Tony Gordon, Genesis Genetics
Kat - Weíve just heard how genetic testing for cancer patients -if not the general population at large - could be useful. But what about taking things back to the very beginning of life? At a recent conference run by the Progress Educational Trust, called Testing, testing, 123, scientists, genetic counsellors and ethicists debated the issues around genetic testing on early embryos, created through IVF. One of the speakers was Tony Gordon, UK lab director of Genesis Genetics, so I caught up with him in his lab in London to find out more about the ways in which he and his team can test embryos and fetuses for genetic disorders.
Tony - We are involved in what we call the reproductive genetic health spectrum. So, we can test embryos basically for their chromosomes to ensure they had the right number of chromosomes which is called pre-implantation genetic screening. We can also test embryos to make sure that they have the correct inheritance of single genes - that is pre-implantation genetic diagnosis. Also, we do here prenatal diagnosis using maternal blood which is known as NIPT Ė Non-Invasive Prenatal Testing. And that tests for Down Syndrome, Edwards Syndrome, Patau Syndrome, and sex chromosomal aneuploidies.
Kat - So, letís go to the embryos first. What sort of stage embryos are we talking about, like the big ones, little ones, how many cells? what's going on?
Tony - We can test for day 3 which is called the blastomere stage. Thatís eight cells and you can take one cell from that eight cells. Increasingly, that's becoming less tested for because you're taking an eighth of an embryo and sort of rationally, thatís possibly not as good as testing at other stages. Primarily, we test now at day five. The embryo is kind of formed, almost what looks like an egg if you can imagine. So, the inner cell mass is the yolk and then on the outside is the trophectoderm which is the shell. The trophectoderm goes on to form the placenta. So itís not actually called the embryo and we can take 3, 5, 8 cells from that day 5 trophectoderm and test that.
Kat - What sort of things are you testing for when you're doing say, the pre-implantation genetic screening, and the pre-implantation genetic diagnosis? What sort of conditions can you look for?
Tony - Pre-implantation genetic screening is a fertility test, as it were, in terms of we are looking to ensure that the embryos that we look at just have the right numbers of chromosomes. You're not looking at anything in terms of genes at that point. But that is just to try and ensure that weíve got an embryo that is more likely to produce a healthy birth. PGD, Pre-implantation Genetic Diagnosis is different because weíre looking at genes there and we can test for the inheritance of about 240 different conditions. PGD patients arenít infertile. They have an inherited condition that they want to avoid.
Kat - So, that might be something say, like cystic fibrosis or a severe genetic condition that one of the parents is carrying and they donít want to pass on.
Tony - Yeah or both parents of course because it could be a recessive disease where they're both carrying it. But there's also oncology disorders like BRCA and then there's also some late onset disorders like the Huntingtonís which you have to be very careful about how you look at the parents because you need to test without informing them that one of them has a late onset disorder. So there are special protocols for how we do that. So there's quite a wide spectrum of diseases with different inheritance. And then finally, under the PGD umbrella, there are people who are carriers of chromosomal translocations that we can test for as well.
Kat - These are all embryos that are being created through IVF. So theyíve been made in the lab from mixing an egg and a sperm together?
Tony - Thatís absolutely correct.
Kat - So letís move on to the foetal testing. So this is when the baby is already growing inside the mum and you can test her blood. What are the conditions that you're looking for? How are you looking for them?
Tony - When the foetus grows within the woman, the placenta forms and the placenta is kind of slightly leaky and it leaks small amounts of DNA into the bloodstream. We can test for some fairly straightforward chromosomal abnormalities and changes in the sex chromosomes as well.
Kat - What's the purpose of doing this? Is it just so women can decide, ďI donít want to have this baby. I want to have a termination.Ē What do people do with this information? How does it help to know this?
Tony - Every patient that we have that has a positive result is screened by one of our genetic counsellors. It is a personal decision. You could quite feasibly have a Down Syndrome positive result and then go on to have a Down Syndrome child. Thatís perfectly reasonable outcome. Different people have different desires for what they want to do with their pregnancy. We help with our genetic counselling to give them the information as to what the outcomes might be. Down Syndrome, it has a very large different amount of penetrance, so presentation of phenotypes. We can't predict that. So thatís something that the patient and genetic counsellor has to discuss.
Kat - So, some children could be very, very severely affected and some children could be very high functioning.
Tony - Absolutely and quite a lot of Down Syndrome pregnancies donít actually progress to full term as well. So, there's a really big spectrum of presentation of Down Syndrome.
Kat - When you think about genetic testing, you think about like, ďis that there? Yes, no.Ē But the more we understand about genetics, itís becoming clear that itís not quite as simple as one gene, one fault, one disease. Is this kind of testing capturing that kind of complexity? Are there some areas that are a bit challenging for the link between the gene and how you come out?
Tony - Itís a fascinating area because the more advanced our genetic testing gets then the more interesting and sometimes complicated difficult questions we come along to. So you're absolutely right. None of this is straightforward and that goes right through to prenatal testing where actually, weíre testing the placenta sometimes isn't representative of the embryo itself so, these interesting questions that you have to consider at that point as well.
Kat - There's a lot of questions that are raised by this kind of technology Ė some of them technical, some of them ethical, some of them societal. Where is the debate now about how this technology moves forward? What's acceptable? What can we look for? What should we look for? What should we do with this information?
Tony - I think weíre very fortunate in the UK that the HFEA, The Human Fertility and Embryology Authority, they have a very good programme that looks at these future questions, whether new conditions should be licensed. So any new condition you want to bring forward has to be licensed. So, there's very vigorous debate about where this can go and I think as science progresses faster than legislation, as always, there's new ethical questions of genome editing, CRISPR, things like that. I think already, weíve begun to address them and really, I think weíre in a pretty good state in the UK in terms of being ethically very considering every view of the new ethical issues that are coming up. Itís a fascinating area.
Kat - And to sort of run the sci-fi thing to its logical conclusion, would this technology end up with a perfectly homogenous population of perfect humans where every single disease is screened out?
Tony - No and the reason is that if you do PGD for a single recessive disease and you also test for the viability of the embryos, half of the embryos roughly would be suitable for transfer if you just looked at a single gene. If you add in chromosome with the normal embryos, you get to about a quarter of the embryos. If you add in another disease, it gets to about 12.5 per cent, and if you start to look for more than one or two things, you would never have any IVF embryos to transfer. So, we can only look at serious disorders that we know about upfront. We could sequence embryos but frankly, nobody would ever transfer an embryo at that point because there'd be too much information and too much risk. So, we look at really specific medical questions before anything is transferred.
Kat - And also, for many diseases, there are many, many different small subtle variations that all add up. So, I guess something like a test for heart disease isn't really going to work.
Tony - Well, I mean multigenic disorders are very prevalent. Yeah, we can only do single gene disorders. People come to us and ask us to do autism testing. Itís a multigenic disease with no known genes that are really clearly loss of function from the majority of autism patients. There's a small subsection of autism patients that have clear genetic disease. Thatís classic example. You can't and you probably will never be able to do PGD for autism. There's questions that we won't be able to answer and unfortunately, you're back to the old fashioned way of producing children at that point.
Kat - Genesis Geneticsí Tony Gordon. And you can find out more about the work of the Progress Educational trust - who aim to raise the public understanding of science, law and ethics around genetics, at progress.org.uk