genelogic

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Our new building...

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My latest in Pacific Standard, on the powerful but ethically fraught gene drive technology.

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Decades of work, hundreds of papers, and dozens of researchers: That’s the basic research it takes to come up with new drugs and therapies, according to a new study that I discuss in my latest piece for Pacific Standard. Technological and medical progress is built on a big foundation of basic research.

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I’m slowly digging myself out from under a pile of overdue commitments and coming back to life online. In the next few posts, I’ll recap what I’ve been up to over the past few months.

But first I should point our that our friends at Hudson Alpha - mainly the excellent Dan Savic, are out with some new massively parallel reporter assay results, published in Genome Research, on what I think is one of the key questions in functional genomics: what makes for a functional transcription factor binding site.

Go check out Dan’s fascinating results. 

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In 2009, researchers could credibly write that “incontrovertible evidence for or against Neanderthal and modern human admixture has yet to be identified.”   

In 2015, researchers identified a 40,000 year old man who had a stunningly close Neanderthal ancestor -- a great-great-great-great-grandparent.

My latest piece in Pacific Standard is about the huge and rapid paradigm shift in the science of Neanderthals that’s happened in the last few years.

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Those who, in the face of all the evidence, still insist that guns are not the cause of the American epidemic of gun violence have decided that the deaths of Wednesday’s victims, Alison Parker and Adam Ward—like those of the children at Newtown—are the cost, to be blithely endured, of the symbolic pleasures that guns provide. Since the cure is known for certain, those who refuse it can only have decided that they enjoy the disease.

Adam Gopnik at the New Yorker  http://www.newyorker.com/news/news-desk/roanoke-and-the-value-of-guns

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This, in a nutshell sums up why I oppose the Reproducibility Project (emphasis mine):

The email that arrived in Richard Young's inbox in October 2013 was polite but firm. The writer was part of a group of researchers who “are conducting a study to investigate the reproducibility of recent research findings in cancer biology.” A paper that Young, a biologist at the Massachusetts Institute of Technology in Cambridge, had published in Cell in 2012 on how a protein called c-Myc spurs tumor growth was among 50 high-impact papers chosen for scrutiny by the Reproducibility Project: Cancer Biology. The group might need help with materials and advice on experimental design, the message said. It also promised that the project would “share our procedure” to ensure “a fair replication.”

Young wrote back that a European lab had already published a replication of his study. No matter, the project's representative replied, they still wanted to repeat it. But they needed more information about the protocol. After weeks of emails back and forth and scrambling by graduate students and postdocs to spell out procedures in intricate detail, the group clarified that they did not want to replicate the 30 or so experiments in the Cell paper, but just four described in a single key figure. And those experiments would be performed not by another academic lab working in the same area, but by an unnamed contract research organization.

This past January, the cancer reproducibility project published its protocol for replicating the experiments, and the waiting began for Young to see whether his work will hold up in their hands. He says that if the project does match his results, it will be unsurprising —the paper's findings have already been reproduced. If it doesn't, a lack of expertise in the replicating lab may be responsible. Either way, the project seems a waste of time, Young says. “I am a huge fan of reproducibility. But this mechanism is not the way to test it.”

That is a typical reaction from investigators whose work is being scrutinized by the cancer reproducibility project, an ambitious, open-science effort to test whether key findings in Science, Nature, Cell, and other top journals can be reproduced by independent labs. Almost every scientist targeted by the project who spoke with Science agrees that studies in cancer biology, as in many other fields, too often turn out to be irreproducible, for reasons such as problematic reagents and the fickleness of biological systems. But few feel comfortable with this particular effort, which plans to announce its findings in coming months. Their reactions range from annoyance to anxiety to outrage. “It's an admirable, ambitious effort. I like the concept,” says cancer geneticist Todd Golub of the Broad Institute in Cambridge, who has a paper on the group's list. But he is “concerned about a single group using scientists without deep expertise to reproduce decades of complicated, nuanced experiments.”

