RNA

New site, new stories

jhalper — Sun, 03 Jan 2016 05:05:53 +0000

New site, new stories

Cells that “spit” out their contents and messenger RNA that is not so swift at delivering its message. Those are two brand new stories on our new and improved website. Check it out and let us know what you think.

The first story arose from a simple question: How do secretory cells – those that produce copious amounts of such substances as tears, saliva or all those bodily fluids – manage to get their contents out of the cell? Cells are walled all the way around; they don’t really have doors for letting things the size of a drop of fluid out. Instead, they use the vesicle system – small globes made of the same stuff as the cell membrane that transport the drops out to the edge. The vesicles then fuse with the membrane, releasing their cargo to the outside.

Prof. Ben-Zion Shilo and his group realized that this was all well and fine for small amounts of biochemicals, but secretory cells would need a better system. Their results, which involved a lot of intricate time-lapse observation in the saliva glands of fruit-fly larvae, are beautiful to watch as well as instructive.

Salivary gland of a larval fruit fly. Vesicles (red) carrying the glue must empty their contents quickly and efficiently

The second story arose from a surprising observation: Certain liver cells that are involved in metabolism seemed to have large amounts of messenger RNA in their nuclei. Why would RNA stick around in the cell nucleus, instead of rushing out to make proteins? Dr. Shalev Itzkovitz and his group followed up on this question by asking further questions: How many cells keep RNA in their nuclei? How long does this RNA tend to stay? Which genes produce the homebody RNA?

Although they have not yet answered every one of their questions, they have uncovered a new level of regulation in the cell – one that is not immediately intuitive.

Nuclei of liver cells, mRNA of certain genes in white

Revealing how some cells get rid of their contents or discovering that others hoard things deep within – neither finding will cure disease tomorrow. Both are changing our understanding of how the human cell functions, and both are going to contribute, in the future, to human health and welfare. We promise to keep bringing you these stories and more.

jhalper Sun, 01/03/2016 - 00:05

Tags

basic research

biochemistry

biological regulation

Biophysics

biological regulation

Biophysics

genes

Religious fundamentalists try to prove fetal DNA in vaccines causes autism and fail

oracknows — Tue, 09 Sep 2014 04:00:28 +0000

Religious fundamentalists try to prove fetal DNA in vaccines causes autism and fail

There are some myths, bits of misinformation, or lies about medicine that I like to refer to zombie quackery. The reasons are obvious. Like at the end of a horror movie, just when you think the myth is finally dead, its rotting hand rises out of the dirt to grab your leg and drag you down to be consumed. Of course, the big difference between zombies and these bits of zombie quackery is that in most stories a single shot to the brain will kill the zombie. The same is not true of zombie quackery. You can empty clip after clip of reason, science, and logic into the “head” of the zombie quackery at point blank range, and the best you’ll do is to drive it away for a while, only tor rise up again when you least expect it.

Of course, antivaccine pseudoscience, in my experience, is one area of quackery that is rich, if not the richest, in zombie quackery and zombie memes. The same old lies keep popping up again and again and again, like Whac-A-Mole. Sure, they’ll sometimes go away for a while (or appear to go away for a while), but sooner or later the exact same misinformation, occasionally with minor alterations. Think the claim that the CDC conspired at Simpsonwood to “hide” that thimerosal in vaccines causes autism, a myth first popularized by antivaccine icon Robert F. Kennedy, Jr. back in 2005 whose rotting corpse recently been resurrected to shamble about like so many extras on The Walking Dead. One of the advantages of having been at this blogging thing for nearly a decade is that I’ve come to recognized many of these zombie memes immediately on sight. Where other people think they’re new, I recognize them as something old, often something I’ve written about before at least once, if not many times. The disadvantage, on the other hand, is a tendency to become jaded or bored with refuting the same nonsense over and over again. Sometimes I marvel that in December it will have been a decade since I started blogging and sixteen years since I started refuting online nonsense.

The latest zombie meme struggling to make a comeback is a particularly brain dead one, even by antivaccine zombie meme standards. It comes in the form of a press release on ChristianNewsWire for a new “study” (and I do use the term loosely, even though apparently it was published in a peer-reviewed journal) entitled New Study in Journal of Public Health and Epidemiology Correlates Autism Disorder Increase and Human Fetal DNA, Retroviral Agents in Vaccines. The first thing that you should notice about this press release is that it is on ChristianNewWire, whose news sources consist mainly of—you guessed it!—fundamentalist Christian and conservative Catholic organizations, with very few legitimate scientific organizations.

The next thing you should notice is who put out this press release: Katie Doan of the Sound Choice Pharmaceutical Institute. A quick click rapidly reveals that the SCPI believes vaccines cause autism and that it’s somehow related to “fetal DNA” in vaccines, complete with a list of “aborted fetal product”- This, you might recall, is part of another antivaccine zombie meme, namely the claim that vaccines are made using “aborted fetal tissue.” This comes from the simple fact that a human cell line originally derived from an aborted fetus decades ago is used to grow the viral stocks used to make some vaccines. This is such a non-issue that even the Catholic Church says it’s acceptable to use these vaccines because “the risk to public health, if one chooses not to vaccinate, outweighs the legitimate concern about the origins of the vaccine” and because parents “have a moral obligation to protect the life and health of their children and those around them.” That doesn’t stop radical antiabortionists from trying to represent cells hundreds of cell divisions removed from the original fetus from which they were derived as somehow being “fetal tissue” or “fetal parts,” rather than what they are: A cell line.

A second part of this antivaccine zombie meme is that it is in actuality DNA from these “fetal cells” that somehow gets into human neurons, recombines with the DNA there, producing foreign proteins that show up on the surface of the neurons and provoke an immune response, thus damaging the neurons. I’ve already explained in my usual painful detail how utterly ignorant of biology and homologous recombination one has to be to accept this hypothesis as anything other than incredibly implausible at best, with no evidence to support it, to boot.

So what are the hypothesis and conclusion of this “study” being touted? Let’s take a look at the press release and then go to the study itself:

A new study published in the September 2014 volume of the Journal of Public Health and Epidemiology reveals a significant correlation between autism disorder (AD) and MMR, Varicella (chickenpox) and Hepatitis-A vaccines.

Using statistical analysis and data from the US Government, UK, Denmark and Western Australia, scientists at Sound Choice Pharmaceutical Institute (SCPI) found that increases in autistic disorder correspond with the introduction of vaccines using human fetal cell lines and retroviral contaminants.

Even more alarming, Dr Theresa Deisher, lead scientist and SCPI founder noted that, "Not only are the human fetal contaminated vaccines associated with autistic disorder throughout the world, but also with epidemic childhood leukemia and lymphomas."

Theresa Deisher? Where have I heard that name before? Oh, right. Here. She’s the founder of SCPI and has been laying down the serious stupid about “fetal DNA” in vaccines since at least 2009, when I first noticed her. It explains much about why the press release also mentioned the whole “CDC whistleblower” manufactroversy being flogged by the antivaccine movement right now. It also explains why this press release cherry picks information from an FDA presentation from 2005 by Keith Peden at the Division of Viral products on Issues Associated With Residual Cell-Substrate DNA.

Funny how they fail to note that 10⁶ or 10⁷ μg of cellular DNA would be needed to produce an oncogenic event, and that the oncogenic risk for 2 ng DNA would be around 5 x10⁸ to 5 x 10⁹. In actuality, it’s even higher than that, around 7.5 x10¹³ to 7.5 x 10¹⁴, given the size reduction of DNA to around 200 bp fragments that occurs. The authors in the study itself claim that there is anywhere from 142 ng to 2000 ng of “fetal DNA,” but, one notes, that they didn’t do PCR on this DNA to prove that it was fetal DNA, rather than DNA used to make the virus, nor did they show any gels demonstrating the claimed size of the DNA fragments. All they did was to use an ELISA for single- and double-stranded DNA and called it a day. From a molecular biology perspective, this is not nearly enough to prove that the DNA they are measuring, even assuming they are using the assay kits correctly, is in fact fetal DNA. Particularly amusing is this passage:

Notably, the viruses in the Meruvax, MMRII, and HAVRIX vaccines are mRNA viruses, not DNA viruses, and since the mRNA was degraded by heat treatment prior to oligonucleotide measurements, the DNA results are indeed specific for human DNA, the only DNA in the mRNA virus vaccines.

Of course, one wonders whether Deisher et al took the specificity of PicoGreen into account. Its specificity for dsDNA over RNA is not perfect; indeed, take a peak at the graph here. It’s clearly at least 100=fold more sensitive to dsDNA at 520 nm than it is for RNA, but remember, there’s a lot of RNA in a concentrated solution of RNA virus relative to the contaminating dsDNA. True heating the RNA will result in its degradation, but not as much as Deisher et al apparently think. Anyone who’s done plasmid preps the old fashioned-way before columns existed to remove RNA contamination knows that a lot of small RNA fragments remain in such preps, even after heating. If Deisher et al had really wanted to measure only DNA, they should have treated these vaccine vials with RNAse to guarantee that no small fragments of RNA were left. In any case, there’s no evidence presented that these small amounts of DNA are dangerous, much less that they have anything to do with autism. Remember, we’re talking about nanogram quantities, at most a microgram or two, injected intramuscularly. As I explained, the thought that such a tiny amount of DNA could cross the blood-brain barrier and get into neurons in sufficient quantities to actually recombine with host DNA sufficiently to cause neuroinflammation is incredibly implausible. To really do this rigorously would have required measuring the RNA, dsDNA, and ssDNA in several vials, and then to subject some of the vaccine solution to PCR using appropriate primers to prove the source of the RNA and DNA.

Of course, none of this really matters, at least for purposes of this study, because the investigators never demonstrate that there is a correlation between the introduction of “fetal human cell”-containing vaccines and increased rates of increase of autism prevalence. True, the authors do the mother of all studies confusing correlation with causation, complete with a lot of linear regressions between autism prevalence in multiple datasets and the uptake of vaccines such as Varivax and Hepatitis A for specific birth cohorts. It’s an excellent demonstration of the adage that if you look hard enough you can fit almost any data in a linear regression.

Then there’s the change point analysis. A change point is, as it sounds, a point where the slope of a curve changes suddenly, most commonly seen when one curve consistent with a straight line “changes slope.” Of course, the assumption that the relationships between change points between time and autism prevalence are linear is a rather dubious assumption right off the bat. Of course, as Mark Chu-Carroll put it:

One big catch here is that least-squares linear regression produces a good result if the data really has a linear relationship. If it doesn't, then least squares will produce a lousy fit. There are lots of other curve fitting techniques, which work in different ways. If you want to treat your data as perfect, you can use different techniques to progressively fit the data better and better until you have a polynomial curve which precisely includes every datum in your data set. You can start with fitting a line to two points; for every two points, there's a line connecting them. Then for three points, you can fit them precisely with a quadratic curve. For four points, you can fit them with a cubic curve. And so on.

Similarly, unless your data is perfectly linear, you can always improve a fit by partitioning the data. Just like we can fit a curve to two points from the set; then get closer by fitting it to three; then closer by fitting it to four, we can fit two lines to a 2 way partition of the data, and get a closer match; then we can get closer with three lines in a three way partition, and four lines in a four way partition, and so on, until you have a partition for every pair of adjacent points.

The key takeaway is that no matter what you data looks like, if it's not perfectly linear, then you can always improve the fit by creating a partition.

Which appears to be exactly what Deisher et al did, as I described. Mark Chu-Carroll also described how using this sort of “iterative hockey stick” analysis is a completely inappropriate analysis for this sort of data, as well as how it is very difficult to identify real change points without massive data sets and a very dramatic change in slope, neither of which qualify here. Basically, this study appears to be more of the same thing as the last study; I look at it as the previous “study” put out by Deisher, only on steroids of stupid. My main thought was this: It took them over four years to produce this after their last study? Really?

Not surprisingly, Deisher et al reported change points very similar to what they found last time, too: 1980, 1988, 1996. These are the same change point years as last time, give or take at most a few months. I can’t resist recycling what I wrote last time, because it’s so freakin’ appropriate, although I’ll spare you quoting it exactly.

Apparently the tainted DNA from ground-up murdered babies is so powerful in causing autism that it can do so immediately. These “change points” correlate within a year to the introduction of vaccines made from ground up cells from murdered babies. For example, the rubella vaccine was approved in the U.S. in 1979, and the first changepoint detected was in 1980. The second dose of the MMR vaccine was added to U.S. recommendations in 1988, and in 1988 there was a changepoint. Then the chickenpox vaccine was recommended in 1995, and there was a changepoint in 1996. Autism is usually diagnosed between ages 2 and 4; so, unless the power of these evil tainted vaccines to contaminate the DNA of our precious children can also travel back in time, it’s hard to take correlations between these change points and vaccine introduction as anything more than spurious pseudo-correlations. It would be so hilarious if the consequences of such fear mongering weren’t so dire, although even then it’s still useful as a cautionary tale worthy of extreme mockery of how not to do linear regression and inflection point “hockey stick” analysis.

oracknows Tue, 09/09/2014 - 00:00

So, if these vaccines have the ability to "immediately" induce autism (the stories we hear about children immediately regressing after their vaccines - then why are the vast majority of children diagnosed with autism between ages 2 - 4....long after the receipt of these "ebil" vaccines?

"...even though apparently it was published in a peer-reviewed journal)..."

And a quick check at Jeffrey Beall´s website "Scholary Open Access" shows that "Academic Journals", which publishes the "Journal of Public Health and Epidemiology", is a typical "predatory publisher" that prints everything you want as long as you pay their fees. The peer review in the case of this paper was most likely only verifying that the authors´ cheque didn´t bounce.

There's one point I'd like to raise about the ethics of using an aborted foetus to generate the cell lines used to make the vaccine.
The woman pregnant with the foetus in question developed rubella, and the foetus would almost certainly have been born with Congenital Rubella Syndrome. The Catholic Church permits abortion for medical reasons. This would have been a valid medical reason.
I suspect that the extremists are trying to insinuate that the foetus was aborted for the sole purpose of making vaccines, and not what actually happened.

the foetus would almost certainly have been born with Congenital Rubella Syndrome. The Catholic Church permits abortion for medical reasons.

Sadly, some fundamentalists won't even accept abortion for medical reasons, even if the mother should die of it.
For Pete's sake, they don't accept abortion for ectopic pregnancy, if I am to believe Jen Gunter's blog posts.
The fetus is dead, will be dead soon, or isn't even a fetus at all, but no, don't touch it.

