Class of the business models

clash by Lenny Montana
PLoS stays afloat with bulk publishing : Nature News:
[Via Nature]
This is a very provocative article, especially since it starts this way:

Public Library of Science (PLoS), the poster child of the open-access publishing movement, is following an haute couture model of science publishing — relying on bulk, cheap publishing of lower quality papers to subsidize its handful of high-quality flagship journals.

It is a little unseemly for a for-profit publisher with a closed access approach to openly attack an open access competitor. Especially since many of the PLoS journals have very high impact factors and are widely read for their important articles.

The comments are a lot of fun to read and demonstrate where online conversations are taking us. An example:

Editor Clarke, Perhaps you could then elaborate on just what the intent with this piece? Clearly many of those reading it saw it as a naked and blatantly self-serving screed against open-access publishing. In short, an attempt to undercut the business of a competitor by the method of reputation-trashing. Can you confirm or deny that this was the intent? If you confirm that this was the intent, please let us know why it was ethically sound not to make a firm declaration of COI in the piece? If you deny this was the intent, by all means please let us know what the intent actually was…?
Posted by Drug Monkey

Drug Monkey has some more discussion at his own site, especially the lack of a conflict of interest statement (ironic since every scientist who publishes in every journal today, including Nature, must sign such a statement delineating all conflicts of interest.). Also he has some more links to other bloggers, including the Online Community Manager for the PLoS journals who is taking a “Don’t feed the trolls” approach.

Then there is this little bit of dead-on snark:

Apparently the “bulk, cheap … lower quality papers” published by PLoS aren’t beneath the notice of Nature. Three of the Research Highlights articles in this issue (p 5) report on articles published in PLoS journals (two from PLoS One! and one from PLoS Genetics). If it is not interesting enough to publish in Nature, at least it provides enough free copy to help round out an issue.
Posted by Scott Ramsey

So, Nature is perfectly happy to use the freely available information from the competitor it trashes, in order to make sure it has enough content for its own journal.

Finally, it is a little weird for a commercial company that makes a profit to criticize the business model for a non-profit organization. I mean, horrors, they get grant money. That is what a non-profit can do. Many do not set themselves up to be commercial in the sense of a company like Nature.


Here are the stated
mission and goals of PLoS:

The Public Library of Science (PLoS) is a nonprofit organization of scientists and physicians committed to making the world’s scientific and medical literature a public resource.

Our goals are to:

  • Open the doors to the world’s library of scientific knowledge by giving any scientist, physician, patient, or student - anywhere in the world - unlimited access to the latest scientific research.
  • Facilitate research, informed medical practice, and education by making it possible to freely search the full text of every published article to locate specific ideas, methods, experimental results, and observations.
  • Enable scientists, librarians, publishers, and entrepreneurs to develop innovative ways to explore and use the world’s treasury of scientific ideas and discoveries.

Here are Nature’s:

First, to serve scientists through prompt publication of significant advances in any branch of science, and to provide a forum for the reporting and discussion of news and issues concerning science. Second, to ensure that the results of science are rapidly disseminated to the public throughout the world, in a fashion that conveys their significance for knowledge, culture and daily life.


Nature does really well at the first section but does it really ensure that the results are rapidly disseminated to the public throughout the world? Or does charging for access fulfill the ‘fashion that conveys their significance’? if you pay for something does that enhance its significance?

Interestingly, Nature did not make a profit of more than 30 years.

Despite the boom in periodical publishing in Victorian Britain in the 1860s, the fledgling Nature did not make a profit for more than 30 years and only survived because of the commitment and belief of its first publisher, Alexander Macmillan, co-founder of Macmillan Publishers, and the hard work of the first editor, Norman Lockyer.

Sounds like charity to me. Yet it is critical of PLoS after 6 years!

I guess there is one thing positive for Nature. While it might be a little unseemly for such a hit piece to come from Nature, they deserve kudos for sticking around for the conversation. even one that takes them to task.

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Scientific community building

sand by …†∆†¡∆µ∆
[Crossposted at SpreadingScience]
Building scientific communities:
[Via business|bytes|genes|molecules]
Here is an interesting point that should be discussed more, especially with scientific community building (my bolding).

I will start with something I have quoted all too often

Data finds data, then people find people

That quote by Jon Udell, channeling Jeff Jonas is one that, to me at least, defines what the modern web is all about. Too many people tend to put the people first, but in the end without common data to commune around, there can be no communities.

A community needs a purpose to exist, a reason to come together. Some communities arise because of similar political or gardening interests. Most research communities come together for one major reason - to deal with data.

Now data simply exists, like grains of sand. It requires human interaction to gain context and become information. In social settings, this information can be transformed into the knowledge that allows a decision to be made, decisions such as ‘I need to redo the experiment’ or ‘I can now publish.’

It used to be possible for a single researcher, or a small number, to examine a single handful of sand in order to generate information needed to answer scientific questions. Now we have to examine an entire beach or even an entire coastline. A much larger group of people must now be brought together to provide context for this data in any reasonable timeframe.

However, standard approaches are too slow and cumbersome. When one group can add 45 billion bases of DNA sequence to the databases a week, the solution cycle has to be shortened.

