Michael Eisen: ‘The Past, Present and Future of Scholarly Publishing

Very important manifesto – from PLOS co-founder Prof. Michael Eisen's lecture at the California Commonwealth Club:

…Universities are, in essence, giving an incredibly valuable product – the end result of an investment of more than a hundred billion dollars of public funds every year – to publishers for free, and then they are paying them an additional ten billion dollars a year to lock these papers away where almost nobody can access them.

It would be funny if it weren’t so tragically insane.

To appreciate just how bizarre this arrangement is, I like the following metaphor. Imagine you are an obstetrician setting up a new practice. Your colleagues all make their money by charging parents a fee for each baby they deliver. It’s a good living. But you have a better idea. In exchange for YOUR services you will demand that parents give every baby you deliver over to you for adoption, in return for which you agree to lease these babies back to their parents provided they pay your annual subscription fee.

Of course no sane parent would agree to these terms. But the scientific community has.

…So what would be better? The outlines of an ideal system are simple to spell out. There should be no journal hierarchy, only broad journals like PLOS ONE. When papers are submitted to these journals, they should be immediately made available for free online – clearly marked to indicate that they have not yet been reviewed, but there to be used by people in the field capable of deciding on their own if the work is sound and important.

The journal would then organize a different type of peer review, in which experts in the field were asked if the paper is technically sound – as we currently do at PLOS ONE – but also what kinds of scientists would find this paper interesting, and how important should it be to them. This assessment would then be attached to the paper – there for everyone to see and use as they saw fit, whether it be to find papers, assess the contributions of the authors, or whatever.

This simple process would capture all of the value in the current peer review system while shedding most of its flaws. It would get papers out fast to people most able to build on them, but would provide everyone else with a way to know which papers are relevant to them and a guide to their quality and import.

By replacing the current journal hierarchy with a structured classification of research areas and levels of interest, this new system would undermine the generally poisonous “winner take all” attitude associated with publication in Science, Nature and their ilk. And by devaluing assessment made at the time of publication, this new system would facilitate the development of a robust system of post publication peer review in which individuals or groups could submit their own assessments of papers at any point after they were published. Papers could be updated to respond to comments or to new information, and we would finally make the published scientific literature as dynamic as science itself. And it would all be there for anyone, anywhere to not just access, but participate in.

…If we all do this, them maybe the next time someone like Aaron Swartz comes along and tries to access every scientific paper every written, instead of finding the FBI, they’ll find a giant green button that says “Download Now”.

The lecture transcript.

 

Bisphenol A (BPA) found not harmful, yet again — so why did so many reporters and NGOs botch coverage, yet again?

Jon Entine recently published an absolutely terrific review of the ongoing fight between evidence-based science and the anti-science fear mongering against BPA. Jon opens with this:

One of the most disturbing trends in science reporting is what The New York Times’ Andrew Revkin calls “single-study syndrome”— the increasing tendency of reporters and non-governmental organizations (NGOs) to trumpet research that supports a pre-determined perspective, no matter how tenuous—or dubious—a study might be.

and closes with this:

Why, after such a massive accumulation of evidence do activist NGOs, many reporters and even some scientists continue to reject the emerging, evidence-based scientific consensus? “At this point,” one prominent government scientist told me, “with all the recent studies in hand, calling BPA harmful and dangerous, that’s just mass hysteria.” Clinicians call this apophenia—a neurological condition in which people insist they see meaningful patterns or connections in contradictory or random data.“There are people who believe in the low dose effect of BPA and will always believe its disruptive effect, regardless of the evidence,” Dr. Gray told me. The ‘BPA-is-harmful’ crowd appears impervious to peer reviewed studies,” he added. “That’s a religious position. But as scientists and regulators, we have to go where the data takes us.”

You will be rewarded by reading Jon’s entire essay. Now. I promise you will better understand the source of all the alarming headlines you see about the dangers of “endocrine disruptors” and BPA.

Kevin Folta: Atomic Gardening- the Ultimate Frankenfoods

University of Florida plant scientist Kevin Folta wrote the following sharp, very pointy little essay. By comparing transgenic technology to mutation breeding Kevin illustrates clearly what the anti-GMO minions are truly after – it is “who makes the product”, not what the product is nor the process by which the product was created. These snippets will motivate you to read the whole thing:

 gf-l.gif A powerful radioactive source in the center of this field hammers surrounding plants with gamma rays. This treatments induces random damage DNA that results in new genetic variation.