I suspect that the extremists are trying to insinuate that the foetus was aborted for the sole purpose of making vaccines

You can scratch the "I suspect" part. Extremists are on record for accusing "liberals" of pushing for abortions; accusing them of using baby corpses for witchcraft is just the next step.

The woman pregnant with the foetus in question developed rubella, and the foetus would almost certainly have been born with Congenital Rubella Syndrome.

And the antivaxxers are doing their level best to ensure that there are lots more such tragedies.

Julian Frost, @3

The Church does not permit abortions, the same way the Church does not permit divorce. Period.*

In the case of an ectopic pregnancy, the surgery is _solely _ to save the life of the mother, and we simply don't yet know how to save the baby at the same time.

Ask any Jesuit.

fusilier
James 2:24

*Unless, of course you are a prominent (current or former) US Representative or Senator.

Fusilier, with respect, I'm a catholic (albeit a lapsed one) and you are wrong. The church DOES permit abortion for medical reasons. Oh, and there are circumstances where the church will grant an annulment.
Please do not speak on things when you have no knowledge or an incomplete understanding.

@ fusilier

In the case of an ectopic pregnancy,[...] and we simply don’t yet know how to save the baby at the same time.

We are going on a derail tangent here, but I just want to precise my point:
In ectopic pregnancy, it was my understanding that there isn't even a baby to save. The fertilized egg has nested outside of the uterus and, since it's not in the proper environment to do so, it is not going to develop correctly into a fetus.
The egg's cells will proliferate until they colonize the Fallopian trumps and burst them under the pressure.
Unless you can rewind time before the egg nested outside of the uterus, or slightly more realistically unless you can surgically relocate the egg in the next few days after implantation, I am afraid it's too late for the fetus. The egg needs a very specific environment to organize rapidly dividing cells into an embryonic sack and tissues. The proper parts of the uterus wall and the fetus cells should collaborate to form the placenta.
If this environment is not available on time, you don't get a baby. You get chaos and pain...

"scientists at Sound Choice Pharmaceutical Institute (SCPI)"

This alone is enough to get the manure meter pinging loudly. It's almost as bad as "researchers at the NaturalNews testing lab".

Julian, you are a bit confused:

The Catholic Church has no doctrine that permits abortion for medical reasons. None. However, to understand this, you must first understand how the Catholic Church defines abortion. To qualify as an abortion under Catholic law, the act must be undertaken with the INTENT of ending fetal life. That's it.

The Catholic Church's stance is that if a medical procedure is undertaken that results in the termination of fetal life as a SIDE EFFECT, that is morally permissable, since the intent was not to terminate the fetal life, but to treat the mother.

This came up several years ago because a Salon writer alleged that Rick Santorum, who was a presidental candidate at the time and rabidly pro-life, had consented to an abortion for his wife. However, it was not true. Santorum's wife was pregnant, developed an infection, and was administered antibiotics that resulted in her pre-term labor, the birth of their very premature son and his death. Catholic doctrine permits this, since the treatment was administered with the intent to save her life and the loss of the pregnancy was a side effect.

The portion of Catholic law that deal in terminations is Canon 1398. It makes it extremely clear that the Church makes no exception for any acts which intent to end fetal life. The exception you argue for simply does not exist within Canon Law. Now, I think you can argue that it actually does exist in a very round-about way, but you're technically incorrect that the Church condones any abortion, in any form.

That is enough of this derail, although I must say I'm thrilled that my Theology doctorate has finally proven itself useful on a science-based website! I never thought I'd see the day.

Sound Choice Pharmaceutical Institute

All these lovely buzzwords like "safe," "natural," "sound"...I have the same reaction when I read of any group with "patriot" or "freedom" in their name, because they aren't and that's the last thing they want.

Another case of data being tortured until it confesses. The "analysis" reminds me of much of the economic "analysis" I have seen in the last decade: people who already know the desired conclusion interpret the data in such a way as to support the desired conclusion.

Thanks to SIASL@2 for investigating the journal in question. It's hard, without making a full time effort of it, to keep track of all the journals out there and figure out which ones are really in the field of nocturnal aviation. The question arises: were the authors of this paper scammed, or did they know it was a scam journal and published there precisely because, as noted above, the peer review would consist of making sure the check wouldn't bounce?

@ Shay
I suppose those groups with 'freedom' in their name, are mostly for their own freedom, but they don't care about other peoples freedom.

Funny you conveniently contextualize the issue of fetus cell lines and RNA particles, etc..as a fanatical anti-vax, anti-abortion, anti-science, nutcase type of thing...

In reality, most parents are unaware of the use of such things and I know very well that many are alarmed after finding out what is actually injected into their children. It does not matter if a parent is for or against abortion - using aborted cell lines in whatever regard rightly raises a few eyebrows. SV-40 and a host of other possibilities come to mind. Again, nothing to do with anti-X...it's sound questioning and about informed choice. I personally am not interested in participating in such an experiment - I do not want x-cross specie or human cell line fragments injected in any form or fashion into my body (though it has happened in the past - I receive experimental flu vaccine in the military and damn near took me out)...this blog, nor anyone in the scientific community fully knows the impact of these substances - in other words we are in the midst of ongoing study - and a group of unelected people have decided the whatever benefit outweighs the risk..as citizens become more informed, the more they will push back (you already see it) and become enraged at the presumptuous and arrogant attitudes of those in the science community. This is further exacerbated by conflicting studies (you can attempt to debunk them all you want - science is never settled - to say so defies the very nature of scientific inquiry) and the fact that scientists are coming forward to express fraud in a meaningful way - the PA courts allowed the Merck whistleblower case to move forward (I see you have not spent much time on that story) and let's see what the 100K documents released Snowden style to the Congressman have to say....Scienceblog has a lot to lose (like many others who pushed in all of their chips) if the whistleblowers prevail. Your desperation shows in the recent articles where you attempt to bash and slam any possibility that you might be wrong. Or that there is a flaw in the science - of which, there has to be - too many variables, too many opportunities for corruption, not enough checks and balances, etc...happens all the time and the level of scandal and fraud seems to get bigger and bigger.

I attempt to read your material objectively but good lord, one day it's the disgruntled anti-vax scientists, the other it's the misinformed, stupid anti-vas parents and now it's those crazy anti-abortion religious nuts...at some point the entire world can't be crazy - it might be you....Again, there is a lot of reputations on the line - you want those damn whistleblowers to go away. Many sleepiness nights searching for articles that slip by the mainstream black hole...yes, you catch those articles and revelations that are forced into the alternative space and then scienceblog goes into hyper mode asking the rhetorical question "if it was legit, why are these nut jobs not covered by the mainstream - and here they are on some conspiracy site...the Merck whistleblower case is a perfect example - this story along with Thompson should be headline news....

So please keep up with you bashing...you are fully exposing yourself to those who came here seeking an objective opinion - nice work!!

Funny you conveniently contextualize the issue of fetus cell lines and RNA particles, etc..as a fanatical anti-vax, anti-abortion, anti-science, nutcase type of thing…

In this particular case, if the shoe fits...

Seriously. The lack of understanding of science that went into the SCPI travesty of a "study" is truly astounding. Also, I don't actually blame most parents (just a few of them who have risen to become leaders of the antivaccine movement) because they honestly don't know any better and have an insufficient scientific background to understand why the line they're being fed about "fetal DNA" and "contamination" is utter piffle and that the claim that somehow that fetal DNA from vaccines (1) can cross the blood-brain barrier in sufficient quantities to become and issue; (2) can get into neurons in sufficient quantities to become an issue; and (3) can homologously recombine with host (the baby's) DNA in such a fashion to produce mutant proteins that provoke an autoimmune reaction is so far beyond the pale, so inconsistent with our understanding of molecular biology, that it deserves the ridicule it gets.

"This is further exacerbated by conflicting studies (you can attempt to debunk them all you want – science is never settled – to say so defies the very nature of scientific inquiry)"

Translation- it doesn't matter what the data tell us, I can choose to believe any "study" I want so long as it confirms my beliefs.

@Michael... The thing is, you read here and its backed up by scientific facts, theories, Testing techniques etc. If Orac is wrong he is called out on it and if needed he adjusts his opinion and his article (Good scientists do this agreed?) .. Orac is very well known among these groups that publish misinformation but i have yet to see any of them come here and form a cogent argument as to why Orac is wrong. its just push bad science until it breaks then start insulting people. then of course they go back to their holes and whine on their own one sided, comment moderated, no dissent, websites. If you can't see that then stop reading now because its pointless!

Funny you conveniently contextualize the issue of fetus cell lines and RNA particles, etc..as a fanatical anti-vax, anti-abortion, anti-science, nutcase type of thing…

When the word "fetal" is brandished as the verbal equivalent of eerie theremin music playing in the background -- as if the DNA of a human cell culture carries some sort of cellular memory of parturition status, and is radically different for a fetal source than for an adult human source -- then it is nothing but magical thinking and oogie-boogie words. Yes, "fanatical anti-vax, anti-abortion, anti-science, nutcase" seems appropriate.

Maybe I'm not paying close enough attention, and perhaps Google hasn't picked it up yet, but I don't think anyone has mentioned the PBS special on vaccines tomorrow night. Paul Offitt and some other luminaries are credited, so hopefully it will give a fair and balanced view (I mean truly balanced, not balanced by including Barry, who believes vaccines are milked from the teats of Satan's familiars).

Michael:

In reality, most parents are unaware of the use of such things and I know very well that many are alarmed after finding out what is actually injected into their children.

Only when it's framed dishonestly, as the antivaxxers in this case have done.

Aborted fetal cell tissue is simply not in the vaccines. Cell cultures derived from a single fetus aborted decades ago (actually before the parents of today's young children were even born) are used to grow rubella virus. This virus is then taken and used to produce the vaccines. The odds of any fetal DNA getting into the vaccine is very slim, along the lines of cow's milk getting from a washed saucepan into some ground beef that's cooked in the pan next, yet Orthodox Jews will not tolerate that even if the pan is washed so thoroughly that a person with severe bovine casein allergy will not react to it. This is along those lines. The quantity of fetal DNA would be *homeopathic*. Even if it weren't, how could it even cause a problem? It would be, at worst, fragmentary human DNA floating around loose. It can't "infect" anything; with the rather specific exception of the sperm cell, human cells lack any mechanism for adding their DNA to that of another.

I'm glad you attempted to read this material objectively. However, you appear to have come to it with a fairly strong opinion ahead of time that would predispose you against the content. And it did. You are attempted valiantly to read objectively, but I do not think you succeeded.

Funny you conveniently contextualize the issue of fetus cell lines and RNA particles, etc..as a fanatical anti-vax, anti-abortion, anti-science, nutcase type of thing…

Well, some vocal objectors do say they are against the use of fetal tissues for moral reasons.
And this is the angle used by opponents: hinting at cannibalism and baby-killing.
Others objectors are just rejecting mainstream science, preferring to believe the few conflicting studies, and pulling the card "science is never settled" if their favored article is debunked. That's anti-science in my book.
Rationalization by grasping for supposed risks comes after.

In reality, most parents are unaware of the use of such things and I know very well that many are alarmed after finding out what is actually injected into their children.

This I can grant, to some extent. In my country, most people finishing high school would have had a chance to learn that vaccines are made of gross stuff, but it could easily be overlooked.
On the other hand, I blame Hollywood science, where good science is sanitized, made of crystal clear liquids (or occasionally funky green, but in a jolly way).
In reality, biology is gross. A vaccine is made of more or less killed germs. So yeah, there is some gross organic stuff in a vaccine. What did you expect?

By the same token, did you know that milk is coming from the udder of cows? Or worse, that eggs come from the @ss of hens? That doesn't stop you from giving it to your children. More or less raw (if the yolk is running, that's not fully cooked, sorry - still somehow raw) .

It does not matter if a parent is for or against abortion – using aborted cell lines

If it doesn't matter, then why do you say "aborted cell lines"?
The cells were not "aborted". These are fetal cell lines.
Or were. The currently used cell lines are the great-(great)x-great-daughters of the original cells.
It's like I was calling myself Spanish because more than 6 generations ago, my ancestor came from Spain.

I was looking at this "paper" yesterday. In the analysis, the refer to their combined hockey stick model in panel E, but I could not find panel E anywhere in the paper. To me, the first sign of a suspicious paper is that it reads like crap and is not easy to follow and is riddled with errors that should have been caught in proof reading.

Orac said:
" I don't actually blame most parents (just a few of them who have risen to become leaders in the antivaccine movement)

Totally agreed: I feel this way generally even far beyond the issue presently under consideration. Parents who rise in status in the movement are adept at disseminating mis-information in an emotionally engaging way: Jon Brock ( CrackingtheEnigma) wrote about a focus group that illustrated how parents accepted vaccine information more readily from *other* parents rather than from professionals.

Sites like AoA and TMR maintain readership because of this mode of proselytisation:
the contributors ( and to a degree, commenters) tell their tales, give their reasons and empathise with readers who may be in similar predicament because their child has an ASD. They mis-represent themselves as educators and experts- which can seem attractive to readers who may feel shunned by parents of NTchildren, family members, uncaring professionals and society at large. Isolated people with difficult daily lives make the best captive audience.

Unfortunately, a few who form the ( rotten) core of this unrealistic counselling bureau/ group therapy gone wrong have a background in psychology and social work and thus know how best to gather adherents and incite loyalty with their own histrionic antics. In addition, at least one has been in marketting lending a professional stamp to their messaging.

I often find it hard to feel sympathy for a distressed parent ( usually mother) who becomes an active voice against vaccines and SBM / psychology and leads naive parents into the same bad choices and actions.

I do not want x-cross specie or human cell line fragments injected in any form or fashion into my body

Given the absence of any evidence indicating whatever cross-specie or human cell line fragments may remain in final vaccine preparations engender increased risk or cause actual harm, one has to wonder why you're concerned this might happen.

Funny you conveniently contextualize the issue of fetus cell lines and RNA particles, etc..as a fanatical anti-vax, anti-abortion, anti-science, nutcase type of thing…

I have, however, only seen thisobjection advanced by people who are fanatically antivax or anti-abortion, who are anti-science and who far, far too often do qualify (on the basis of their own statements) as nutcases. Noting that fact is descriptive rather than pejorative..

x-cross specie

I think this means "coins which have been marked with a cross" (possibly Spanish doubloons, in preparation for breaking them into pieces-of-eight).

