Podcast Review: Babbage – The unfinished genomics revolution

This Babbage from the Economist podcast episode is a timely look back at the Human Genome Project, hosted by Alok Jha, the Economist's science and technology editor, including interviews with the UK's top geneticists conducted by Natasha Loder, the Economist's health editor.

The Human Genome Project was set up in 1990, and within a decade President Bill Clinton and Prime Minister Tony Blair were announcing that the first sequence had been drafted.

'Genome science will have a real impact on all our lives, and even more on the lives of our children. It will revolutionise the diagnosis, prevention and treatment of most, if not all, human diseases' drawled Clinton, as scientists, including Loder, celebrated at 10 Downing Street, London. By 2003 the Human Genome Project was declared finished. So where are we now, 20 years on, and where will we be in 20 years' time? To find the answers, we must go to Cambridge.

'If you want to learn about the past, present and future of the Human Genome, the place to go is Cambridge' explained Loder. She spends much time there in this episode, including the Wellcome Genome Campus (where the first human chromosome was sequenced), and the Wellcome Sanger Institute.

The Sanger Institute has recently been a key player in understanding the genome of the coronavirus. Incoming director Professor Matt Hurles said future directions will include rare diseases, 'which really requires international collaboration, as there may only be one patient in the country with that condition.'

Research into common diseases will also continue to be revolutionised by genomics – both understanding risk factors and designing drugs: 'Twenty years from now it will be much more common, if not completely pervasive, that people will have their genomes sequenced' he said.

The trend has already begun, with the Newborn Genomes Programme being run by Genomics England which is sequencing the DNA of 100,000 babies to predict and detect diseases earlier (see BioNews 1172).

'This will be used in conjunction with other layers of multi-omic information… combining DNA, RNA and protein information', Professor Hurles said. 'The future is incredibly exciting, and actually now is the time for genomics to deliver on some of the promises and expectations of the Human Genome Project – and we've got a lot of the tools that we can use to do that'.

One example is 'saturation mutagenesis – where you work out what every single variant of a gene does' in libraries of millions of cells, in order to pinpoint the damaging mutations.

'Essentially all of human biology research and human disease research today uses the Human Genome Sequence in one form or another' summarised outgoing director Professor Mike Stratton, adding that 'genomics bought in the age of large data into biology'.

On the subject of big data, Loder dives into the unglamorous underbelly of genomics – data servers. Matthew Davies, an engineer at the data centre, takes Loder to the state-of-the-art facility full of whirring fans on hot servers. There is an increasing push for new equipment to become water-cooled, which will allow for denser, quieter storage centres. The resulting hot water may be used to heat buildings or generate electricity. The practicalities are fascinating but I'm left wondering how citizen's privacy will be preserved in this new era. There is little discussion of this ethical concern.

Next, Loder interviews Professor Ewan Birney, head of the European Bioinformatics Institute (EMBLE EBI), who was a key player in the Human Genome Project. He explained how all this research will translate to medicine; and how it is already happening.

Today if a clinician thinks that a child has a rare genetic disease (in total around two percent of children), the clinician can schedule that child to have their genome sequenced, alongside the parents.

'Thirty percent of those children will receive an accurate diagnosis through genomic sequencing, and occasion can receive transformative cures – one example is a mutation in the RPE65 gene, which causes blindness. Thirty children a year are now treated with a gene therapy injection behind the retina to prevent blindness' explained Professor Birney. He expects this type of gene therapy to be extended to more diseases in the future.

He also sees genomics being used to assess risk – even for chronic diseases like type 2 diabetes 'where you sort of slide into it over many year' due to a combination of lifestyle and genetics. A UK trial has already begun to calculate risk in order to decide when medical interventions should be implemented. 'It will not feel like a revolution; it will feel like… better lifestyle recommendations for type 2 diabetes,' he predicts. (The trial is not named, but I assume it is Our Future Health – I signed up last week, and you can too!)

Loder also asked his view on consumer genetics companies (see BioNews 1046). 'Ah yes, the 'discover how much Viking you are' and this sort of thing?' said Professor Birney, somewhat disdainfully, before using an analogy about how the first people to start using x-rays were fairground owners. He asked 'What is a Viking? When you dig under the hood it's really storytelling, just like bone portraiture in the late 19th century'. Despite saying this, he has done a heritage test himself!

Finally, Loder reminisced with Geoff Carr, the Economist's senior editor of science and technology, about the incredible developments since the completion of the human genome project. Carr was most surprised by the DNA of the Neanderthals and Denisovans showing up in modern Homo Sapiens populations in Europe and Asia. Looking to the future of genetics and personalised medicine, Loder predicts that 'AI is going to be driving it all.' This triggers a squabble over who can really take the glory for the genetics revolution – IT specialists, physicists, or chemists? 'Yeah, no, it's biologists' laughs Loder, getting the last word in.

Overall, 'The unfinished genomics revolution' will provide 43 minutes of fascinating listening to all biology fans – especially those too young to remember the hype!