Today I would like to take you on a journey through human genetic testing and give you a glimpse of the very near future. Fasten your seat belts, this is as significant as the evolution from giant mainframe computers to personal computers. There are now techniques for altering DNA, the ability to reprogram human cells. The potential is enormous in treating cancers and other health conditions like heart disease, diabetes, and incurable infections like HIV.
Let’s start with some DNA vocabulary:
- DNA, deoxyribonucleic acid, the carrier of genetic information and the main component of our chromosomes.
- Chromosomes, the carriers of the genetic information that determines our fundamental and distinctive characteristics. Humans have 23 pair of chromosomes in most cells and the chromosomes carry genes.
- Gene, a unit of heredity that is transferred from parent to offspring.
- Genome, the complete identification of all of the genes on the chromosome.
- Gene sequencing, the map of our genomes on the chromosome.
To get an idea of the magnitude of this information, imagine a library containing 1000 books. These books would contain about 3 billion letters. Just a fraction of these letters, about the number of letters in one of the 1000 books, are the letters (genomes) that make each of us a distinct, unique individual, different from everyone else unless you are an identical twin. These letters (genomes) also cause, or give us the propensity, to develop certain diseases.
Before gene sequencing physicians could only test for a single gene, for example, the breast cancer gene or the cystic fibrosis gene. Scientists now know that single-gene diseases are relatively rare. Instead of arising from a single gene, most diseases result from mixes of many genes and environmental factors, as is the case not only with cancers, but also with diabetes, heart disease, and mental disorders. Therefore, it is better to view most human diseases not as directly inherited from a single gene, but rather inheriting a predisposition or higher risk of developing a disease. This ability to detect for predisposition/increase risk of common diseases is important because with this knowledge people can modify their behavior in ways that can reduce the likelihood that the disease will develop at all. Rather than treating diseases, doctors can counsel patients on strategies to diminish their risk of ever developing the disease.
Each of us is at some genetic risk of disease development, carrying between 5 and 50 mutations that carry some risk for disease. We may not develop the disease because we are not exposed to relevant triggers, or we might not live long enough. Every day there are more genetic tests to identify these mutations. Every day there are new drug and gene therapies that target diseases by replacing, manipulating, or supplementing those mutated genes.
Pharmacogenomics is a growing field focusing on genetic differences that cause drugs to work well in some people and less well in others. Someday physicians will use genetic tests to match drugs to an individual’s body chemistry, so the safest and most effective drugs can be prescribed.
Gene therapy is another strategy for identifying, cloning, and sequencing disease-related genes. Typically a copy of a normal variant of a disease-related gene is introduced into a disease-affected gene to alter its function.
Another form of gene therapy involves providing new or altered functions to a cancer cell by introducing new genetic material. This alters the cancer cells’ metabolism so that it dies. Similar techniques that can make cells immune to infection are being studied.
Finally, there is a very new and exciting technique called CRISPR-Cas9. This technique can reprogram or edit human cells, altering DNA. It does this by searching for disease-causing DNA, cutting it out, and the cell can then repair itself or corrected DNA can be patched in.
So where is all of this leading, where does this fit with the practice of medicine?
One day your complete DNA sequence or map may be part of your medical record. You may know for which diseases and cancers you are at high risk of developing and be able to adopt proactive behaviors to lessen your risk. If you learn you have a gene sequence that increases your risk for an untreatable disease, you may be able to remove that sequence from your DNA. One day it may be possible to alter the DNA of cancer cells, causing them to die. If a disease condition develops your doctor may be able to design individual therapy compatible with your specific DNA. You may be able to map your unborn child’s DNA and repair any DNA defect before birth.
While this information will dramatically improve human health, there are a number of complex ethical, legal, and social issues. What if parents could tailor-make their kids, increase the likelihood that their unborn child would be particularly athletic or have a certain hair or eye color? What if an unborn child is prone to a debilitating disease when they reach adulthood? Would that be a valid reason to terminate the pregnancy?
Physicians and patients have to consider the right to privacy, the right not to know, and religious beliefs among many other ethical factors. Knowledge is critical to help individuals make reasoned decisions about genetics and health. Once you go beyond looking for specific genetic mutations such as Down’s syndrome or cystic fibrosis, to mapping a fetus’ whole genome, things become fuzzy. The information is no longer a diagnosis but rather a predisposition, a question of odds. How likely is it to occur? Patients with their physicians will have to make prudent decisions when it is uncertain whether an event will actually occur.
Take home message?
Today we are still in the zone of starting with a disease that may have a hereditary component and doing the testing, rather than looking for things in pregnancy or in healthy people with good family histories. However, fasten your seat belts, we are moving rapidly towards an individual’s genome sequence as a fundamental part of his/her medical record. We are rapidly moving towards prenatal genome sequencing in unborn children. If you have specific concerns about your family’s history, talk with your doctor.
References
Klitzman, Robert, MD, Doctor, have you had your DNA tested? New York Times 02/05/15
Landro, Laura, The tricky impact of knowing your genetic data, Wall Street Journal 06/26/16
Mandal, Ananya, MD, History of genetics, www.news-medical.net/life-sciences/History-of-genetics/aspx
Park, Alice, A revolution in genetics, Time Vol. 188, No1, 42-48 , 2016
Reiland, Randy, Will genome sequencing make us smarter about dealing with diseases in our genes-or just more anxious? www.smithsonianmag.com 07/13/16
Understanding human genetic variation, NIH Curriculum Supplement Series-NCBI Bookshelf 1-23