It’s like I was calling myself Spanish because more than 6 generations ago, my ancestor came from Spain.

Given the number of generations these cells are removed from the original tissue sample, it's more like calling yourself an australopithecine.

I know one thing -- if DNA would really happily cross the blood-brain barrier, enter neurons and start expressing proteins just by giving it as an intramuscular injection, then molecular neuroscience would be a LOT easier than it is. Either that, or the people I worked with wasting a lot of time engineering those fancy vectors. Hell, it isn't that easy to get DNA inside a cell that's just sitting in a tissue culture dish.

Oh, there are plenty of people who claim that the Supreme Court allowed abortions because other countries were doing away with them and there was a concerted effort by Big Pharma, natch, to decriminalize abortions in order to have a steady supply of aborted fetuses. Because, you know, we don't grow flu vaccine in eggs, we grow it in fetuses, rows and rows of aborted fetuses. It's like a scene from the Matrix or something.

Worse yet, people who claim that foreign DNA injected into their bodies will somehow do all of these horrible things don't stop for a second and think of all the times they have been exposed to foreign DNA through eating, drinking, having sex, kissing, scraping their knee on the ground, cutting themselves while cooking chicken or beef or whatever. It's all about the vaccines. That's where the money's at. No one is going to donate to your cause (or your mansion in Texas) if you expose yourself to all of "teh toxinz" naturally, as in just by the mere fact that you're alive.

But we're the sheeple.

From the last paragraph: "For example, the rubella vaccine was approved in the U.S. in 1979, and the first changepoint detected was in 1980."

There a decade error in the rubella vaccine, it was approved in 1969 in the USA. Then included in the first MMR vaccine in 1971.

There was a change in rubella strain in the MMR in 1978. And it was not due "market share" issues, but that Hilleman and others thought it was better.

From one of those evil Pharma dudes who developed an early rubella vaccine: The History of Rubella and Rubella Vaccination Leading to Elimination:

Over the next decade, accumulating evidence led to changes in the United States. First, the duck embryo and dog kidney vaccine strains caused significant joint reactions [24–27]. Second, reinfection on exposure to wild rubella virus was demonstrated frequently with all strains except the RA 27/3 vaccine [28–30]. Third, the good safety record of the RA 27/3 vaccine in Europe, plus the majority opinion of scientists, led the US Food and Drug Administration to license RA 27/3. Important pressure for this decision came from Dorothy Horstmann at Yale, who was convinced by her comparative studies of rubella vaccines [31], and by Maurice Hilleman at Merck, who sought a better rubella strain for measles-mumps-rubella (MMR) vaccine.

One of the studies showing joint pain issues with the original American rubella vaccine is fully available:
http://aje.oxfordjournals.org/content/95/1/59.full.pdf

re the 'foreign DNA' list Ren gave
And how many of Orac's minions have ever been scratched unto bleeding by a cat.? If this were true, I'd have cat DNA.

DW: This would explain my fondness for tuna and naps.

The same old lies keep popping up again and again and again, like Whac-A-Mole.

Why don't we see this game around any more? Nothing is more fun than trying to bash things with a hammer while half-drunk!

Does the plastic bag in which it travels somehow magically remove DNA and RNA from whole blood bound for transfusion?

@Doug - but "its the vaccines!!!!" whatever super-special, super-secret process the reptilian factory workers use to make the vaccines gives their ingredients the incredible ability to perform biologically impossible feats...don't you know that?

O/T:

Re #13 "I have the same reaction when I read of any group with “patriot” or “freedom” in their name, because they aren’t and that’s the last thing they want."

Different kingdom. Science covers a domain limited enough that truth can be objectively decided; politics covers an area of recursive confusion. It is also attempting to act upon the subject, not only to observe and model it.
............
A group of x label could simply be a reaction to the corrupt nature of politics (necessarily corrupt, as its based on human nature), without the full realization that complete escape from that condition is impossible.
Were I forced to choose, I'd prefer the delusions typically included under the patriot label to those growing on the utopian farm.

Does the plastic bag in which it travels somehow magically remove DNA and RNA from whole blood bound for transfusion?

Very good point and to add, transfusions are gasp IV infused. Vaccines are SQ or IM.

@ Science Mom:

According to many anti-vaxxers, vaccines are IV too.

Spectator:

politics covers an area of recursive confusion.

Recursive confusion -- that is a truly fantastic description of politics. Thank you!

"…don’t you know that?"
I guess I haven't been educating myself or doing my own research adequately.

The long lists of horrible things in vaccines are, all by themselves, evidence that the compilers of the lists know remarkably little whereof they whinge.
The last list I saw had "formalin" listed right after "formaldehyde". I can't remember if "both" phenoxyethanol and ethylene glycol monophenyl ether were listed, but the latter was, with the usual "antifreeze" nonsense. Curious (OK, not really) how they pick up on the ethylene glycol (not a whole lot more toxic than the antifreeze, preservative, biocide, fuel and industrial solvent consumed at TMR) but completely ignore the benzene in the molecule.

As others can attest, it is incredibly hard to get functional DNA into living cells in an animal or human. Lots of techniques have been tried, but the overall record of gene therapy has been pretty poor. Perhaps some new method will improve the odds, but attempts at treating muscular dystrophy by putting in a part or all of the Dystrophin gene have been weak. That's one reason that the world has been moving towards stem cell therapy -- at least you know that there is a functioning cell going more or less where you want it, and maybe it will do something good.

One reason that there has been so much work on vaccines against viral illnesses is that until recently, there haven't been anything equivalent to the antibiotics that go after bacteria. The other reason is of course that vaccines have been very effective. For a lot of us, smallpox was a real thing earlier in our lives, and for me, polio epidemics happened within my memory. The idea that there might be some risk associated with the Salk vaccine against polio was a lesser consideration than the idea that we could stop worrying about getting polio. When you have an uncle who spent 3 weeks in an iron lung in County General, the message is pretty clear.

My view is that the anti-vaccination movement is more or less equivalent to something growing underneath a rock. It's up to the mass media to turn that rock over and shine a light on it. This is gradually starting to happen, but it has been a slow process. I think this topic is worthy of a few more columns and letters to the editor.

As a former Catholic, I can easily refute the claim from fusilier about ending a marriage:

My sister, still a Catholic, has one. My sister is not a member of the Government, in fact, she was born in Scotland.

"As others can attest, it is incredibly hard to get functional DNA into living cells in an animal or human."

Agreed. Even DNA transfections in vitro in the lab are hard when first getting started. And that's with microgram quantities of DNA that won't get diluted when injected with a vaccine.

There a decade error in the rubella vaccine, it was approved in 1969 in the USA. Then included in the first MMR vaccine in 1971.

So these people can't even torture their data right? Why am I not surprised?

Why don’t we see this game [Whac-A-Mole] around any more? Nothing is more fun than trying to bash things with a hammer while half-drunk!

There is a place called Funspot, in Weirs Beach, NH, which has a couple of them (or at least did a few years ago), as well as some other video games you may remember (if you are about my age or older) from the early 1980s, like an original PacMan machine. But storefront arcades went out a while back, and other places that would have had such games, like restaurants and bars, have gotten rid of them over the years. Today all of those arcade games are collectors' items. I blame PlayStation, Xbox, Wii, and the like.

"So these people can’t even torture their data right? Why am I not surprised?"

Actually is not quite so simple. The original rubella strain in the first MMR was not from fetal cells, but from other things. From the paper I linked to: "Parkman, Meyer, and colleagues [14] attenuated rubella virus in AGMK cell cultures (HPV-77), Hilleman et al. [15] in duck embryo cells (HPV-77/DEV), Prinzie et al. [16] in rabbit kidney (Cendehill), and I and my colleagues [17] in a human diploid fibroblast cell strain. The HPV-77 virus developed by Parkman was also adapted for commercial use in dog kidney cell cultures."

Except there were some serious side effects from the original non-fetal cell strain.

I was actually confused by the dates in the last paragraph, so I looked at the Dr. Deisher's paper, and did a PubMed search on the history of the rubella vaccine. I now realize that she could not blame the first MMR vaccine.

But, and this is a big "but", Deisher is ignoring that the fetal cell line single rubella vaccine, RA 27/3, was being used in the USA and Europe in the early 1970s. In the UK it was just being given to girls. She does not include this in Table 3.

Thank you for offering the discussion on this. My perspective views the inflammation process and predisposition. While I can't follow the poster presented all the way through its conclusion (how they came up with autism ??), gaining information on cell behavior isn't that bad an idea to try and get a better handle on predisposition.

It's lies, falsehood, and hatred like this that makes me wish we could just unleash another crusade, another Inquisition upon the people who spread misinformation like this. You know, purge them from society so that their impurity can no longer defile us?

(forgive me, I'm feeling in a very vengeful mood right now and have no room for nonsense like this)

Ren: 'people don’t think of all the times they've been exposed to foreign human DNA through having sex and kissing.'
Yea, for I am Righteous, I doth not commit Adulterous Original Sin, nor Fornicate with my Wife but for God's Command to Go Forth and Multiply. We Kiss, but not as the Damned French who extend their Serpants' Tongues. As the Lord hath brought us Together and Blessed our Holy Matrimony, I know He has Insured that our DNA shall only interact to the Glory of His Divine Plan. And should we ever require a Tranfusion, or otherwise contact the DNA of the Unholy, the Lord hath Revealed to us the He shall Smite and Purify anything that enters Our Sacred Bodies with His Grace.

SIASL: 'The peer review of this paper was most likely only verifying that the authors´ cheque didn´t bounce.'
Just as Blonde Jesus drove the Hook-Nosed Philistines from the Temple, the Righteous shall not publish the Work of God's Science with money-grubbing Christ-Killers. The only True peers of Dr. Dreisher's Team are Godly Medical Scientists like the Honorable Dr. Paul Broun (R) of Georgia, who have surely vetted the Study with proper Scrutiny to The Scriptures. I pray for the sake of your Eternal Soul that you shall Repent your Blasphemous Calumny against these Righteous Researchers, accept Christ as your Personal Savior, and get Right with God.

Amen.

@ sadmar:

I'm impressed.
However I usually riff off of the Apocalypse.

So, why is it that we can't simply take our revenge out on these people? I'm sick of their lies and hatred.

Lucario, what revenge? That is not a thought process nor potential action that would gain support from any here. That would make us no better than they. That kind of talk is not welcome.

Lucario, Science Mom nailed it. In addition, I'd like to give you a quote from Terry Pratchett. I'm paraphrasing, but I think I give the meaning.
"There are a lot of stupid people in the world, and it often felt like giving them a slap would make the world a better place, but...
1) It would only make the world better for a very short time;
2) It thereafter make the world a good deal worse, and;
3) You're supposed to be smarter than they are."

Unsurprisingly, Age of Autism is trumpeting this nonsense. Anne Dachel's idiotic comment?

The mainstream press refuses to cover challenging research like this and their failure to do so is making them obsolete and irrelevant.

Or, to translate;

Listen to MEEEE!!! ME! ME! ME! LISTEN TO MEEE!!!

their failure to do so is making them obsolete and irrelevant.
"I am going to ignore a prominent though flawed channel of information because it is not telling me what I want to hear."
I remember hearing this sentiment decades ago, when still at university, from the old-school Trotskyites.

As a former Catholic, I can easily refute the claim from fusilier about ending a marriage:

My sister, still a Catholic, has one. My sister is not a member of the Government, in fact, she was born in Scotland.

To be precise, Catholic Church does allow, in certaincases, declaration that marriage was not valid (sorry if I use wrong terminology at times, my legal English is a bit rusty). It is functionally different from divorce, which is institution of civil law.

The annulment (see my caveat about terminology) of marriage is given by Church only if one of few circumstances listed in canonic law happened to render it null and void from the very beggining. Technically people who got such verdict from the church were never actually married, at least in the eyes of the church.

People say that revenge is bad because it makes you no better than the enemy, but where in history is this borne out? It seems like all I hear in the media is revenge, revenge, revenge, and it always seems to be portrayed in a good light, as a way to get what one wants in the world when one is wronged.

@Lucario: That explains why My Little Pony has somehow become a hot TV show.

*But, and this is a big “but”, Deisher is ignoring that the fetal cell line single rubella vaccine, RA 27/3, was being used in the USA and Europe in the early 1970s. In the UK it was just being given to girls. She does not include this in Table 3*

It was also only given to teenage girls.

My Bad for not including a "/sarcasm" tag.

I would point to the late US Sen. Theodore Kennedy and former US House Speaker Newt Gingrich as individuals whose divorces were ... not condemned ... by the Church. And many are familiar with the last pregnancy that the wife of former Sen. Santorum and how it turned out.

Not that anyone is interested, but, I have 16 years of Catholic education, 42 years experience as a lector and eucharistic minister at various parishes in the midwest, and, when we got married, the Lutheran pastor of My Beloved and Darling Wife's congregation had a family friend (my side) co-officiate. That fellow later became Provincial of the Detroit Province of the Society of Jesus.

fusilier
James 2:24

I'd still like to know about a time in history when an act of revenge made an individual or a group sink down to the level of the enemy. You know, evidence, that this philosophy has merit.

@Lucario

People say that revenge is bad because it makes you no better than the enemy, but where in history is this borne out?

Bush going to war in Irak? A selling point was to get revenge for 9/11. See how it did pan out. Wrong target, religious extremists reinforced and having now their own state, political destabilization of the whole region. And all sympathy the US may had in European countries for 9/11 evaporated.

"Ils n'auront pas l'Alsace et la Lorraine". German-France war of 1870. First World War. Second World War.
Any endless circle of vendetta in the history of, notably, Italy, Spain, and a few other Mediterranean countries.
The never-ending conflict between Israelis and Palestinians.

For a fictional example of revenge having nefarious effects, (although likely based on true events), the Red Wedding in Games of Throne.
Many parts of Games of Throne actually, starting with the boy king ordering the beheading of a fallen political opponent for petty revenge and ending with a queen taking revenge on almost anything that moves, to disastrous political effect (trying to avoid spoilers here).

And anyway, what does "revenge" has to do with vaccination?
If you start killing people because they are mislead into taking wrong decisions, there won't be many people left on Earth.
Please bring your bloodthirsty suggestions somewhere else.

So, pretty much a lot of history, then. And could you recommend a few good beginner's books on the Franco-Prussian War or WW1? (I've been meaning to read the ASOAIF series myself, so it looks like I've got my fall reading cut out for me.)