Science is an intellectual pursuit, whether it is formal academic science or just casual common interest. That’s where all the tools available today come into the picture. The data has always been there. Whether at the backend, or at the front end, we can think about how to get everything together, but being able to discovery and find some utility is very important. One of the reasons the informatics community seems to thrive online, apart from inherent curiosity and interest in such matters, is that we have a general set of interests to talk about, from programming languages, to tools to methods, to just whining about the fact that we spend too much time data munging. Successful life science communities need that common ground. In a blog post, Egon talks about JMOL and CDK. Why would I participate in the CDK community, or the JMOL one? Cause I have some interest in using or modifying JMOL, or finding out more about the CDK toolkit and perhaps using it. Successful communities are the ones that can take this mutual interest around the data and bring together the people.

Part of what is being discussed here is a common language and interest that allows rapid interactions amongst a group. In some ways, this is not different than a bunch of people coalescing around a cult TV show and forming a community. A difference is that the latter is a way to transform information that has purely entertainment value.

The researchers are actually trying to get their work done. What Web 2.0 approaches do is permit scientists to come together in virtual ad hoc communities to examine large amounts of data and help transform that into knowledge. Instead of one handful at a time, buckets and truckloads of sand can be examined at one time, with a degree of intensity impossible for a small group.

The size and depth of these ad hoc communities, as well as their longevity, will depend on the size of the beach, just how much data must be examined. But I guarantee that there will always be more data to examine, even after publication.

So my advice to anyone building a scientific community (the one that jumped out at me during the workshop was the EcoliHub) is to think about what the underlying data that could bring together people is first. Data here is used in a general sense. Not just scientific raw data, but information and interests as well. Then trying and figure out what the goals are that will make these people come together around the data and then figure out what the best mechanism for that might be. Don’t put the cart before the horse. In most such cases, you need a critical mass to make a community successful, to truly benefit from the wealth of networks. In science that’s often hard, so any misstep in step 1, will usually end up in a community that has little or no traction.

EcoliHub is a great example of a website in the wild that is supported almost entirely in an Open Source fashion. This is a nice way to create a very strong community focussed on a single, rich topic. On the wide open Internet, though, it may be harder for smaller communities to come into existence, simply because of how hard it might be for the individual members of the community to find one another.

But there are other processes allowing other communities to come together with smaller goals and more focussed needs. The decoupling of time and space seen with Web 2.0 approaches, frees these groups from having to wait until the participants can occupy the same space at the same time. These group can examine a large amount of data rapidly and move on. There is not the need to assure the community that it will be around for a long time.

This is the sort of community that may be more likely to come into existence inside an organization. There are other pressures that drive the creation of these types of groups than simply a desire to talk with people of similar interests about some data.

A grant deadline for example.

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Louisiana devolves

Andrew Jackson by dbking
Louisiana governor signs creationist bill:
[Via National Center for Science Education]

Louisiana’s Governor Bobby Jindal signed Senate Bill 733 (PDF) into law, 27 years after the state passed its Balance Treatment for Evolution-Science and Creation-Science Act, a law overturned by the U.S. Supreme Court in 1987. Jindal’s approval of the bill was buried in a press release issued on June 25, 2008, announcing 75 bills he signed in recent days. Houma Today reports(June 27, 2008) that the bill “will empower educators to pull religious beliefs into topics like evolution, cloning and global warming by introducing supplemental materials.”
[More]

I guess they just made it harder for Louisiana students to get accepted to good universities, at least if they want to be a scientist. Should be interesting as parents sue school districts about teaching religion in their science class. This typically results in the school district losing and having to pay a whole lot of money.

But what does that matter to the politicians who pander? Of course, some school districts apparently have no problem with having creationist teachers. It took this one 11 years before the teacher was fired in Ohio for directly disobeying the school board. I mean , he only burnt crosses into the arms of students while he was supposed to be teaching science.

I am always amazed at the fortitude of those amazing students who make it through this sort of ignorance. Of course, it also explains why we do not have enough graduate students from America and have to import so many.

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Norms are changing

columns by TankGirlJones

[Crossposted at SpreadingScience]

Column on NIH and Harvard policies:
[Via Open Access News]
Karla Hahn, Two new policies widen the path to balanced copyright management: Developments on author rights, C&RL News, July/August 2008.

A light bulb is going off that is casting the issue of author rights management into new relief. On January 11, 2008, the National Institutes of Health (NIH) announced a revision of its Public Access Policy. Effective April 7, 2008, the agency requires investigators to deposit their articles stemming from NIH funding in the NIH online archive, PubMed Central. Librarians have been looking forward to such an announcement, especially since studies found that the voluntary version of the policy was achieving deposit rates of affected articles on the order of a few percentage points.

Since we as taxpayers pay for this research, it should not be bound up behind access control. Now, because of the NIH’s revision, it won’t.

With the article deposit requirement, researchers can no longer simply sign publication agreements without careful review and, in some cases, modification of the publisher’s proposed terms. While this may be perceived as a minor annoyance, it calls attention to the value of scholarly publications and the necessity to consider carefully whether an appropriate balance between author and publisher rights and needs is on offer.

