Genomics has great promise but also faces hurdles in personalised medicine

February 23, 2017
Sharon Horesh Bergquist, physician, teacher, researcher in preventive medicine and healthy aging at Emory University, writes about this effort as part of a research team that hopes to discover novel biological markers that can be used to diagnose and treat common chronic conditions, including Alzheimer’s disease, heart disease, diabetes and cancer.

Personalized medicine, Bergquist writes, has the potential to transform how we diagnose, prevent and treat disease. Mapping a person’s unique susceptibility to disease and targeting the right treatment has deservedly been welcomed as a new power to heal. But even as the human genome, a complete set of human DNA, was identified and mapped a decade ago, genomic science remains in its infancy. The Human Genome Project has yet tot directly affected the health care of most individuals.

No full understanding yet

 ‘It’s not that there haven’t been tremendous breakthroughs. It’s just that the gap between science and its ability to benefit most patients remains wide. This is mainly because we don’t yet fully understand the complex pathways involved in common chronic diseases.’

The research team Bergquist is part of, has taken on the ambitious goal of narrowing this gap. New technologies are allowing us to probe DNA, RNA, proteins and gut bacteria in a way that will change our understanding of health and disease. Our hope is to discover novel biological markers that can be used to diagnose and treat common chronic conditions, including Alzheimer’s disease, heart disease, diabetes and cancer.

Of course, genomics and precision medicine are only part of the answer.  Chronic diseases are only partially heritable. Genes inherited from parents aren’t entirely responsible for the risk of getting most chronic diseases. The estimated heritability of heart disease is about 50 percent. For Type 2 diabetes mellitus it’s 64 percent, for Alzheimer’s disease it’s 58 percent. The environment and lifestyle choice are also major factors; they can change or influence how the information coded in peoples  genes is translated.

Another hurdle is the complexity of chronic diseases. Rather than being controlled by a few genes that are easy to find, they are weakly influenced by hundreds if not thousands of genes, the majority of which still elude scientists. ‘Unlocking the infinite combinations in which these genes interact with each other and with the environment is a daunting task that will take decades, if ever, to achieve.’

Prevention simpler solution

In the meantime, prevention is a simpler solution, since many of the deadliest chronic diseases are preventable. For instance, among U.S. adults, more than 90 percent of Type 2 diabetes, 80 percent of coronary arterial disease, 70 percent of stroke and 70 percent of colon cancer are potentially avoidable.
Smoking, gaining weight, poor diet alcohol consumption are all risk factors that have a profound impact on gene expression, or how instructions within a gene are manifested. addressing these factors will likely remain fundamental in preventing these illnesses.

Genomics for personalised medicine

Using genomics for personalised medicine has yielded some results. For instance, variants in genes that control an enzyme that metabolizes drugs can identify individuals who metabolize some drugs too rapidly (not giving them a chance to work), or too slowly (leading to toxicity). This can lead to changes in medication dosing.

When applied to prevention, however, identifying our susceptibility at an earlier stage has not aided in avoiding chronic diseases. Research challenges the assumption that we will use genetic markers to change our behavior. More knowledge may nudge intent, but that doesn’t translate to motivating changes to peoples lifestyle. Increased knowledge may even have the unintended consequence of shifting the focus to personal responsibility while detracting from a joint responsibility for improving public health.

Developing targeted treatments

Perhaps the most awaited hope of the genomic era is the ability to develop targeted treatments based on detailed molecular profiling, in other words: subdividing diseases into new classifications. Rather than viewing Type 2 diabetes as one disease, for example, we may discover many unique subtypes of diabetes.

 This already is the case with some cancers like melanoma, leukemia or metastatic lung, breast or brain cancers. A more tailored treatment here can improve the chance of survival. But for complex, chronic diseases, relatively few personalized targeted treatments exist. Customizing treatments based on uniqueness will be a breakthrough, but also poses a challenge: Without the ability to test targeted treatments on large populations, it will make it infinitely harder to discover and predict their response.

‘The very reason we group people with the same signs and symptoms into diagnoses is to help predict the average response to treatment. There may be a time when we have one-person trials that custom tailor treatment. However, the anticipation is that the timeline to getting to such trials will be long, the failure rate high and the cost exorbitant.’

But despite the inherent limitations to the ability of genomic medicine to transform health care, medicine in the future should unquestionably aspire to be ‘personal’,  Bergquist concludes. Genomics and molecular biosciences will need to be used holistically – in the context of a person’s health, beliefs and attitudes – to fulfill their power to greatly enhance medicine.