Last updated on June 18, 2020
The last few weeks, I have written about the complex molecular immunity mechanism of CRISPR and how we can harness it to precisely edit genes in a gamut of cells. But the ability of CRISPR to treat genetic disorders, predispositions, and susceptibilities relies on our understanding of the genetic basis of disease. Since the completion of the Human Genome Project (HGP) in 2003, which sought to sequence the entire human genome, scientists have made great strides in connecting diseases and disorders with their genetic backgrounds. In the meantime, the invention of Next Generation Sequencing (NGS) in 2006 has drastically reduced the required time and cost of sequencing. The sequencing involved in the HGP cost over 1 billion dollars and took 13 years to complete. Since then, that cost has been declining and, in 2014, it dipped below $1000. There are even companies that have offered whole-genome sequencing for as little as $200. A whole industry has popped up around genotyping (which only involves sequencing specific genes and is thus much cheaper), where companies like 23andMe offer gene reports on health, ancestry, and certain traits. The lowering cost of genome sequencing, along with the increased understanding of the genetic basis of disease, has created a new opportunity for genetically personalized medicine. Not only will personalized medicine revolutionize how we diagnose and treat disease, but it will also help to eliminate some of the race-based and gender-based discrimination that arrises in one-size-fits-all medicine.
For years, medicine has relied on the oversimplified assumption that we are all, to some extent, the same. This is the basis of clinical trials, which test a particular treatment on a “representative” subset of people before making it available to the general public. Historically, this “representative” subset has consisted overwhelmingly of white men. In the 20th century, researchers avoided including women in clinical studies because they believed fluctuating hormones would needlessly complicate their results. In 1977, the FDA, spurred on by the birth defects caused by Thalidomide use in Europe, formally banned women of “child-bearing potential” from the early phases of clinical trials, where researchers were trying to determine a drug’s safety. The ban was lifted in 1993, and the NIH now requires women to be included in most clinical studies. But a gender gap still persists, and it contributes to a bias that can result in worse health outcomes for women. And even as clinical studies begin to narrow the gender gap, there is still a persistent race gap in clinical trials that contributes to minority discrimination within healthcare.
There are real medical differences between men and women as aggregate groups. For instance, women are more likely than men to experience nausea and shortness of breath during a heart attack, rather than the easily recognizable chest pain. But even these generalizations aren’t as clear-cut as they may seem. Every individual, regardless of sex, gender, or ethnicity, is composed of their own sliding scale of genetic and non-genetic factors. Large, inclusive clinical studies can give us a statistical basis to believe a treatment is safe and effective, but, on the individual level, there will always be outliers and variability. As we focus on subgrouping and labeling different “types” of humans, we actually lose a great deal of predictive power with regard to the individual. The goal of personalized medicine, therefore, is to regain that personal predictive power through careful consideration of an individual’s genetic and environmental risk factors.
With the help of faster, cheaper genetic screening, personalized medicine is already being done. In many forms of cancer, genetic screening can be used to subtype the cancer and choose the best possible treatment. Genetic screening has also made it easier to enact personalized preventative measures. For example, we now know that women possessing the BRCA1 or BRCA2 gene mutation have a higher risk of developing breast or ovarian cancer. Women known to have one of these gene mutations are, therefore, encouraged to get screenings earlier and more regularly.
According to the NIH’s Genetic Testing Registry, there are currently over 76,000 different genetic tests for more than 16,000 different conditions. Some of these tests can help doctors catch diseases earlier, decreasing overall mortality. Additionally, some of these tests can help doctors choose effective and safe treatments for patients, increasing quality and length of life. Undoubtedly, as scientists seek to understand the genetic basis of disease, more of these tests will be developed. And, hopefully, personalized medicine will become a more ubiquitous tactic for disease prevention and treatment.
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