Whole genome sequencing - a policy discussion

Whole genome sequencing and the future of medicine: A discussion of policy implications ranging from genome privacy to designer babies.


The presidential race of 2016 was tight. That is, until information was leaked that Hillary Clinton has a genetic predisposition to early onset Alzheimer’s disease. How her genetic info was obtained is unknown; her campaign staff followed strict protocols to collect and destroy everything she touched – toothbrushes, bed sheets, cups. It may be that years before she was a candidate, a cunning opponent attended her book signings and patiently preserved the pages she penned until the moment was ripe. But the method and legality of the leak is irrelevant. Unlike in a jury case, one can’t instruct an entire electorate to ignore information that may have been illegally obtained. Thus began a new era of American politics: no longer was it simply video or written evidence of your past that was under scrutiny. Now, the DNA code prophesizing your future was also campaign material.

Presently, the above scenario might sound like science fiction. But an emerging technology called whole genome sequencing (WGS) is poised to blur the distinction between imagination and reality. WGS is the ability to decode the entire DNA sequence that makes an individual unique. While this technology is still too expensive and cumbersome to be applied on a population scale, the cost-per-genome is dropping at an astounding rate, much faster than has occurred with computing power.  WGS is beginning to enter the clinic as more physicians use it to help with diagnosis and treatment determination, but policies related to WGS are still in their infancy. In May, the Penn Science Policy Group gathered to discuss the emerging use of WGS and the implications it will have for medicine and society.

Privacy is a huge concern. One’s genome is like their medicine cabinet, except it reaches both backward into the past and forward into the future. The opening scenario might seem a little dramatic and highly specific, but there are already indications showing that government officials take measure to protect the President’s DNA and collect DNA samples from foreign leaders. Scenarios can be envisioned within the lives of civilians, too. Imagine a child custody case in which WGS showing a parent’s predisposition for cancer or neurological disease is used as evidence against their fitness for parenting.  The Genetic Information Nondiscrimination Act of 2008 (Pub.L. 110–233, 122 Stat. 881, enacted May 21, 2008, GINA) was enacted to prohibit the use of genetic information in employment and health insurance situations.  However, it does not cover life insurance or long-term care insurance, which is already proving problematic for some. How this law would apply to genetic sequencing obtained covertly or used for persuasion in civil courts or the public sphere is unknown.

Even consenting to undergo WGS has some privacy risks. A study published this year re-identified 50 individuals from de-identified genetic sequences using public access information like age and surname. Although the group of samples used represents a low hanging fruit for such hacking, it demonstrates the need for more focus on protecting anonymity of sequencing information.

A 2012 report to the President indicated that stronger baselines for privacy of WGS data are needed. Privacy protections at the state level are inconsistent. And although samples collected through federal agencies like the NIH and CDC have federal laws mandating confidentiality, privacy, and security, “currently, there are no overarching federal or industry guidelines indicating how commercial genetic testing companies should operate, what privacy controls they should implement, or what limits they should put on the use of genetic data and information.”

One hotly debated topic is the ethics of incidental findings from WGS. When a physician orders WGS because it may help explain a patient’s particular medical condition, they are “looking” for relevant information. However, many more things may be found in the genome that are not relevant to the original reason it was ordered, but may have health consequences for the patient or their family members. These consequential discoveries are known as incidental findings.

What happens when results incidentally find that a patient carries the gene for Huntington’s disease? Or a gene that predisposes them to colon cancer? Or for adverse reactions to certain anesthetics? Recently the American College of Medical Geneticists published recommendations urging that every WGS result be analyzed for the presence of mutations in 57 genes that are highly predictive of diseases with actionable interventions. ACMG recommends these findings be reported to the patient regardless of consent and age (includes children), and the patient’s only chance to not receive this information is to decline sequencing. Opponents argue that this practice goes against patients’ right to refuse unwanted medical tests and information, even if it might be beneficial. Opinions on this topic among PSPG members were diverse and conflicted, which showcases the need for thorough public discourse on this issue.

Additionally, there are applications of WGS that warrant discussion. Even seemingly benevolent intentions, such as preventing genetic disorders, can conjure up fears of a deterministic society rife with prejudices based upon genetic identity. The 1997 movie Gattaca portrays a grim vision of the future where fertilized embryos are screened to deliver babies with desirable qualities like a certain gender, perfect vision, and resistance to addiction. Children born naturally are considered invalids and forced into a working class that supports the more glamorous careers of those with superior genes. 

But this scenario is pretty far-fetched, right? Actually, not quite. A technique called preimplantation genetic diagnosis (PGD) already exists to enable carriers of certain genetic disorders to have healthy babies – the first child born from this procedure is now 23 years old. The real concern is that this technology will be used beyond preventing terrible diseases to selecting merely preferential traits. Some countries have enacted laws to prevent this application, such as the UK and Canada, but in the US there is no federal regulation of PGD. In fact, some parents have even purposely selected for children that are deaf. The two largest obstacles for widespread use of PGD are the cost (it must be combined with in vitro fertilization) and our lack of knowledge about the complex genotypes that determine many of the desirable qualities depicted in Gattaca. However, given the pace at which science and technology move, these possibilities should not be underestimated when considering policies for the future.

When the first human genome was sequenced, a wave of excitement rushed through the media as it anticipated a new era of medicine, one that was tailored to the uniqueness of our individual genetic identities. In a word: “personal.”  Personalized medicine has thus far been a disappointment, but that should have been anticipated. Only when the cost of genome sequencing and analysis drops to a point where it can become commonplace can we expect to benefit from its potential. 

Will WGS reach the tipping point soon and become a standard part of medical practice? It seems that although the cost is dropping, other limitations exist that will limit widespread integration of WGS in the near future. Many of the biologists in our group identified the bottleneck of WGS as the analysis and interpretation of genomic data. Trained professionals that can interpret and communicate this massively complex information are at a premium, and the clinical interpretation is still mostly meaningless. Nearly every genetic association identified with common diseases is too insignificant to be clinically useful. As a result, right now genomic data is more confirmatory than predictive. That is, knowing a patient’s DNA sequence is useful in diagnosing the cause of a disease, but rather useless in predicting whether or not it will develop. WGS on a newborn is not a crystal ball, yet still this information could assist in medical care throughout a person’s lifetime, making it an attractive companion to a patient’s medical record that will become more valuable as science progresses.

Although maybe not for another decade, we will eventually see the tools, professions, and knowledge of WGS progress to the point where it transforms medicine and everyday life. Current policies regarding WGS are lacking, varied, or incomplete. Federal regulations are needed that ensure security, privacy, and informed consent of WGS and restrict its malicious use while protecting the liberty of individuals and the benefits obtained from it. A future of personalized genetics is inevitable; it is our duty now to ensure we enter a future that uses WGS for minimal harm and maximal gain.

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