The norm in science has been to always quickly sign over copyright so that the paper could be published. This sometimes resulted in the absurd prospect that the author of a paper could not use his own data in slides, since he no more owned the copyright of it than any other random scientist. Now there is a little leverage for the author to retain some aspects of copyright.

As institutions, as grantees, become responsible for ensuring that funded authors retain the rights they need to meet the NIH public Access Policy requirements, there is a new incentive for campus leaders to reconsider institutional policies and local practices relating to faculty copyrights as assets. …
The February 2008 vote by the Harvard Faculty of Arts and Sciences to grant Harvard a limited license to make certain uses of their journal articles is another important indicator of an accelerating shift in attitudes about author rights management, and also reveals the value of taking an institutional approach to the issue. …

Academic pressure is coming to bear on these policies and it will be interesting to see how it all plays out. In most instances, providing open access will be the better route but now the individual institutions will be responsible for providing the necessary infrastructure.

Perhaps something like Highwire Press will appear. Here , instead of each scientific association having to develop their own infrastructure, Highwire does it for many of them, greatly simplifying publishing for all. Highwire now has almost 2 million article published with free access. Perhaps something similar for institutional storage would be helpful.

Norms are always more difficult to change than technologies. We are now witnessing a key shift in norms for sharing scholarly work that promises a giant step forward in leveraging the potential of network technologies and digital scholarship to advance research, teaching, policy development, professional practice, and technology transfer. …

What scientists expect when they publish a paper is changing rapidly. What once took 6-9 months from submission to publication can now happen in weeks. Where once all rights had to be assigned to the publisher, now the authors can retain some for their own use.

What will the norms be like in five years?

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Depressing

deathstar
Image credit: X-ray: NASA/CXC/CfA/D.Evans et al.; Optical/UV: NASA/STScI; Radio: NSF/VLA/CfA/D.Evans et al., STFC/JBO/MERLIN

Apparently, Belief in Evolution Makes You a Minority Figure:
[Via Genome Technology Online Current Issue]

What a day for creation theory. John Lynch at Stranger Fruit blogs about the latest results of a Gallup poll on political leaning and belief in creation, intelligent design, or evolution. Republicans emerged with 60 percent believing in creationism, 32 percent believing in ID, and just 4 percent believing in no-strings-attached evolution. Democrats were an even split on creationism and ID (38 and 39 percent, respectively), with 17 percent opting for evolution. Independents had the highest rate of belief in evolution — 19 percent — but still had 40 percent opting for creationism and 36 percent for ID.

While we’re on the subject, members of the American Society of Plant Biologists are urging Louisiana Governor Bobby Jindal to veto the creation-in-the-classroom bill that’s on his desk. Pamela Ronald includes the full text of the letter at her Tomorrow’s Table blog.

I was really depressed by this until I actually looked at the data, something worth doing. It is even more depressing. They asked “which comes closest to your views:

  1. Humans developed over millions of years, God guided
  2. Humans developed over millions of years, God had no part
  3. God created humans as is within the last 10,000 years.

So we are not just talking creationism, where God did it. We are talking God did it within the last 10,000 years! 60% of the Republicans feel that mankind was created as is within the last 10,000 years. That is a really horrifying number. An overwhelming number of Republicans believe in a total fantasy for which there is not only no proof but actually a huge amount of information showing it is false. There is absolutely NO evidence at all for proposition 3.

The people who founded Jericho left behind tools and pottery that have been dated to 14,500-11,000 years ago. There is evidence of farming from 11,000 ago. But these Republicans just ignore that evidence. I wonder how they place Neanderthal in their histories. Probably just make stuff up.

But 40% for independents and 38% for the Democrats is not something to cheer about either. Why is this? Why are so many americans ignorant of such basic facts about our natural world. The data answers that question. It is going to church that produces this error.

Gallup Evolution

Those that attend church weekly are the most likely to believe this myth, probably because they hear it all the time. Most never got any education regarding evolution in school at all. This drops to 24% for those that seldom attend church (I’d be worried more about that high number except something like 20% of those surveyed believe the Sun goes around the Earth.)

I guess the one hopeful thing is that those that believe proposition 2, that mankind evolved over millions of years without God, has risen since 2000 from 9% to 14% in 2008. This is higher than the sapling error. Maybe there is hope.

But then again, these questions have been asked since 1982 and essentially 44% of Americans have always believed in something that is demonstrably false. This unchanging level of ignorance

So, while religion may be useful for many things, it is substantially responsible for perpetuating a fable that can be shown to be false by a plethora of methods. Well, at least there are a small percentage of us who can actually deal with the world as it really is. I guess this is how Dwayne Elizondo Mountain Dew Herbert Camacho gets elected in 500 years.

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Posted in Science. 1 Comment »

Who is pollinating whom?

Firedoglake puts it all together. Colony Collapse Disorder is worrying because there is very little research to really determine how bad the problem is.

Most plants native to America do not require honey bees for pollination, since the honeybee is an introduced species. However, many of our crop plants need the bee because it allows us to stage large numbers of pollinators at a single time for our agricultural crops. So loss in the number of bees for commercial use could be devastating.