If you hate transgenic (GMO) technologies, just wait until you hear about mutation breeding!

(…) Actually many cultivars have been produced using this technique. Barley, wheat, corn, bananas, grape, tomato, sunflower… at least 3000 induced-mutant plant lines in the Mutant Variety Database. Some are ornamentals, so not all food crops.

Transgenic techniques come under fire for many reasons. Let’s hold mutation breeding to the same criteria and compare the two techniques.

table1.JPG How do transgenic (GMO) plants compare to plants derived from mutation breeding for commonly raised criticisms?

What about labels, organic cultivation, growth in the EU? No problem if the plant’s DNA has been scrambled by radiation or chemicals!

table2.JPG Angry citizens demand to know what is in their food… unless it is mutation bred, then not so much.

For intellectual consistency, mutation breeding of crops must be considered much more random, unpredictable, un-assessable and imprecise. There is no question that genetic changes have been made, as traits of interest are selected based on visible traits, such as resistance to drought/cold in wheat. There is no easy way to assess what additional genetic baggage comes along with that new trait.

Don’t get me wrong, I don’t see any problem with mutation breeding. The techniques are proven successful at producing useful genetic variation that results in improved plants. Awesome. As a scientist, it is difficult to reconcile how this method is freely accepted, while transgenic techniques are harshly criticized. Or is it?

Maybe it simply points out that the scientific and intellectual arguments against genetic alterations are not the real concerns– they are just strawmen for the actual political, business or social agendas. The science of transgenics is a convenient place to cultivate misunderstanding and fear. But somehow the same fear mongers miss mutation breeding. It tells us a little about the real agenda. It is not about the process or product, but rather, who makes the product.

Kevin Folta: What is “Genetically Modified”? and the Frankenfood Paradox

University of Florida plant scientist Kevin Folta is a remarkable resource for science-based information on agriculture and (surprise!) plant science, which includes genetics. The personal-time-generosity of scientists like Kevin really facilitates understanding at least the key issues in these policy debates.

One excellent example of bad policy is the misguided California GMO labeling referendum. For background, in the captioned post Kevin provides a “keeper reference” that outlines the six methods by which plants come to exhibit new traits: What is “Genetically Modified”? and the Frankenfood Paradox. I just want to reference this excerpt: 

Jennifer Mo @noteasy2begreen asked for a concise reference for what Genetic Modification really means. To me, it means, well, modifying genetics.  It is when something is added to the genome, that is DNA added (or deleted or changed) in a cells genetic material.

This is not the definition used in popular discussions.  Genetic Modification in the common vernacular means a gene (or genes, usually a couple) that are added to an organism to confer a valued trait.  This requires a lab and recombinant DNA technology.

But this is what I call the Frankenfood Paradox.  Transgenic modification in the lab is the least invasive genetically, it is the most well understood, yet it is the one most shunned by those that oppose biotech.

Here is a table that might help.  Click to enlarge.

 

 
Here are the ways that plants are genetically altered.  Note that all of them are acceptable to most people, despite having no idea what the heck is being changed, and the huge number of genes affected. 

Here is the paradox!  What you will find is that transgenic technologies are much more understood, predictable, traceable and safe.  Fewer genes are moved and we know what the genes do. We can determine where genes land in the genome and where/if/when/how much they are expressed. However, these  are not allowed in organic cultivation and people want to label them. The acceptable methods move or alter tons more genes in random ways that cant be traced or even remotely understood.

(…) 

Please check out Kevin’s post and associated comments. Kevin has a popular magazine article in preparation — stay tuned. Among Kevin’s science outreach efforts is the offer to make a personal appearance in “Getting Science to the Public“. Excerpt:

To paraphrase the late Carl Sagan, while our society is increasingly dependent on science and technology, we know very little about science and technology. The reasons are many. In today’s society anti-scientific rhetoric swirls around us on such important topics as stem cell research, climate change, GMO-food safety, and many others. Understanding science is difficult. 

But scientists are part of the problem. We are taught to do science and communicate with scientists, not necessarily with the public at large. To combat this I have participated in many lectures and debates on topics of interest.

