The Cost Of A Human Life

Genetic screening describes a procedure in which embryos from an infertile woman (during IVF) are collected and tested for the presence of genetic anomalies caused by mutations- for example, detection of the genetic disorder polydactyly (the presence of extra fingers or toes) Genetic screening is recommended as some disorders are genetic- i.e., they can be passed down through alleles from generation to generation. Alleles are types of genes that present a certain characteristic (in this case, the presence of cystic fibrosis), and are dominant or recessive. Dominant alleles are alleles that always express their phenotype, whilst recessive alleles must be homozygous for its phenotype to be present. Therefore, with the knowledge of what type of allele causes cystic fibrosis, one can determine the chances that a child could inherit cystic fibrosis.

As expected, it is a highly controversial process, as if genetic screening highlights the presence of a debilitating genetic disorder is present in the foetus, the parents will face the tough decision of being offered an abortion. As such, the data used to suggest whether a child may suffer a genetic disorder from genetic screening must be extremely reliable, since it influences thesevital decisions over life and death.

On December 5 th 2023, Orchid Health (a provider of IVF treatment for fertility clinics in the USA) announced that instead of just testing embryos for genetic disorders, they would sequence the entire genomes of embryos, thus enabling clinics to look beyond single-gene mutations, but also multigene disorders and ‘rare gene variants’, allowing them to generate a risk estimate per embryo for a myriad of disorders. This differed from regular genetic screening as it promotes choosing embryos with desirable characteristics whilst discarding ones without them, which not only reduces birth to a calculated, mathematical affair, but is also akin to the ideas presented in eugenics.

This would mean (as in Fig.1), parents would be able to choose an embryo which has what they deem to be the best qualities from the ‘possible combination of alleles in offspring’. For each embryo tested, Orchid Health Clinic charges £2500, promising a highly accurate analysis after screening 99.99% of each embryo- thus allowing richer people to pay for more embryonic screening, allowing them to find embryos with the ‘lowest polygenic risk score’ whilst people unable to afford the treatment are left in the dark overthe possibledisorders their child may have.

The mechanism of achieving these polygenic risk scores begins with genetic screening, usually through amniocentesis (see Fig 2.). This involves the collection of amniotic fluid from the placenta, where it is then centrifuged at high speeds, with the resulting pellet of cells being cultured. This cell culture solution can then be screened for certain genes in its DNA, or (in the case of Orchid Health) have its wholegenome sequenced.

As expected, this raised objection from scientists globally, most notably the PGC (Psychiatric Genomic Consortium, whose data was used to determine Orchid Health’s risk estimates) as their “goal is to improve the lives of people with mental illness, not stop them from being born”. Concerns arise when speaking of the future use of polygenic risk scores in genetic screening. With increasingly more accurate technology and data analysis, will society be able to accurately predict characteristics (not just diseases) of each embryo? Some also argue that the financial implications of this treatment may further increase the inequality divide whilst also putting a cost on the difference between a healthy life and life of a sufferer of a genetic disorder (e.g., polydactyly). This implies the suffering of people with genetic disorders is quantifiable to a grand sum of £2500, thus further raising ethical issues as that clearly disregards the physical and psychological impact a genetic disorder can have on thesufferer and thepeople around them. Proponents of this research (like geneticist Mark Daly) argue that the point of genetic research should be to understand the ‘mechanisms of disease’, allowing for the discovery of new treatments to combat genetic disorders. A study in the Delaware Journal of Public Health supports this view of genetic screening, citing how understanding of the pathway of PelizaeusMerzbacher disease helped create 'novel gene therapies’ to stop the spinal muscular atrophy associated with this genetic disease.

To conclude, it is clear to see that genetic screening is a tool that can be used to effectively treat many genetic disorders and improve the lives of countless sufferers. However, in the words of Andrew McQuillin (a researcher at PGC), ‘Society must soon have a broader discussion about the implications of this type of genetic screening’, due to the worrying ethical dilemmas that arise from paying for whole genome sequencing.

Keywords:

Mutations: A change in the gene in the genetic sequence Homozygous: Having two identical alleles of the same gene Phenotype: The set of observable characteristics resulting from a specific genotype

Eugenics: a study on how to pass down desired characteristics within a human population. This ideology was used in Nazi Germany to justify their massacre of minority groups like Jews and the Romani.

Genome: The entire set of DNA in a cell

Centrifuged: A process that uses centrifugal forces to separate substances of different densities

Synoptic Links:

GCSE: 4.5.3.6 The use of hormones to treat infertility (the problems that require the need for IVF treatments and genetic screening)

4.6.1.4 DNA and the genome (how does DNA determine certain characteristics)

4.6.1.6 Genetic inheritance

4.6.1.7 Inherited disorders (how certain genotypes can lead to certain phenotypes and thus disorders, thus why genetic screening is necessary)

A Level: 3.7.1 Inheritance (determining the chances of a phenotype- a genetic disorder- being expressed)

3.8.4 Gene technologies allow the study and alteration of gene function allowing a better understanding of organism function and the design of new industrial and medical processes (how processes like genetic screening can be a beneficial tool for treatment)

References:

1.Funanage, Vicky L. “Impact of Genetic Testing on Human Health:: The Current Landscape and Future for Personalized Medicine.” Delaware journal of public health vol. 7,5 10-11. 15 Dec. 2021, doi:10.32481/djph.2021.12.005 Available from: https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC9124557/#r1

1. doi: 10.1126/science.zrxw8mv https://www.science.org/content/article/geneticsgroup-slams-company-using-its-data-screenembryos-genomes
2. Carango, P et al. “Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet repeat expansion in myotonic dystrophy.”Genomics vol. 18,2 (1993): 340-8. doi:10.1006/geno.1993.1474 Available from: https://pubmed.ncbi.nlm.nih.gov/8288237/

4.First clinical validation of whole genome screening on standard trophectoderm biopsies of preimplantation embryos Yuntao Xia, Willy Chertman,DhruvaChandramohan , Maria Katz, Elan Bechor, Ben Podgursky,Michael H oxie, Qinnan Zhang, Jessica Kang, Edwina Blue, Justi nChen, Justin Schleede, Nathan Slotnick, Xiaoli Du, Jonathan Kort,Robert Boostanfar, Eric Urcia, Barry B ehr, Noor Siddiqui bioRxiv 2022.04.14.488421; doi: https://doi.org/10.1 101/2022.04.14.488421