Author: Yunning Yuan
Artist: Shangyu Chen
Editor: Yuen Bing Ooi
“Every year 3,000+ babies could benefit from life-saving or life-changing interventions thanks to whole genome sequencing (WGS).’’ This is a statement asserted by Genomics England in its vision document for the Newborn Genomes Programme (NGP), launched in December 20211. Genomic medicine, which describes the use of information from a human’s genome to guide clinical care, has been put under the spotlight for its enormous potential to diagnose diseases, and the concerns about whether predicting a baby’s future is morally right. In this article, I will discuss the technical advantages as well as the ethical challenges of the NGP program to argue why and how we should use WGS for newborn screening.
As we enter the post-genomic era, WGS technology has become cheaper and faster than ever and has begun to change the practice of screening tests for babies. Newborn Genomes Program (NGP) is a UK-based national research project which has started recruitment in 2023 to sequence the genomes of over 100,000 newborns. Its aim is to investigate the benefits, challenges, and practicality of WGS in early diagnosis and treatments of diseases, as well as the feasibility of using this data to drive scientific research. Currently in the UK, blood spot tests are offered to all babies to check for 9 specific monogenic conditions. Some suggest that we should expand the screening criteria to include additional genetic conditions, and that WGS could be an effective way of doing this. Revealing the individual genetic makeup can be used to calculate the risk of various diseases, thus allowing earlier supervision as well as personalised treatment.
However, others argue that using WGS to look for a broad range of conditions in healthy babies may not be reasonable due to limitations of the technology and possible unsolicited results. According to a 2020 study, the genome sequencing technology for detecting errors of metabolism at birth had a sensitivity of 88% and specificity of 98%, which is not sufficiently accurate to become the primary screening method2. If the risk of developing diseases calculated by WGS data analysis is not conclusive enough, should it be returned to pre-symptomatic babies? Furthermore, interpreting the WGS results is difficult since various non-treatable diseases and complicated pathogenesis are not well understood yet. These findings may vary greatly in clinical significance and actionability – should results be given to patients when they are not preventable or extremely difficult to cure? How would this impact the family’s dynamic? In terms of unanticipated results, there are certain circumstances where a conflict may arise between the child’s rights and the family’s interest. As newborns lack the legal capacity to consent, their guardians are decision-makers of treatments. The controversies now centre on how WGS results should be managed and returned to benefit the family as well as protect the baby’s rights.
Although WGS may generate some clinically non-relevant or non-actionable outcomes, it is still the most efficient tool to detect rare pathogenic variants. On average, it takes 6 years from the initial symptoms to the accurate diagnosis of rare diseases when using conventional approaches. WGS could give insights on the genetic disease within a few days, which allows suitable treatments to be delivered as soon as possible. In addition, WGS provides the best means of identifying rare causal variants of polygenetic conditions like autism, connective tissue disorders and cardiomyopathies3. The accuracy could be further improved by combining with other screening tests to avoid false-positive results.
While there are concerns about letting healthy children wait to develop an illness, I would argue that genetics alone cannot dictate their destiny, and lifestyle pulls the trigger for most multifactorial diseases. Knowledge about a high risk for a disease can encourage parents to adopt lifestyle modifications to mitigate the risks. Most importantly, the focus should always be placed on conclusive findings where interventions exist to potentially reduce harm. For individual families, diagnosis of genetic conditions by WGS screening and early treatment is not only associated with the physical comfort for the child but also closely linked to the parents’ spiritual pursuit of bringing up healthy offspring. For the development of society, building a genomics data infrastructure through broad WGS data collection would help advance genetic research, transform personalized medicine, and stimulate a vibrant genomics industry, which would ultimately bring long-term benefits to the healthcare infrastructure and population.
In order to decide what kinds of results should be returned, we must consider the adequate protection of child’s rights. According to the Convention on the Rights of the Child (CRC), a child has the following rights related to the screening tests: survival, respect of the view, privacy, and non-discrimination, with provisions for extreme circumstances such as abandon or abuse. Although parents have the duty and ability of making medical decisions, screening results should be returned on the basis of the child’s best interest. Children could grow up to have the capacity to understand genetic information and decision making. Adolescents should have access to their genetic data and have rights to choose appropriate therapies. Personal sequencing data can be kept for future access, but privacy protection policies must be made to ensure the safe storage of DNA information and prevent it from being used for commercial purposes. Furthermore, sensitive findings like disorders in sex development, ancestry and intellectual capacity which have less clinical relevance should not be informed or retained.
In conclusion, WGS can effectively boost early disease diagnoses for babies, but the child’s rights and interests should always be given due weight when returning the medical findings. The application of WGS to newborn screening is a promising trend to improve supportive experience for the baby and the family.
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