(…) 

If you are interested in hearing about bringing a scientific perspective to your group’s discussion please contact me. I’m particularly interested presenting to Sunday Morning Science church groups, anti-GMO interests and those seeking the real evidence on climate change.

 

Michael Eisen: Transferring genes from one species to another is neither unnatural nor dangerous

Evolutionary biologist, PLoS co-founder, and UC Berkeley professor Michael Eisen is a resource for science-based commentary that you need to follow. Michael blogs at MichaelEisen.org, and is guaranteed to add value to your Twitter timeline at @mbeisen.

Michael caught my attention when we were prompted to update our understanding of GMO by the recent anti-GMO vandals’ attack on the wheat research being conducted by the U.K.’s famous Rothamsted Research.

The captioned post is Michael’s first delivery on his promise to address the nine myths/questions he has culled from the anti-science campaigners. Michael has tagged the topic as #GMOFAQ. Here is his personal nine-point assignment, which was introduced in his post titled “The anti-GMO campaign’s dangerous war on science“:

1) Isn’t transferring genes from one species to another is unnatural and intrinsically dangerous

2) The most widely consumed GM crops now produce their own herbicides and pesticides. Isn’t it obvious that it’s bad to eat these?

3) Why should I believe GM food is safe? Why should I trust the big companies that develop these crops? Didn’t it take years to realize PCBs, DDT, ‘good’ cholesterol, etc. were bad for us?

4) What about studies that show GM foods cause allergies, destroy organs and make mice sterile?

5) Why won’t GM crops will escape and contaminate non-GMO crops (and maybe the planet)

6) GM crops initially reduced spraying. But now we have resistant weeds&insects. Aren’t we on a ‘pesticide treadmill’?

7) Don’t GMOs destroy biodiversity?

8) Don’t GMOs undermine local agriculture in the developing world?

9) Aren’t Monsanto’s business practices enough to want to boycott GMOs?

Hopefully you have read enough to motivate you to plug yourself into a well-written stream of commentary – written for critical thinkers. His blog tagline is “a blog about genomes, DNA, evolution, open science, baseball and other important things”. We don’t care about the baseball, but are very keen on all the other topics. And you can see from the first paragraphs on #GMOFAQ Question 1) that you are in for a good ride:

Last week I wrote about the anti-science campaign being waged by opponents of the use of genetically modified organisms in agriculture. In that post, I promised to address a series of questions/fears about GMOs that seem to underly peoples’ objections to the technology. I’m not going to try to make this a comprehensive reference site about GMOs and the literature on their use and safety (I’m compiling some good general resources here.)

I want to say a few things about myself too. I am a molecular biologist with a background in infectious diseases, cancer genomics, developmental biology, classical genetics, evolution and ecology. I am not a plant biologist, but I understand the underlying technology and relevant areas of biology. I would put myself firmly in the “pro GMO” camp, but I have absolutely nothing material to gain from this position. My lab is supported by the Howard Hughes Medical Institute, the National Institutes of Health and the National Science Foundation. I am not currently, have never been in the past, and do not plan in the future, to receive any personal or laboratory support from any company that makes or otherwise has a vested interest in GMOs. My vested interest here is science, and what I write here, I write to defend it.

S0, without further ado:

Question 1) Isn’t transferring genes from one species to another unnatural and intrinsically dangerous

The most striking thing about the GMO debate is the extent to which it contrasts “unnatural” GMOs against “natural” traditional agriculture, and the way that anti-GMO campaigners equate “natural” with “safe and good”. I’ll deal with these in turn.

The problem with the unnatural/natural contrast is not that it’s a mischaracterization of GMOs – they are unnatural in the strict sense of not occurring in Nature – rather that it is a frighteningly naive view of traditional agriculture.

Far from being natural, the transformation of wild plants and animals into the foods we eat today is – by far – the single most dramatic experiment in genetic engineering the human species has undertaken. Few of the species we eat today look anything like their wild counterparts, the result of thousands of years of largely willful selective breeding to optimize these organisms for agriculture and human consumption. And, in the past few years, as we have begun to characterize the genetic makeup of crops and farm animals, we are getting a clear picture of the extent to which traditional agricultural practices have transformed their DNA.

