How close are we to genetic medicine?

A couple of posts ago ("The future of medicine, and other fantasies") I commented on a recent Scientific American article on the future of medicine (1). The author of the piece focused on the promises of stem cell research and potential payoffs from the genome project. I share his hopes for medical breakthroughs from stem cell research, but I find his take on genomic medicine rather naive:

“[The] one-size-fits-all medicine we have seen for the past 100 years will yield to medicine tailored to each individual. Doctors will prescribe a custom prevention program and make comprehensive diagnoses according to each patient′s genes, bacteria, allergens, fungi, viruses and immune system.

Studying the specific combinations of genes and environmental factors can lead to changes in diet, drugs and behavior, helping us extend our healthy years.

Your genome will get sequenced every year or so to check for the emergence of cancer cells, autoimmune cells, inflammation, and so on and will help predict what treatment may work best if a disease appears” (1)

What′s so improbable about this scenario? It ignores the causal role of the food and drug industries in our health crisis. How do you develop custom prevention programs, improve diet, and change behaviour while food companies do everything in their power to peddle junk food and drug companies maintain an iron grip on the medical profession and their "healing" monopoly?

The authors of two recent articles on the promise of genome-wide association studies (GWASs) — the prediction of disease risk from the patterns of genetic mutations — are a good deal more realistic in their assessment of the promise of genetic medicine (2,3). They point out that so far genome-wide screening has neither lived up to expectations nor is it clear that it would be cost-effective.

Genome-wide screening has identified a number of alleles (gene variants) associated with various diseases, but to date no major susceptibility alleles have been found; each of the known risk-associated alleles has at most a small effect on disease risk. Even their combination accounts for only a small percentage of known genetic risk variations, likely because the relationship between genetic variation and environment is as yet poorly understood:

"What is becoming clear from these early attempts at genetically based risk assessment is that currently known variants explain too little about the risk of disease occurrence to be of clinically useful predictive value." (2)

Even if GWASs led to reliable predictors of disease risk, population-wide screening would hardly be justified; medical expenses already threaten to bankrupt most industrialized countries. Screening everyone would at best identify those who are genetically predisposed to develop a certain disease but have no family history of that disease. Even then genetic screening would only be worthwhile if saving lives depended on identifying and treating individuals at risk before clinical symptoms appeared.

Genetic risk factors only predispose to disease; actual disease development depends on gene-environment interactions. Prevention would therefore mostly consist of lifestyle changes like smoking cessation, dietary improvements, and exercise. It is questionable whether the threat of a possible future illness will motivate people to make the necessary changes; and without implementing preventive measures genetic screening is pointless:

"Before genetic information is used in public health screening, it must be shown that:

• such information predicts disease risk better than phenotypic information;
• cost-effective interventions exist for those at increased genetic risk;
• these interventions are more cost-effective than population-level interventions;
• genetic risk information motivates desired behaviour change.

Currently there are no examples of genetic screening for disease risk that satisfy these criteria." (3)

Sequencing the human genome was a major scientific achievement, but we are unlikely to derive significant health benefits from it. Population-wide lifestyle changes offer by far the greatest potential pay-off, and for that you don′t need your genome sequenced. Healthy living is a good idea for everyone, regardless of genetic make-up.

Sources:

1. Church G. Medicine I can call my own. In What comes next: Experts predict the future. Scientific American September 2010.
   http://www.scientificamerican.com/article.cfm?id=what-comes-next&page=5
2. Feero WG, Guttmacher AE. Genomewide association studies and assessment of the risk of disease. New Engl J Med 2010;363(2):166-176.
   http://content.nejm.org/cgi/reprint/363/2/166.pdf
3. Hall WD, Mathews R, Morley KI. Being more realistic about the public health impact of genomic medicine. PLoS Medicine 2010;7(10):e1000347.
   http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000347