15 February 2016
ByAppeared in BioNews 839
An offshoot of the popular 'edutainment' website How Stuff Works, Stuff You Should Know is an incredibly prolific biweekly podcast, with over 800 episodes recorded over the course of the last seven years. In fact, with over 100 million downloads on iTunes and a long history of receiving critical acclaim, I'm amazed that it's taken me this long to hear about it.
In the classic podcast format, every episode a topic is picked and discussed, in this case by two of the senior editors from the How Stuff Works team, Josh Clark and Chuck Bryant. In this recent episode, they covered a topic close to the heart of the BioNews crew – 'How Personalized Medicine Works'.
Personalised medicine – the idea of using individual characteristics to tailor a patient's therapy specifically to them, in order to maximise response or minimise side-effects – is increasingly being hailed as 'the next big thing' in medical treatment. However, as the two hosts admirably point out at the top of the show by quoting Hippocrates' famous adage that it is '...far more important to know what person the disease has than what disease the person has', this is not a new concept.
Over the course of forty minutes, Josh and Chuck take the listener on a whirlwind tour of personalised medicine, outlining the concept, how it's come about and giving us a few choice examples of current successes.
Key to the emergence of personalised medicine was the completion of the Human Genome Project, and the associated technological advances that followed. Being able to sequence our DNA, and compare it against reference sequences, doctors were never more able to stratify patients into different groups based on their biological makeup. This provides a path running opposite to the direction of most of modern medicine, in which – as the hosts report – a largely trial and error-based approach is used to apply findings from one group of people to another, in the hope what works for one will work for all.
The idea of using genomics to identify subsets of patients for a particular treatment is demonstrated in one of the examples which popped up during Josh and Chuck's conversation. Ivacaftor (sold under the name Kalydeco) is a very effective treatment for cystic fibrosis, but only for the few percent of patients who have certain mutations in the cystic fibrosis gene; if you don't have those mutations, the drug just won't work for you.
Other examples provided in the show demonstrate that personalised medicine isn't just about DNA. The breast-cancer therapy trastuzumab (Herceptin) binds to a protein that is found on the surface of some cancerous cells – but only in a fraction of people. Therefore, if you can find the patients whose breast-cancer cells do express this protein, you have found the people for whom trastuzumab might be effective. They also talk about a more bioengineering-type approach to personalised medicine, such as the development of artificial pancreases which could monitor a person with diabetes' sugar levels in real time, allowing them to give themselves the right amount of insulin at the right time.
Josh and Chuck cover a lot of ground, skimming across a number of the major highlights, in keeping with their mission to give people a decent grounding in a given topic. What's more, they do so in a very enjoyable way; they have an engaging, easy rapport and their frank and casual presentation style makes for enjoyable and digestible listening. It's as if they've distilled the essence of sitting in a pub with friends, amicably chatting over the stories of the day.
However there are a few downsides to this easy-going approach. With the pub-chat vibe they have cultivated, the largest problem is one of accuracy. As neither host is a necessarily an expert in the topics they discuss, and with at least one of them (I'm looking at you, Chuck) not always being that familiar with the details of the story at hand, I certainly caught a few inaccuracies and exaggerations that slipped through.
That is not to say the boys don't know their stuff or haven't done their research. In fact, during their discussion of DNA sequencing (which is technique that I make frequent use of in my own research) they displayed an impressively nuanced appreciation of some of the subtle and not-so-obvious downsides, such as the hidden cost of analysis and the dangers of commercial companies holding widescale genomic data.
I would have liked it if the conversation had touched on some of the barriers to or pitfalls involved with personalised medicine, such as regulatory barriers and technical hurdles to new treatments, or how we're going to need to start increasing the diversity of the people whose genomes we investigate if we want to be able to understand and treat the whole of human disease. However, both this and my resentment of the slightly annoying adverts are very minor complaints, weighed against a much greater store of enjoyment and stimulation.
All told, this episode was a pleasant romp through the topic, and it was only my pre-existing knowledge of this particular field that let me catch the tiny number of mistakes they made. The conversation was intelligent and illuminating, and the banter was flowing: the format works. In combination with the frankly stunning back catalogue of episodes covering an enormous range of topics means that my commute soundtrack is set for weeks.