27 χρόνια συμπληρώνονται σήμερα από ανακοίνωση της πρώτης προεμφυτευτική γενετικής διάγνωση στον κόσμο, που κάναμε στο Hammersmith Hospital του Λονδίνου.
Πόσο περήφανη ένιωσα όταν βρήκα την ανακοίνωση για την συνέντευξη Τύπου που οργανώθηκε μία μέρα πριν τη δημοσίευση του επιτεύγματός μας στο Nature.
Ένας από τους λόγους που έγινε η αποδοχή και η δημοσίευση της εργασίας μας άμεσα από το Nature, είναι ότι θα γινόταν ψηφοφορία εκείνες τις ημέρες στο Βρετανικό Κοινοβούλιο για το αν θα επιτρεπόταν ή όχι η έρευνα στα έμβρυα. Η εργασία μας ήταν η απτή απόδειξη ότι η έρευνα στα έμβρυα είναι αυτή που μπορεί να βοηθήσει τους ανθρώπους να αποκτήσουν ένα υγιές παιδί, απαλλαγμένο από βαριές γενετικές παθήσεις.
Η βρετανική βουλή ψήφισε υπέρ της έρευνας στα έμβρυα και ελπίζω πάντα η έρευνά μας να έβαλε ένα λιθαράκι και να βοήθησε να ληφθεί αυτή η απόφαση.
41 Portland Place, London
2.30 pm 18th April 1990
The first pregnancies from sexed human preimplantation embryos for prevention of sex-linked inherited diseases.
Dr. Alan Handyside
Prof. Robert Winston
Institute of Obstetrics and Gynecology,
Royal Postgraduate Medical School,
Hammersmith Hospital, London W 12 0NN.
To be published in NATURE 19th April 1990
Pregnancies from biopsied human preimplantation embryos sexed
by Y-specific DNA amplification.
Handyside, A.H., Kontogianni E. H., Hardy, K, and Winston, R.M.L.
Over 200 sex-linked inherited diseases, typically only affecting boys, have been recognized many of which are severe and eventually fatal in early life. Examples include Duchenne muscular dystrophy (one of the most prevalent inherited diseases affecting 1 in 3500 boys) hemophilia and fragile X syndrome. Girls inherit two X chromosomes one from each of their parents, boys inherit one X chromosome from their mother and a Y chromosome from their father. If a mother is a carrier of one of these diseases because of a genetic defect on one X chromosome, there is 50-50 chance of a girl being born a carrier and a boy being born affected by the disease.
For couples known to be ‘at risk’ of transmitting these diseases to their children either because they already have an affected boy or have a close relative suffering from the disease, prenatal diagnosis is available. This involves sampling fetal cells from the placenta, which can now be performed as early as 8 to 10 weeks, and genetic analysis of fetal DNA diseases for which the genetic defect has not been identified, the same procedure is used to identify the sex of the fetus. If the fetus is diagnosed as affected or male, however, the couple faces the difficult choice of whether or not to terminate the pregnancy.
Using in vitro fertilization (IVF) or ‘test tube’ baby techniques developed for the treatment of infertile couples, we have now been able to identify the sex of an embryo three days after fertilization allowing us to replace only unaffected or carrier female embryos in the mother and have established several pregnancies. This offers couples ‘at risk’ of sex-linked disease an alternative to conventional prenatal diagnosis with the risk of therapeutic abortion and the opportunity to start a normal pregnancy.
Women were induced to ovulate several eggs in a single cycle. These eggs were collected, inseminated with the husband’s sperm and normal fertilization was confirmed the following day. Normally fertilized eggs were cultured for a further two days during which time the eggs divided three times and developed into 8-cell embryos. Each embryo was the ‘biopsied ‘by removing a single cell (and in a few cases two cells). At this stage, the embryo is only a tenth of a millimeter across the surrounded by a protective jelly coat or zona. Therefore, micromanipulation was necessary to hold the embryo steady while a hole is made in the zona and a pipette inserted to gently remove to the cell by suction. Biopsied embryos were returned to culture while the DNA from the single cell was prepared for amplification.
The polymerase chain reaction (PCR) allows short fragments of DNA to be amplified a millionfold so that detectable amounts can be prepared from very small numbers of cells. To identify the sex of the biopsied embryos, we amplified a fragment of DNA present in hundreds or thousands of copies only on the male Y chromosome. The amplification process is rapid as well as sensitive and was completed in 3-5 hours. This enabled the sex of embryos biopsied in the morning to be identified by late afternoon and female embryos were transferred late on the same day.
Five couples have been treated over a period of six months. Three out of the five women are now pregnant. Two of the women are pregnant with twins (approaching 25 weeks) and all four fetuses have been confirmed as normal females by conventional prenatal diagnosis and ultrasound scanning.
We have also been able to amplify sequences associated with cystic fibrosis and Duchenne muscular dystrophy and are hopeful that it should be possible to use the same approach for the specific diagnosis of these relatively frequent inherited diseases. But more research is needed on human embryos to establish safe and reliable methods before ‘at risk’ couples could be offered preimplantation diagnosis. This work will be stopped if Parliament votes to ban embryo research.
This research was approved by the Research Ethics committee of the Royal Postgraduate Medical School and the Interim Licensing Authority for Human Fertilization and Embryology of the Medical Research Council and the Royal College of Obstetricians and Gynaecologists. We are grateful to Karin Dawson, Joe Conaghan, Dr. I. Souskis and the IVF team at the Wolfson Family Clinic, Hammersmith Hospital, Professor Charles Rodeck and Graham Davis for the prenatal diagnosis. This work was supported by the Muscular Dystrophy Group of Great Britain and Northern Ireland.
Μπορείτε να διαβάσετε περισσότερα:
https://www.ncbi.nlm.nih.gov/pubmed/2330030 Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification.
http://assets.cambridge.org/97805218/84716/excerpt/9780521884716_excerpt.pdf Introduction to preimplantation genetic diagnosis (Joyce C. Harper)