With that motivation, do read the complete essay.

Adventures in Synthetic Biology

Synthetic biology explained by comic

Prof. Drew Endy, Isadora Deese & The MIT Synthetic Biology Working Group have just published in Nature a comic introduction to synthetic biology (requires Flash). There’s a text version here with no graphics.

Sadly the full article, Foundations for engineering biology, requires subscription or payment (science is still captive at Nature).

But a subscription is not required to enjoy the story of how this comic came to be. From that story we learned we need to order a copy of Larry Gonick’s The Cartoon Guide to Genetics.

Antibiotic resistance: NDM-1 alarm in the UK

My understanding is that about 16% of infections are now resistant to multiple classes of antibiotics. The Scientist polls readers on the topic (79% real danger, 21% media hype):

The front page of The Guardian featured an article highlighting the apparent waning efficiency of antibiotic efficiency due to the global spread of certain drug-resistant bacteria.

(…)

The Guardian interviews one of the principal authors of The Lancet paper:

A new gene conferring high levels of resistance to almost all antibiotics has been found to be widespread in forms of gut bacteria that can cause potentially life-threatening pneumonia and urinary tract infections.

In just three years, says Professor Tim Walsh of Cardiff University who discovered the gene, it has grown in prevalence from being rarely observed at all to existing in between 1% and 3% in patients with Enterobacteriaceae infections in India.

“It is absolutely staggering,” said Walsh. “Because of international travel, globalisation and medical tourism, [the gene] now has the opportunity to go anywhere in the world very quickly.”

Some of the comments are useful, e.g., this one from UK molecular biology researcher Jim Caryl whose Gene Gym profile reads “Bad bugs, drugs and antibiotic resistance, all in a day’s work at The Gene Gym, brought to you from the gym floor by a researcher (fitness instructor) in bacterial evolution“:

I would find it hard to answer either way. I think multidrug resistance is a serious and potential threat, and there have been recommendations for some time that reports, such as that published by Walsh et al. in Lancet Infectious Diseases, be published and acted upon.

Molecular epidemiological studies are a crucial underpinning to work on predicting antimicrobial resistance (PAR), especially when these elements are associated with, or are in the same ecological niche, as promiscuous mobile genetic elements, and arising in nosocomial environments.

However, whilst the a/biotic pipeline could certainly have been considerably better stocked, the efforts of numerous small biotechs and academic researcher looking at alternatives to the rather poultry introduction of new a/biotic classes, seems to be chronically undervalued. There are valiant efforts to target bacterial virulence, the mechanisms of horizontal transfer, and to inhibit the means by which bacteria resistant antibiotics – in all cases rendering more time for new drug discovery, but crucially more time in clinical therapy.

“Is it likely that we will be dealing with infections in the UK that are completely resistant to antibiotics within 10 years? Or is this simply a case of media hysteria?”

Yes, if the funding is not made available and we rely on the efforts of a (majority) disinterest of large pharmaceuticals to invest in new drug class leads, we will be dealing with increased prevalence of multidrug resistance – as we already are in isolated pockets with some strains of Gram (+)ve bacterial pathogens.

Media hype should be reflective, and not doomsaying. They should be pointing out the threats, but identifying the huge efforts being taken to provide alternative solutions – brought about by the lack of real investment. We know so much more about bacteriology, molecular epidemioloigy and drug discovery now than we did in the heyday of a.biotic discovery. A/biotics were used for years without a full understanding of their mechanisms, nor the mechanisms of resistance. Many instances of a/biotic resistance spread could (and should) have ben predicted and prevented.

Ironically, some of the systems biology, high-throughput infrastructures that have been stealing so much of the research funding pot (that could have gone into a/biotic and resistance research), could actually now be of some considerably use in speeding up the whole process of recognising new resistance determinants, tracking their spread and identifying resistance trends that can be exploited to clinical benefit.

Jim’s Gene Gym blog looks to be an excellent resource on antibiotic resistance. Back to the UK NHS brief on NDM-1, who says “not to worry just yet” but:

(…) The NDM-1-positive samples from the UK and India also came from a diverse range of bacterial strains, which means the presence of NDM-1 was not confined to a few common strains of E. coli and Klebsiella pneumonia (the most common types of Enterobacteria carrying NDM-1). Worryingly, this suggests that this was not just a single international outbreak with the same strain of a particular bacterium. This finding supports the fact that the NDM-1 gene, being located on the bacterial plasmid, can be easily transferred to other bacteria. As one of the researchers says, the NDM-1 gene may have “an alarming potential to spread and diversify among bacterial populations.”

