TWO million babies worldwide have been born following in vitro fertilisation, and the embryos of at least 1000 of these were screened for genetic diseases before implantation.
These successes were celebrated by fertility experts at a conference on pre-implantation genetics in London last month. And it is only the beginning: in the future more and more clinics will be offering pre-implantation genetic diagnosis (PGD) for an ever-growing range of diseases.
Until recently there were several obstacles in the way of the widespread use of PGD and its extension to new diseases. Standard genetic tests require relatively large amounts of DNA, extracted from millions of cells. But in PGD the tests have to be done on single cells taken from three-day-old embryos, and completed in time for the selected embryos to be transferred on day four or five.
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鈥淚n five years鈥� time embryos could be screened for autism, and possibly also for diseases such as schizophrenia鈥�
That means special tests have had to be developed that work with such tiny amounts of DNA. The tests must also be carried out in special clean labs, adding to the costs, since any contamination might wreck the results.
But these barriers are falling. Last year, researchers showed that a technique called multiple displacement amplification, or MDA, for generating millions of copies of all the DNA in a cell, could be used for PGD (New 杏吧原创, 24 July 2004, p 7). Once a cell鈥檚 DNA has been amplified in this way, standard tests can be used and contamination is much less of a problem.
Now Belen Lledo鈥檚 team at the Bernabeu Institute in Alicante, Spain, has used the method in PGD for the first time, to screen embryos from a couple in which the man has a serious connective tissue disorder called Marfan syndrome. His wife is now pregnant.
The use of MDA marks a new era for PGD, Lledo says. Among other things, it should make it easier to carry out multiple tests on the same embryo, such as combining tests for specific inherited diseases with screening for chromosomal abnormalities, which some experts argue should be a routine part of IVF (New 杏吧原创, 28 May, p 11).
PGD is extending its reach in other ways, too. Doctors can now test for diseases caused by mutations in mitochondria, the energy-producing units in cells. Screening for mitochondrial diseases is tricky, because while each cell contains many mitochondria, the mutation may occur in only some of them.
At the London meeting, Julie Steffann of the Necker Children鈥檚 Hospital in Paris reported the first birth of a child after screening for the mitochondrial mutation that causes a syndrome called NARP, the symptoms of which range from muscle weakness to lack of coordination. Of the three embryos Steffann tested, two were mutation-free while in the third almost all the mitochondria had the mutation.
It may soon be possible to screen embryos for another class of mutations called copy number polymorphisms (CNPs), caused by the deletion or duplication of segments of DNA. Until recently, these have been difficult to detect, but a team led by Michael Wigler of Cold Spring Harbor Laboratory in New York state has developed a DNA chip that can spot thousands of different CNPs.
James Watson, the co-discoverer of the double helix, who is president of the laboratory, told the conference that Wigler has recently identified numerous CNPs found only in people with autism. In five years鈥� time the method could be used to screen embryos for autism and possibly also for diseases such as schizophrenia, Watson predicted. 鈥淲e should work as hard as possible to rid these diseases from families,鈥� he said. But extending PGD to autism and other mental conditions is likely to prove controversial because the gene variants that contribute to these disorders might also contribute to desirable traits such as creativity.
鈥溾�橶e should work as hard as possible to rid these diseases from families,鈥� James Watson told the conference鈥�
For all its promise, though, PGD does not tell doctors what they most want to know: whether an embryo is viable. 鈥淚t is not enough to test genes alone,鈥� says Peter Nagy of Reproductive Biology Associates in Atlanta, Georgia. Nagy hopes it will be possible to develop tests that reveal which genes are expressed in embryos and at what level. That might reveal which embryos are doomed to die despite having a seemingly normal genome and which will implant and develop into a healthy baby after being transferred into a woman.
