DNA and genetics

DNA (AKA “deoxyribonucleic acid” and “the blueprint of life”) was first identified as a component of cells almost 150 years ago. In the following decades, its chemical nature was determined.

At about the same time, genetics developed an understanding of the inheritance of traits. These two threads came together in the first half of the 20th century with the understanding that DNA provided the molecular basis for genes; and that the inheritance and variation of traits depended on the conservation and mutation of DNA, respectively.

The latter half of the 20th century saw the development of technology for rapidly sequencing DNA (determining its underlying chemical structure, or “sequence”), followed shortly by the initiation and use of international, open access database resources for accumulating, standardizing and using DNA sequence data.

Over the past 20 years, technology has greatly accelerated our ability to sequence DNA: over longer stretches (scientists now routinely determine the complete DNA sequence, or genome, of many different species and individuals within species), from long-dead specimens (e.g., pre-historic remains), at lower cost ($10K and step right up!), more rapidly (a few weeks for a complete genome), and with less stringent requirements for the amount and integrity of the source DNA.

Using DNA to decide

As our ability to sequence DNA took off, researchers sequenced the same region of DNA across many different individuals: both within a species (e.g., two people) and across different species (e.g., a cow and a duck). As a result, we now understand both that there are DNA differences between even very closely related family members (e.g., visually identical twins), and that more distantly related species have more differences (mutations) in their DNA than more closely related species.

The applicable use of DNA to identify or categorize the source organism has also greatly expanded, and often well beyond the range of traditional methods, because the DNA is for the most part the same for any organism regardless of the organism's stage of development, sex or body part.

Perhaps the first broadly used and widely touted test based on DNA analysis was DNA profiling, for which several loci of the human genome are sequenced to determine the number of copies of a short repeating DNA sequence. This test is now routinely used for determining parentage (e.g., paternity testing), convicting crime suspects and exonerating prisoners whose original convictions were based on other evidence. Because of the need for the tests to hold up in a court of law, and because they were an early example of DNA-based analytical test, there was healthy debate about the conclusions that could be drawn from such tests and with what degree of confidence, certification of the laboratories performing the tests, and reliability of protocols for capturing, archiving and retrieving the source of the DNA and the analytical results.  The Innocence Project, for example, has been involved in nearly 300 examples where previously convicted and imprisoned individuals have been exonerated of the crime based at least in part on subsequent DNA analysis.

Another, more recent application has been the use of DNA barcoding, in which the same short sub-region of the same gene is sequencing across a number of organisms to build a reference database that allows any sequence of the same region in a new specimen to be identified by comparison to the database. This approach has been put forward for a number applications for which species identification is important, and has been used to identify mislabeled fish in restaurants, unadvertised plant material in herbal teas and other herbal products, birdstrike identifications on airplane wings from submerged wreckage. The use of DNA barcoding for such tests is just now crossing over into the mainstream: the U.S. FDA, for example, has recently posted a Standard Operating Procedure for identifying fish with DNA barcoding in the context of meeting FDA regulatory requirements.

A final example is the use of genetic variation in patients to support physicians deciding whether or not and which therapies to administer.  DNA mutations can affect the kinds of proteins in our cells, and these differences can affect both the degree and kind of negative side affects and positive therapeutic responses a patient experiences.  As an example, the FDA has simultaneously approved a new biotherapeutic drug for treating non-small cell lung cancer as well as a new diagnostic test that identifies the 1 in 20 patients -- based on re-arrangments of their DNA -- who are most likely to benefit from the new drug.  This patient-by-patient optimization, or personalized medicine (AKA precision medicine), is just beginning to have an impact on treatment of disease.

In addition to the scientific and technological challenges associated with establishing innovative uses of DNA analysis, a host of economic, societal, ethical and legal issues arise and have to be addressed by the community as new technologies and applications come into play.   Examples include: individual privacy, "Direct to Consumer" administration of genetic testing, legal admissibility and statistical rigor as well as laboratory practice, certification and training.