Again, like climate change, the worst case scenario is horrible but in this case, the research is meager in comparison. But there are some interesting developments.

Here are some quotes from Firedoglake:

A reader recently sent me an article on the deepening problems with hive collapse and honeybees:

A record 36 percent of U.S. commercial bee colonies have been lost to mysterious causes so far this year and worse may be yet to come, experts told a congressional panel Thursday.

The year’s bee colony losses are about twice the usual seen following a typical winter, scientists warn. Despite ambitious new research efforts, the causes remain a mystery….

So, how much research is being done? Not enough. This is what shook me:

So far, Agricultural Research Service Administrator Edward Knipling told the House panel, scientists believe that “various stresses” — such as parasites, pathogens and pesticides — can build up in a bee colony and cause its demise. Some research has specifically identified a particular virus, called the Israeli acute paralysis virus, which is closely associated with colony collapse.

Meanwhile, there isn’t enough money to probe all the pollen and bee samples that researchers have collected, said Penn State University senior extension associate Maryann Frazier.

There are some 2,000 samples on shelves waiting to be analyzed by the federal government for $200 a pop, she said.

“The bee research community is quite small,” she said. “The research and money has been very minimal. What we need is more manpower to tackle this.”

Further illustrating how political pollination works, Pien and bee-friendly representatives hosted a Capitol Hill briefing Wednesday that lured participants with lots of free Vanilla Honey Bee ice cream cups. Dozens of congressional staffers fluttered by for a quick taste. Haagen-Dazs has retained a D.C.-based public relations firm to help make its case, while the American Honey Producers Association paid the lobbying firm Winston and Strawn $860,000 in the last two years, records show.

The article states that the farming bill that was just approved over President Bush’s veto authorizes $20 million for bee-related research but does not guarantee that it will actually be spent. The President decides that. So, Haagen-Dazs has said it will provide $250,000 for research. That should just about pay for the testing of the 2000 samples. A lot more will need to be done as well before we can determine just how bad this could get.

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Watch out for microwave popcorn

popcorn by Darren Hester

This all started out following a question my mother had. When she says research it, I usually do. And what I found out makes me glad I don’t eat microwave popcorn and I wish everyone else would stop.

Popcorn lung is one worry of microwave popcorn preparation that I had heard about. But I found some others that may also impact all of us.

Maybe not everyone has heard about the data regarding PFOA and microwave popcorn bags from a few years ago. Perfluorooctanoic acid (or PFOA) is a surfactant with many industrial uses, such as making Teflon or Gore-Tex. It is also a suspected carcinogen.

Turns out that most people have 4-5 parts per billion of PFOA in their blood. But no one really knew where the PFOA originated. Some suspected overheated Teflon pots. This paper, Perfluorochemicals: Potential sources of and migration from food packaging, from researchers at the FDA, opened a lot of people’s eyes. Here is the abstract:

Perfluorochemicals are widely used in the manufacturing and processing of a vast array of consumer goods, including electrical wiring, clothing, household and automotive products. Furthermore, relatively small quantities of perfluorochemicals are also used in the manufacturing of food-contact substances that represent potential sources of oral exposure to these chemicals. The most recognizable products to consumers are the uses of perfluorochemicals in non-stick coatings (polytetrafluoroethylene (PTFE)) for cookware and also their use in paper coatings for oil and moisture resistance. Recent epidemiology studies have demonstrated the presence of two particular perfluorochemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human serum at very low part per billion levels. These perfluorochemicals are biopersistent and are the subject of numerous studies investigating the many possible sources of human exposure. Among the various uses of these two chemicals, PFOS is a residual impurity in some paper coatings used for food contact and PFOA is a processing aid in the manufacture of PTFE used for many purposes including non-stick cookware. Little information is available on the types of perfluorochemicals that have the potential to migrate from perfluoro coatings into food. One obstacle to studying migration is the difficulty in measuring perfluorochemicals by routine conventional analytical techniques such as GC/MS or LC-UV. Many perfluorochemicals used in food-contact substances are not detectable by these conventional methods. As liquid chromatography-mass spectrometry (LC/MS) develops into a routine analytical technique, potential migrants from perfluoro coatings can be more easily characterized. In this paper, data will be presented on the types of perfluoro chemicals that are used in food packaging and cookware. Additionally, research will be presented on the migration or potential for migration of these chemicals into foods or food simulating liquids. Results from migration tests show mg kg-1 amounts of perfluoro paper additives/coatings transfer to food oil. Analysis of PTFE cookware shows residual amounts of PFOA in the low µg kg-1 range. PFOA is present in microwave popcorn bag paper at amounts as high as 300 µg kg-1.


You can download the paper and have a look at it. They show that very little PFOA migrates onto food from non-stick pans, even when the pans are abused. But it can migrate from the paper-coating in a microwave popcorn bag into the oil, which ends up on the popcorn we eat. Actually, what probably is important is that we ingest other types of fluorocarbons and they are converted to PFOA, which complicates things.