Anyway, what is a person supposed to do, other than seek revenge for a wrong, perceived or otherwise?

Anyway, what is a person supposed to do, other than seek revenge for a wrong, perceived or otherwise?

Act like a grown-up?

"92% of children who are vaccinated have been potentialy injected with DNA from an aborted fetus."

What about DNA from other sources? Is that ok as long as it's not from those evil aborted fetuses? Eg Bacteria, viruses, mycoplasma DNA - all been in your blood at some point. BTW there are the remnants of about 30,000 retro viruses in the modern genome, but we still seem to survive.

I came on here for a scientific viewpoint of the study but your hatred filled post is annoying, can't you stick to the facts rather than name call and bash. Science should be open to questions, debate and critique which you've provided somewhat but it's very very difficult to read through the ranting.
Scientists should be encouraging an environment of continuous safety testing and research for vaccines or anything else we put into our bodies, you may not agree with every paper but maybe critique it in a more eloquent way, you are only encouraging walls and we will learn nothing that way!

The Catholic Church does not accept abortion for "medical reasons." It accepts abortion to save the life of the mother, that is, if, by taking medical action to save the life of the mother the baby dies, that is not a moral evil. There's a big difference; I think you probably know this.

You may be right in your conclusions; I will be glad to read this, because the truth is what matters. But I'd be less suspicious of your motives and honesty if you adopted a far less arrogant and dismissive tone with people who disagree with your agenda.

And don't see "don't seek revenge" as "do nothing about the situation".

Sometimes acting like a grown up is called doing something productive about the situation that seeks justice and creates something better in the world. Especially when it is something that isn't just "one of those bad things that will happen to you eventually". Sort of the weather didn't decide to rain on you and only you out of some vendetta against you and only you. It's raining on everyone.

One example I always think of is John Walsh. Sure after his kid was kidnapped and killed in a horrific way he could have gone all vengeful vigilante stalking anyone he thinks may hurt kids and kill them before they have the chance. He could have chosen revenge on which ever criminal they kinda thought maybe was the one that did it this week, but instead he ended up doing something that helped a lot of people, IMO.

A lot of parents do that, probably why we have so many laws named after children. Sure there is some desire to just do to the criminal what they did to your kid, but which is better. Spending the rest of your life in prison for killing a bad person, or try to do some good in the world that may mean some other family who you may never know gets to live the life you felt you deserved and never got to have.

increases in autistic disorder correspond with the introduction of vaccines using human fetal cell lines and retroviral contaminants

Ah, yes, retroviral contaminants. What does it actually say? Oh, wait, this machine won't cut and paste from a PDF. Let me paraphrase: "Something something HERV-K transcriptase activity something schizophrenia."

Hardly worthy of putting in the hed of a press release.

ha ha ha, oh dear lord, not again Orac. Are you still writing? I see the fear is still there in you, and rightly so. There is an ever growing anti vaccine movement as well as those who are unsure. Medicine is slowly losing it's power as it is slowly being exposed through countless books, articles etc.
I have no doubt that you are a very intelligent individual, and probably a high achiever and successful surgeon. However, this has nothing to do with common sense or understanding science.We can learn from scientific research and we can learn from experience, our own experiences and the experience of others.
With the exception of trauma care, the entire medical system is built on 3 lies - we have no control over our health, that we are a victim of good or bad luck, and that you can't heal yourself.
Up to 35 shots by around five years of age? Anyone would think that this child must live in the most atrocious conditions surrounded by disease after disease all the time.
I will stick with the 'Scientific law of nature', the only true science, not medicine who have been blinded by science. Medications, vaccinations are not natural and should only be used if absolutely necessary.

Christine: "It was also only given to teenage girls."

Not in the USA, a much larger country than the UK. From the Plotkin article I linked to in comment #30:

When rubella vaccination became feasible, both the United States and the United Kingdom embarked on vaccination programs. In the United States, the strategy was to vaccinate infants, so that eventually the reservoir in childhood would be abolished [52]. In contrast, the United Kingdom decided on a program of vaccinating adolescent girls [53]. Both strategies were partial successes, in that CRS incidence began to decrease. However, both were also partial failures, because in the United States pregnant women were still being exposed to rubella in children and adults, and in the United Kingdom unvaccinated girls who refused vaccination were still exposed to rubella cases because of circulation of virus in the male population and children.

The RA 27/3 was not one the types used in the USA. It was used enough in Europe, though the article does not clarify which strategy was used. It only says the safety was demonstrated over ten years enough for the FDA to approve it in the USA.

Still, it was used in the USA starting with the 1978 MMR II. I have been seeking documentation that autism increased substantially before 1990. The bizarro "change point" graphs are not convincing.

@Tone Troll Tracy:

Scientists should be encouraging an environment of continuous safety testing and research for vaccines or anything else we put into our bodies, you may not agree with every paper but maybe critique it in a more eloquent way, you are.

Vaccines are tested thoroughly before being released, and there are stringent post-release systems to catch problems. Case in point: rotarix, withdrawn after monitoring suggested an increased risk of intussuception (apologies if I spelt that wrong).
@Neil:

[T]he entire medical system is built on 3 lies – we have no control over our health

Better keep that gargantuan strawman away from any open flames. I have never heard that. In fact, many doctors encourage us to give up smoking, eat correctly, and get enough sleep and exercise.

that we are a victim of good or bad luck

A lot of diseases are genetic in origin. There are things you can do, but if you have the genes for Type 1 Diabetes or Retinitis Pigmentosa, you're flat out of luck.

and that you can’t heal yourself.

A semi-strawman. Healthy living can reverse or delay many problems, but it can't fix everything.

Up to 35 shots by around five years of age?

Please list the shots and how many times each one is administered. I'm getting rather tired of this demonstrably false claim.

Neil, kids do not get 35 shots by age five unless they're very sick. The sources that have misinformed you tried counting up the names of things being vaccinated for in order to inflate the number of shots and make it look scarier.

You want to talk about learning from scientific research? First start by learning about intellectual honesty. Because that claim is dishonest, and designed to mislead.

Meanwhile, your "three lies" that supposedly underpin the medical system are strawmen. Of course we have control over our health; that's pretty much the point of medical science. If you get strep throat, you don't have to just let it run its course; you can actually *do* something about it. And most of medicine is about helping the body heal itself. You know all those kids in the hospital with that new enterovirus? They're getting supportive care -- keeping their bodies alive and taking some of the burden of maintaining the system while the kids' immune systems destroy the virus. And pretty much all of surgery depends critically on the body's ability to heal itself. And while doctors acknowledge that you can't control how you're born and many events in life are outside your control, they tend not to think of patients as helpless "victims". No, that's alt-med that does that, right before it blames them for their predicament, as if that's somehow helpful.

I definitely agree that medications and vaccinations are unnatural. So is clothing. So is central heating. But they have value. Remember, nature doesn't have your best interests in mind. Nature has no mind at all. It is completely indifferent to your personal survival. Trust it at your peril.

@ Julian Frost I am aware of the current safety tests pre release however I believe there should be more and there should be continuous post-release tests. I believe vaccines play their part in medicine but I really don't think they are foolproof, only through further continuous rigorous testing can we improve upon. I resent being called a troll for expressing my opinion.

Anyway, what is a person supposed to do, other than seek revenge for a wrong, perceived or otherwise?

I beleive forgiveness is rated highly but if you must seek anything in response to a perceived wrong, seek justice instead of revenge, and work to redress the harm that wrong might cause.

As in this case, by countering anti-vax proselytizing with accurate facts and evidence demonstrating their misinformation is...well, just that and no more.

Ther's an old saying (I forget from which culture) that goes "If you would seek revenge first dig two graves". Think they had the right of it.

Tracy, are you serious?
Gardasil was tested in a sample of tens of thousands. How much more rigorous do you want the tests to be? As for post-release, have you not heard of VAERS and VSD? Post release surveillance of vaccines is fine tooth comb level. And nobody here says or even believes vaccines are foolproof. However, they are exceptionally safe, far safer than getting the diseases.
The reason I called you out for being a troll was not for expressing your opinion, it was the way in which you expressed your opinion.

Lucario, I recommend that you read "The Better Angels of Our Nature" by Steven Pinker.

He presents a compelling case that the world has become far less violent (which, ironically, leads us to perceive it as more violent - as violence becomes the exception rather than the rule, it paradoxically captures our attention more and appears to be larger.)

He also makes a very compelling case that, contrary to what many of us would expect, the pursuit of "justice" is one of the factors that pushes the world towards more violence, not less - because we all view things from an inherently self-centered perspective, and we are very good at seeing when someone else has sinned against us ... not so good at seeing and understanding when we are the ones who did wrong.

A society in which it's considered normal and acceptable to go out and get your own "revenge" is going to be a society full of senseless violence. The Santa Barbara spree killer thought HE was getting revenge.

Chris...from the CDC Pink Book-Rubella Chapter:

http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/rubella.pdf

Rubella Vaccine

Three rubella vaccines were licensed in the United States
in 1969: HPV-77:DE-5 (duck embryo), HPV-77:DK-12 (dog
kidney), and GMK-3:RK53 Cendevax (rabbit kidney) strains.
HPV-77:DK-12 was later removed from the market because
there was a higher rate of joint complaints following vacci-
nation with this strain. In 1979, the RA 27/3 (human diploid
fibroblast) strain (Meruvax-II, Merck) was licensed and all
other strains were discontinued.

My daughter was born 1970 and received one of those vaccines. I received a rubella vaccine, prior to conceiving my son who was born in 1976.

None of us quacked like a duck, barked liked a dog or hopped like a rabbit...in spite of receiving those vaccines which contained foreign DNA.

@ Julian Frost: Nice post about the three rota virus vaccines which were licensed in the United States. A wee nit pick; Rotashield vaccine was voluntarily removed from the marketplace by the vaccine manufacturer, just before the government ordered the vaccine removed, after the VAERS reports showing upticks in cases of intussusception:

http://www.ncbi.nlm.nih.gov/pubmed/18202442

Clin Microbiol Rev. 2008 Jan;21(1):198-208. doi: 10.1128/CMR.00029-07.

Rotavirus vaccines: an overview.

Dennehy PH.

Abstract

Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

Neil,

ha ha ha, oh dear lord, not again Orac. Are you still writing?

He's still writing, still getting more attention than AoA and lately being quoted as a reliable source by CNN and other major media outlets. Do CNN come to you for accurate information about vaccines? Thought not.

I see the fear is still there in you, and rightly so.

Projecting Neil? I see no sign of fear in Orac's post.

There is an ever growing anti vaccine movement as well as those who are unsure.

As evidenced by less than 1% of children not being vaccinated? It's a little worrying, but hardly a huge movement.

Medicine is slowly losing it’s power as it is slowly being exposed through countless books, articles etc.

From where I'm sitting it looks as if medicine is growing in power, as effective treatments are found for more and more diseases. In the UK, where I live, more than 50% of cancer patients live more than 5 years, an amazing triumph of medicine over a very tricky disease (many diseases, really).

I have no doubt that you are a very intelligent individual, and probably a high achiever and successful surgeon. However, this has nothing to do with common sense or understanding science.

Spending years learning about science, doing research and practicing medicine doesn't lead to understanding science? Who knew?

As for "common sense", that often seems to be used as an excuse for ignoring cognitive biases and all the ways we fool ourselves, which is the main reason science was developed in the first place. So, if academic qualifications and years of experience don't teach a person about science, what does? Google University?

We can learn from scientific research

I'm with you there.

and we can learn from experience, our own experiences and the experience of others.

Not so much. Anecdotal evidence can be very misleading. That's why randomized clinical trials were invented.

With the exception of trauma care, the entire medical system is built on 3 lies –we have no control over our health,

Why does my doctor insist on giving me advice on a healthy diet, exercise, keeping my weight, cholesterol and blood pressure down, checking my blood glucose. Why is preventative medicine such a big part of modern medicine?

that we are a victim of good or bad luck,

There is no doubt that getting cancer, and a number of other diseases is largely down to luck. If the right bits of DNA are damaged and our repair mechanisms screw up, we get cancer. We can reduce or increase our risks, but only within fairly modest limits. If you have no immunity to measles and someone sneezes out billions of viable viruses that you then inhale, you will almost certainly get measles (irrespective of whatever diet and health regimen you believe in). You can't practically control who sneezes near you, but you can get vaccinated and prevent getting measles that way.

and that you can’t heal yourself.

Some things heal by themselves, some things don't. A surgeon depends on his patient's body healing itself. Somehow I suspect you don't mean that, and that you believe in some unproven CAM modality. What is it? Acupuncture? Homeopathy? Naturopathy? Therapeutic touch? Reiki? Or all of the above?
It's ironic that your three lies are themselves lies.

Up to 35 shots by around five years of age?

That is the maximum possible for a sick child who gets the flu vaccine every year, but I fail to see why that number should frighten anyone. Surely getting 35 shots is better than getting any of the diseases they protect against.

Anyone would think that this child must live in the most atrocious conditions surrounded by disease after disease all the time.

You don't need "atrocious conditions" to catch any of the VPDs the vaccine schedule protects against. Most are airborne, or transmitted by close contact, like you get in institutions like schools.

I will stick with the ‘Scientific law of nature’, the only true science, not medicine who have been blinded by science.

Ooh, the scientific law of nature. What's that exactly?

Medications, vaccinations are not natural and should only be used if absolutely necessary.

There is no such thing as "natural". It's a meaningless word, used by the ignorant to label things they don't like. You could just as well argue that acupuncture is unnatural, as is homeopathy, taking vitamin tablets, juicing, fasting, and any number of other alternative medicine interventions.

It isn't "absolutely necessary" for children to get the MMR, but without it we would see large numbers of sick children, permanent disabilities and deaths. Surely a vaccine with side effects that are extremely rare is better that that, isn't it?

Science should be open to questions, debate and critique which you’ve provided somewhat but it’s very very difficult to read through the ranting.

Science is open to questions, debate and critique. Not all questions are menaingful and relevant, however, and some questions (such as whether or not there's evidence of a causal association between routine childhood vaccination and autism specrtrum disorders) have been answered. Debate is only apprpriate when there's roughly equal bodies of evidence supporting the two or more opposing sides--and that isn't the case with resepct to vaccine safety and efficacy. ANd citicism must be genuine--i.r., be both relevant and rooted in fact (which again isn't the case with anti-vax 'critiques' of vaccine safety).

