Genomics, The Long View, and Picking Winners

The Atlantic recently posted an interview with Eric Lander and managed to capture two very interesting views for anyone looking in on biomedical research from the outside.  The first highlights how different it is from most things in for-profit environments:

I’m not Pollyanna. This is not around the corner. It’s not for next quarter; it’s not for next year. We play for the long game. I don’t want to overpromise in the short term, but it is incredibly exciting if you take the 25-year view.

And the second, how similar 'picking winners' in life sciences research is to deciding on projects to invest your money in:

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.

Duons Press Release from University of Washington, not WashU

Thanks to those that pointed out my mix-up between WashU and the University of Washington in the post about the duons press release.  The text has been corrected.

Apologies to all.

An Interview with Robert Birgeneau, Former Chancellor of Berkeley

Here's an excerpt from one of my recent articles that's based on a recent interview with Robert Birgeneau, the former Chancellor of Berkeley and former President of the University of Toronto before that.  He happens to be an alumnus of St. Michael's College at the University of Toronto, where I also did my undergraduate degree.  The article was published in a special fall issue of the St. Michael's College alumni magazine.

Everyone is familiar with the common phases of matter—solids, liquids and gases—and the transitions between them. Whether it’s freezing condensation on a window or ice melting in water, materials constantly change from one phase to another.

Much of Dr. Robert Birgeneau’s professional life has been dedicated to understanding how different materials go through phase transitions, and there’s much more to them than temperature. “What you learn very quickly is that the nature of a material’s phase transition depends on many other features,” says Birgeneau, adding that part of the challenge in his research is finding good models for phase transitions in systems that might exist in worlds with more or less than three dimensions. ...

Read the rest of the original article at the St. Michael's College Alumni site.

University of Washington DNA "Duons" Press Release Overshadows Science Paper

In what's ending up as a abject lesson against using hype to publicize scientific papers, a WashU University of Washington Science paper entitled "Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution" by Stergachis et al. was accompanied by a press release that's been pretty much hung up to dry at Forbes by Emily Willingham:

The hype began with the way hype often begins: an institutional news release offering us the holy grail/huge breakthrough/game-changing finding of the day. This kind of exaggeration is the big reason any science consumer should look well beyond the news release in considering new findings. A news release is a marketing tool. You’re reading an advertisement when you read a news release. In this case, the advertisement/news release not only goes off the rails with the hype, it’s also scientifically garbled and open to all kinds of misinterpretation, as the comments at the link to the release make clear.

The whole news release is found here isn't actually that much more hyped up than a lot of scientific releases coming from the usual biased sources.  Here, a UW press release was written by a media consultant engaged by (and I presume paid by) UW to promote work that - you guessed it - a team of UW scientists just published.  Apart from awkwardly referring to codons as a "64-letter alphabet", I don't think you can fault them for joining the scientific hype arms race that's ongoing if you want to get a publication noticed.

As far as claims for "discovering double meaning in the genetic code", here's the actual abstract from the Stergachis et al. paper:

Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. We used genomic deoxyribonuclease I footprinting to map nucleotide resolution TF occupancy across the human exome in 81 diverse cell types. We found that ~15% of human codons are dual-use codons (“duons”) that simultaneously specify both amino acids and TF recognition sites. Duons are highly conserved and have shaped protein evolution, and TF-imposed constraint appears to be a major driver of codon usage bias. Conversely, the regulatory code has been selectively depleted of TFs that recognize stop codons. More than 17% of single-nucleotide variants within duons directly alter TF binding. Pervasive dual encoding of amino acid and regulatory information appears to be a fundamental feature of genome evolution.

Let's paraphrase and simplify:

DNA encodes protein and transcription factor (TF) binding sites. We mapped TF binding sites within protein coding regions, and found that 1 out of 6 codons also encode TF binding sites.  For convenience, we call these "Duons".  Duons are evolutionarily conserved, probably because they code for both amino acids and TF binding sites.  We also found TFs tend to not recognize stop codons, and that about 1 in 5 SNPs within duons alter TF binding.

And that's it. The abstract itself doesn't claim that this team was the first to find duons, or to find a second genetic code, or anything shocking like arsenic based life forms.  They simply used a term to conveniently refer to known a feature of codons; in other words, they made up some jargon, and others ran with it.

The actual paper is actually pretty good, and helps to explain how evolution/mutation of silent SNPs can change gene transcription patterns without changing (usually damaging) the protein encoded at the site.  Most importantly, there's nothing about a second genetic code, in the classical sense of the term.  There didn't find any secret tRNAs in the study, nor did they find rogue ribosomes that no one noticed over the past 60 years.

I'm going to assume that the team at UW didn't proofread the press release before it went out.  If they did, maybe they brushed it off as 'just another release' that will fall into obscurity on the UW site.  That might have been their mistake, but I'm just speculating here.

In either case, this is a perfect lesson that scientific experts need to be engaged in all parts of the science communications process.  It also shows how even a great Science paper can be overshadowed by what many assume to be a simple press release.

Career Choices: Delivering Mail versus Getting a PhD

Canada's main postal company, Canada Post, is currently undergoing a major overhaul because despite being a government regulated monopoly, it's actually losing money.  This has little to do with science and is probably not an apples-to-apples comparison, but here's an interesting statistic to consider nonetheless: 

• Current minimum wage per hour for a Canada Post mail delivery person hired after Feb.1, 2013: $19.14
• Average wage for a postdoctoral researcher in Canada, who has a PhD and probably 9 to 10 years of post-secondary education: $43,973.  At 50 hours per week that's $17.59.

I like getting mail, but really?

Christophe Lambert of Golden Helix, on the Utility of Electronic Health Records

Christophe Lambert, Chairman of Golden Helix Inc., recently gave a great lecture on the many facets of the health system can be improved using different approaches to analyzing the wealth of information in health records.  He captures the general idea at around 41:00:

I've done some interesting work a project with Medco and Golden Helix , where we were looking at millions of patients records for drug safety and efficacy. 

The end game that we were envisioning, was if you're sick, it would be great to look at tens of millions of records to find patients who were similar to you, anonymously, but then find out evidence based, what courses of treatment led to the best outcomes, and have a set of possibilities to present to a doctor as here are the many outcomes of various drugs, various treatments, and so forth.

Check it out on his Vimeo channel.