When Gattaca was released in 1997, it was fantastical sci-fi fiction or - at best - a future that seemed beyond our lifetime. Twenty years later genome sequencing might not allow us to design individuals, but it does give us unprecedented understanding of our genetic profile. It goes a step beyond genetic testing to understand the whole cells - their structure, sequence and impact - that determine so much of who we are and, increasingly, how we live our lives.
This technology is becoming more available at more accessible price points, raising questions around the management of this data - how it impacts individuals and society, the value of the insights it provides, and at what cost.
What genome sequencing is, and how it differs from genetic tests
How genome sequencing is already being used in research and health care, and how this is translating in clinical practice
The information that can be understood from profiles and how it can be used to alter the health and lifestyles of individuals
The implications of this technology for the privacy of individuals, including the burden of disclosure
How this technology impacts the future of health insurance
Dr Ingrid Winship - Executive Director Research, Melbourne Health
Paul Beaver (PhD) - Co-founder and Chief Scientific Officer, FitGenes
Alex Tighe - Commercial Lawyer, Holding Redlich
First, Genetics 101…
Each of us are made up of billions of cells containing our genetic information. DNA is a strand of sequenced bases (chemicals) that form our genetic code - a gene. Each gene is an instruction on who you are - for example your eye colour, or your height. These genes come together to form chromosomes, and (ideally) 23 pairs of these form a cell.
Almost every cell has the same DNA, and the study of these cells is genomics. Genomics differs from genetics in scale; the former studies your complete DNA (the big picture), and the latter studies individual genes (small scale).
An ‘error’ or mutation in your genes can lead to an illness or condition. Errors are often hereditary - referred to as ‘genetic disorders’ - and include examples such as Huntington’s Disease and Cystic Fibrosis. A mutation in our DNA can occur due to environmental factors or behaviours, such as smoking.
A genetic test can determine if you have a genetic disorder and the likelihood it may manifest in a disease or condition. These tests gained a bigger profile with the announcement of Angelina Jolie’s double mastectomy and (later) the removal of her ovaries after discovering she carried the gene for breast and cervical cancer (BRCA1). Genome sequencing results in a profile that identifies several risk factors which an individual may be vulnerable to, leading to a disease or condition. This information can also assist in understanding how to prevent these risks from manifesting.
So where is this happening?
Genome sequencing is occurring in research and clinical practice right now, and the technology is developing quickly - becoming more affordable, and marketed direct to consumers by companies like 23andMe.
The consumer options are often a small indication of the potential this technology is demonstrating in areas such a autism spectrum disorders, cardiovascular health and fertility. In a research project conducted through LaTrobe University, genome sequencing succeeded in identifying common genetic factors amongst mothers and their mildly autistic sons. FitGenes and LaTrobe were able to pinpoint commonalities in the mothers (such as age of the mothers and exposure to stress) which led to inflammation of the developing brain of the foetus, leaving them vulnerable to free radicals. The gender of these children also played a role, identifying that oestrogen is a natural defence against free radicals. These risks ultimately affected Vitamin D receptors, which in turn manifested in the development of mild autism spectrum disorders. The identification of these led to a treatment plan, where the diets and lifestyles of the children were altered resulting in a decrease in symptoms.
While in cardiovascular research, the ‘one-size-fits-all’ approach is being challenged through the identification of risk based on a genetic signature that goes beyond current standardised calculators. Researchers and practitioners have been able to identify how, for example, individuals who are physically fit and eat a healthy diet still have hypertension. This condition can lead to diabetes, stroke, heart failure and heart disease.
The research that is underway is translating into clinical practice as personalised health plans. These guide your diet and behaviour so that you might prevent the diseases or conditions that you are genetically predisposed to from manifesting.
Does this mean that your genes are your destiny?
In short, no. These tests provide knowledge, and knowledge - in this instance - is both power and a reason for optimism. Understanding the risks of your DNA can also help you to understand what can be done to intervene, while the role of your environment should also not be underestimated. For example, exposure to toxins can temporarily or permanently alter your DNA. Toxins can be introduced by smoking, diet or drugs (for example).