Eating only 10 bags of microwave popcorn a year would be enough to account for 20% of the total body load. Since Americans eat about 160 million bags of microwave popcorn a year, there is a lot entering our bodies. And uneaten popcorn ends up in our trash, along with PFOA.

But if you go to the EPA page about PFOA, there is no mention of microwave popcorn bags. They mention that Teflon is not harmful and that they see no reason for anyone to worry. Here is the EPA’s answer to the question Are there steps that consumers can take to reduce their exposure to PFOA?

At present, there are no steps that EPA recommends that consumers take to reduce exposures to PFOA because the sources of PFOA in the environment and the pathways by which people are exposed are not known. Given the scientific uncertainties, EPA has not yet made a determination as to whether PFOA poses an unreasonable risk to the public. At the present time, EPA does not believe there is any reason for consumers to stop using any consumer or industrial related products because of concerns about PFOA. EPA does not have any indication that the public is being exposed to PFOA through the use of Teflon®-coated or other trademarked nonstick cookware. Teflon® and other trademarked products are not PFOA.

PFOA stands for perfluorooctanoic acid, a synthetic (man-made) chemical that does not occur naturally in the environment. PFOA is sometimes called “C8.” Companies use PFOA to make fluoropolymers, substances with special properties that have thousands of important manufacturing and industrial applications. Consumer products made with fluoropolymers include non-stick cookware and breathable, all-weather clothing. These products are not PFOA, however.


See anything interesting. The EPA does not answer the question that it asked itself! The question was not whether the EPA believed that people SHOULD reduce their exposure. It was how they COULD.

Now scroll to the bottom of the question page. Updates on Friday, June 27th 2008. So, the latest information from the EPA does nothing to help us lower our exposure to PFOA.

And it appears that more of these are a problem than just PFOA. And that PFOA can be aerosolized and dispersed into the air.

So, perhaps even refusing to eat microwave popcorn will not reduce our intake of these compounds. Well, at least Dupont has said it will voluntarily stop production of these compounds by 2015.

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Freeing journal articles

path by fdecomite
Freeing My Father’s Scientific Publications Update:
[Via The Tree of Life]

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Phoenix speaks to me

ice on Mars by NASA/JPL-Caltech/University of Arizona/Texas A&M University

I made the picture bigger so you can see. The ice is in the lower left of the trench, in shadow. The blowups make it easier to see.

Yes, there’s ice on Mars : Nature News:
[Via Nature]

“Whoohoo! Was keeping my eye on some chunks of bright stuff & they disappeared! Sublimated! So it can’t be salt, it’s ice.” That’s the triumphant verdict of the Mars lander Phoenix, which yesterday boldly declared, after 24 Martian days of scratching the planet’s surface, that yes, there is ice on Mars.

Phoenix is constantly sending back information to Earth, which is posted by the mission team using the instant messaging software Twitter (written, in touchy-feely style, in the first person as if Phoenix itself is providing its own commentary on its labours). Twitter, the ‘microblogging’ phenomenon, can thus claim to have brought the watery news to Earthlings’ attention.
[More]

There are a lot of reasons to be happy to be alive today. The Phoenix on Mars is one of those. There are so many things we are going to learn because we were able to land this vehicle on Mars.

But OhMiGod!! I can read what Phoenix (or the humans behind it) is up to by going to its site on Twitter. If I am out and about and Phoenix discovers life on Mars, it will tell me via Twitter. I can be one of almost 25,000 followers of what Phoenix is doing now. here are the three most recent Tweets it has sent as of 12 on Friday the 20th:

This is just too precious. Twitter rocks, even when it is not working well ;-)

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Cancer cell line data

window by danbuck57313
Stock market news and prices:
[Via Houston Chronicle]

Marking another positive step in the collaborative fight against cancer, GlaxoSmithKline GSK announced today the release of genomic profiling data for over 300 cancer cell lines via the National Cancer Institute’s cancer Bioinformatics Grid(TM) (caBIG(TM)). The caBIG(TM) initiative is a network of infrastructure and tools that enables the collection, analysis, and sharing of data and knowledge along the entire research pathway from laboratory bench to patient bedside. By releasing the cell line data via caBIG(TM), GSK could be enabling other cancer research institutions to save considerable drug development time and capital in their future cancer therapeutic research.
[More]

This is a lot of information that will now be accessible to a much wider range of scientists. It can be accessed at the NCI site, caBIG. Anyone can play with the data using the available Open Source tools. I expect this will give people something to work with over the weekend.

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Misleading genetic screening discussions

DNA by net_efekt
A lesson in genetic testing: the I148T mutation [Mary Meets Dolly]:
[Via The DNA Network]

In a followup to what I wrote yesterday is this nice tale of the possible pitfalls of genetic testing when we really do not know as much as we would like to.

There has been a lot in the news lately about how California Health officials have ordered 13 genetic testing companies to stop testing California residents. I think many people do not understand why public health officials are concerned about the flood of new genetic tests offered directly to the public. I think I have an example that may illustrate the problem.

