The third session of the 2025 PET (Progress Educational Trust) Annual Conference explored the origins of preimplantation genetic testing (PGT), with a keynote talk by the PGT pioneer Professor Alan Handyside. Professor Handyside is director of ExOvo Genomics, and his previous roles include principal scientist at Illumina. The session was chaired by science writer and broadcaster Dr Phillip Ball, former editor at Nature and author of numerous books.
When I started my own embryology training at Hammersmith Hospital in 1990, preimplantation genetic testing for monogenic conditions (PGT-M, previously known as PGD) was only just becoming a clinical reality. I remember walking across the hospital site to the genetics laboratory to deliver embryology supplies, observing Professor Handyside at work, and sensing the beginning of something transformative.
Professor Handyside opened by describing the intellectual roots of PGT-M in 1968, when Robert Edwards and Richard Gardner – later to become Professor Sir Robert Edwards and Professor Sir Richard Gardner – published a paper in Nature (one year prior to Edwards' paper describing the first IVF in humans) showing that the sex of rabbit blastocysts could be identified by removing a small number of trophectoderm cells. Edwards speculated at the time that similar approaches might be used in humans to avoid inherited disease, a full ten years before the world's first IVF baby was born in 1978.
Practical implementation had to wait until the mid-1980s, when the development of the polymerase chain reaction (PCR) permitted genetic analysis from single cells. However, the causative mutations for genetic conditions such as cystic fibrosis and Huntington's disease were identified only toward the end of that decade.
At Hammersmith Hospital, under the clinical leadership of Professor (now Lord) Robert Winston, Professor Handyside focused early clinical applications on couples at risk of X-linked conditions such as Duchenne muscular dystrophy and haemophilia. Because the specific mutations were often unknown, embryo sexing was the only option available. Couples were counselled extensively about the experimental nature of the treatment, and any resulting pregnancies were followed closely.
In 1989, the first pregnancies following PGT were achieved, and this was reported the following year in Nature. By the spring of 1990, all four fetuses in two twin pregnancies had been confirmed as female. Embryo freezing and culture to day five were not possible at this time, so testing and result reporting were limited to the eight-hour window between the time on day three when embryos were sufficiently developed for biopsy, and the time when embryos needed to be transferred later that same day.
The Nature paper was published before the resulting babies had actually been born. Professor Handyside explained to us that the decision to publish first was a matter of intense debate – Professor Anne McLaren urged restraint, while Nature's editor John Maddox took the view that it was 'his duty to publish the report, to inform the public and politicians about the potential benefits of human embryo research'. Media interest was immediate and international, and it was in this context that the phrase 'designer babies' gained traction – the term was rhetorically powerful, for a technique applied to deselect embryos.
Professor Handyside explained that the timing of publication was consequential. The paper was (knowingly) published shortly before a Parliamentary debate about embryo research, before the Human Fertilisation and Embryology Act had been passed.
Over subsequent decades, Professor Handyside continued to make key contributions to the science of PGT and to related ethical and policy debate, although he was modest about these achievements in his keynote address. In 2010, for example, he and his colleagues published a landmark paper introducing a genome-wide karyomapping approach that could be used as a universal, linkage-based method for PGT. This enabled the inheritance of almost any single-gene disorder to be analysed at the single-cell level without bespoke test development, and became the foundation of PGT-M practice worldwide.
Far from resting on these achievements, Professor Handyside continues to develop his work. He recently published a paper proposing that single-nucleotide polymorphisms – combined with parental haplotyping analysis – can detect meiotic and mitotic, whole and segmental chromosome imbalances (aneuploidies) in preimplantation embryos, and that this can inform assessments of embryo viability and suitability for transfer.
Following the presentation, Dr Ball asked Professor Handyside whether, when developing PGT, he had imagined we might arrive at today's situation, where commercial organisations across the world offer PGT for an enormous variety of purposes (medical and otherwise). Professor Handyside responded by referring to his opinion piece 'Let parents decide', published in Nature to mark the 20th anniversary of his original PGT paper, and reiterated his argument that 'parents in general have a very sensible attitude to this'. At the same time, Professor Handyside cautioned that there are limitations to what PGT can achieve, observing that sometimes 'people misunderstand this'.
Looking back at the early days of PGT, it is remarkable how far the science has progressed and yet how familiar the societal debates remain. The session's central message was clear – innovation in reproductive genetics is best judged not by its most sensational labels, but rather by its capacity to reduce disease, inform patient choice and be integrated responsibly into clinical care.
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