Scientists should be encouraging an environment of continuous safety testing and research for vaccines or anything else we put into our bodies,

Given that such an environment does exist (did you belevie that VAERS and the National Safety Datalink arose de novo from quantum vacuum?) one must ask: why have you pre-sumed that vaccine safety isn't being assessed continually?

@ julian frost.
Gardasil is banned in Japan with Israel currently considering a ban. Spain has also recalled it. All due to safety concerns with the vaccine.

I am aware of the current safety tests pre release however I believe there should be more and there should be continuous post-release tests.

Why exactly do you believe this--i.e., what evidence suggest that the current testing regimen fails to adequately characterize the the safety profile of newly developed vaccines?

Note also that we do continuosuly monitor the safety profile of vaccines postmarketing, and that monitoring is remarkably efficient, able to detect adverse consequences that occur on the order of one instance in 1 million doses delivered (e.g., encephalopathy associated with MMR vaccination).

Gardasil is banned in Japan with Israel currently considering a ban. Spain has also recalled it. All due to safety concerns with the vaccine.

Japan did not ban Gardasil, Israel did consider a ban but has not acted and Spain's health ministry recalled a single batch as a knee-jerk response.

Gardasil is banned in Japan with Israel currently considering a ban. Spain has also recalled it. All due to safety concerns with the vaccine.

Gardisil has not been banned in Japan. however: Japan’s Health Ministry instead rescinded their recommendation all women receive it. Its use has not been suspended and it is still available upon request.

The decision to cease recommending it was a consequence of concerns that the vaccine was associated with diffuse abdominal pain (complex regional pain syndrome)—a decision that has been extensively criticized by health care professionals both abroad and in Japan.

Such as the researchers at the University of Tokyo) who point out that

This directive was issued due to fears of adverse events, especially complex regional pain syndrome. However, the present system of reporting adverse events does not follow a systematic process for identifying causality; a rigorous scientific approach is needed to investigate adverse events associated with HPV vaccines. Furthermore, the decision to suspend the vaccination programme was taken by a 3:2 vote of the VARRC, without presentation of adequate scientific evidence. (HPV vaccination programme in Japan, Gilmour et al, Lancet, Volume 382, Issue 9894, 31 August–6 September 2013, Page 768)

This is the second time that the Health Ministry has withdrawn recommendation—the first time was with respect to MMR, with no result other than the incidence of the diseases skyrocketing.

Tracy: "Gardasil is banned in Japan with Israel currently considering a ban."

And that is convincing because...?

Japan is not the source of good vaccination policy. They have a habit of bending to political pressure, with deadly consequences.

First it was pertussis. From Impact of anti-vaccine movements on pertussis control: the untold story:

After two infants died within 24 h of receiving DTP, the Ministry of Health and Welfare eliminated whole-cell pertussis vaccine altogether. They later allowed it only for children older than 2 years. Pertussis coverage for infants fell from nearly 80% in 1974 to 10% in 1976. A pertussis epidemic occurred in 1979 with more than 13000 cases and 41 deaths. Japan began replacing whole-cell with acellular pertussis vaccines in 1981, and a striking fall in pertussis incidence followed (figure 2).

Then it was measles. From Measles vaccine coverage and factors related to uncompleted vaccination among 18-month-old and 36-month-old children in Kyoto, Japan:

In Japan, measles vaccine coverage has remained low, and either small or moderate outbreaks have occurred repeatedly in communities. According to an infectious disease surveillance (2000), total measles cases were estimated to be from 180,000 to 210,000, and total deaths were estimated to be 88 [11,12]. Measles cases are most frequently observed among non-immunized children, particularly between 12 to 24 months.

Before you cite a country's vaccine policy as some kind of example, check to see if it caused deaths from vaccine preventable diseases.

This is the second time that the Health Ministry has withdrawn recommendation—the first time was with respect to MMR, with no result other than the incidence of the diseases skyrocketing.

They also did it with DTP several years ago and only realised that mistake after pertussis cases skyrocketed and several infant deaths occurred. Japan seems to have a skewed nationalism when it comes to some things like vaccines; they don't like to import them and would rather manufacture and distribute themselves.

Anteaus: He presents a compelling case that the world has become far less violent (which, ironically, leads us to perceive it as more violent – as violence becomes the exception rather than the rule, it paradoxically captures our attention more and appears to be larger.)

I've heard of Pinkerton's book. I think it's dangerously naive. Crime will always be with us, and humans will always prefer to do the wrong thing than to do the right thing. Also, there are a lot of crimes that aren't defined as such: in the 1950s, rape wasn't a prosecutable crime (unless it crossed racial lines) child murder went unnoticed, and people who murdered women were rarely prosecuted or arrested. Even today, getting the police to take rape or domestic abuse seriously is a waste of time. I think the reason we have more 'crime' now is that more things are defined as crimes.

Ed Palinarius: It accepts abortion to save the life of the mother, that is, if, by taking medical action to save the life of the mother the baby dies, that is not a moral evil.

Isn't saving a woman's life a moral evil in itself?

lilady: "Chris…from the CDC Pink Book-Rubella Chapter:"

Thanks. I was initially confused by saying the dates in the above article, and I tried to find out more. That is when I learned about the other one and why they switched.

The funny thing is that the RA 27/3 was developed by Plotkin in the USA, but only first approved in Europe. It actually took Hilleman and other researchers to convince the FDA that it was better.

This is one reason why I wish folks would remember that more than one MMR vaccine exists, with varying vaccine strains.

To answer question #1, it's because every body claims anecdotally that it's shortly after the 2year old booster shots.

@lilady: thanks for the correction re rotarix and rotashield.
Politicalguineapig @86, I'm going to have to call you out on your comments. Crime may be with us until the last human dies, but that doesn't mean that the crime rate isn't going down. Freakonomics also mentions that deaths from homicide have fallen every century since the 15th century.

Even today, getting the police to take rape or domestic abuse seriously is a waste of time.

They take it far more seriously than they used to.

Antaeus @ #76:

The problem I see with justice is it's too slow, it takes too long. Revenge, at least in my mind, is swift, thorough, final, gets the job done. Or am I just too impatient?

The problem I see with justice is it’s too slow, it takes too long. Revenge, at least in my mind, is swift, thorough, final, gets the job done.

Which argues that we should make dispensing justice more timely--dedicate more resources, streamline court procedures, etc.--but not that we should substitue personal vengeance seeking for justice.

Impatient or more committed to making sure the problem continues on and on and never ends because those you take revenge on will then have to take revenge on you.

Because you can't assume you are the one and only who will take revenge and that the venged upon will just sit there and take it and never do anything back.

That and while it may be fast, do you really want to pay for your vengence in prison or do you assume you would never be caught?

And the best example in history of someone taking revenge on someone and that person taking it back and the whole thing spiraling out of control is...?

JF: They take it far more seriously than they used to.

That's true, they'll show up now and take statements. But that's about it.

Lucario: I have to agree with you on revenge vs. justice. Plus, some people are never, ever going to get any justice. If you're poor, and the person who wronged you is rich, good luck getting a conviction.

And the best example in history of someone taking revenge on someone and that person taking it back and the whole thing spiraling out of control is…?

WWI?

Don't know if I'd call them the best examples, but the Hatfield/McCoy, and the Earp/Clanton feuds come immediately to mind.

ScienceMom@#95:

Could you recommend me any good basic non-fiction reading material on WW1? Now that the centennial is upon us and the ACW's sesquicentennial is coming to an end....

gets the job done

I wouldn't be sure of this.

Look up "lynch mob". It's not just in the past, and it's not just racists on a killing spree.
There were two or three cases in UK and France, a few years back, of presumed pedophiles hunted and in at least one case killed by a mob of righteous citizens. Except, oops, wrong guys.
Did you know that Zimmerman was burgled two weeks before he killed Trayvon Martin? Zimmerman told the police officer on the radio "these [redacted] always get away". Well, Martin didn't get away. But oops, wrong guy.
Let's not even go into witch-hunting.

Also about revenge efficiency, in the case of middle-east conflicts, look up "collateral damage".
Whenever a Palestinian explodes himself on a crowded market or an Israeli tankist shells a house, they do it as retaliation of past actions from the other side. You will have a hard time convincing me any of these actions is "swift, thorough, final, gets the job done". The two sides have been at it for more than 50 years now.
I stopped caring for either side 20 years ago.

I've said it several times, I'll say it again: Could you recommend any good reading material on why revenge is bad? Non-fiction preferred.

And the best example in history of someone taking revenge on someone and that person taking it back and the whole thing spiraling out of control is…?

The Troubles in Ireland get my vote.

“An eye for an eye leaves the whole world blind” as someone once said (probably Gandhi).

The only way revenge really works is if you exterminate your enemies, leaving no one alive to mount a reprisal. But that seems a bit extreme. And probably unethical.

You might want to start with Game Theory.

http://en.wikipedia.org/wiki/Prisoner%27s_dilemma has a fair amount on in it and links to additional resources.

Although it focuses more on why we stop the revenge and counter revenge cycle.

But usually the ones who believe only in revenge seem to count on other people will eventually stop revenging back, and sometimes they just don't.

For a more personal example try this http://en.wikipedia.org/wiki/Hatfield%E2%80%93McCoy_feud

Krebiozen.
Brainwashed.

Thanks for your intellectual crap and insight to conventional wisdom. You can't be challenged, no matter what. You are the typical scientific guru who claims to be right.

People don't attack others unless they are in fear, Orac and alike. Why don't you just stick with what you know instead of criticizing others? Or are you no good at what you do? Haven't you heard the saying ' racehorses don't look sideways'.

Ahh yes, the twisted 5 year survival rate statistic, thanks for that insight.

I said we can 'learn' from scientific research, not ' believe' in scientific research. Science has proven to be wrong OVER AND OVER...............? So yes, google is not too bad after all.

You don't believe in luck because you don't understand or practice optimal health. Only less than one per cent of the current population experience this and truly understand it.

The day i see trials or tests attempted to be done on the super healthy instead of only the super sick will be the day i start thinking differently about modern medicine and big pharma. (the only problem is that you won't get many volunteers).

I don't count, i am not a statistic, medicine makes no money off me, I make no money off medicine, i have no health insurance, i don't exist.

People don’t attack others unless they are in fear,

Of if that person's stated position is wrong and/or their actions result in demonstrablly undesirable consequences (like reduced vaccination compliance, undermining herd immunity and leading to outbreaks of reventable diseases like measles and pertussis (as is the case with respect to antivaccine proselytizers).

The day i see trials or tests attempted to be done on the super healthy instead of only the super sick will be the day i start thinking differently about modern medicine and big pharma. (the only problem is that you won’t get many volunteers).

You mean like every Phase I clinical trial conducted, Neil?

Lucario: for the origins of WW1 you can't beat Tuchman's "The Guns of August."

I just read that book a couple of months ago, with all the interest in the 100th anniversary of the start of WWI. It was excellent and clear. Like most people, when I thought of WWI, I thought of trench warfare, but before the war ground to a stalemate and that iconic trench warfare, I was surprised to learn, it really resembled the Blitzkrieg-style of warfare used 25 years later by Hitler, and I hadn't been aware just how close the Germans came to Paris before they were turned back.

More surprisingly, from my point of view, I had also been unfamiliar with the atrocities committed by Germans as they plowed through Belgium.

@neil

Ah, instead of making any objections to Krebiozen's points, you go straight to insults and ad hominems.

Thanks for proving that your points and assertions are incorrect and that you have nothing positive to contribute here. You admit that you don't have a point, why should any reasonable person bother with you?

@Lucario,
I thought of The Guns of August, too.
A quick check on Amazon shows
The First World War by John Keegan
The Long Shadow by David Reynolds looks interesting because much of the current Arab-Israeli conflict traces back to conflicting promises made by the British during WWI.
Lawrence in Arabia... by Scott Anderson covers some of the same material.
World War I British Poets by Candace Ward gives a different perspective.
John Keegan also has An Illustrated History of The First World War.
There's an abridged version of Winston Churchill's World Crisis series.
I didn't see anything that looked good about Japan's role in that war (we were allies), but Goodreads listed Austro-Hungarian Submarines in World War I, which is of interest simply because Captain Von Trapp's "battleship" referred to in The Sound of Music was actually a captured French submarine!
And, of course for fiction, there is All Quiet on the Western Front.

I'd probably add America's Secret War Against Bolshevism by David S Foglesong, simply because this part of our participation has been so thoroughly buried in the historical records.

In addition to the undoubtedly excellent recommendations issued about WWI and WWII how about just turning on BBC and seeing a contemporary example of the atrocious downward spiral revenge lends re: Israel and the Palestinians.

Criticism from Neil:
Why don’t you just stick with what you know instead of criticizing others?

People are always better at dispensing advice to other people than applying it to themselves.

Neil:

Thank you for confessing that "People don’t attack others unless they are in fear" - that explains why you started your first post in this thread with "ha ha ha, oh dear lord, not again Orac. Are you still writing?" (clearly you need to mock Orac - if you don't, you risk learning something) and your second with ""Brainwashed"

Hope you get over your fear soon, and come back to apologize for your oh-so-revealing attacks.

Neil,
Which particular method of attaining super-optimal health do you subscribe to? Just curious.

I would totally second Keegan's book (there's a wonderful illustrated version of it available).

Tuchman is gold standard, but you might prefer Margaret MacMillan's The War that Ended Peace. If you like graphic novels Joe Sacco's The Great War: July 1st 1916 is amazing. (Even if you don't like graphic novels this is an incredible book.)

Or just read or watch Othello

"You don’t believe in luck because you don’t understand or practice optimal health. Only less than one per cent of the current population experience this and truly understand it."

Let me guess...you have a super-duper immune system, too?

Or Lucario take a look at either this article in psychology today http://www.psychologytoday.com/blog/evolution-the-self/201401/5-biggest… (I'm too tired to wrestle with tags today) or this article http://www.psychologicalscience.org/index.php/publications/observer/201… from the APS Observer.

Let us know what you think

Thanks, folks, for the reading suggestions (but I'll skip anything Arab-Israeli conflict-related, thankyouverymuch). I've got quite a lot to read, it looks like....

Anyway, were there any incidents in the (American) Civil War that might teach me why revenge is bad? That might get me *really* interested....

Fort Pillow comes to mind.

Belay that...read the history of Reconstruction if you want a great example of a revenge-driven, thoroughly bollixed up post-war agenda.

