January 21, 2022, by School of Medicine

50 at 50: Modern medicine: Miraculous or monstrous?

Professor Chris Denning looking into a piece of lab equipmentI’d like to give a personal reflection on the impact of biomedical technologies, including those pioneered in Nottingham, and then raise with you questions surrounding emerging opportunities and challenges.

This year, I turn 49 years of age, just shy of the half century of the Medical School. Based on averages, I’m classed as ‘middle aged’ but equally I could be on borrowed time. You see, my family history isn’t great, with my grandad, uncle and dad all dying of heart attacks aged 39, 41 and 62 years, respectively.

Yet, I remain quietly at ease. A clever algorithm, QRISK, was developed by Nottingham’s own Professor Julia Hippisley-Cox. Now widely used by the NHS and freely available online, this smart gizmo predicts my 10 year risk of stroke and heart attack to be 5.8%, just 2% above my demographic without a poor family history. These numbers sound pretty good…!

Looking back, medical technology has often considerably improved my quality of life. I was troublesome even before birth. Having ruptured mum’s placenta in what must have been a game of ‘bouncy castle’, I was born by emergency C-section. Medicine saved both our lives, with special needs professionals then helping me through both the physical and mental developmental delays that followed.

Perhaps due to that challenging start in life, plus a lot of being bullied as a kid, I’m prone to depression. I’ve spoken openly about this in recent years, with gratitude to many healthcare professionals… Past GPs at Cripps Health Centre, UoN counselling staff, cognitive behavioural therapists at Cripps/Trent PTS and so on. Each steered me back from the very edge of the dark precipice, with the added benefit of teaching me how to look out for others. These people inspire me to create a positive research culture in the Biodiscovery Institute.

The last year has been challenging for many people. My own scare was the agony of a slipped disk that squashed my spinal cord and put me in a mobility scooter for 10 weeks, supplemented by hearty doses of morphine and gabapentin for 6 months. Of course, inventions made at Nottingham, such as magnetic resonance imaging (MRI) by Sir Peter Mansfield and ibuprofen by Professor Stewart Adams, certainly helped, as did the spinal injections of nerve blockers delivered by Mr Nasir Qureshi. We are lucky to be surrounded by such incredible professionals and teams of people.

Nevertheless, technological wins can carry professional, ethical or moral costs. These factors must be considered, and continual honest public engagement is imperative. When Bob Edwards ‘created’ Louise Brown as the first IVF (in vitro fertilisation) baby in 1978, he received death threats for being the devil himself.

Yet, IVF is now commonplace, with Nottingham’s Nurture Fertility contributing to the 5 million births worldwide and the 1-3% of babies produced this way in Europe and the US. In some clinics, IVF is more efficient than the ‘natural’ way. The practice of preimplantation genetic diagnosis (PGD) to screen out embryos carrying potentially devastating mutations is widely accepted. However, less ethically and morally clear is the use of IVF for couples wishing to produce ‘saviour siblings’, where a second child is ‘created’ to be a closely matched donor for a kidney or bone marrow transplants.

Big ethical dilemmas are on the near horizon. The advent of efficient gene editing via CRISPR (clustered regularly interspaced short palindromic repeats) technologies offers enormous opportunities. In my lab, we use CRISPR to introduce or correct mutations in human stem cells, which are then coaxed to become heart cells. The aim is to understand how to fix the sick heart and this receives strong public support.

But, society now needs to decide where the line of acceptability resides. We know from work in China that it is possible to ‘edit’ the genetics of human embryos using CRISPR. So, it’s a fairly small technical step (but an ethical leap) to correct damaging mutations in human embryos and then produce children via IVF.

In your view, would this be acceptable? Does your view change if CRISPR were used to enhance the genetics of an embryo to impart greater physical fitness, for example? In other areas of health, is gene editing of mosquitos to cause infertility in their offspring acceptable to eliminate this species, and hence the transmission vector of malaria? Will the potential and unknown ecological consequences be acceptable?

To go full circle, in January 2022 in the USA, the first ever pig to human heart transplant was performed. Twenty-one years earlier, in 2001, during my second postdoc at Roslin Institute in Scotland, I was first author on a publication in Nature Biotechnology. This described combining genetic engineering with cloning (i.e. the technology used to create Dolly the Sheep) to produce the first ever gene knockouts in a mammalian species other than the mouse. The outcomes were several-fold, including defining the start of my career, allowing me to win the first ever Nottingham Research Fellowship and showing early proof of concept for the pig to human heart transplant performed this month.

For context, in 1996 The Nuffield Council on Bioethics concluded xenotransplantation from pigs to humans was acceptable, including considerable genetic modification needed to achieve these goals. However, that was another era. Principles were different. Veganism and vegetarianism were rare. My own research primarily focuses on human stem cell systems, with a substantial amount of the funding in the last 10 years coming from organisations that support reduction, replacement and refinement approaches.

My final questions to you are… Do you think the conclusion in the Nuffield report is still valid? How would you feel if you or a loved one’s only chance of survival was to be recipient of a genetically engineered ‘humanised’ pig heart? Whatever your thoughts, welcome to the tough choices you will have to make in the next 50 years of the Nottingham Medical School…!

By Professor Chris Denning, Professor of Stem Cell Biology, Director of the UoN Biodiscovery Institute, Academic Lead for the UoN Covid Asymptomatic Testing Service and Director of the BHF Centre for Regenerative Medicine

Posted in 50 Years of Medicine