Genome sequencing seeks to identify the driver that may lead to future conditions or diseases. The keywords for this technology are prevention and intervention. Profiles show us the roadmap and enable us to determine our own destination - a choose your own adventure that gives can give us control over the ending. In the case of fertility, the identification of the MTHFR (methylenetetrahydrofolate) gene can help women to understand why they may have suffered one or more miscarriages, and provides the insights as to how they might avoid future miscarriages (i.e. increasing folate).
But with great knowledge, comes great responsibility (and questions of ethics)
If this testing can tell us so much about ourselves why is it not standardised? This question raises concerns of the right of each individual not to know what their DNA holds. It also draws the distinction between treatment and cure.
Newborn screening tests are performed right after birth. These are an example of standardised genetic testing that checks for a set of rare and serious conditions. However, as we have identified, genomic sequencing is a big picture profile and one that (arguably) every individual should have the right to know, or not to know.
It is important to note that knowing your profile does not provide a cure to conditions one may have now or in the future - for example, disabilities. Genome sequencing is not a path to avoiding all suffering or disability, there is the consideration of the influence of environment as well as the rights of individuals to live and function in society with physical and mental disabilities.
The recommendation of experts is that profiles should not be undertaken in isolation from other health practitioners. Depending on your reason for sequencing, and what treatment or lifestyle changes you may require after your profile is complete, counsellors and other professionals should be (and are) involved in assisting individuals deal with the outcome of their profile. Again, this information cannot be shared between practitioners without the consent of the individual.
But if you do have this information, what are your responsibilities and protections?
The ethics at play in genome sequencing are multi-faceted.
The question was raised, if you and your partner are considering children and one of you has a genetic condition that may be passed down, should you proceed with having children? In these instances it is important to remember that again genes are not destiny, and something that supports this is ‘penetrance’. Penetrance refers to individuals who may carry a genetic disorder that does not manifest, and it should be noted that genomic sequencing does not allow individuals to ‘design’ their children. In the cases of gender-specific hereditary disorders, the gender of an embryo can be chosen with counselling. Beyond this however it is not possible to use genomic sequencing to influence the genetic profile of children in Australia.
There is also the consideration of the burden of disclosure. Should you undertake sequencing and receive a profile, are you required to share this information with relatives, partners or insurers? The answer is complex. With regards to relatives and partners your information cannot be shared without your consent. Consent is accounted for by accredited practitioners when you undertake sequencing. Should you wish to share the information with relatives you can permit your health care professional to do so. They cannot offer this information proactively. In very rare instances, under Australian federal law (which supersedes Victorian state law), a health care professional can disclose information but only if they feel there is an immediate danger to relatives.
While life insurers can require you to disclose any genetic profile or test that you may have done, health insurers currently cannot. However, from a legal perspective caution is highly recommended. While this technology is new, there is no expiry date on this information and it would be naive to expect there would be no ramifications for not disclosing it at some point in the future.
What could this mean for society?
Health insurers have two paths before them. Should genome sequencing become more common, it could be possible for health insurers to require this information be disclosed and that it may then affect the price of your cover. This has the potential to increase the gap between those who can afford private health insurance and those who cannot, or dissuade individuals from having their genome sequenced.
The other path could be to use genome sequencing to offer preventative treatment options to customers. By favouring intervention in identified risk factors, health insurers could play a vital role in empowering individuals to avoid the conditions or diseases individuals may be vulnerable to developing. The economic implications being a reduced burden to the public health purse and that covered by private health insurers.
As prevention is considered to be more cost efficient than treatment the hope is that insurers will proceed down this path.
How can we increase the profile of genome sequencing and where should you go for more information?
Simply - the supply and use of credible sources of information. While there are many offshore companies offering genome sequencing their accuracy and ethics can be questionable. Some user testing carries a risk of 5% error, while others return a report encouraging customers to purchase a range of supplements from a particular company which can leads to questions of credibility.
The first port-of-call should be your General Practitioner. GPs can provide a referral and direct you to an accredited practitioner. Unfortunately, genome sequencing is not yet covered under Medicare. Only children within Victoria with rare conditions or diseases can access the profile at no cost. Other than your GP, Melbourne Genomics Health Alliance is an excellent place to start your research.
As research continues to permeate clinical practice the overall fluency of health care professionals in genome sequencing will increase. This will aid raising the profile of genome testing for the general public and ensure they receive ethical and useful information, along with the support required to improve their health and lifestyle.