For just after the civil war.

http://www.amazon.com/Lincolns-Avengers-Justice-Revenge-Reunion/dp/0393…

OK, I think I have enough reading material on revenge. Now, what would be some good historical examples of forgiveness? (Outside of a religious context, of course.)

Lucario: See what you can find on the Truth and Reconciliation tribunals. Of course, those didn't really work, since the denied South Africans turned, predictably, to violence, often against their near and dears. Might've been better if they got the whole thing over in one big paroxysm, rather than turning the whole country into a giant gangland.

Lucario:
Another problem with revenge is the collateral damage that often results. Think about when revenge becomes part of a divorce proceeding (as it too often does). The "scorched earth" approach wreaks havoc on the children and other family members, as well as the combatants. The only ones who win are the lawyers...

Well, what was history's most famous divorce proceeding that used the "scorched earth" tactic? (One more answer, and then on to talking about forgiveness.)

Now, what would be some good historical examples of forgiveness? (Outside of a religious context, of course.)

The Forgiveness Project might be a good place to start.

I think the Good Friday Agreement in Northern Ireland is an excellent historical example. After centuries of killing and reprisals and reprisals for the reprisals, the vast majority of people had had enough, and drew a line under what had happened in the past. Convicted killers were released from prison, and the loved ones of those they had killed for the most part have, if not forgiven them, at least moved on.

Lucario: I don't know about "most famous" but IIRC wasn't it a Baldwin and his wife that made a pretty messy world for their daughter? And the Wales' (Prince Charles/Princess Diana) book revelations must have wreaked a lot of havoc.

This may be too small a historical event, but a well known story around here that involves forgiveness is chronicled in this book.

http://www.pickingcottonbook.com/buy.html

I'm sorry, but due to having to be elsewhere I have only paid attention to very little of the "Lucario" thread.

All I have to contribute is that "education is better than revenge." That is all.

We present the information on vaccines here not for the AoA crowd, but for those on the fence. If we use data without injurious emotion we are more likely to get those who are the fence sitters. We are here for those with an open mind, and willing to dig into the research.

As one can see I was confused about the dates of "the rubella vaccine", and with a bit of digging I found out that there were those approved in the USA without fetal human cells, but they caused unacceptable side affects.

The one that had human fetal cells that was developed in the USA but first approved in Europe did not have the same joint issues, and was incorporated into the MMR II in 1978/79.

I actually learned this by noticing something I thought was wrong in the last paragraph of this article. But I did a search of the PubMed literature and found out where I was wrong, and learned something. So I changed my mind, due to the actual evidence.

Please note that this is evidence that I have an open mind.

But I'll need more evidence that the MMR II caused a steep increase in autism in the 1980s, that is positively documented before 1990.

As an on the fence person I completely agree with Chris above. There is so much anger and acerbic wit on both sides of the debate that it can seem like those involved are more concerned with ego and point-scoring than with the health and wellbeing of our children. It also doesn't help when the comment thread starts with people citing the time gap between vaccines being administered and autism diagnosis as proof of anything, as most people understand that the NHS can take well over a year to reach an official diagnosis following a parents request for one. I am not a scientist so senior scientific figures on both sides can seem equally persuasive to me when they are arguing in a logical thread, but I am not so ignorant as to believe anyone just because they are telling me in thinly veiled terms that I'm stupid if I don't. So in summary it is very confusing and yes education, evidence, facts, without the anger and arrogance would be very much appreciated and much more effective to convince those like myself. By the by- at risk of inviting a torrent of abuse my way - would it not just be easier to agree to the NVIC demand to have vaccine safety oversight under a neutral body? (no conflicts of interest etc) That way the 'anti-vaxers' will be placated, the general publics faith in vaccine safety will be restored and the rising tide of 'refusers' will be stemmed? Seems like a win win situation for all?

"Education is the best revenge?" Where in history is that borne out?

“education is better than revenge.”
NOT
“Education is the best revenge?”

dippy

@Sarah - since the CDC is a government agency, what Conflict of Interest does it have relating to vaccines?

SimpsonWood @#130:

Sorry about the typo there. (facepalms)

Anyhoo, where in history is "education is better than revenge" borne out?

Lawrence @#131 - re. Conflict of interest I am just going by news articles such as the following . . .
http://www.marketwatch.com/story/national-vaccine-information-center-ca…
Is what they are saying here regarding conflicts of interest untrue? If you could clarify how and why that would be great as its articles like this which can be very confusing to the average parent. Many thanks,

By the by- at risk of inviting a torrent of abuse my way – would it not just be easier to agree to the NVIC demand to have vaccine safety oversight under a neutral body? (no conflicts of interest etc) That way the ‘anti-vaxers’ will be placated...

Based on their track record so far, I can assure you the antivaxers will NOT be placated.

"Lawrence @#131 – re. Conflict of interest I am just going by news articles such as the following . . "

That is not a news article Sarah. It is a press release from the curiously name National Vaccine Information Center, which is an anti-vaccine, anti-science group; the NVIC paid for placement of that press release.

I suggest you open this link to the CDC to see how strictly monitored vaccine safety is accomplished in the United States....it is an exemplary program.

http://www.cdc.gov/vaccinesafety/index.html

Here's the organizational chart for the NTSB:

http://www.ntsb.gov/about/organization.html

Lucario, the Marshall Plan in Europe and the occupation of Japan after WWII. Both required support and educational programs to create stable economies.

Check out Hans Rowling videos at http://www.gapminder.org/. He has some on the effect of education on health and welfare.

Politicalguineapig, as a South African, I have to take issue with your labelling of the Truth and Reconciliation Committee as a failure. Atrocities were committed on both sides, so it was decided that revenge was useless. The TRC's main goal was to get at the truth.

Sarah,
The NVIC is a notorious antivaccine organization that is devoted to spreading misinformation about vaccines. I wouldn't trust a word they say.

@Sarah - just stating that a COI exists isn't enough to "prove" that one exists.

As lilady has posted above, there is an extremely robust safety tracking system in place for vaccines, on top of the already rigorous safety testing and clinical trials that occur during the development and licensing process by the FDA.

In fact, vaccines have a better safety record than most other drugs and treatments on the market today - vaccines have been proven to be safer than driving car or even as safe, if not safer than flying on an airplane.

People like those at the NVIC do nothing more than spread fear by lying and misrepresenting the facts about vaccines today.

"@Sarah – since the CDC is a government agency, what Conflict of Interest does it have relating to vaccines?"

The CDC provides factual information about vaccines, their usefulness, possible side effects etc.
From reading CDC materials, one would get the impression that vaccines possess a high degree of safety and are an important part of public health measures.

So obviously the CDC has a "conflict of interest:" with regard to vaccination, since their findings conflict with the interests of antivaxers.

Hope that helps.

Is what they are saying here regarding conflicts of interest untrue? If you could clarify how and why that would be great as its articles like this which can be very confusing to the average parent. Many thanks,

Sarah, if you read your link and follow the links within the press release, it becomes rather obvious that NVIC is a notorious anti-vaxx group posing as a vaccine-safety advocacy group even if you didn't think that to begin with. For example, BLF claims, "he non-profit National Vaccine Information Center (NVIC) is renewing its call for oversight of vaccine safety to be removed from the Department of Health and Human Services (DHHS), which is responsible for vaccine development," That is false and very misleading. The NIH for instance does research on a multitude of topics including but not limited to therapeutics and biologicals. Occasionally, something works, is patented and sold to a pharmaceutical company. The vast majority of drug research and development is done by the pharma industry. BLF misleads readers into thinking that everything from start to finish is done in-house.

BLF also states, “It is a conflict of interest for DHHS to be in charge of vaccine safety and also license vaccines, and take money from drug companies to fast track vaccines, and partner with drug companies to develop and share profits from vaccine sales, and make national vaccine policies that get turned into state vaccine laws, while also deciding which children will and will not get a vaccine injury compensation award. That is too much power for one federal agency,” But offers no substantiation for these statements which are mostly false. The DHHS does not "partner" with drug companies to develop vaccines and share profits. The DHHS does not get paid to "fast-track" vaccines. States make their own vaccine requirements and are not compelled by the CDC even if their recommendations are a basis. BLF helped to draft the VICP system and because it doesn't act like a personal piggy-bank for anyone claiming vaccine damage, she's suddenly critical of it.

Next, BLF states, "In 2011, NVIC called for the creation of an independent vaccine safety monitoring agency modeled after the National Transportation Safety Board (NTSB) and Consumer Products Safety Commission (CPSC) and has also called for independent vaccine research into health outcome differences between children who are and are not vaccinated according to the federally recommended vaccine schedule. "

There is ongoing research into unvaccinated cohorts and at least one should be shortly. BLF is dishonestly veiling her own knowledge of a group well known to her who has also conducted a vaxx v. unvaxx study. As for independence, the IOM is an independent group with stringent COI requirements for it's members and have conducted numerous reviews of vaccine safety and adverse events: http://www.iom.edu/Reports/2013/The-Childhood-Immunization-Schedule-and…

BLF suggests in her "independent" reform draft that, "This independent entity would provide oversight on, but not necessarily operation of, the federal Vaccine Adverse Event Reporting System (VAERS) and would take the lead in setting priorities for and oversight of vaccine safety research into the biological mechanisms and high risk factors for vaccine injury and death for the purpose of minimizing vaccine risks for individuals and populations. In addition, this independent entity would be informed by a consumer advisory committee composed of non-governmental, non-
industry representatives with the authority to recommend investigations and make special reports to the President on specific vaccine safety issues of public concern."

That's code for she wants or a group of her cronies to be the "independent entity" who will guide "vaccine safety" in the direction she wants it to go. So her agenda is far more nefarious than those overseeing human health currently ever could be real or imagined.

Question: Neil, above, has his location as Australia. This is the same Neil who boasts he has no health insurance and medicine never makes money off him, correct? In a country with Universal Health Insurance? Or can you opt out entirely?

@Julian #138--PGP routinely makes sweeping pronouncements about stuff she knows little or nothing about based on her own Eeyore-like view of the world, possibly as some sort of protective armor against having to interact with real people.

Several faith-based online platforms have severely criticized Deisher's work. I have been informed that several more are in the works.

I am keeping track of the critiques at Critical Evaluations of "Impacts of Environmental Factors on the Prevalence of Autistic Disorder after 1979" , Deisher et al. 2014.

JF: Atrocities were committed on both sides, so it was decided that revenge was useless. The TRC’s main goal was to get at the truth.

I hope they got it. But I do think that the TRC bear a lot of responsibility for the violence in South Africa now.

bandf: I do interact with people fairly regularly, I just have to be aware that a lot of them do want to harm me, and plan exit strategies at all times.

PGP: a lot of people want to harm you? are you serious? unless you are some sort of CIA agent, I have to wonder if you have some sort of paranoia dysfunction. The world is not usually out to get specific individuals--sometimes you are in the wrong place at the wrong time so keeping alert and wits about you is reasonable--but most of the time nobody really cares.

bandf: a lot of crimes are simply opportunistic. Look like a sheep and the wolves will come; it's common sense. I don't smile in public, try to interact as little as possible, and get where I'm going as soon as I can. I suppose it comes of growing up in a span of years where the homicide rate was one every three days. There are still parts of my city I wouldn't visit without a tank or armor.

And I know this is true of many states and countries. I'm sure South Africa and India are lovely, but I'd pack a suit of armor to visit them. Statistically (and all human interaction boils down to stats) it ain't worth it.

I do however have more to fear from "friendly" people who act nice but aren't. Easiest way is to avoid having many friends in the first place.

I have to spend as little time as possible in my local library because of a very nice woman who stabbed me in the back while I was working there- every time I'm there I spend more than half my visit avoiding the staff.

Love is unrealistic- sure, it could be great, but it's also a deadly drug. And everyone knows the tale of the 'nice guy' and the 'friendzone.' Thus, exit plans are needed.

Look like a sheep and the wolves will come; it’s common sense. I don’t smile in public, try to interact as little as possible, and get where I’m going as soon as I can.

That sounds more like reeking of delicious fear than avoiding some sort of imaginary sheepledom.

@MI Dawn
Australia has a public health system rather than universal health insurance. That is, the government directly pays for hospitals and some doctors and so on rather than paying the money to insurance companies to pay to doctors and hospitals. Neil is absolutely able to state he has no health insurance, but it’s a claim that’s less impressive in Australia because his medical costs will be covered by the public system regardless. He cannot, however, claim that medicine makes no money off him as the public system is funded through tax and even if he is avoiding all personal taxes he will still be paying the Goods and Services Tax on almost everything he purchases.

Narad and PGP

That sounds more like reeking of delicious fear than avoiding some sort of imaginary sheepledom.

in response to PGP’s

I just have to be aware that a lot of them do want to harm me

Followed by

I don’t smile in public, try to interact as little as possible

Sounds to me more like paranoia and self-fulfilling prophesy.

From BLF

a consumer advisory committee composed of non-governmental, non-industry representatives

If I can add my 2 cents, while setting an independent oversight committee is a laudable goal in itself, the above restrictions may lead to a very ineffectual one.
If "governement" includes academics and already existing health agencies, and if on top of this you exclude people who have a relative working in either the government or a chemical-related industry, you won't have many people left. These restrictions will also exclude all people with a passing knowledge in the field.
You will end up with people who very likely don't know much about biology or chemistry and thus could easily be misled.
On the other hand, there is no independent expert. Everybody who knows about a field has necessarily interacted with this field, and thus likely gained some biases.
There is no perfect solution.

Politicalguineapig, I'm afraid I have to agree with BrewandFerment's comment that:

PGP routinely makes sweeping pronouncements about stuff she knows little or nothing about based on her own Eeyore-like view of the world.

The violence in South Africa has NOTHING to do with the TRC. South Africa was (and still is) a very violent country with a strong paternalistic culture. A lot of people (on both sides) were brutalised during the fight against apartheid. Add to that, we have a shockingly incompetent and corrupt government that's riddled with factionalism and that has attempted (not without success) to undermine institutions like the Prosecution Service and the Public Protector to shield politically connected individuals, and it's no surprise that violence is so common.
Not only are you wrong about the TRC being a reason for the violence in South Africa, you are not even wrong. I can make a case that without the TRC, the cycle of violence and revenge would have perpetuated, and a bad situation would have been even worse.

"Statistically....it ain't worth it."

Perhaps you should study statistics.

Given that violent crime rates in the US have decreased year over year (and dramatically over the past 40 years), I think your "fears" are a bit unfounded....and exhibiting more than a trace of paranoia.

