ANGELINA JOLIE WAS JUST THE START
No, this is nothing to do with a woman jumping around a cave, shooting villains while wearing an impracticably tight vest. Janske Nel talks about how people like Angelina are making brave decisions about their future health based on their genetics. Welcome to the new era of personalised medicine.
Your mind and body are numbed by the news. Plunged into a confused fog, you struggle to think, feel, or even move. You know that there is talking but you the words lack meaning: your mind is trying to adjust to a new world wherein your body, a perfectly healthy specimen a few seconds ago, now has cancer. Picking out the words, “… in Stage
IV. Your options are limited…”, your attention is drawn inwards once more as, hands trembling, you think only of two words: “Too late”. Being told that you have cancer is something everyone dreads. Everyone reacts to the news differently and sadly, one in three of us will be faced with such a diagnosis at some point in our lives. But what if this weren’t the case? Instead of it being “too late”, what if your doctor was able to advise you on the perfect treatment to prevent the disease you would have been ‘destined’ to develop? In the future, predictive personalised medicine could mean that you need never have that terrible consultation.
Needles and haystacks
Predictive medicine (PM) brings together the study of our DNA, proteins and cells to try to weigh up the chances that an individual may develop a certain disease – cancer, say. Doctors use this information to help pinpoint the best therapy for that particular individual, or the treatment that might prevent the disease occuring altogether. At the heart of PM lie complex computer programs that analyse the details of a person’s genetic sequence. As we continue to understand our biology better, so PM will become an incredibly powerful tool of the future. Predictive medicine has emerged from two immense, collaborative endeavours called the Human Genome Project and the International HapMap Project. The Human Genome Project ran from 1990 to 2003, combined the efforts of six countries, and had one outrageously ambitious aim: to work out the order of every single ‘ letter’ (called a nucleotide) in a human being’s DNA. And this was no mean feat, given that the human genome is written out in a sequence of 2.85 billion letters. (A printed version can be found at the Wellcome Collection in London.) In many ways, the International HapMap Project picked up where the Human Genome Project left off. While the Human Genome Project recorded the DNA sequence of a ‘typical’ person, the HapMap project tries to work out the DNA differences between people. The mission is then to tie the most common DNA differences to the likelihood of an individual developing a certain disease. But it’s a scientist’s equivalent of finding a needle in a haystack: 99.9% of the ‘letters’ in the genome are exactly the same for everyone. It’s the remaining one in a thousand letters that makes me different from you – and a change in just a single ‘letter’ in our genome is enough to have dramatic effects on a person’s body. For example, the inherited disease cystic fibrosis occurs when there is a change (a ‘mutation’) in a single gene called the CFTR gene.
A personal prediction with a drop of blood
Testing people before they suffer a disease will give predictive medicine its true power. When the HapMap Project has found out more about how tiny genetic changes can upset the delicate equilibrium of the body, these ‘faults’ can be detected in our DNA before they cause any symptoms. And action can be taken as a result, like Angelina Jolie did. After undergoing genetic testing, she was found to have changes in her BRCA1 gene that are known to increase the chances of developing breast and ovarian cancer. Based on her personalised 87% risk of getting breast cancer, she chose to protect herself by having a double mastectomy. It goes beyond simple surgery: predictive medicine will mean that the treatment of disorders can be fine-tuned. Traditional approaches to medicine essentially treat all patients equally; treatments are based on symptoms, medical and family history, and assume all patients will respond to the same treatment in a similar way. Personalised medicine does away with the notion of ‘ one size fits all’. Instead, the decisions, options and management of the disease is custom-made according to the patient’s specific genetic specifications. The revolution in medicine has already started. For example, the breast cancer drug Trastuzumab (also known as Herceptin) is used to treat breast cancer – but only in women found to have an ‘over-active’ form of a gene called HER2. If the individual has a normally functioning gene then Herceptin won’t work and another treatment strategy would be chosen instead.
Book an appointment at the Biobank
The reality is that PM is still in the early phases of development. At the centre of this new era in medicine are biobanks, computerised libraries that store data on genome sequences from the world over. They hold the key to each combination of genetic cause and best treatment strategy. But it takes a lot of time to turn information into successful treatment strategies. And there is also the small issue of cost… Although the recently released HiSeq X Ten Sequencer can process the genomes of 16 people in 3 days for US $1000, this is still too expensive for most people to get a genetic ‘check-up’. And then there are the moral implications. Such dramatic advancements in science invariably invite controversy. If your entire genome is sequenced from your day of birth, who owns that information, and who should be allowed access to it? Medical aids? Insurance companies? Employers? Could you be hired or fired based on predictions based on your genes? If, for example, it is known that you have an increased risk of developing a debilitating genetic disease, could you be deemed “unfit” for your dream job …simply because of a single mislaid genetic letter? The exact ethical dilemmas we will soon face are still an unknown – but what PM promises is not. Angelina Jolie’s example is not the first, nor the last, of someone taking precautionary and life-saving steps based on their genes: many have already done the same. But with genetic sequencing becoming cheaper and more reliable every year, and as the HapMap Project reveals more insights, many more of us will be able to live past the numbing shock of cancer. Or never face it at all.
• Systems Biology and New Technologies Enable Predictive and Preventative Medicine
• Cancer genomics: from discovery science to personalized medicine
• Nanopore sequencing
• The Human Genome Project 10 year anniversary
• The possible ethical implications for DNA sequencing as shown by the movie GATTACA
Janske Nel is currently busy with her second year of a Master’s in Nanotechnology, centred specifically on nano-oncology, at the University of the Western Cape, South Africa. She shows no fear in the face of spiders, snakes or long hours in the laboratory, but shudders at the thought of books left face down.
ABOVE: An Illumina Genome Analyzer II sequencing machine.