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The GOP leadership of the so-called House Science Committee isn’t happy with the NSF’s funding decisions. Rep. Lamar Smith would like the agency to fund only research that he considers “core science” and “in the national interest,” rather than wasteful research on subjects like climate change, fundamental mathematics, or political science.  In my latest Pacific Standard column, I argue that this is misguided. I review the obscure origins of CRISPR to show that “letting scientists, rather than politicians, define important scientific questions is definitely in our national interest.”

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Great interview with the great Ford Doolittle. Here’s his answer to why he’s stuck with Dalhousie University in Nova Scotia:

I don’t actually like a lot of pressure, and Harvard and Stanford are great institutions, but they are not places where you can relax, particularly. At Dalhousie you don’t feel like you’re being threatened by your colleagues.

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Check out the latest SF Signal Mind Meld for some great book recommendations. In my contribution, I make the case for three very weird but very good post-apocalyptic novels, from 1912 to 2012.

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That there is “…already compelling evidence that DNA methylation has critical roles in initiating and maintaining dynamic shifts in gene expression” (1) is a view that has been held with variable conviction and in the absence of compelling evidence over the last 40 y...

http://www.pnas.org/content/112/17/E2117.full

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While working up my upcoming Pacific Standard column on newly approved GMo apples, I ran across this PBS piece. It lays out the environmental case for GMOs, a case few people want to hear (especially in my home town of Ithaca, NY - which is heavily featured in the piece). 

But it’s a case we need to reckon with. As I wrote before, when it comes to agriculture we need to keep running just to stay in place, and the world’s population is still growing.

A teaser:

In the late 1990s, the agriculture corporation Monsanto began to sell corn engineered to include a protein from the bacteria Bacillus thuringiensis, better known as Bt. The bacteria wasn’t new to agriculture—organic farmers spray it on their crops to kill certain insects. Today more than 60% of the corn grown within the United States is Bt corn. Farmers have adopted it in droves because it saves them money that they would otherwise spend on insecticide and the fuel and labor needed to apply it. They also earn more money for an acre of Bt corn compared with a conventional variety because fewer kernels are damaged. Between 1996 and 2011, Bt corn reduced insecticide use in corn production by 45% worldwide (110 million pounds, or roughly the equivalent of 20,000 Olympic swimming pools).

Between 1996 and 2001, Monsanto also produced Bt potato plants. Farmers like Duane Grant of Grant 4D Farms in Rupert, Idaho, welcomed the new variety. Grant grew up on his family’s farm, and his distaste for insecticides started at a young age. As a teenager, he recalls feeling so nauseous and fatigued after spraying the fields that he could hardly move until the next day. Today, pesticides are safer than those used 40 years ago, and stiffer U.S. federal regulations require that employees take more precautionary measures when applying them, but Grant occasionally tells his workers to head home early when they feel dizzy after spraying the fields. He was relieved when GM potatoes were introduced because he didn’t have to spray them with insecticide. He was warned that pests might overcome the modification in 15 to 20 years, but that didn’t deter him—he says the same thing happens with chemicals, too.

Unlike Bt corn, you can’t find any fields planted today with Bt potatoes. Soon after the breed hit the market, protestors began to single out McDonald’s restaurants, which collectively are the biggest buyer of potatoes worldwide. In response, McDonald’s, Wendy’s, and Frito-Lay stopped purchasing GM potatoes. In 2001, Monsanto dropped the product and Grant returned to conventional potatoes and the handful of insecticides he sprays on them throughout the summer.

“There is not a single documented case of anyone being hurt by genetically modified food, and yet this is a bigger problem for people than pesticides, which we know have caused harm,” he says. “I just shake my head in bewilderment at the folks who take these stringent positions that biotech should be banned.”

In the decade after Monsanto pulled their GM potatoes from the market, dozens of long-term animal feeding studiesconcluded that various GM crops were as safe as traditional varieties. And statements from science policy bodies, such as those issued by the American Association for the Advancement of Science, the U.S. National Academy of Sciences, the World Health Organization, and the European Commission, uphold that conclusion. Secondly, techniques to tweak genomes have become remarkably precise. Specific genes can be switched off without lodging foreign material into a plant’s genome. Scientists don’t necessarily have to mix disparate organisms with one another, either. In cisgenic engineering, organisms are engineered by transferring genes between individuals that could breed naturally.

