Three is company!

A fertility treatment spawns babies with the DNA of three parents, instead of two

Published: Friday 15 June 2001

-- the first genetically altered human babies have been born and are healthy, claim researchers in the us . These babies have dna (deoxyribonucleic acid) of three parents, instead of two. The children were born to infertile mothers who were treated using a technique called ooplasmic transfer. This technique involves taking some of the contents of a donor cell and injecting it into the egg cell of an infertile woman. Jacques Cohen and Jason Barritt at the Institute for Reproductive Medicine and Science of St Barnabas in New Jersey, usa , used this technique to treat women who were unable to conceive because of defects in the cytoplasm of their eggs -- the fluid surrounding the nucleus. While the vast majority of our genes are in the nucleus, the cytoplasm contains tiny energy-producing structures called mitochondria, which have their own set of 13 genes.

The researchers injected cytoplasm from the eggs of fertile women into the eggs of infertile women. Injecting donor cytoplasm into an egg also involves transferring mitochondria and their genes. This fact gave rise to a question: do the babies have genes from three persons -- the infertile woman, the man whose sperm fertilised the egg and the woman whose egg was the source of the additional cytoplasm? The scientists used a genetic fingerprinting method to answer the question. After testing 12 of the 30 babies born with the help of the technique, they found that two one-year-old babies were carrying donor mitochondria. The children's cells contain mitochondria, and hence genes, from two women as well as their fathers. The researchers say that this "is the first case of human germline genetic modification resulting in normal healthy children." The additional genes that the children carry have altered their germline (collection of genes) that they might pass on to their offspring.

However, the researchers are not sure whether the added mitochondria was the reason for their success. Other, non-genetic components of the cytoplasm might be responsible for the success. "We think every patient is different. Some might need mitochondria for extra energy and some might need proteins," says Barritt.

The researchers say that the added genes are of no consequence. They are of a type that does not vary much from person to person and have no effect on human characteristics. They do nothing except provide energy.

Some researchers now want to go further. James Grifo of New York University will try to treat infertile women by removing the nucleus from their egg and inject it into a donor egg, whose nucleus has been removed. In this case, all the mitochondria of any baby would come from the donor. This technique could also help prevent women who have mutations in mitochondrial dna from passing this problem to their children. Such mitochondrial diseases cause problems that can be fatal.

Mitochondrial disorders affect one in every 10,000th child in the uk . There are tests that can screen women for mitochondrial defects, but because of the rarity of the condition these are generally prescribed only after the birth of an affected child.

But the critics of Cohen and Barritt are many. They have been mainly criticised for not disclosing the fact that two foetuses were suffering from Turner's syndrome and, therefore, were aborted. Turner's syndrome is a disease where the female child has just one chromosome instead of two and is consequently infertile. "Two turner cases out of such a small number born is quite abnormal.

This ratio is almost seven times higher than the normal incidences of the disease," says Masoud Afnan, director of the assisted conception unit, Birmingham Women's Hospital, the uk . Afnan believes that the technique is to be blamed.

David Barlow, clinical director of the assisted reproduction unit at the John Radcliffe Maternity Hospital in Oxford, the uk , feels that the feat would have been more relevant if the results of the diseased babies had also been disclosed. Eric Juengst of Case Western Reserve University, usa , said: "The technique should trouble those committed to transparent public conversation about the prospect of using 'reprogenetic' technologies to shape children's future." Joe Cummins, a professor at the University of Western Ontario in Canada, said, "It is not the time to bring in human germline gene therapy through the back door."

Mark Frankel and Audrey Chapman of the American Association for Advancement of Science are of the opinion that such experiments show that there is a need for a new oversight system that reviews all proposals involving modification of humans. Without such oversight, researchers in the fertility industry would extend this approach to improving normal genetic traits, thus widening the gap between society's 'haves' and 'haves-nots'.

The us government's Recombinant dna Advisory Committee said that the researchers had carried out this work without government money. The committee said that in no circumstances would it consider any request for government funds that would result in modification of the human germline.

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