Cracking the Code: Medical Genetics and its Past, Present, and Future

A, T, G, C.  These four letters form the code that is the basis of all life on Earth, from the simplest bacteria to the complex consciousness of humans.  Yet while this ubiquitous system of heredity is truly incredible, it is not infallible; genetic disorders produced by errors in the code have been a part of life for as long as life has existed.  Recent science, though, has found a way to fight back against nature.  The emerging field of medical genetics makes use of modern sequencing techniques, the availability of huge sets of genomic data, and statistical comparisons to pinpoint disease-causing mutations in patients.  While very promising for the future of medicine, the use of readily available genetic information also raises some difficult ethical hurdles that must be cleared.


When Gregor Mendel first began performing his experiments on pea plants in the mid-19th century, not much was known about heredity except that children usually resembled their parents.  Mendel’s now famous research, which hypothesized “particles” of inheritance passed from parents to offspring, was overlooked until 1900, when its discovery led to the accelerating growth of genetic study [1].  Genetic diagnostic methods up to this point had mainly consisted of examining a patient’s family history of disease, illustrated by pedigree charts that could trace a trait of interest [2].  While this technique is still used today to determine the possible identity of a disease or the probability of acquiring it, it does not do much to illuminate the causes or possible treatments.

In the early 20th century, Mendel’s theory was refined and the “particles” were pinpointed by Boveri and Sutton to be chromosomes located in the nuclei of every eukaryotic cell [3].  Chromosomes are dense bundles of DNA that are replicated whenever a cell divides; a normal human body cell has 46 chromosomes divided into 23 pairs (one from each parent).  Cytogenetics, the examination of chromosomes under a light microscope, is another old but useful diagnostic technique that can identify chromosomal deletions or other aberrations [4].  Disorders such as Down syndrome or Jacobsen syndrome can be diagnosed through cytogenetics.

In the 1950s, a number of scientists, including Franklin, Watson, and Crick, elucidated the structure of the genome-encoding molecule, DNA.  It is now known that DNA, or deoxyribonucleic acid, is a long chain made up of a series of four different nucleotide subunits (A, T, G, C) linked by a sugar-phosphate backbone; this sequence of nucleotides makes up the genome that contains the genetic information for the entire organism.  Their discovery revolutionized the life sciences and kickstarted the fields of molecular biology and molecular genetics, allowing researchers to examine genetic information at its most basic level.  The extremely long, as many as 3 billion nucleotide pairs in humans, stable chains of DNA can be divided into genes, each of which codes for a sequence of transient RNA (ribonucleic acid) which in turn codes for a specific protein.  Thus, a mutation in the DNA of a gene can lead to an incorrectly formed or even non-existent protein, which can have drastic consequences for a person’s health.

Since the discovery of DNA’s structure, techniques for DNA sequencing have emerged, meaning that researchers can now deduce the physical sequence of nucleotides in a genome.  These, along with DNA amplification through polymerase chain reaction (PCR), have become some of the most useful techniques in modern medical genetics and molecular biology [1].  In the last 20 years, entire genomes of multiple species have been sequenced, including Homo sapiens, which was accomplished in 2003 through the Human Genome Project, after a decade of work and $2.7 billion spent.  Today, a human genome can be sequenced in just a few days for around $5,000, illustrating the rapid pace at which genetic technology is advancing [5].

The full implications of personal genomic sequencing for medicine are just beginning to become apparent.  Whereas pedigrees and cytogenetics are still useful for identifying certain disorders, they lack the fidelity to pinpoint many diseases and provide no suggestions for treatment at all.  However, DNA analysis allows clinicians to examine a patient’s body at the molecular level.  This can provide insight into potential future health risks, such as the recently discovered BRCA tumor-suppressor genes in which certain mutations cause an increased incidence of breast cancer, or APOB and LDLR gene mutations which cause higher cholesterol levels [6, 7].  With this kind of information, a doctor can recommend pre-emptive steps or medication to reduce a patient’s chance of developing a serious disease down the road.

However, wide-scope sequencing also raises some difficult ethical considerations. Suppose that in examining a person’s genome for BRCA alterations, a doctor happens to find the mutation that is known to lead, in later life, to Huntington’s disease, currently incurable and fatal.  The doctor must decide whether it is their moral duty to give the patient this potentially serious and life-changing information, or to leave them in blissful ignorance.  Earlier this year, the American College of Medical Genetics and Genomics released a document listing dangerous but treatable mutations that doctors were recommended to inform patients of, while leaving other mutations up to discretion; these suggestions have proven to be extremely controversial though, and there is currently no consensus on dealing with this issue [8, 9].