Cystic Fibrosis (CF) is a devastating disease that is caused by mutations in the CFTR gene. To have CF, you must inherent one mutation from your mother and one from your father, which means that both copies of your CFTR gene do not work properly. If you only have one mutation in your CFTR gene you are called a carrier for CF, which means that while one copy of the CFTR gene isn’t up to snuff, you at least have one working copy. The one working copy is enough to prevent you from developing CF symptoms.

So having two bad copies produces the disease but even a single bad copy can have ramifications, such as being wary of marrying other carriers. (I’ll have to check on just how 23andme deals with different alleles from different chromosomes. Many genetic diseases are only a real problem there are 2 bad copies.) Anyway back to the story:

So that brings us to the I148T mutation. When researchers were studying the causes of CF, they discovered that there were a significant amount of people that had CF that also had a mutation in the CFTR gene that causes a substitution of a threonine amino acid for an isoleucine at position 148 of the CFTR protein. Hence the name I148T. Researchers made the assumption that the I148T was one of the two mutations that caused the patients’ CF.

So, anyone who was found to have the I148T mutation, but did not have CF symptoms was labeled a carrier for CF. The I148T mutation was included in the testing panel for many labs, including mine.

But as is sometimes the case, it turns out that the apparent linkage of the mutation I148T with disease was just a fluke and the mutation was not directly involved with the disease. Yet this test was included in a genetic panel run by commercial labs.

Unfortunately, that isn’t the end of the story. As more people were tested, researchers found that there were people who had the I148T mutation with another known mutation, but did not have CF. If the I148T mutation was actually was a disease causing mutation, then these people should definitely have symptoms of CF, but they did not.

What researchers eventually found was that I148T was actually what is called a benign polymorphism, which means that it is a mutation that does not cause disease. What they found was that the disease causing mutation is really a deletion of 6 base pairs at nucleotide number 3199. The mutation is called 3199del6 and just happens to be inherited in high frequency with the I148T mutation.

So, lots of people were told they were carriers when they really have nothing to worry about. And this was with validated commercial labs. This does not deal with the problem of errors that I mentioned yesterday. This is about the being able to technically do something before we actually understand the science.

It seems to me that there is a real danger of the data from genotyping labs being misleading to many people unless there is much better informing, vetting and validating, not only of the data but of the science and of the people who provide the samples. I’ll leave you with Rebecca’s words, but I expect we will have a lot more discussion about this before we reach real consensus:

So the lesson is, just because a mutation is present does not mean it causes disease. Any genetic test has to have a mound of research proving that it has any clinical relevance. A reputable genetic counselor would be able to sift through the data and give you an interpretation of your results.

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Fun with graphs

fractal by Fábio Pinheiro
Fishy phylogenetics figures found. [T Ryan Gregory's column]:
[Via The DNA Network]

Currently working on a paper about fishes, I came across some interesting figures. (Well, mildly interesting, as they are more of the same actually). Let me say, first of all, that much of what we have learned about genome size evolution is thanks to the work of Ralph Hinegardner in the 1970s. He did some of the most substantial investigations of DNA content diversity in groups such as molluscs, crustaceans, echinoderms, and fishes — in some cases, his work remains the main source of information. So, needless to say, I have a lot of respect for his work. Second, I want to note that I think FishBase is absolutely excellent. It is a model for how online databases should be, and I use it frequently. In fact, without it the study I am writing up could not have been accomplished.
[More]

It is always fun to look at graphs and figure out what is wrong with them. He links to another series he has discussed. I got it right away but that is because I know what to look for. it is one of the common fallacies used when discussing evolution and something that Stephen Jay Gould discussed often.

Here is a big hint from the Boston Globe Magazine (Dec. 31, 1995):

The outstanding [misunderstanding of evolutionary theory] is clearly the equation of evolution with progress. People believe that evolution is a process that moves creatures toward greater complexity through time. This makes our very late appearance in the history of the Earth a sensible outcome. The word evolution means progress, but for Darwin, evolution is adaptation to changing local environments, which are randomly moving through time. There is no principle of general advance in that.

Complexity is an ill-defined criteria. What makes something complex? Number of genes. Size of the genome. Number of different cell types. Etc.

Anything that places us at the top or the terminus of any hierarchy is misleading and species-centric. It usually involves cherrypicking. In a scientific sense, how are we more complex than a gorilla? Exactly how are we more complex than a dog?

Attempts have been made for several hundred years now to put humans at the top of any hierarchy, using whatever means necessary. The truth is that no real measure of complexity, by any definition, puts us at the top without some sort of jury rigging of the criteria.

And, frankly, complexity has absolutely nothing to do with successful survival. If complexity is what evolution strives for, then why are the most successful species some of the simplest? Bacteria make up the largest number of organisms on Earth. They were here when life started and will be here when life ends.

There is no progress in evolution. We are not the culmination of a billion years worth of natural selection. We are one of a multitude of species trying to survive TODAY on this planet. We do alright but we will disappear much sooner than many other species will. That is how evolution works. Simple is more often a survival trait than complex.

