Genetics in the News
November 6, 2013
It seems like every week there is a new genetics story in the news. Angelina Jolie made the headlines last summer with her decision to have a double mastectomy, which was based on her family history and BRAC genetic tests. A couple who had struggled with infertility used genetic screening to select healthy embryos from their IVF procedure. And, recently, the NIH announced that they are looking into the ramifications of requiring genetic testing for all U.S. infants.
Genetic testing raises many questions: How reliable are the results? What should one do with the results? Does one have a right to not know his or her genetic history? Will genetic testing in utero lead to abortions? What about false positives or false negatives? Who else will know the results of the genetic tests? Can insurance companies penalize people with “bad” genes?
Interestingly, at the very time when we are able to sequence an entire human genome rapidly enough that infant genetic testing is feasible, we have learned that the genetic sequence is only part of the story. Epigenetic factors, those factors that are not related to the actual DNA sequence, also play a role in disease and whether a particular gene is turned on or off. This means that a read-out of an individual’s sequence of A’s, T’s, G’s, and C’s may not provide as much information as we once thought.
Let’s take a look at how genome sequencing works, and why it still doesn’t tell us everything. By looking at the science and how it is applied, we can readily see that there are many unanswered questions for bioethicists to consider:
By way of definitions, genome sequencing, or genetic sequencing, involves acquiring a read-out of the DNA nucleotides in an individual’s genome. Sequencing technology has advanced in the last decade since the human genome was first sequenced. The technology used in the Human Genome Project to sequence the genome was remarkably tedious. This technique, a process known as Sanger sequencing, involves looking at thousands of fragments of DNA and reading only the terminal nucleotide. The fragments are made from a template piece of DNA. Each fragment is longer than the one before because it adds nucleotides until it has re-built the original DNA sequence.
Today, scientists use “next generation sequencing” (NGS). This method involves a high throughput, allowing for much quicker sequencing and results. No longer do they look at individual pieces of DNA; instead, thousands of segments of DNA are sequenced at one time. An entire human genome can be sequenced in a matter of days. This technique involves taking fragments of DNA and using them as templates. These templates are washed with known nucleotide sequences that are “tagged” with markers (e.g., a fluorescent marker). These tags are then read, and a sequence is determined through complicated data analysis methods. (See here for a good discussion of this technique.)
Genetic screening involves looking for certain genes, traits, markers, or indicators of a disease. In screening, scientists are usually looking at a particular segment of DNA or checking for a particular chromosome that is a known marker for a disease. For example, when doctors screen for Down syndrome in an unborn child, they do so by looking at the genome of a fetal cell to see if it has an extra chromosome.
Additionally, there are a few diseases for which a particular gene codes. If a person has a certain gene, for instance, it will lead to that person eventually getting Huntington’s disease. Most diseases, however, do not have such a direct gene-to-disease connection, even when they are associated with a known genetic marker. The idea that one’s genetic sequence necessarily results in getting a particular disease or even having a particular disposition is known as genetic determinism. The BRCA gene is a counter-example to genetic determinism.If someone has the BRCA gene, then that person has a higher probability (or susceptibility) of getting breast cancer. This doesn’t mean she will certainly get breast cancer, though. This is why some people questioned Angelina Jolie’s decision to get a pre-emptive double mastectomy on the basis of her BRCA screening results. This is also partly why genetic screening is rife with ethical concerns.
About ten years after the completion of the Human Genome Project, the results of the ENCODE project were announced. ENCODE demonstrated that there is more to DNA than coding for proteins, and DNA is more complex than merely having a gene. Epigenetic factors, such as chemical tags on nucleotides, affect whether and how a gene is expressed. These factors arise for various reasons, including environment and behavior. Even if someone has a gene for a particular disease, the right epigenetic factors may also be necessary for that gene to be turned on. Furthermore, scientists are finding that some diseases are caused by epigenetic factors that have gone awry rather than a mutation in a particular gene.
One of the key bioethical concerns with genetic screening is what to do with the information from sequencing an entire genome, or even just from screening for a particular disease. Oftentimes genetics deals with probabilities, not certainties, and if individuals’ behavior cannot affect whether or not they develop some diseases anyway, then what advantage is there in knowing that they could possibly get one of those diseases? Is it even appropriate to tell such a person that he or she has the markers for a disease when the causes and probabilities for getting the disease are largely unknown? Another related issue deals with incidental findings. Here an individual may seek genetic testing to find out if she has the BRCA gene, only to find out that she carries the marker for some other disease, for which she was completely unsuspecting. Additionally, genetic markers often run in families, so now the individual must decide whether or not she is obligated to tell her family. Doctors are put in a similar position of whether or not he is obligated to tell a patient about incidental findings.
The NIH is considering making genetic sequencing standard practice for newborns. Current technology is already such that IVF combined with genetic sequencing allows particular embryos to be selected based on their genetic sequence. A recent news story reported the birth of a baby boy to the Scheidts-Levy’s; their doctors had used NGS to select one embryo (from the eight they had created through IVF) which did not have a particular chromosomal abnormality. The idea was that a healthy embryo would be more likely to implant and not lead to miscarriage. According to the Washington Post, “The big advantage of using NGS is that multiple embryos can be screened simultaneously, significantly reducing costs.”
There is a certain disquiet surrounding genetic technologies. The rhetoric is in terms of helping people, either helping them to find cures for diseases or helping them know more about themselves so they can make informed decisions in regards to lifestyle, preventative measures, or financial planning. . But knowing your baby’s genetic make-up before he or she is born, or at birth, is different from using a genetic test to diagnose a disease. The rhetoric too easily slips from that of healing by identifying the cause of a disease to preventing (or controlling) “undesirable” effects of a genetic make-up by predicting them. The 19th and 20th centuries testify to how easy it is to use genetics to make predictions and draw conclusions about how such predictions should be interpreted that are deeply and often subtly influenced by societal prejudices. It is important to be cautious when it comes to genetic predictions; the difference between diagnosis and prediction is important in responsible ethical analysis.