Monkeying With Nature
A genetically altered primate could aid the study of human disease
It has been four years since Dolly, the cloned sheep, put a reassuringly sweet face on the new era of Frankenstein biology. You would think with all the cloning, genetic engineering, and general monkeying around scientists have done since then, they would have produced at least one grotesque monster. Instead, the mutants just keep getting cuter.
Enter ANDi, the most adorable member of the biotechnology petting zoo yet. ANDi (the name stands for "inserted DNA" backwards) is mostly monkey, rhesus macaque to be precise. But nestled somewhere in his chromosomes is a short stretch of DNA that makes him part jellyfish, too. His birth announcement, made last week in the journal Science, removes what little doubt was left that genetic engineering isn't just for mice and soybeans. As the world's first "transgenic" monkey, ANDi is living proof that the technique can work on our closest biological relatives--and therefore on us.
As disarming as he may appear, ANDi raises more questions than he answers. Scientifically, the experiment demonstrates just how technically difficult it is to do genetic manipulation in higher animals. At the same time, even a preliminary advance with our genetic next of kin ignites all the ethical concerns about tinkering with human DNA and the prospect of designer babies.
Like all of us, ANDi started out as an unfertilized egg. A team of scientists at the Oregon Health Sciences University used a modified virus to carry the jellyfish gene into monkey eggs, which were then injected with sperm and implanted in surrogate mothers. The gene itself is just an easy-to-spot marker used by biologists to test new procedures. But, says team leader Gerald Schatten, now that they've shown the technique works, "We can use the same method to insert almost any gene we want." That would be a boon to researchers hunting for cures for everything from blindness to Parkinson's disease, who currently use genetically modified mice for their work.
Of mice and men. As useful as those lesser critters are, sometimes the differences between mice and humans are too great to make them useful tools for researching human disease. Only primates have a monthly menstrual cycle, for example, which can have important impacts on breast and ovarian cancer. Rodents also lack a macula, the part of the eye's retina that is lost in macular degeneration, the leading cause of blindness in the United States. Perhaps most significant, rodent brains are just too simple to show the subtle effects of psychiatric and neurodegenerative diseases such as schizophrenia and Alzheimer's.
Still, you don't have to be an animal-rights activist to balk at the thought of tinkering with the genetic makeup of complex, social animals like monkeys. "You have to consider how great the benefit to humanity will be," says neurogeneticist Carolee Barlow of the Salk Institute in San Diego. "If you can use monkeys to cure a disease, you'll be helping people who have no other options. But you have to remember that anything you do with a monkey affects it as a being. They deserve the best life we can give them."
Beyond the welfare of lab animals, ethicists also worry about the implications of moving genetic engineering into the world of primates, the group that includes humans. ANDi's arrival was more inevitability than surprise, but his hybrid DNA does underscore just how possible it would now be to start engineering humans, whether to prevent inherited disease or for some less noble cause. That may not be an immediate concern, however, since the technique requires considerable refinement. Schatten's team attempted to engineer a total of 224 monkey eggs, and ANDi was the only one of three healthy babies born that carries the jellyfish gene. The researchers still aren't sure if that piece of DNA is actually functional.
ANDi, at least, shouldn't have to worry about the issues he raises, whether technical or ethical. By and large, his career as an active research subject is over. For the rest of us, a new age of experimentation is just beginning.
Redoing monkey DNA
Scientists created the world's first genetically modified primate by adding a jellyfish gene to an unfertilized rhesus monkey egg. Here's how they did it:
[Drawing is not available]
1 Modified virus particles carried the new gene into the monkey's egg. The viral coat fell off, and the foreign DNA was inserted into the monkey chromosome.
[Drawing labels] Syringe; Monkey egg cell; Virus particles; Viral coat breaks away; Jellyfish gene; Monkey chromosome
2 A monkey sperm cell was injected to fertilize the modified egg, and the embryo was implanted into a surrogate mother.
It took scientists 224 attempts to produce one healthy transgenic monkey, born on October 2.
[Drawing labels] Nucleus; Monkey sperm; Monkey egg cell
Source: Gerald Schatten, Oregon Health Sciences University
This story appears in the January 22, 2001 print edition of U.S. News & World Report.