Despite the ethical issues to be dealt with, the future is bright for applications of medical genetics.  It is now becoming possible for treatments to be individualized to a patient’s specific genetic makeup.  “Most medications that are developed for diseases truly help only a very small percentage of the people who take them,” says Dr. Eric J. Topol [10].  “It’s not that they’re bad medications, it’s just that every person is unique, and medications are developed for extremely broad populations.  The future will be different … We’ll eventually be able to tailor medications to a person’s specific genomic make-up, and we’ll know whether a person can be helped by a certain medication or not.”  An example of this kind of tailored therapy is RNA interference, in which short pieces of RNA deactivate mutant genes while leaving normal variations untouched [11].  Because RNA interference is specific down to a single nucleotide, this type of treatment is being considered for conditions like sickle cell anemia, which is caused by a single point mutation [12].

Sequencing technology has now advanced to a point that allows medical geneticists to perform mass comparisons between the genomes of groups of interest.  Cancer research in particular is benefiting from approaches like this, as cancer is one of the most complex, varied, and widespread genetic diseases facing the medical community.  “Big data” of the sort acquired from sequencing allows clinicians and researchers to make some sense of genetic aberrations in the context of disease.  For example, the Pediatric Cancer Genome Project is an ongoing group effort that aims to sequence the genomes of hundreds of childhood cancer patients, and to then use this information to find the individual mutations that occur most often in various types of cancers [13].  Researchers can then perform functional analyses on these mutations in controlled settings to determine their effects on the disease.  These kinds of studies have yielded huge results since their inception, such as the recent identification of brain tumor-causing mutations in genes like BRAF and H3F3A [14].  Eventually such discoveries will lead to more specific diagnoses and treatments.

The widespread availability of and relative ease with which a genome can be sequenced is good news for the medical community, but as this information becomes more accessible, many legal questions must be answered.  Should a man’s ability to get health insurance be affected if it is known that he has certain mutations that increase his risk of catastrophic liver failure?  Should a school hire a teacher if her genetic information shows a predisposition to schizophrenia?  The United States government has already set up laws for these sorts of pressing issues: the Genetic Information Nondiscrimination Act of 2008 makes it illegal for health insurance companies and employers to discriminate against a person based on their genetic information alone [15].  What, then, is an acceptable use of a person’s genetic code?  All of these conundrums will soon be at the forefront of medicine and law, as whole genome sequencing becomes more prevalent in everyday society.

Humanity has long been subject to random, often harmful mutations in its genetic code, but for the first time in our history we have the ability to combat the ailments caused by these mutations.  Through the examination of life’s most basic elements, medical genetics has and continues to open doors to incredible possibilities.  Though the technology is still developing, and there are increasingly pressing ethical and legal issues to be faced, medical genetics is creating a revolution in human health that will sweep across society for years to come.


1. Ananya Mandal.  “History of Genetics.”  News Medical.  Accessed Sept. 21.
2. Laura M. Gunder McClary and Scott A. Martin.  2010.  “Diagnostic Techniques in Medical Genetics.”  In Essentials of Medical Genetics for Health Professionals, 21-30.  Jones and Bartlett Learning, LLC.  
3. “Genetics and Genomics Timeline: 1902.”  Genome News Network.  Accessed Sept. 21.
4. R.E. Pyeritz. 2013.  “Fundamentals of Human Genetics.”  In CURRENT Medical Diagnosis & Treatment 2014 edited by M.A. Papadakis, S.J. McPhee, M.W. Rabow, T.G. Berger.  New York: McGraw-Hill.  Accessed September 21.
5. National Human Genome Research Institute.  “The Human Genome Project Completion: Frequently Asked Questions.”  Last modified Oct. 30, 2010.
6. National Cancer Institute.  “BRCA1 and BRCA2: Cancer Risk and Genetic Testing.” Last modified Aug. 5, 2013.
7. “Hypercholestorolemia.”  Genetics Home Reference.  Last modified March 2007.
8. Robert C. Green, et al.  2013.  “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing.”  American College of Medical Genetics and Genomics.  Accessed Sept. 21.
9. Ira Flatow et al. “Whole Genome Scans Could Reveal Too Much.”  Interview. June 7, 2013.
10. Eric J. Topol.  “Scripps Genomic Medicine.”  Scripps Translational Science Institute.  Accessed Sept. 21.
11. Kseniya Gavrilov and W. Mark Saltzman. “Therapeutic siRNA: Principles, Challenges, and Strategies.”  Yale Journal of Biology and Medicine 2012; 85(2): 187–200.
12. D.S. Schwarz, et al.  2006.  “Designing siRNA that distinguish between genes that  differ by a single nucleotide.”  PLoS Genetics 2006; 2(9):e140.
13. St. Jude Children’s Hospital and Washington University in St. Louis School of Medicine.  “Identifying Cancer Mutations.”  Pediatric Cancer Genome Project. Accessed Sept. 21.
14. J. Zhang et al. “Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.”  Nature Genetics 2013; 45(6):602-12.
15. National Human Genome Research Institute.  “Genetic Information Nondiscrimination Act (GINA) of 2008.”  Last modified March 16, 2012.

Jake is a second-year student at the University of Chicago majoring in Chemistry.  He is interested in the interplay between chemistry and biology and has experience working in a cancer genetics lab. Follow The Triple Helix Online on Twitter and join us on Facebook.