Podcast Review: The G Word – David Bick, newborn sequencing

The podcast series 'the G word', which is produced by Genomics England, has a mission statement to 'bring the benefits of genomic medicine to everyone'. As part of this series, Vivienne Parry, the head of public engagement at Genomics England, sat down with Dr David Bick, one of the clinical advisors to the Newborn Genomes Programme, for a podcast entitled 'David Bick: Newborn Sequencing'.

The Newborn Genomes Programme is a pilot research project undertaken by Genomics England to prototype how full genome sequencing could be implemented by the NHS. This podcast is primarily dedicated to outlining how this pilot study might be designed.

Genomic medicine has long been the focus of much science-fiction speculation, particularly along the lines of 'designer babies' whose genomes are edited to remove traits which have been described as undesirable. Consequently, the topic of whole genome sequencing (WGS) for newborns can be quite a delicate topic, and in an attempt to avoid any controversy Dr Bick and Parry present a very clinical overview of how this project might be launched in the UK.

Currently, newborn screening in the UK is performed via blood spot screening, also known as the heel prick test. However, this pilot study might lead to full genome sequencing replacing this test. The heel prick test involves taking four blood spots from each baby, which can then detect nine child-onset disorders, including sickle cell anaemia, cystic fibrosis and several metabolic diseases. Inclusion of new diseases into the heel prick test is limited by how much blood can be collected from each child. Dr Bick highlighted in the episode how flexible WGS can be; the addition of new diseases requires only a couple of extra lines of code in the analysis as the whole genome has already been collected.

I was interested in how Dr Bick described WGS as a means for equity in testing for rare diseases. One of the criteria for a disease's inclusion in the heel prick test at the moment is that all patients with that disease must be identified (ie, there are no false negatives). This means that every single disease-causing mutation for each disorder must be known. This would require significant scientific effort, and consequently rare diseases, which receive less funding, are less likely to be included as not all of the disease-causing mutations are known. This is reflected in the current diseases that are included in the heel prick test: sickle cell anaemia and cystic fibrosis are two of the more common inherited disorders, with prevalence of 1 in 2000 and 2500 live births respectively.

Dr Bick suggested that for WGS this requirement would be relaxed, and diseases could be included even if all of the diseases-causing mutations are not known. This would mean that as many children with diseases as possible were being identified, even if some slipped through the net. As a researcher in rare diseases, I know how crucial age of treatment can be in dictating children's disease progression with time (see the SPR1NT trial for spinal muscular atrophy), and I believe that inclusion of rare diseases is one of the key drivers for genomic screening.

Dr Bick then outlined the three criteria for disease inclusion in the screening: the disease should be child-onset, it has to have an available treatment that directly interacts with the disease pathway (rather than just managing symptoms) and there has to be another test to confirm the presence of the disease, in order to give clarity to parents. He also suggested that there could be a type of 'grey' list, where diseases could be earmarked for inclusion for when therapeutic trials have been completed.

This podcast also positioned the NHS as the leaders in the global push for genomic newborn sequencing and mentions that several other pilots are looking to the Newborn Genomes Programme for guidelines of how it could work. I really acquired a feel for how complicated this project is, and how cautiously it is being treated. There is such a broad range of people who are invested in this project, including clinicians, patients and parents, and it is crucial that each viewpoint is being considered fairly. Currently the initial enrolment of 200,000 newborns is due to start in mid-2023. While it is important to consider all of the factors and to make sure the pilot is implemented correctly, for some this implementation will come too late.

Despite giving an interesting insight into a topic that non-specialists will find easy to understand, this podcast is very much one-sided, only presenting arguments for genomic screening. They mentioned at one point that 'there are lots of ethical dilemmas in genomic screening', but never elaborate on this. In some ways I appreciate that the podcast tried to stick purely to the scientific facts, but the podcast presented an incomplete picture of genomic screening by not elaborating at all. There are several factors that should be considered as cons for WGS, including the associated costs and the issue of consent. WGS necessarily provides information on the genomes of relatives, and so consent of the parents may not be sufficient.

This was not the easiest podcast to listen to as it came across as stilted in parts. However, Dr Bick made the argument for WGS of newborns well, and it is clear he is very passionate about the project.