The authors say that the emergence of NDM-1 positive bacteria could be a serious global public health concern as there are few antibiotics that are effective against NDM-1. It is also worrying that the isolates in India came from people presenting with common community-acquired infections, suggesting the bacteria with this enzyme may be widespread in the environment, in India at least.

As the researchers conclude, there is the potential of NDM-1 to be a worldwide public health problem, and coordinated international surveillance is necessary.

So don’t be going to India and Pakistan for that cheap surgery. The Lancet paper that is the cause of this UK alarm is Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study (available to the public as a service). From the Summary:

Interpretation: The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.

Antibiotic resistance: Bugs and drugs…

Jim Caryl at Gene Gym is laboring to make antibiotic resistance understandable by the lay public. In Jim’s post Bugs and drugs… he explains the various resistance mechanisms, and in particular “The worrying cocktail” which we must do everything we can to avoid. This is why the emergence of NDM-1 is a potential nightmare:

(…) Thus what the NDM-1 report (raised in my last post) describes is a heady cocktail ripe for troubled times:

Ecological contact + promiscuous mobile genetic elements + multidrug resistance = not good. These tick all the boxes for a situation that should be carefully monitored, as you would any invading pest species in a zoological sense.

In the previous post Future-proofing antibiotics… Jim attempts the optimist’s perspective on Tim Walsh’s NDM-1 study. He links five commentaries on the Walsh study. One of more accessible of these is by microbiologist Hugh Pennington:

(…) A paper describing this new enzyme was published last September. It is full of technical molecular detail, but it uses plain English to say things that send shivers down the spine. The Klebsiella carrying the new gene was fingerprinted to find its type. It was ST14, a type almost identical to ST 15, which is branded as being the “new MRSA” due to its wide international distribution and carriage of other antibiotic resistance markers. So the Klebsiella was already particularly good at spreading and travelling long distances.

Just as unsettling was the finding in stools from the patient of a strain of Escherichia coli that was also carrying the NDM-1 gene. It was on a plasmid, a small DNA structure that can transfer quite easily from bacterium to bacterium. It is very likely that it had jumped from the Klebsiella to the Escherichia while they were living quietly in the patient’s bowels (vice versa is possible, but the practical consequences would be no different).

The original Klebsiella plasmid carried other antibiotic resistance genes as well. No surprise there; they often do. So more bad news. The paper doesn’t mince its words: “The rapid dissemination of this plasmid throughout clinical bacteria would be a nightmare scenario.”

(…) The nightmare scenario is that NDM-1 producers are close to becoming true superbugs that are resistant to everything. The horror model is XDR-TB – extensively drug-resistant tuberculosis, which broke out in South Africa in 2006, and is a significant problem in Russia, among other regions. It is reasonable to say that such strains, which for all practical purpose are so hard to treat that sufferers from them might as well be living in the 1930s, have evolved because of poorly controlled anti-TB drug prescribing. The same is true for the prescription of antibiotics in the Indian subcontinent. But it is hard to see changes coming there any time soon. Even in the UK we could do better. And hoping for new antibiotics remains just that.

Denmark: results of stopping NTA (non-therapeutic antimicrobials)

Denmark chicken economics better after ATA banDenmark has proven conclusively that industrial production of pigs and chickens does NOT require feeding antibiotics to healthy animals. Denmark now has twelve years of positive experience resulting from the 1998 ban on NTA use (i.e., non-therapeutic antimicrobials). At their own expense, researchers from the Danish National Food Institute testified to the US Congress in 2009 on the success of Denmark’s ban on NTA.

The Danes were concerned that Congress did not understand the significance of their results. So Prof. Frank M. Aarestrup, Danish Technical University, wrote a letter to Pelosi enclosing some of the slides from their testimony. Click the thumbnail at left for one of the enclosed slides, demonstrating that the economics of chicken (broiler) production IMPROVED after the ban.

