by Patrick Landon Ferree, Emilie Balk-Møller
DNA is a molecule that stores information in cells. It is essentially a sequence of digits that specifies the types and structures of molecules that contribute to cellular function. Every cell in your body has a collection of DNA molecules and the complete collection is called your genome.
Developments until now
It has been a herculean task to acquire and interpret human genomes. The protocol is invariably one that involves molecular extractions and biochemistry and costly machines that speed it all up. And then you still have to do loads of computer science to assemble the sequences into sensible arrangements. It’s like translating a super complicated book that was written by an alien species. It took an army of researchers 15 years and cost something like 3 billion dollars to sequence the first human genome, completed back in 2003. And in 2007 it still cost about 100 million dollars. Now it’s down to less than 1000 dollars, and people sequence their own genomes for the heck of it.
Perhaps the most common example of genomic-type stuff out there for the public is 23andMe and other similar services. They send you a kit, you spit into a tube, and you send it back. But it is important to recognize that those tests do not actually sequence your whole genome. They sequence targeted segments of the genome (less than like 1% of the whole genome) that allow them to track ancestral relationships. This works because over the course of many millennia our genomes have collected small mutations (mostly harmless), and the more of these we share, the closer we are related.
Similar strategies are old hat in the clinic. For instance, it is common practice to test women for the presence of certain genetic mutations that are associated with breast cancer. This is called genetic screening and it has allowed doctors to realize one of the ambitions of modern medicine, which is to prevent the onset of disease rather than treat the symptoms. Another example of this is non-invasive pre-natal screening for known genetic aberrations that cause things like cystic fibrosis, Down’s Syndrome, and so one.
What may the future bring?
Currently genetic screening only looks at targeted regions of the genome, leaving the rest of it a black box. The future is in the whole thing. There are now reported instances in which the genomes of patients in the clinic were sequenced in a matter of hours and used to identify underlying genetic disorders. This is important because as many as 1 in 50 people suffer from rare genetic disorders that are difficult to diagnose. Ultra-rapid sequencing technology could be the future of diagnostics.
No matter what, we are going to see a lot more sequencing: as DNA sequencing technologies become more affordable and accessible, more applications will emerge (many of them we can hardly imagine), and the demand will grow as the services become more widely available. For instance, there are literally hand-held DNA sequencers on the market today that have been used to track the spread of coronavirus variants. This kind of technology may move into households and revolutionize the way we interact with our own bodies. When we get sick, prior to visiting a doctor, we may just swab our nose and run it through a DNA sequencing machine at home to identify the source and its severity. But more than that, these types of devices could be used to identify infectious diseases in wildlife, and in applications outside the clinical setting, such as investigation tools, e.g., for bacterial or viral contamination of water reservoirs, soils testing or marine biology (subject to privacy concerns). Perhaps domestic DNA-sequencing will bring about the next generation of “smart” appliances.
Whatever the future of medicine is, though, it is likely to be personal. We are all human, but our bodies have their own idiosyncrasies. A sure way to improve primary healthcare is to understand each person’s body at the individual level and this would likely include an annotated copy of your genome. Some will argue that that is just going to be too much data. But we are in an age of data and data manipulation, and that is becoming less of a worry. Fresh off the DNA sequencer the human genome is about 200 gigabytes, but the genome itself is only about 4 gigabytes. These are manageable numbers.
Even healthy people will benefit. Early routine DNA sequencing of healthy individuals found that about 1 in 5 had a variant in their genome that was associated with a rare, sometimes serious, genetic disease. Another possible future though, and the one commonly talked about in this context, is the one in which everyone (or almost everyone) has their genome sequenced and scrutinized before birth. To many this screams Brave New World-type dystopias and all the other ethical problems that come along with it, like designer babies and human genome engineering. 23andMe has already inspired debates about who should have access to genomes (should insurance companies?) and law enforcement agencies have even used their databases to find and convict people.
The ethical dilemmas only get deeper though when we start to wonder whether DNA can be used to predict other outcomes. A recent book called The Genetic Lottery, for instance, has caused quite stir and re-inserted genetics into the culture wars regarding social and economic class. So even if the overarching motivation for the DNA sequencing industry is to better human health, we will ultimately have to face the big questions, too.