Genomics and the Power of Public Health

On a bad day in the lab, we sometimes joke that if we really wanted to help save lives, we’d forget about molecular biology and go help people quit smoking. Relatively simple public health efforts – clean water, washing your hands before moving from one sick patient to another, basic vaccines – generally save many more lives that the cures that come out of the high tech stuff we do in the lab. Cancer immunotherapy may turn out to be a major advance in cancer treatment, but we’d reduce cancer even more if we could get everyone to quit smoking, lose weight, and stay physically active.

Genomics, whose near-term medical benefits have been the subject of a lot of hype, may turn out to be a high-tech, scientifically complex effort that actually does to have a big impact on people’s lives. As I discuss in my Pacific Standard column this week, part of that will be the long-term medical benefits that grow out of a better understanding of biology. But a more dramatic – and more near-term – impact may be how genomics changes public health. As some sort of genome analysis becomes a routine part of normal medical care, genetics will be integrated with other public health screenings (like testing your cholesterol), which, as two recent studies show, could have a big impact on avoiding preventable consequences of common diseases. Once exome sequencing is cheap enough, there could be a possible benefit of combining genomic screenings using existing medical knowledge – we don’t need to wait for distant future discoveries.

The takeaway is that policy and the infrastructure of the healthcare system, and not science, may soon be the rate-limiting step for realizing the medical benefits of genomics in some cases. Physicians, insurers, hospitals, and the health care system in general is utterly unprepared to handle the kinds of genomic data that could, in the near future, improve routine medical care.

The Genetic Nightmare of Diabetes

After 10 years of genomic studies, our understanding of the genetic architecture of diabetes is… still a mess. Or, if you prefer, a nightmare. That’s the message of the most extensive Type 2 Diabetes GWAS to date. Looking for rare genetic variants linked with diabetes, researchers performed whole-genome or exome sequencing on 15,000 people… and came up with nothing new.

This is an important negative result, in that it advances our knowledge of the genetic architecture of diabetes – odds are that many common genetic variants, each with individual small effects, contribute to one’s total genetic risk for the disease. It also illustrates just how hard it will be to realize the goals of personalized medicine. So let’s avoid the hype when we talk about how genomics is going to revolutionize medicine.

I explain the study and its implications in my piece this week at Pacific Standard.  Go read it to learn more about the challenges ahead that face personalized medicine.

Music of the Spheres

This was something I wrote for the “review” assignment of my writing course.

2016-01-20 17.44.32There is a time and a place for complex atonal music, and perhaps the drinks reception of a genomics conference at the Excel Centre was not it. Through the chatter it wasn’t always easy to hear what the string quartet was doing, and meeting attendees were confused about the performance. “I thought they were still tuning”, said one of the guests.

There was a good reason the Kreutzer Quartet was playing here, at the Festival of Genomics, surrounded by exhibit stands for DNA sequencing companies and clusters of geneticists. Their performance was a crucial part of an art piece by Charlotte Jarvis, which explored the possibilities of encoding complex information in DNA.

Jarvis and Goldman introducing the Kreutzer Quartet.
Jarvis and Goldman introducing the Kreutzer Quartet.

The work, Music of the Spheres (named after a Byron poem), combines music, science, and a bubble machine. It requires some effort on the part of the audience to grasp how all the components fit together.

The core of the work is a three-movement musical composition, written by the Kreutzer Quartet, and inspired by DNA. The musicians performed the first and third movements live during a drinks reception at the Festival of Genomics, on January 20th. They used asynchronous glissando scales to express the coiling strands of DNA, and tapped the strings with the wooden part of their bow (col legno) to suggest the sound of large machines handling genetic information.

Movement 2, however, was not performed – at least not by the string quartet. This middle movement was converted into DNA code according to a system developed by Nick Goldman at the European Bioinformatics Institute. He initiated this collaboration with Jarvis to illustrate the enormous potential of using DNA code to digitize large amounts of information: in this case, a recording of the Kreutzer Quartet playing the middle movement of their genetics-inspired piece. This segment of custom-designed DNA was then created and mixed into a soapy solution. So it wasn’t the string quartet playing the middle movement of the piece, but a bubble machine. While the musicians rested, Jarvis switched on the machine, and the music travelled in the air – unheard, but tangible and visible. If you were to capture a bubble, isolate the DNA and sequence it, you might be able to get the data for the recording back out of its unconventional storage format.

2016-01-20 17.48.45This was not the first performance of Music of the Spheres. It had previously been set up in a large empty building, a gallery along the coast, and Hornsey Town Hall. The string quartet can’t be everywhere, but the bubbles are always there, and form the core part of the work. In fact, Jarvis turned on the bubble machine a few times during breaks at the Festival of Genomics. Without the string quartet, this created an effect of simple party entertainment, not out of place at this conference, which also featured a lively talk show and a treadmill challenge. People engaged with the bubbles by photographing them, popping them, or shielding their coffee cups from soapy surprises. Many of them were unaware that each bubble contained fragments of DNA encoding a piece of music.

2016-01-20 15.29.00

But while the bubbles alone were a good match for the hectic venue, the live performance unfortunately was not. It seems a shame that the talented Kreutzer Quartet came all the way here to perform for a crowd that could barely hear them and was more interested in catching up with colleagues over a drink.

Music of the Spheres is a work that makes us think about the potential of DNA as a data storage method. It requires thoughtful reflection, and is best experienced against a quiet backdrop – not one of clinking wine glasses and murmuring conversations.

You can’t do transformative science without wasting money

This is a great statement by Eric Lander from an interview he gave to James Fallows at The Atlantic last year:

“When will genomics cure cancer?”

Young scientists who need to look at 100,000 cancer samples, or do functional tests inhibiting all the genes in the genome, or explore the use of chemicals in ways they never could before—they need an NIH [National Institutes of Health] that is able to place bets. With sequestration, and the NIH budget falling by about 25 percent in real terms over the past decade, the people reviewing grants naturally become more conservative. When there’s less money, reviewers don’t want to run the risk of wasting money on something that doesn’t work.

I’ve got to tell you, if you aren’t prepared to waste money on things that might not work, you can’t possibly do things that are transformative. Because for every successful transformative idea, there’s five times as many nonsuccessful transformative ideas. Nobody knows how to figure out in advance which ones they’re going to be.

I don’t agree with everything Lander says in the interview – specifically, the statement that we’ll have a “complete catalogue” of disease genes in another five or six years has no basis in reality. But overall, he makes some great points about the transformative potential of genomics.

Midden DNA

Some people don’t like the term “junk DNA”, because they assume all that extra DNA in the human genome must be doing something. Some of those people are tenured faculty, members of the ENCODE project, and have trouble penning reasonable definitions of biological function.

Other people have experimental data to show that random sequences of DNA can be biochemically active without physiological effect, understand that the genome’s complexity resists easy classification, and can, simultaneously, understand that these swathes of non-functional DNA are valuable because they contain the history of our evolution.

In that light, I am going to propose that we abandon the misleading phrase “junk DNA” and adopt a word from archaeology used to describe piles of informative waste: midden*.

A midden…is an old dump for domestic waste which may consist of animal bone, human excrement, botanical material, vermin, shells, sherds, lithics (especially debitage), and other artifacts and ecofacts associated with past human occupation. The word is of Scandinavian via Middle English derivation, but is used by archaeologists worldwide to describe any kind of feature containing waste products relating to day-to-day human life. – Wikipedia

Now, if you want to call it midden DNA or the DNA midden, that I am happy to leave up to personal taste and style.

*A potential confusion might arise when researchers sequence DNA from biological samples in an actual midden heap – a risk with which I am willing to live.