The letter and slide presentation are unambiguous. Here is the first Conclusions slide:

• Major increase in Danish food animal production

• Total antimicrobial consumption reduced from 100 to 49 mg/kg (51%) from 1992 to 2008

• Major reductions in resistance among animal pathogens, indicator bacteria and zoonotic bacteria

• Probably easier with larger reductions in other countries where the initial usage is higher –eg would equal 80% reduction in USA

USATAantibioticabuse.jpg

If that last point is not clear, Dr. Aarestrup is simply reminding the Congress that the US consumption of NTA is so HUGE that the result of a US ban would be much more dramatic than the Danish experience. Click the thumbnail at left for the usage profile:

If you are searching for studies on this topic, note that some researchers use the terms “antibiotic growth promoters (AGP)” to describe the suspended practice.

Growing Pressure to Stop Antibiotics In Agriculture

This Drug Discovery & Development 4 Jan 2010 article summarizes some of the current agitation for US policy changes:

(…) Researchers say the overuse of antibiotics in humans and animals has led to a plague of drug-resistant infections that killed more than 65,000 people in the U.S. last year – more than prostate and breast cancer combined. And in a nation that used about 35 million pounds of antibiotics last year, 70 percent of the drugs went to pigs, chickens and cows. Worldwide, it’s 50 percent.

“This is a living breathing problem, it’s the big bad wolf and it’s knocking at our door,” said Dr. Vance Fowler, an infectious disease specialist at Duke University. “It’s here. It’s arrived.”

The rise in the use of antibiotics is part of a growing problem of soaring drug resistance worldwide, The Associated Press found in a six-month look at the issue. As a result, killer diseases like malaria, tuberculosis and staph are resurging in new and more deadly forms.

In response, the pressure against the use of antibiotics in agriculture is rising. The World Health Organization concluded this year that surging antibiotic resistance is one of the leading threats to human health, and the White House last month said the problem is “urgent.”

“If we’re not careful with antibiotics and the programs to administer them, we’re going to be in a post antibiotic era,” said Dr. Thomas Frieden, who was tapped to lead the Centers for Disease Control and Prevention this year.

(…) Here’s how it happens: In the early ’90s, farmers in several countries, including the U.S., started feeding animals fluoroquinolones, a family of antibiotics that includes drugs such as ciprofloxacin. In the following years, the once powerful antibiotic Cipro stopped working 80 percent of the time on some of the deadliest human infections it used to wipe out. Twelve years later, the New England Journal of Medicine published a study linking people infected with a Cipro-resistant bacteria to pork they had eaten.

(…) Johns Hopkins University health sciences professor Ellen Silbergeld, who has reviewed every major study on this issue, said there’s no doubt drug use in farm animals is a “major driver of antimicrobial resistance worldwide.”

The article includes an anecdote regarding a Missouri pig farmer who acquired a resistant strep infection from a boar tusking. His experience prompted him to eliminate antibiotics from his farm. His success echos reports from Dr. Greg Cook [University of Otago]  that Danish and Dutch studies showed industrial antibiotics did not in fact benefit the farmers:

(…) Back in Missouri, farmer Kremer finally found an antibiotic that worked on his leg. After being released from the hospital, Kremer tested his pigs. The results showed they were resistant to all the same drugs he was.

Kremer tossed his hypodermic needles, sacked his buckets of antibiotic-laced feed, slaughtered his herd and started anew.

“I was wearing a syringe, like a holster, like a gun, because my pigs were all sick,” he recalled. “I was really getting so sick and aggravated at what I was doing. I said, ‘This isn’t working.'”

Today, when Kremer steps out of his dusty and dented pickup truck and walks toward the open-air barn in the foothills of the Ozark Mountains, the animals come running. They snort and root at his knee-high gum boots. There are no gates corralling the 180 pigs in this barn. He points to a mound of composting manure.

“There’s no antibiotics in there,” he says proudly.

Kremer sells about 1,200 pigs annually. And a year after “kicking the habit,” he says he saved about $16,000 in vet bills, vaccinations and antibiotics.

“I don’t know why it took me that long to wake up to the fact that what we were doing, it was not the right thing to do and that there were alternatives,” says Kremer, stooping to scratch a pig behind the ear. “We were just basically killing ourselves and society by doing this.”