I lived in DC during the worst years of the crack epidemic & not even the better parts of the city, yet I never felt threatened or scared, even once. In fact, it wasn't until I moved out to a rural area of Maryland that I experienced my first crime....

This is a win. At Rational Catholic, Problems with Deisher’s study— Part I: The numbers by Laura C. at Rational Catholic (September 12 2014)

(emphasis added)

In such a scenario, I would have been able to say to myself, like most other people in the scientific blogosphere are doing with the Deisher study, “This is just too absurd, too poorly done to waste any more time refuting it!” But, I can’t do that because you, my brothers and sisters in Christ, deserve to know how badly you are being deceived by a study that is so abominable, it would be an insult to bad science to call it bad science.

Shay @#118:

Wasn't there also a thread of forgiveness in Reconstruction as well (e. g. Lincoln's and Johnson's amnesty declarations)?

>clip

Lucario -- Lincoln got shot and Johnson was impeached, so any attempts by the Administration to temper the wind to the shorn lamb was tossed to the side by a vengeful Congress.

"were." I can't blame scienceblogs for my lack of subject/verb agreement.

Shay @#159-160:

And yet, as the politicans sought vengeance, the common citizens and especially the soldiers on both sides sought forgiveness and a healig of wounds between the two sides. At least that's how I understand it.

Lucario: And yet, as the politicans sought vengeance, the common citizens and especially the soldiers on both sides sought forgiveness and a healig of wounds between the two sides. At least that’s how I understand it.

Um, no. The former Union soldiers and the northern civilians simply forgot, the Southerners just crawled into holes, licked their wounds and raised their children on lies. Why do you think the South is slithering toward secession once again?

@Politicalguineapig, you despise the South and Southerners. You view them with fear, loathing, hatred, and contempt. Why do you object to secession? Why don't you see it as "good riddance to bad rubbish"?

PGP, that question was for Shay to answer. In fact, between you saying that it was immoral to save the life of a woman (like me), and insulting Southerners (which I consider myself, even though I was born in the North) with that last comment, I suggest you kindly stay out of this conversation before you step on any more toes.

Also, I (and a few other posters on this board) are worried you might have clinical depression. Please seek help ASAP.

@ Lucario:

You may have something there.

I think that PGP has several valuable qualities- she really supports science; she values education; she can certainly take alties to task; she is intelligent. HOWEVER she tends to go overboard when catagorising political and demographic groups.

Like all of us, she displays attitudes derived in some manner from personal experience, perhaps magnified by emotional issues. Anxiety and depression can act as distorting lenses and skew our beliefs and interactions with other people. There is help for this.

Free conversation and interaction with other sceptics @ RI can possibly lead her towards change: other commenters tell her how she is mistaken frequently. Because she supports science, pointing her towards DATA may help, e.g.; the political spectrum is not set in stone by location. We can show that as easily as we can show the true after effects of vaccines as opposed to the mythical ones.

The other day, I was forced to talk with two rather prejudiced people visiting from outside my area who made the expected remarks about my own liberal utopia- you can imagine- it concerned crime rates and immigrants/ non-whites.
Perhaps they supposed that because I am rather ridiculously white that I would be as prejudiced as they are..

I simply pointed out that the crime rate where I live was approximately one third of that where they lived ( and where to look up figures like these easily) PLUS the population density was many times more where I live making my point even more salient ( the figures I use don't control for population density although they note it).

Similarly, I narrated how my education consisted of far-flung universities well-known for diversity, how I played tennis with people from all over the world and how my clients represent many different ethnicities. ( To be perfectly frank, the people who have given me the most trouble in my life were nearly all as white as I am - and often related to me- which I didn't tell them).If you isolate yourself from other people, you'll never learn what they're like and your prejudices remain intact and un-challenged.

I doubt that my statements will have any effect on them as they are older, rigid and set in their ways. PGP though, is a youngster and there's more hope for her.

Lucario: Simply put, I doubt the South would have any reason to preserve habitat or parks. Plus they have no infrastructure of their own.

You didn't read carefully. God thinks it's immoral to save women's lives, I don't. In fact, I intend to live as immoral a life as possible, just so I don't get stuck with the sanctimonious twits who make up Heaven.

Please don't use the 'get help' gambit on me. I *know* I have depression. It's manageable.

pgp:

(citations needed) on:

1. The South being unwilling to preserve habitat/parks;
2. the South not having infrastructure of its own;
3. God thinking it's immoral to save women's lives (chapter and verse, please).

Deisher also claims that axons can be conduits for fragmented DNA to bypass the blood-brain barrier. And in other news, Verizon is now telling us that FIOS can now transfer small food particles and they'll be offering Smell-o-Vision this spring.

"How could this contaminating DNA reach the neurons in the brain of a young child? DNA injected into a muscle can be picked up by receptors on the nerve ending. Once DNA has been taken up in to the nerve endings, it can be transported back up the nerve’s axon to the brain." (http://sc.fiatinsight.com/wp-content/uploads/2012/08/Dec_2009_Faith_and…)

I would like to apologize for my co-religionists. They do NOT speak for us!

Should mention, though, Orac, that you did make an error. While Deisher claims that 1988 was the year the 2-dose MMR schedule came into being, the official recommendation by ACIP was not until December 1989 (http://www.cdc.gov/mmwr/preview/mmwrhtml/00041753.htm). The prior deviations from a 1-dose schedule were for outbreak control (1987 http://www.cdc.gov/mmwr/preview/mmwrhtml/00022967.htm) or for areas of recurrent measles (Jan 1989 http://www.cdc.gov/mmwr/preview/mmwrhtml/00001328.htm) and is reflected in the 1989 CDC schedule (http://www.cdc.gov/vaccines/schedules/images/schedule1989s.jpg)

Oh my God in heaven above- at the "Children of God for Life" website, Theresa Deisher actually refers to herself as "the Sarah Palin of Stem Cells."

I wonder if she gets into brawls at birthday parties.

There are three words that no self-respecting person should aspire to "Sarah Palin of...."

Too funny.

We should ignore the scientists>? http://www.collective-evolution.com/2014/09/05/human-fetal-dna-fragment…

When the purported "science" is terrible, Heather, we don't say "oh, but it's a SCIENTIST pushing this BS, so somehow it's still plausible." That is antithetical to the very meaning of science.

We are constantly ingesting food containing large amounts of intact DNA and absorbing DNA fragments (mice do, so humans very probably do too). Worrying about vanishingly tiny amounts of DNA fragments with a couple of hundred base pairs seems more than a bit foolish to me. The leap from in vitro studies of DNA fragment uptake to the claim that, "these contaminating fragments could be incorporated into a child’s genome and disrupt normal gene function, leading to autistic phenotypes" is both enormous and unjustified, it seems to me.

After reading this article. I see parallels with quackwatch and we all know who supports the running of the website. Sitting back as an observer, I think the vaccine argument is a lost cause. I know the western media won't publish adverse articles on vaccines. No, they avoid the big stories such as Japan and European countries banning Pertussis vaccines. No mentions of the class action in Spain and many other countries including Japan regarding HPV vaccine. Want me to continue. No, I have better things to do than read about Zombies from Orac. The web is an amazing place and it is the web that will be the downfall of the toxic drugs that Giant Pharma are feeding the populace.

Richard D.: "I know the western media won’t publish adverse articles on vaccines."

Really? How come I see them all the time, though often without much data. Like this recent story.

"No, they avoid the big stories such as Japan and European countries banning Pertussis vaccines."

Oh, do give some citations about that. I have this one: Impact of anti-vaccine movements on pertussis control: the untold story

Be sure to look at the graphs comparing those who stopped pertussis vaccination and those who did not. Check out what happened in Japan, from that paper:

After two infants died within 24 h of receiving DTP, the Ministry of Health and Welfare eliminated whole-cell pertussis vaccine altogether. They later allowed it only for children older than 2 years. Pertussis coverage for infants fell from nearly 80% in 1974 to 10% in 1976. A pertussis epidemic occurred in 1979 with more than 13000 cases and 41 deaths.

Hmmm, what I see in is a marked increase in the deaths of babies. So if you think "Great Phama" is bad, you must be in the favor of dead children.

That is what will be assumed until you can come up with PubMed indexed studies by reputable qualified researchers that show any vaccine on the American pediatric schedule is more dangerous than the diseases they prevent.

"After reading this article. I see parallels with quackwatch and we all know who supports the running of the website."

We know you've been visiting Patimmy's blog, where the deadbeat blogger has been trying to get his greedy fists on the money dispensed by Wakefield's and Hooker's wealthy benefactors.

Jake has a new post up and he's trashing Emily Willingham. Looks like the cub reporter is insanely jealous of Dr. Willingham's journalism talents and the prestigious journalism prize she was awarded.

There's no hope for Jake as an epidemiologist...or as a journalist. His BFFs Wakefield and Hooker haven't responded to his inquiries and no one provided Jake with this latest communication from Brian Hooker:

http://www.ashotoftruth.org/blog/warm-thank-you-brian-hooker-phd

In spite of the retraction of Hooker's "reanalysis" of the 2004 DeStefano et al study and this latest communication, I won't be counting on Hooker's downfall. As long as Hooker has the support of his wealthy benefactors...he'll keep cranking out those bogus studies and appearing at those anti-vaccine conferences.

No, they avoid the big stories such as Japan and European countries banning Pertussis vaccines.

Except Japan didn't actually ban the pertussis vaccine, did they? Instead, in 1975 they raised the age at which children received pertussis vaccination by two years--and what were the consequences?

In the three years prior to 1975, there were 400 cases of pertussis and 10 deaths from pertussis. In the three years following there were 13,000 cases of pertussis and 113 deaths from pertussis.

It should also be noted that although the side effects of the old pertussis vaccine were high, no child in Japan died as a consequence of receiving pertussis vaccine--the same certainly isn't true with regard to children becoming infected by pertussis.

Of course, given that in 1981 Japan introduced acellular pertussis vaccines, 40.3 million doses of acellular pertussis vaccine were given to 2-year-olds from 1982 to 1988 and 59.3 million doses of acellular pertussis vaccine were given to 3-month-olds from 1989 to 2001, one must ask: did you have a point, other than perhaps that newer acellualr pertussis vaccines are far, far safer than older whole-cell vaccines?

Except Japan didn’t actually ban the pertussis vaccine, did they?
Nor did European countries. So the news media "avoid the big stories such as Japan and European countries banning Pertussis vaccines" because those stories are bullsh1t.

No mentions of the class action in Spain

You think this is a "class action"? A "big story" that the "western media" is avoiding?

Here's an idea: How about you go find the actual suit and it's promised follow-ons rather than just barfing up some mangled version of a post from "Sane"Vax?

Now I find myself imagining alternative-universe dystopian scenarios in which pertussis vaccines *have* been banned in European countries, with long prison terms awaiting those who are caught in possession of a contraband syringe, while an underground Acquired-Resistance of doctors do their best to smuggle doses into the continent.
Someone else can write the screenplay as long as I get credit and a share of the take.

Sitting back as an observer, I think the vaccine argument is a lost cause. I know the western media won’t publish adverse articles on vaccines.

I can see how a credulous and scientifically ignorant person lacking any critical analytical abilities might come to that conclusion. It's hard work figuring out of what you have read on the internet is true or just a lie invented by someone with an axe to grind, like the claim that vaccines have been banned in Japan.

I was prompted to look at Deisher's CVs today, and it seems that this paper followed a tortured path to the "bogus, Nigeria-based publisher."

Here (PDF), "US Autistic Disorder (1970–2002) Changepoints Do Not Coincide with Changepoints for Suspected Sociologic and Environmental Causes” (LaMadrid M, Brown C, Deisher T) was submitted to Autism Research in 2011 March (in a 2013 CV).

Here (PDF) "Impact of Environmental Factors on the Prevalence of Austistic Disorder after 1979" (Deisher TA, Doan NV, Omaiye A, Koyama K, Bwabye S, la Madrid M) was submitted to Pediatrics in 2011 April.

One might wonder where else the same "changepoint" routine was submitted...

... before Deisher decided to skip the barrel entirely.

It also turns out that she was gunning for a VSD fishing expedition (PDF) at one point.

Gunning, as well, for a $260,000 payment-in-advance for expert-witness testimonial.
Judging from a skim of the document, Deisher seems to have shot down the fishing expedition with her own signed declaration, wherein she testifies that each dose of "the rubella component of the MMRII contain[s] approximately 200 nanograms [of] human fetal DNA"... inspiring the Special Master to conclude that "Dr. Deisher does seem to already have the information petitioners now seek", and to reject the application for access.

Do Special Masters often use words like "brazen"?

@ Herr Doktor #184, you might need to fight for your share of the take with Ben Elton.

http://en.wikipedia.org/wiki/Blind_Faith_(novel)

It turns out that LBRB covered this last year.

microRNA Might Manage Mood Disorders

jhalper — Thu, 19 Jun 2014 14:00:56 +0000

microRNA Might Manage Mood Disorders

Since mental health problems are estimated to affect some 10% of the world’s population, it stands to reason that if you don’t suffer from depression, anxiety or bipolar disorder yourself, you are probably close to someone who does. So you might be pleased to read about a new finding that could eventually lead to a whole new approach to treating this group of common mood disorders.

The finding is that a tiny scrap of RNA – a microRNA that works in the brain – acts as a sort of mood regulator. It works something like the needle in a steam valve. Mice that had high levels of this particular molecule in one part of their brains were able to take the heat and remain calm. And those with the lowest levels were more quickly frazzled, acting depressed and anxious when exposed to stressful conditions. That second group also had a weaker response to antidepressant drugs than the average mouse – a possible clue as to why these drugs don’t really work for up to two thirds of the people who try them.

The microRNA “steam valve” Prof. Alon Chen and his group discovered regulates levels of the feel-good neurotransmitter serotonin in the brain. It turns out that people who suffer from depression have low levels of this microRNA in their blood, hinting that, at long last, we might have a standardized, quantifiable way to diagnose the disease – one that could be done in any clinic. But it also suggests we might find a way to adjust that needle up or down, to effectively treat mood disorders.

