The Origins of Preimplantation Genetic Testing

The third session of the 2025 PET (Progress Educational Trust) Annual Conference explored the origins of preimplantation genetic testing (PGT), with a keynote presentation 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 began his presentation 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, see BioNews 1304) 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. Embryo freezing and culture to day five were not possible at the 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. By the spring of 1990, all four fetuses in two twin pregnancies had been confirmed as female.

All of this was reported in April 1990, in a paper in Nature that was published before the resulting babies had actually been born. Professor Handyside explained 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 the timing of publication was consequential.

The paper was (knowingly) published less than a week before a debate about the Human Fertilisation and Embryology Bill took place in the House of Commons. At that debate, Conservative health minister Kenneth Clarke discussed the work 'by Professor Robert Winston and his colleagues at Hammersmith hospital', and explained that 'The technique that they have developed may now become more widely available as part of IVF treatment'.

Many other MPs discussed the Nature paper in their contributions to the Commons debate, with several of them praising the work. One MP referred to 'the excellent work done in Hammersmith hospital', while another argued that the use of PGT 'is a world first and we should be proud of that achievement'. Other MPs were more critical – one of them described PGT as 'a terribly hit-and-miss method', and went on to claim that 'the sinister shadow of Dr Mengele falls across this debate'. Ultimately, however, the Human Fertilisation and Embryology Act was passed in November that same year and it permitted PGT.

During subsequent decades, Professor Handyside has 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 conference presentation. 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 (see BioNews 481, 515 and 797). This enabled the inheritance of almost any single-gene disorder to be analysed at the single-cell level, without bespoke test development, and it 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 ever envisaged 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 there 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, and observed 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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PET would like to thank the sponsors of its conference (the British Fertility Society, ESHRE, PRECAS, Remaking Fertility, the Adelphi Genetics Forum, the Anne McLaren Memorial Trust Fund, Born Donor Bank, CooperSurgical, Ferring Pharmaceuticals, Merck, Salve, Theramex, Xytex, Juno Genetics and the Institute of Medical Ethics.).

Register now for PET's next free-to-attend online events.

• Fertility and the Workplace: Can Employers Help? Should They?, taking place online on Wednesday 14 January 2026 – register here.
• Understanding Egg Donation: The Give and Take, taking place online on Wednesday 28 January 2026 – register here.
• Ancestry, Ethnicity, IVF Outcomes: Why Do Some Patients Fare Better than Others?, taking place online on Wednesday 4 February 2026 – register here.