Podcast Review: Making Better Medicines – Unlocking the promise of genomics for drug discovery

This podcast by Genetics Unzipped discussed some of the genomic advances that have occurred since the Human Genome Project and their contribution to the development of a new and improved pharmaceutical industry.

Like many of the episodes by the Genetics Society, Dr Kat Arney hosts and converses with a range of interesting speakers currently working in the field. Making better medicines: unlocking the promise of genomics for drug discovery offers a blend of perspectives, giving an insight into the increasing role of genomics within disease treatment and how it is shaping new drug discoveries.

Dr Arney began by asking Steve Rees, who leads the discovery biology group at AstraZeneca, exactly why research is so focused on finding new drug targets for treating disease. Currently, many medications are failing to progress further than phase 2 clinical trials, simply because there is not enough understanding of the genomic changes that take place in certain diseases. Without this knowledge, it is often difficult to find a drug that is effective against an individual's illness. Of course, going back and forth to discover drug targets that are suitable is expensive and time-consuming.

Rees explained that instead of looking at where already identified drug targets may be expressed in the body, and then working out which diseases it may treat, scientists are now taking another route; looking at the genetic changes in a patient with disease, and asking if there is a drug that would interfere with these changes. With genome sequencing now only costing around $800, it is likely that we are approaching an era where the pharmaceutical industry uses genomics to take a much more personalised approach to disease treatment.

Something that particularly interests me, is how quickly we might see this progression to precision medicine with regards to patient management. Professor David Goldstein, a professor of genetics at the Columbia University Medical Centre in New York, acknowledged that in the last two decades, genomics is yet to make the impact that many hoped it would. However, now that knowledge and understanding of the subject has grown, he said that we can now expect to move further towards the steep part of the J curve, which is used to describe the nature of genomics' involvement in modern medicine, indicating an initial loss immediately followed by a dramatic gain.

Professor Goldstein made an interesting point, that often drugs are trialled to treat very broad diseases, such as heart failure, without much regard for the different forms these diseases take. He added that a given therapeutic may be more effective in one subgroup of a disease compared to others. Genomics give scientists the ability to pinpoint the differences in disease and subsequently stratify individuals with the same illness into groups. Therefore, focus going forward, needs to be channelled into not only finding better drug targets, but also whether treatment of the same illness needs to become a lot less generalised.

Professor Goldstein mentioned that one of the biggest challenges for the progression of genomics in the pharmaceutical industry, is the need to synthesise all of the raw genomic data from individuals at different stages of disease, with their clinical presentations.

Dr Dave Michalovich, the vice-president of precision medicine at BenevolentAI, London, agreed that significant resources are needed for this. However, he went on to discuss some of the breakthroughs that have already taken place, such as the development of deep learning and knowledge graphs. Dr Michalovich compared the way that knowledge graphs work to Netflix's way of predicting which film you might like to watch next. It uses algorithms to combine the known data into a suggestion of the most effective drug target. I felt that the use of real-world analogies throughout the podcast helped to illustrate some of the more complex concepts, making it a relatively easy listen for anyone interested in the subject.

All speakers shared how they believe the future will be shaped by genomics. Personalised medicines, a better mechanistic understanding of disease, and artificial intelligence to help scientists and healthcare professionals make better decisions about specific drug targets, were just some of the changes the speakers alluded to. As a medical student, I find it incredibly interesting to see how advances in these different areas of genomics could contribute to a significantly changed approach to patient management.

Following the amount of media coverage regarding the COVID-19 vaccine, the podcast comes at a time when people can really appreciate the importance of developing medicines quickly and safely for clinical use. I think what was clear in this episode, is that the use of genomics will significantly reduce the number of potential drugs that fail in clinical development.

Better hypotheses of which drug targets will prove most effective in the treatment of disease, could mean that we see more drugs going from theory to clinical use in a shorter space of time.

This episode sets out to raise understanding of this, but also of the impact genomics might have in the discovery of new and more accurate medicines, which it does very well through the relevant structuring of questions by Dr Arney. Genomics is a fairly complex subject, but this episode explores it in a way that is both understandable and engaging. I am excited to hear more about genomics and the future of modern medicine in upcoming episodes.