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Some bumps in the road

sequencing machines by jurvetson
Your SNPs are your information:
[Via business|bytes|genes|molecules]

A quick follow up to my previous post. Reading Rob Carlson’s wonderfully written post on the C&Ds sent out by the California Department of Public Health to 13 consumer genetics companies got me thinking. He writes

There appears to be some tension between the interpretation of tests ordered for diagnostic purposes, which probably should require a prescription, and sequencing or genotyping services that provide information about a consumer’s genetic makeup.
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There is a really interesting conversation going on about various genotyping companies and their interaction with the California Department of Public Health. There are some real questions about its jurisdiction and some people really wonder why doctors have to be involved. (i.e. Pay the cost of a doctor's visit to get a prescription to have my own DNA examined. That sounds odd? Why can't I just send in a cheek swab?)

Some of this also seems to run afoul of the state's consumer protection focus. Again, this seems a little odd but I guess a point could be made to apply some sort of precautionary principle (i.e. the companies need to demonstrate that they are able to accurately produce a genotype with a very low level of errors) since it is likely that a large percentage of the people using the services may view the results as something more than just informational. Look what happened to Alec Guinness when he was given incorrect information regarding a medical condition.

Having been doing molecular biology since the the late 70s, I know that these techniques are not necessarily an exact science. What level of redundancy will be needed? What are the error rates? How good are the microarray chips used? What are the verified QA/QC procedures and who does the verification? The results had better have a high degree of accuracy.

I was interested in the accuracy of the chips used by these genotyping services. I am basing the following on my own research experience and what is actually written on the web sites. If i have made some fundamental error, please let me know. It would not be the first time I went off on a ragged trail to be brought up by a fatal assumption. But I think I have done the math right.

The important use for 23andme is the generation of a very deep and rich database that can be used to find linkages between important genes and SNPs. The accuracy of an individual's sample is not strictly that important for this purpose since the law of large numbers means any individual errors will be swamped out. But individual errors in an individual's sample may be important for that individual (Yes, I am channeling Po from Kung Fu Panda - 'Legend tells of a legendary warrior whose kung fu skills were the stuff of legend'. Or Criswell from Plan 9 from Outer Space - 'And remember my friend, future events such as these will affect you in the future.')

I had to do a little digging to get some numbers but 23andme claims a call rate that averages 99%, meaning that 1% of the SNPs can not be called. With nearly 600,000 SNPs to look at, this means that 6000 SNPs are not called in a single sample. But that is based on an average. Without knowing the standard deviation, it is possible that some samples will have much higher 'No call' rates. So someone who might have a SNP linked to an important trait would not know that they had it.

While there is no data given for what percentage of incorrect calls are made, they do say that reproducibility is 99.9%, so that if the sample is run again 99.9% of the information will be the same. (I would assume this also means that the 6000 'No Calls' are also 'No Calls' the second time.) So, for 600 SNPs in an individual sample there will be an ambiguity.

Is this a problem? I really do not know, not being an expert. For a research database that will be examining thousands of genomes, this may all be irrelevant. There will be some redundancy from the power of large numbers. The 'noise' from errors will be swamped out by the overall SNPs called. So it would be possible to find links between SNPs and phenotypes with this level of error.

But, for individuals who will examine their own data, this could be a little more problematic. Using my rough rule of thumb from all those years I did Poisson distributions, in a group of about 3000 samples, there is a greater than 90% chance that there will be at least one ambiguity (error?) for every one of the 600,000 SNPs on the chip. So if say there was a SNP that tracked an important phenotype, such as Alzheimer's, someone in that group would most likely get the wrong information.

And in a group of about 300 people, there will be a 'no call' for every SNP when there should be a call. So while each individual would have a low probability of having an error in their data, it is very likely that someone in the group will have a error at an important SNP.

Like the lottery, the chances are low of 'winning' but you can be assured that someone will 'win.'

Of course, they would not know they had 'won.' And considering that 23andme claims to have performed 10 billion genotypes since 2007, there are a lot of individual samples with important errors. Not important if you are creating a database of 10 billion genotypes but it might be of some concern to an individual.

I understand the principles behind all of this and recognize the extreme scientific importance of such a database. But I do not believe the average person does. In 1988, 21% of the people surveyed thought the Sun revolved around the Earth. Similar numbers were seen in 1999. Only 47% of the people answered correctly said that it takes a year for the Earth to go around the Sun. Only half the people in one survey understood probabilities (which explains the popularity of lotteries). This is from last year:


The most recent National Science Foundation Science Indicators report draws on different surveys to tell us that only about 54 percent of Americans realize that antibiotics do not kill viruses, fewer than half know that genetically modified foods are in their neighborhood grocery store, and only 44 percent believe that human beings developed from other animal species (about three-quarters of those responding realize that the theory of evolution says this, but many reject the theory).

Indeed, more people believe that houses can be haunted than accept the theory of the Big Bang, and 29 percent are not certain that the earth revolves around the sun rather than vice versa. (my emphasis)

Now sometimes I think we really are headed towards Idocracy but not everyone has the time or inclination to understand the ramifications of what they are doing when they engage biotech. (I have had so many dinner conversations about genetically modified foods. I sometimes feel like my father having to explain the oil industry, where he worked as an exploration geologist for 30 years, to those who do not understand its complexity. Although I think people have a greater visceral fear of 'Frankenfoods' than they do of OPEC )

But these same people make real life decisions based on the results of a 23andme scan. They do not have the time nor ability to understand deeply what the results really mean (at least the 50% that do not understand probabilities). How many errors are usually present? What does level of confidence really mean?Which companies are really legit and which are just jumping on a money-making opportunity? Few people are able to figure this out. (23andme does an excellent job trying to provide this information, though.)