Even some organic farmers bristle when asked about the anti-GMO movement. Under the U.S. Organic Foods Production Act, they are not allowed to grow GMOs, despite their ability to reduce pesticide applications. Organic farmers still spray their crops, just with different chemicals, such as sulfur and copper. Amy Hepworth, an organic farmer at Hepworth Farms in Milton, New York, says that they, too, can take a toll on the environment.

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Great piece on the mind-bending surrealist SF cover art produced by Richard Powers in the 50′s and 60′s. SF books covers really suck today, by comparison.

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I’m glad someone is saying what needs to be said about the overly broad claims regarding a reproducibility crisis in science:

The Biophysical Society (BPS), publisher of BJ, agrees wholeheartedly with the intent of the guidelines—to encourage reproducible, robust, and transparent research. However, in their specifics, these guidelines are primarily directed at large correlative statistical preclinical and clinical studies and are not pertinent or applicable to the types of science published by BJ. Therefore, BJ, along with several other basic science journals, did not sign on to the document. Basic and applied sciences in general, and biophysics in particular, can require the use of diverse, highly specialized research instrumentation and techniques along with complex customized computational analysis. The diversity of the research methods and the types of data that are produced requires a flexible approach to the important issues of reproducibility of scientific results, transparency, and data sharing.

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Results of a meeting on the state of biomedical science concludes that we’re destroying it in the U.S.:

There was near unanimity among the attendees that the system is under tremendous strain, which threatens the vitality of science in the United States. To paraphrase one attendee, the root cause of the problem is the fact that the current ecosystem was designed at a time when the biomedical sciences were consistently expanding, and it now must adjust to a condition closer to steady state. Another way of stating the problem: today too many people are chasing too little money to support increasingly expensive research. It was generally conceded that without some concerted action, this problem will only get worse. Most attendees agreed that a major consequence of the current imbalance is a hypercompetitive environment that reduces both the time available for thinking creatively and the likelihood that scientists will take risks to pursue their most imaginative ideas...

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Genetics editor in chief Mark Johnston makes the case for journals run by experienced, practicing scientists:

If you are a graduate student who has written up the story that will get you your degree, or a postdoc seeking the publication that may land you your first job, or a young investigator seeking to publish the paper that will win you that big grant, who do you trust to decide whether the manuscript merits being sent out for review? Who do you depend on to arbitrate the reviewers’ opinions and decide whether your manuscript warrants revision or acceptance for publication? Who do you ask whether your response to the reviewers’ critiques meets the grade? We often entrust those tasks to journal editors who have little experience and relatively scant achievement as scientists. We rely on these editors to recruit well-qualified, fair, responsible reviewers. We give them the responsibility for synthesizing reviewer opinions—which can sometimes be capricious or biased or overly demanding or uninformed—into a decision on whether the story meets the standards of the journal. We allow these editors to contribute to setting the standards of the field with each decision they make... Why do we send so many of our best stories to journals whose editors are not accomplished, experienced, practicing scientists? Why do we give professional editors of journals that are not directly responsible to our community the authority to set the standards of our fields by deciding what gets published in top-tier journals? Most importantly, why do so many people serving on faculty hiring-and-promotion committees and grant review panels give these editors so much influence over who gets hired, promoted, and funded? Wouldn't we, and science, be better served if we entrusted our best stories to journals with peer-editors whose authority is well founded, who have earned the respect of their peers, who are qualified to set the standards of the field?

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In my latest Pacific Standard column, I take on the latest worries about people making genetically engineered babies with CRISPR/Cas9 technology. We’ve been worried about the hypothetical possibility of genetically engineered babies for a century. Though gene editing technology has made huge strides, genetically engineered babies are likely to remain hypothetical for a long time yet.