To assist our members and the general public, CiS will be listing new blogs regularly on different science topics.
Disclaimer: We will be asking top scientists in their fields to author the blogs, but the thoughts expressed are the authors.
I have often said that I am fortunate in that nearly the whole of my career unfolded in the ongoing ‘Golden Age of Genetics’. It is really exciting that we have seen and are seeing the results of basic research now being used in ways that are beneficial to individuals and to society (and indeed, on a wider scale, to Earth itself). Thus, back in December, doctors at Great Ormond Street Hospital in London (www.gosh.nhs.uk) announced a ‘first’. A 13-year-old girl, Alyssa, whose T-cell acute lymphoblastic leukaemia had resisted all other treatments, was cured by use of DNA base-editing, as reported by the BBC (Base editing: Revolutionary therapy clears girl’s incurable cancer – BBC News). I will explain what they did later in this article but for the minute I want to go back a few years.
DNA base-editing is a very precise and sophisticated form of genome editing (targeted removal or inactivation of specific genes or other DNA sequences). Genome editing was used in 2015, also at Great Ormond Street, to treat a baby, Layla Richards, who had an equally resistant acute lymphoblastic leukaemia. The technique was completely new; it had never been used on a human patient but the local medical ethics committee readily gave permission for its use because without it, the little girl was certain to die. As I have previously described, donated T-cells (T-cells are the immune system’s hunters) were subjected to very specific and targeted genetic modification combined with genome editing, to enable them to hunt down and eradicate the cancer cells. The modified T-cells were infused into Layla and within two months she was completely cancer-free. Building on this success, the team used the same technique a few months later to treat another very young leukaemia patient.
Returning to the present day, the team treating Alyssa again used donated T-cells. These were then modified by DNA base-editing as shown in the diagram. There we see three different base-editing steps and one genetic modification (the latter at 4). As with the earlier treatments, the genetic modification step was required to enable the edited T-cells to bind to and destroy the cancerous T-cells.
Alyssa is part of a trial that also includes nine other patients but she is the first for whom results of the treatment are available. She says ‘”You just learn to appreciate every little thing. I’m just so grateful that I’m here now. It’s crazy. It’s just amazing [that] I’ve been able to have this opportunity, I’m very thankful for it and it’s going to help other children, as well, in the future.”
One of the inventors of DNA base-editing, Dr David Lui, was delighted that the technique had been used in this life-saving way: “It is a bit surreal that people were being treated just six years after the technology was invented. Therapeutic applications of base-editing are just beginning and it is humbling to be part of this era of therapeutic human gene-editing.”
 Introduction to Bioethics, 2nd ed’n, John Bryant and Linda la Velle, Wiley, 2018. p139
John qualified at Cambridge with a degree in Natural Sciences and a PhD in Plant Biochemistry. After post-doctoral research at the University of East Anglia he held academic appointments at the Universities of Nottingham and Cardiff before being appointed to the newly established Chair of Cell and Molecular Biology at Exeter University. He is now Professor Emeritus. His research has focussed on various aspects of DNA and genes with particular emphasis on the regulation of DNA replication and cell division and also on developing climate resilience in crop plants. John also has a keen interest in bioethics – the ethical issues arising from modern science and medicine – and, with (now Dame) Suzi Leather, set up one of the first UK university courses on Bioethics for Bioscience students. In 2002, he was appointed, with Dr Chris Willmott of Leicester University, as Bioethics adviser to the Higher Education Academy (now Advance HE). John is a former Chair of Christians in Science and a past-President of the Society for Experimental Biology. He was also a Visiting Research Associate at the Brookhaven National Laboratory, USA and Visiting Professor of Molecular Biology at West Virginia State University, USA. His most recent book, written with Dr Graham Swinerd, Southampton University, is entitled ‘From the Big Bang to Biology, Where is God?’