The origins and impact of DNA sequencing

Interviewer: Anand Jagatia

A, T, C and G: letters that represent the base pairs which code for life on earth… DNA. The earliest attempts to read this sequence of letters in DNA molecules were painfully slow. In 1973, it took researchers 2 years to sequence the gene for a binding site that was a mere 24 bases long. But then, 40 years ago, in 1977, two papers were published that gave methods for DNA sequencing, allowing researchers to read hundreds of bases in an afternoon. Since then, sequencing technology has improved at and incredible pace – becoming faster, more reliable and less expensive. And today, the latest generation of machines can sequence an entire human genome, that’s three billion bases, in just 1 hour.

Interviewee: Eric Green

Really over the past decade or so we’ve essentially reduced the cost of sequencing DNA by about a million fold and that has just changed everything in terms of what you can use DNA sequencing for.

Interviewer: Anand Jagatia

This is Dr. Eric Green, Director of the National Human Genome Research Institute at the US National Institute of Health. Eric has been working in genomics since 1987 and was involved in the Human Genome Project throughout its duration. He told me that it’s hard to think of an area where DNA sequencing has had a bigger impact than in health and in medicine.

Interviewee: Eric Green

Well, in terms of sheer numbers the most widespread clinical applications have been in the arena of prenatal genetic testing for abnormal numbers of chromosomes such as trisomy 21: three copies of chromosome 21, which causes Down Syndrome. This is a practice that has been going on for many, many years but has previously required invasive methods to access fetal DNA, but these new DNA sequencing technologies are so exquisitely sensitive that they now allow the detection of the small amounts of fetal DNA that float around in the maternal bloodstream – in mom’s blood. In fact, it’s now estimated that something in the order of 4 to 6 million women who are pregnant will get that test worldwide each year now and it’s expected to grow over time.

Interviewer: Anand Jagatia

This growth in prenatal testing isn’t the only growth in how we do testing. DNA sequencing has also transformed the diagnosis and treatment of cancer.

Interviewee: Eric Green

Cancer is a disease of the genome and so we could use these new methods to sequence the genome of a tumour, of a cancer sample and tailor the care of that patient with that cancer based on what you learned and that will help guide many aspects of the patient’s care. Another exciting development, especially looking towards the future is something that’s referred to as liquid biopsies. In other words, if a patient has cancer, their tumour will often shed small amounts of its DNA, which has some abnormal signatures in it, into the bloodstream, and so one is now able to sequence the DNA in the blood, looking for signatures of cancer.

Interviewer: Anand Jagatia

In the research arena, as the technology behind DNA sequencing has improved, scientists have become increasingly hungry for sequence data. The Human Genome Project successfully sampled the first human genome in 2003, and since then researchers have gone on to complete the 1,000 Genome Project and are soon set to complete the 100,000 Genomes Project. But generating such vast amounts of sequence data has its problems.

Interviewee: Eric Green

We are now able to generate prodigious amounts of DNA sequence data and then we immediately hit a blockade of being able to interpret it and understand it as effectively as we’re able to generate it. We need very large data sets, not just the genome sequence; we need to know many other aspects of their lives to tease out all the complexities of human health and disease which of course is a choreography between our genome, I mean our blueprint, but also our lifestyle, our environmental exposures, social context and so forth.

Interviewer: Anand Jagatia

But it’s not just in the lab or the clinic that DNA sequencing has changed things. Smaller, cheaper devices have democratized sequencing technology which no longer means it’s just big rich labs who can use it.

Interviewee: Eric Green

There are instruments that are coming online now that can be basically operated with a laptop out in the field to basically look for certain types of microbes. And increasingly as one can imagine as more mobile devices become available and prices go down, maybe people in the food industry will be monitoring specific foods by DNA analysis and so forth. One can imagine using it in your home. There may be applications where you want to read out some DNA in your home for various personal reasons.

Interviewer: Anand Jagatia

These reasons could be very personal indeed. Perhaps you have a DNA sequencer installed in your toilet to monitor the health of you and your family in real time. And according to Eric, this could just be the tip of the iceberg.

Interviewee: Eric Green

What is very clear is that we probably can’t accurately predict all the applications for DNA sequencing in the future. One of the analogies I sometimes make is a smart phone. I mean I never anticipated 10 years ago, all the different ways I’d be using a smart phone. I thought it was just going to be used for phone calls. Now I barely use my smart phone for phone calls. I use it for all sorts of other things. I think we’ve already seen a similar circumstance with DNA sequencing.

Interviewer: Charlotte Stoddart

Dr. Eric Green from the US National Institutes of Health talking to Anand Jagatia.