That is why the American people have designated surrogates in the government to do this for them. Thus the FDA, or the California Department of Public Health. They attempt to bring some sort of validation to very complex processes.

I mean, I know that those 'natural' pills will have no real effect on my prowess, no matter how big a smile that guy has. But apparently lots of people believed him. While caveat emptor applies, these sorts of companies are hit all the time with fines and notices by the FDA. The makers of Enzyte apparently defrauded people of $100 million! Its president, his mother and others were found guilty. He may have to serve 20 years in prison, yet the company's web site is still there, it looks like you can still buy Enzyte and all they are doing is mulling whether they should change their name.

So there is a role for some sort of oversight here and I would expect these companies to welcome some. Now the key question is really who should do the overseeing? I would prefer a Federal group rather than a state but, just as we seem to need New York Attorneys General to go after high tech companies, there may be a need for states to intercede if no Federal one will.

[Lest anyone think I am picking on 23andme, they are the epitome of an open site, providing all the information I needed and obviously stating in very open and transparent terms exactly what is going on. They appear to possess as much integrity as any organization I can find out about online. The main benefit of 23andme is the database being generated. They are open about sharing this information for research pirposes. Their blog is a constant source of very interesting science. I would not hesitate in giving them a sample because I would not care at all what the results really were. My sample really helps them more than it helps me. I actually kind of like their mission, but I am a well-educated guy who knows that the Earth goes around the Sun in a year. I am not an average customer.]

Of course, this is another example of the rapidly changing world hitting up against regulations that were developed for something completely different. It took some time for DNA fingerprinting techniques to be readily accepted and even then individual labs screw up without proper oversight. While I do not believe the same sorts of consequences to arise from genotyping, I expect that oversight will be worked out because the technology is just too easy to use.

This collision of old and new smacks of the similar problems copyright has when dealing with the digital world. The game has changed and bureaucracies that were created to deal with old style medicine will have to learn how to deal with this newfangled biotech. Because it is likely that in just a few years, it will be possible to sequence a person’s entire genome in perhaps a single day for under $1000.

Garage Biotech will really be in full swing. How will the California Department of Public Health deal with that?!

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Confusing will not work

key by ul_Marga
[Crossposted at SpreadingScience]

There is a possibly interesting paper in Genome Biology by Barend Mons et al: Calling on a million minds for community annotation in WikiProteins. I say possibly because the paper itself is quite confusing to me but the overall goal seems to be a cool concept. This group has created and is encouraging the use of “WikiProteins” a community annotation system for “community knowledge.” Sounds a bit fuzzy? Well, reading the paper does not completely help. For example here is the abstract

WikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a ‘million minds’ to annotate a ‘million concepts’ and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at http://www.wikiprofessional.org webcite.

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This is an interesting attempt but the community they are asking for is not in existence yet. The goal is extremely worthwhile, since the best way to create knowledge from the huge mountain of data being created is to incorporate large social networks. But the community must be created first.

However, at the moment in the science community there is a large activation energy (yes, human social interactions also require energy to be expended in creating the network before the information flow can become self-sustaining). First, there needs to be demonstrable proof that putting time into community annotation will be productive and rewarding. There is no proof of this yet.

Second, most scientists are creatures of habit; they have developed a workflow that is successful. In order to get them to change, it had better be easy. Again, time is important, especially in the early phases of community building.

I spent some time at the site trying to get an idea of what was involved. I still did not really figure it out. I do not believe many working scientists will either.

However, this is an important site and one that should be watched. Simply because the initial site is not there yet does not mean it will not quickly get a lot closer to perfection. It is a beta. It is easy to incorporate feedback and move rapidly to something more usable. Lowering the barrier to entry would help a lot.

These sorts of tools are too useful for them to remain unused. A million minds will someday be involved in this work. But it will not happen until a strong community is created.

Online communities will be how we solve the difficult problems facing us. The sooner they are functional, the sooner we can begin finding solutions.

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CTT and global climate change

chains by Clearly Ambiguous
The Denial Industrial Complex:
[Via Deltoid]

Matt Nisbet reports:

A new study by a team of political scientists and sociologists at the journal Environmental Politics concludes that 9 out of 10 books published since 1972 that have disputed the seriousness of environmental problems and mainstream science can be linked to a conservative think tank (CTT). Following on earlier work by co-author Riley Dunlap and colleagues, the study examines the ability of conservative think tanks to use the media and other communication strategies to successfully challenge mainstream expert agreement on environmental problems.

(Clarification: A couple of readers thought Nisbet was saying that one particular CTT was linked to 90% of the books. Nisbet means that 90% of books can be linked to CTTs.)

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A thorough debunking of some of the denialist literature. Most of it comes from ideologically driven groups who just do not want to examine the science. Knowing why this is will help in further debunking.

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