In 1990, the Human Genome Project began with the goal of sequencing the entire human genome. Taking 13 years and costing $2.3 billion, its completion was heralded as a landmark event. Since then, with increasing interest and commercial competition, genome sequencing has seen rapid progress and costs have plummeted while accessibility has risen significantly. Now, individuals can have their entire genome sequenced for less than $1,000 and see their results in a few days.
Whole genome sequencing is the process of figuring out the DNA sequence of an individual’s entire genome. Using current diagnostic tests, doctors are only able to diagnose a disease after their patients have already developed it. However, genome sequencing allows a doctor to predict whether an individual is at risk of developing certain diseases in the future, the mechanisms under which these conditions will develop and to pre-emptively treat the patient based on their own unique genetic make-up. Will whole genome sequencing be the breakthrough that truly unlocks personalised medicine?
Genome sequencing and personalised medicine
Despite patients’ differences in race, gender, background, diet and a multitude of other factors, treatments for diseases are remarkably similar for patients, usually involving a combination of medications, surgery, chemotherapy and/or radiotherapy. This is because, for most diseases, treatments are based on ‘standard care’, which mean applying the same treatment protocols that are effective for the majority of patients. However, this approach can leave those patients who do not respond to standard treatments in a precarious position. Especially with cancer, serious or rare diseases, this can result in some patients being subjected to rounds of ineffective treatments which may not offer any reasonable chance of success, leading to significant waste of time, money and effort.
Whilst most diseases are associated with genomic variations, how it affects individuals can differ based on their own genetic codes. The increased insight from whole genome sequencing can improve treatment survival rates and minimise costs and time by ensuring patients are provided with appropriate therapies either to prevent a condition from arising or to intervene quickly when it occurs.
While therapies have always been individualised to a certain extent regarding specific medicines and dosages, all these involve treatment plans based on ‘standard care’. With the rapid advances in genome sequencing, it is possible for many individuals to have their whole genome sequenced quickly. Although genome sequencing cannot predict that an individual will definitely develop a particular condition, it enables doctors to make more informed decisions regarding future management of their patients.
The vanguards
Personalised medicine is now possible due to breakthroughs in whole genome sequencing. Founded in 2014, Prague-based Futura Genetics provides a direct-to-consumer service allowing individuals to find out if they are at risk of developing any of the 28 most common diseases, including lung cancer, lupus and Alzheimer’s disease. The process begins with an individual ordering a genetic test online and then being sent a DNA collection kit. A sample, the person’s saliva, is collected and then sent back to Futura where their DNA is analysed in specialised laboratories. Four weeks later, the company produces a report which contains possible genetic risks which would indicate the possibility of an individual developing any particular condition and recommendations on lifestyle modifications are subsequently given. This can include avoiding tanning salons, changing one’s diet or minimising alcohol consumption.
However, other companies have taken a different approach. Oxford Nanopore, spun-out by the University of Oxford in 2005, has developed a whole genome sequencing device the size of a smartphone called MinION. Launched in 2015, it is a portable, real-time, low-cost device designed to be used in ‘real-world applications’ in a wide range of research in different fields, including cancer, microbiology and clinical development.
Meanwhile Counsyl, formed by a group of Stanford University graduates in a dorm room in 2008, offers a service for pregnant women called Prelude Prenatal Screen which allows couples to see as early as ten weeks into a pregnancy whether they are at risk of giving birth to a child with genetic and chromosomal disorders, including cystic fibrosis, Tay-Sachs, spinal muscular atrophy, sickle cell and Pompe diseases, and Down’s and Turner’s syndromes.
In 2016, Veritas Genetics of Massachusetts made a big stir with the launch of its MyGenome service, offering whole genome sequencing which comes with a report detailing the results of the customer’s tests and lifestyle recommendations for $1,000. Unlike Futura’s service, MyGenome requires a doctor’s approval. In addition, it provides access to genetic counsellors who provide individuals with detailed explanation of their results, coupled with tailored recommendations to prevent any potential conditions. Interestingly, MyGenome brings to life the exciting field of pharmacogenomics. It can screen an individual’s genetic make-up and assess how effectively they metabolise or react to over 200 drugs that pose particular challenges for doctors, including clopidogrel, digoxin, phenytoin, rifampin, warfarin and especially medications used in oncology, psychiatry and pain management.
The road ahead
Although whole genome sequencing has reached a level whereby it may soon become common practice, personalising medicine still has some way to go. Current medicines, subject to rigorous and standardised assessments for approval and manufacture, will continue to be used in the usual way for the majority of patients. Another consideration is whether doctors should continue to classify certain diseases like cancers, based on bodily anatomy (e.g. lung cancer, breast cancer), rather than their DNA make-up, as some cancers share similar genetic features and molecular pathways despite originating in different parts of the body. Also, will insurers and payers reimburse for genome sequencing given that they are showing reluctance in paying for some existing diagnostic tests?
Until personalised medicine catches on, the benefits from whole genome sequencing are yet to be fully realised. Although whole genome sequencing can equip doctors with a deeper insight into their patients’ genetic make-up, it is unlikely to develop to a point where it can accurately predict if a person will develop a particular disease at a precise time in the future, and any follow-on recommendations are likely to be the usual lifestyle advice or prescribing current medications in an unpersonalised manner. While working towards making whole genome sequencing more affordable and ubiquitous enough to become accessible to all, its widespread application may be limited until it is coupled with the development of truly personalised medicines to treat individuals who are predicted to develop certain diseases in the future. Nonetheless, it will be an important tool in guiding scientists to develop personalised treatments for patients in the near future.
James Huang is a policy researcher and Stephen Huang is a pharmaceutical medicine consultant, both at SCP Medical
