at all. The researchers try to justify it as a model for human gene therapy and as a test for vaccines. At the beginning of the paper, they also give the impression that they were trying to create transgenic primates because primates were closer to humans and therefore better than transgenic mice models. All of these reasons are ethically unacceptable in terms of animal suffering.

Many people also regard the experiment as a slippery slope to germline human gene therapy. But the distinction between somatic and germline gene therapy is semantic, as the GM constructs/vectors can get into germ cells even when applied to the body, and not directly to the germ cells.

The second question is why the success rate is still so low. The survival rate to term, depending on how it is calculated, is one out of 40 implanted embryo, 2.5%, or, more likely, one out of 126 embryos, 0.8%, assuming that only the normal embryos were chosen for implantation. As percentage of injected eggs, the 'success' rate is still lower, less than 0.5%. So why is it so low?

The retroviral method would seem to circumvent all the problems of damaging the embryo by injecting directly into the egg. So the problems must be associated with the transgenic process itself. First, there is as yet no method whereby the GM construct can be accurately targetted to the genome, and that must account for a high proportion of the failures.

Another reason for the low survival rate may be the vector itself, which raises safety concerns. The moloney retroviral vector has been known to recombine with proviral sequences (integrated viral DNA) in the genome of cells to regenerate virulent viruses [2]. Has anyone checked the failures of transgenesis for signs of viral infection?

  1. Chan AWS, Chong KY, Martinovich C, Simerly C and Schatten G. Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science 2001: 291: 309-312.
  2. Munk C., Lohler J, Prassolov V., Just L, Stockschlader M and Stodking C. Amphoteric murine leukemia viruses induce spongiform encephalo-myelopathy. PNAS 1997: 94: 5837-5842.

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