Healthcare has changed. Infectious diseases used to ravage populations, devastate countries,
Healthcare has changed. Infectious diseases used to ravage populations, devastate countries, but advents in personal hygiene, sanitation and medical therapy have resulted in a huge decrease in mortality. Now we face a new problem, the ageing population, and our focus has shifted as well. We now focus on chronic diseases, those that affect the elderly, and also look towards preventative measures to enact in the community. These are through public health projects, awareness campaigns and medications such as statins that lower risk rather than treat symptoms.
But as our clinical knowledge grows, so does our knowledge of the individual. Genomics research has become more affordable, more accurate and has shown our knowledge of the human DNA is woefully incomplete. Furthermore, it has shed light on how our DNA affects the treatment we are given, and why some people benefit from their medications whilst others suffer. In this brief review we will go through the new, emerging world of precision medicine and what this could mean for the future of healthcare.
THE HUMAN GENOME
The genome is who we are. It is the genetic code held within our cells, within our DNA that has the blueprints of who we are and what we will become. It tells our cells what to make, what to become, how to interact with other cells and even the environment around us. Through our genome we gain our skin colour, our eyes, our hair, but we also gain our health, and in some cases our ailments. Understanding our genome has been a key part of research over the past few decades, and with the Human Genome Project we thought we had cracked the code, only to realise it is even more complicated than we thought. Our DNA is not concrete, it is not absolute. It changes depending on what we do, what we eat, whether we exercise, smoke, travel. Like with all things in biology it is everchanging, and this has required more research and more time.
Precision medicine is a new emerging branch of medicine that takes into account an individual person’s variation in genes, lifestyle and the environment we live in. It is an evolution of “personalised medicine”, the concept that each patient will receive a personally tailored medicine for their ailment. Whilst this is financially and technically impossible at this time, research has shown that some drugs act differently on subpopulations of patients based off their genetic code. An understanding of our DNA, as well as the effects our environment, our stressful lives, our diet can all have on it has been crucial un finding these links.
This all started with DNA sequencing. Ten years ago finding out the individual codes that made the DNA in all of our cells cost over US$1 billion, and took a decade or more. Now, we can be sequenced for as little as US$1000 in just a few hours. This has led to extraordinary changes in research, into cancer genetics, population genetics and more. So far the DNA of over 50,000 cancer patients have been sequenced in their entirety, with the aim of sequencing millions by 2030. The more data that is gained, the more links can be formed between the mutations in our DNA and the problems they create.
WHAT WE HAVE LEARNT
From the sequencing we have gained a great understanding of cancer. We know the genes that can stop them, we know the genes that can promote them, and we have created drugs that can target very specific cancers. For instance lung cancer is diverse with many different causes, some with a specific mutation are more easily targeted by modern immunotherapy. Such targeted therapy will ensure that only cancer cells are destroyed, rather than current chemoradiotherapy that leads to widespread collateral damage.
One example of targeted therapy is with Chronic Myeloid Leukaemia. Whilst before bone marrow transplants were considered the best option, they were only feasible in children and had significant mortality. With new advents in molecular genetics it has been able to identify new receptors that can be targeted in 95% of patients. With this it is possible to achieve an 80% response rate in newly diagnosed patients.
This research goes beyond cancer. It can also affect the drugs we take. Our studies on drugs focus on two things. How much of a drug a patient needs to take to get its benefits, and how the drugs act on target cells. We currently assume that drugs will affect everyone in a similar manner; we rarely delve into how a drug can affect sub-populations of people, how it can affect people from different ethnic backgrounds, people with different genetic mutations. And it is through genetic research that we are beginning to understand some of these differences.
Some patients who are treated with normal doses of the immunosuppressive drug azathioprine (used in autoimmune disorders) are at risk of developing life threatening complications if they harbour genetic variants that prevent the drug from being metabolised properly. Similarly 6% of the European population carry a gene mutation that results in hypersensitivity reaction if they are treated with the antiretroviral drug abacavir. Our understanding of the human genome has been instrumental in figuring out why these reactions occur. In the future we may be able to routinely test patients to ensure they do not have the mutations that cause such reactions, and therefore prevent such life threatening complications in the patients we aim to treat.
So where does this lead us? Currently our ability to sequence the human genome is very important in research, but has limited use in clinical medicine. It is important to integrate the two to be able to take advantage of the vast amount of data that has become available to us. By using genetic data in everyday clinical medicine we will be able to gain a better understanding of which mutations are more prevalent and more important for our patients. We will be able to better understand the risk factors that can influence the diseases that affect us. And we will be able to tailor medicines that better suit different populations of people, rather than assuming one drug will affect all 7 billion of us in the same way.
But it will also be important to get more data. Currently 96% of all genome wide association studies are from people of European Descent. India has 20% of the global population but only represents 1% of existing data. Trying to obtain this from the underrepresented population may help make key discoveries and associations in cancer detection and treatment that are more relevant to the Indian patient.
Dr Rachana Dwivedi, Second Medic Expert
MBBS, FRCOG, FICOG, PGC ( USS), DFFP
Consultant Obstetrics & Gynaecology
Royal Bournemouth & Christchurch Hospital
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