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After we had seen how relatively easy it was to change the switches in mouse embryos, we thought that perhaps the same could be true of human embryos. In IVF, you also have the embryo for a brief period of time in a culture dish. And so we were asking the question whether as in a mouse embryo, the mere fact of human embryos having been in a culture dish, or been manipulated, could alter their epigenetic switches?
Wolf knew that Beckwith-Wiedemann syndrome was caused by a faulty switch.
So what we were looking at was a group of babies and children that have the Beckwith-Wiedemann syndrome. What proportion of those were conceived by, by IVF.
Could IVF be switching genes on or off? Could IVF itself cause the syndrome?
What we found was an increased occurrence of this epigenetic syndrome in the IVF population.
Although the disease is extremely rare, the risk appeared to increase three to four times with IVF. It seemed that the simple act of removing the embryo from its natural environment could trigger the disease.
And, I do feel frustrated that Karen might possibly have Beckwith-Wiedemann syndrome as the, because we had IVF. But at the time, it was the right decision to make.
And I think that we should look again at the IVF procedures, the conditions that are being used and carry out better and more precise experiments to see how we can avoid throwing these epigenetic switches.
Wolf had shown a simple change in environment was enough to turn a gene on or off. But there was more. Everyone thought that any altered switches could not be inherited. He took some mice with altered gene switches and bred them.
Our expectation was that as the altered genome was passed to the children that any epigenetic changes would be wiped clean.
When he looked at the gene profile of the offspring, he was amazed.
You have dots that you were looking at, and every dot means a gene is on. And all of a sudden, you know, somebody said, "Wow, Look at that".
The epigenetic switch thrown in one generation was clearly also present in the second generation.
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