The Israeli firm miCure, which now has the license to develop a diagnostic test and drug based on these findings, was founded to develop two different microRNA applications, both stemming from Weizmann Institute research. The second is a possible ALS treatment based on the discovery of the role of certain microRNAs in the survival of motor neurons. The field of small RNA-based drugs is really in its infancy, so this development is somewhat daring. If it pays off, however, it could truly be part of a new era in treatment for any number of diseases. In other words, watch this space for future developments.

jhalper Thu, 06/19/2014 - 10:00

Tags

Hello, I was upset by your claim that "these drugs don’t really work for up to two thirds of the people who try them.", after a bit of research, I found on medscape that, on the contrary :
"With appropriate treatment, 70-80% of individuals with major depressive disorder can achieve a significant reduction in symptoms, although as many as 50% of patients may not respond to the initial treatment trial.

Twenty percent of individuals with major depressive disorder untreated at 1 year will continue to meet criteria for the diagnosis, whereas an additional 40% will have a partial remission. Pretreatment irritability and psychotic symptoms may be associated with poorer outcomes. Partial remission and/or a history of prior chronic major depressive episodes are risk factors for recurrent episodes and treatment resistance."
Sincerely

Experimental Biology Day 4

dr. dolittle — Fri, 02 May 2014 00:06:29 +0000

Experimental Biology Day 4

Day 4 of the meeting turned out to be pretty exciting for a comparative physiologist as well.

The first session that I went to was called "RNASEQ approaches to understanding extreme physiological adaptations." Considering the Comparative and Evolutionary Physiology section business and dinner meeting was the night before, I was impressed at my ability to make it to an 8:00am session the following morning.

The first seminar from Dr. Brooke C Harrison (Univ. Colorado, Boulder) was on "Extreme cardiac growth and metabolism in the Burmese python after feeding." He spoke about how the cells of the heart become larger as opposed to developing more cells after a meal. His research focused on characterizing the transcriptome (the RNA that can be translated into proteins) of the heart to determine which genes are up or downregulated with feeding that may cause this cardiac hypertrophy (growth).

Dr. Matthew Andrews (Univ. Minnesota, Duluth) gave a seminar entitled, "Genes that control hibernation in mammals," which was interesting as he spoke about how thirteen-lined ground squirrels (shown below) are "fat burning machines." His research focused on the brown adipose tissue found in these animals and how it changes with hibernation.

Image from http://en.wikipedia.org/wiki/Thirteen-lined_ground_squirrel

I also attended the Robert M. Berne Distinguished Lectureship of the APS Cardiovascular Section. This year's recipient of the award was Dr. Virend Somers, MD, PhD (Mayo Clinic). His research on the effects of sleep apnea was really interesting. He mentioned that the sympathetic nervous system of people with sleep apnea essentially runs on overdrive even while awake, which is similar to what happens in people with heart failure. He also discussed Brugada syndrome, which is a disease characterized by sudden cardiac death usually around the 4th decade in life. This part of his talk caught my attention as we lost a family member awhile back from a sudden heart attack and he was only in his 40's. These patients usually have arrhythmias while they are sleeping which may make them more prone to death from a heart attack.

Props to Dr. Somers for also mentioned sea lions in his talk, which are amazing divers that can stay underwater for 30-40 minutes without air (as mentioned in the prior post). The animals reduce their heart rate and shunt blood away from non-essential organs to protect the heart and brain.

The Comparative and Evolutionary Physiology Section also had their Distinguished Lectureship, the August Krogh Lectureship. This year's recipient of this prestigious award is Dr. Hannah Carey (Univ. Wisconsin, School of Vet. Med, Madison) who spoke about "Hibernation, guts, and microbes: bringing symbiosis into animal physiology." Dr. Carey gave such an inspiring talk about her journey as a scientist. She also presented work in her laboratory on characterizing the gut microbiota in hibernating animals (thirteen-lined ground squirrels). It is so fascinating to hear about how our gut microbes interact with us.

She had also mentioned that the use of antibiotics early in life is associated with increased body fat as antibiotics change the microbiota in the gut. This is why many doctors recommend taking probiotics while taking antibiotics.

dr. dolittle Thu, 05/01/2014 - 20:06

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Knowing how our brains work and how is amazing, more blogs should be done to give further understanding on this topic

Bio Databases 2014

sporte — Thu, 09 Jan 2014 00:25:02 +0000

Bio Databases 2014

By @finchtalk (Todd Smith)

In 2014 and beyond Finchtalk will be contributing to Digitalbio’s blog at this site. We kick off 2014 with Finchtalk’s traditional post on the annual database issue from Nucleic Acids Research (NAR).

Biological data and databases are ever expanding. This year was no exception as the number of databases tracked by NAR grew from 1512 to 1552. In the leadoff introduction [1] the authors summarize this year’s issue and the status of the NAR index. The 21st issue includes 185 articles with 58 new databases and 123 updates. In the 1552 database repository, 193 had their URLs corrected and 24 were removed because they were deemed obsolete.

In previous posts (below) I’ve made the point that biological databases are increasing in specialization as the overall numbers increase. That trend continues. Six of the articles, highlighted in the introduction, illustrate the degree of specialization and roles different databases serve. When the databases are examined in more detail, several challenges can be noted that limit the utility of these tools. These databases include miRBASE [2], miRNEST [3], NOCODE [4], miRTarBase [5], PolymiRTS [6], and starBase [7]. All focus on non-coding RNA (ncRNA).

We often look at gene expression by examining the mRNA levels for genes under different conditions or in different tissues. The fact of the matter is mRNA is only a single type of RNA. The majority of RNA molecules do not code for proteins. Instead they are either involved in the process of creating mRNA (splicing), translating the mRNA into protein (rRNA, tRNA), or regulating the abundance of mRNA molecules (ncRNA). This later class is highly diverse with respect to the lengths of RNA molecules and their mechanisms of action. Four of the databases, miRBase, miRENST, miTarBase, and PolymiRTS focus specifically on micro or miRNA. NOCODE and starBase attempt to be comprehensive for all forms of ncRNA.

The ncRNA family is diverse and represents a next frontier in RNA research. Starting with the discovery that double stranded RNA (dsRNA) could inhibit gene expression by turning on RNA interference (RNAi) pathways [8], new RNAs were identified, micro (miRNA) and small interfering (siRNA), as essential to the RNAi pathway. Some ncRNAs are large, like lincRNAs (large intervening non-coding RNAs) [10], but most are small between 18 and 31 nt. Within in the small ncRNA group are piwi-interacting (piRNA), repeat associated small interfering (rasiRNA), small temporal (stRNA), and transcription initiation (tiRNA) RNA. Recently, new kinds of circular RNAs (circRNA) have been discovered that bind miRNAs, thus working as regulators of regulators.

How are the databases used?

Databases help researchers study ncRNAs in two ways. First they provide ways to organize sequences and biological information (annotations) about the sequence such as the organism where the RNA was found, papers describing its discovery, algorithms used to predict its existence, and whether there are precursor forms of the active molecule. These kinds of databases can be classified as repositories and are commonly used to look up information in experiments designed to measure which RNAs are present in different tissues, at different times, or in response to environmental stimuli. For example miRBase is a collection of miRNA sequences with evidence from the literature for 206 organisms and contains 24,521 records, whereas miRNENST includes miRNA sequences that come from other databases and / or are predicted by sequence analysis programs and contains 39,122 records from 522 organisms. NOCODE is the largest repository with 148,172 records for eight organisms.

The second application is to develop an integrated resource to understand the RNA’s mechanism of action at a molecular level. Researchers create these resources to store data from experiments, but also mine the data contained to predict new kinds of interactions that can be tested in later experiments. The miTarBase, PolymiRTS, and starBase databases are examples that combine data from miRBase, other databases, literature, datasets, and predictive algorithms to create records about specific kinds of interactions and sequences at interacting sites. Each database varies with respect to the classes of RNA stored, organisms, and specific methods for identifying interactions; miTarBase (18 species, 51,460 interactions) and PolymiRTS (human and mouse, 18,514 interactions) focus on miRNA and starBase (human, mouse, C. elegans) include all ncRNA (>500,000 interactions). PolymiRTS also includes validated interactions (2944) and provides data regarding sequence variation and mutation in ncRNA function.

As a specific example, in cancer research, a scientist might want to look at miRNA expression between tumor and normal cells to see if there are miRNAs that are present in normal cells but not observed in a tumor, hence unavailable to turn off that activity of an oncogene. They would purify small RNA fragments, convert them to DNA, and sequence the products for each cell type. Next, they would compare expression profiles between the samples. Annotations from miRBase would be used assign names to the miRNAs and later look up potential functions for miRNAs that are differentially expressed between the tumor and normal cells. Using miTarBase or starBase, they could see if information about these RNAs was present and further explore how the miRNAs interact with their targets to develop hypotheses about how missing the miRNA leads to uncontrolled growth.
In some cases novel sequences can be discovered. These are either mutated forms of miRNA, or miRNAs that have not been reported in the literature. In the later case an expanded search could be conducted in miRNEST or NOCODE (to test the idea that the sequence was from a different kind of ncRNA). The researcher could also see if the sequences are present in PolymiRTS to see if their candidates have a known polymorphisms. As in the above example, the integrative resources could be used to learn about known and predicted interactions between the ncRNAs and other molecules, like the mRNAs for known cancer genes. In the case where no database matches are found, it is still possible that a completely novel, unpredicted, ncRNA could be discovered.

Clearly, these are diverse resources from a content and scientific mission perspective. They also have substantial variability regarding their technical implementations. While all strive to make their data available, only starBase provides an API for programatic access, and, at the same time is the only one lacking bulk data downloads. In the cases where bulk data is accessible, the formats vary, with tables being in tab delimited text, GFF3, BED, or other formats and sequences being commonly in a fasta format. One can also expect variable quality too. Giving the large differences between the numbers of records and how they were created, false positive data (unverifiable predictions or literature that cannot be reproduced) are expected, but levels or estimates of the number are not provided.

Organizing data in ways to create new knowledge is an important aspect of modern biology. These databases are significant in that they can provide new insights into gene regulation and biological systems. The challenge for researchers is understanding the diversity of specialized resources, application fit, and their unique methods for data delivery. These six examples focus on a common aspect of molecular biology, yet are a very diverse tip of the iceberg. The miTarBase web site alone links to an additional 23 resources that include analysis tools and other ncRNA databases, and the NAR index now references 1552 databases organized into 14 categories and 41 subcategories.

Further Reading

Small RNAs Get Smaller - http://finchtalk.blogspot.com/2009/05/small-rnas-get-smaller.html
Databases of Databases - http://finchtalk.blogspot.com/2011/01/databases-of-databases.html
Bio Databases 2012 - http://finchtalk.blogspot.com/2012/01/bio-databases-2012.html
Bio Databases 2013 - http://finchtalk.blogspot.com/2013/01/bio-databases-2013.html

Small RNAs:

ncRNA - http://nar.oxfordjournals.org/cgi/reprint/35/suppl_1/D178
snoRNA - http://en.wikipedia.org/wiki/SnoRNA
siRNA - http://en.wikipedia.org/wiki/SiRNA
miRNA - http://en.wikipedia.org/wiki/MicroRNA
piRNA - http://en.wikipedia.org/wiki/Piwi-interacting_RNA
rasiRNA - http://en.wikipedia.org/wiki/RasiRNA
stRNA - http://jcs.biologists.org/cgi/content/full/116/23/4689
tiRNA - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170176/
circRNA - http://en.wikipedia.org/wiki/Circular_RNA

microRNAs and Cancer - http://scienceblogs.com/pharyngula/2013/10/12/micrornas-and-cancer

References

[1] Fernández-Suárez XM, Rigden DJ, Galperin MY (2014) The 2014 Nucleic Acids Research Database Issue and an updated NAR online Molecular Biology Database Collection. Nucleic Acids Research 42(1): D1-D6.

[2] Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Research 42(D1): D68-D73.

[3] Szcześniak MW, Makałowska I (2014) miRNEST 2.0: a database of plant and animal microRNAs. Nucleic Acids Research 42(D1): D74-D77.

[4] Xie C, Yuan J, Li H, et al. (2013) NONCODEv4: exploring the world of long non-coding RNA genes. Nucleic Acids Research 42(D1): D98-D103.

[5] Hsu S-D, Tseng Y-T, Shrestha S, et al. (2014) miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Research 42(D1): D78-D85.

[6] Bhattacharya A, Ziebarth JD, Cui Y (2014) PolymiRTS Database 3.0: linking polymorphisms in microRNAs and their target sites with human diseases and biological pathways. Nucleic Acids Research 42(D1): D86-D91.

[7] Li J-H, Liu S, Zhou H, et al. (2014) starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Research 42(D1): D92-D97.

[9] Fire A, Xu S, Montgomery MK, et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669): 806-811.

sporte Wed, 01/08/2014 - 19:25

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Spotlight on X-STEM Speaker Dr. Robert Tjian

carlyo — Tue, 05 Nov 2013 17:04:53 +0000

Spotlight on X-STEM Speaker Dr. Robert Tjian

X-STEM - presented by Northrop Grumman Foundation and MedImmune - is an Extreme STEM symposium for elementary through high school students featuring interactive presentations by an exclusive group of visionaries who aim to empower and inspire kids about careers in science, technology, engineering and mathematics (STEM). These top STEM role models and industry leaders are sure to ignite your students’ curiosity through storytelling and live demonstrations.

Our spotlight on our X-STEM Speakers continues with Biochemist Dr. Robert Tjian from Howard Hughes Medical Institute (HHMI).

Ask colleagues about biochemist Robert Tjian and the qualities that best define him, and you will most likely be told such accolades as: "A distinguished, first-rate scientist... a person of impeccable talent and taste in science who commands a great breadth of understanding across the life sciences... a highly productive scientist but also a committed teacher and mentor of young scientists."

These characteristics are among the traits that have molded Robert throughout his prominent career as a researcher and professor, and led to his appointment in 2008 as president of the prestigious Howard Hughes Medical Institute (HHMI) -- one of the world's largest philanthropies, and an organization which plays a powerful role in advancing biomedical research and science education in the United States.

"This is the most interesting job for a scientist in the nation - if not the world - because of its impact on research in the life sciences," says Robert of his job at HHMI. "I feel a sense of responsibility after more than 20 years as an investigator with HHMI. It is a great opportunity to give back in a significant way."

The Institute, a non-profit medical research organization with an endowment of more than $17.5 billion, has over the past two decades made investments of more than $8.3 billion for the support, training and education of the nation's most creative and promising scientists.

Before assuming his position as president of HHMI in 2009, he was a distinguished professor and researcher of biochemistry and molecular biology at the University of California, Berkeley, where he had also served as an HHMI investigator since 1987, carrying out groundbreaking science with his team at UC Berkeley as well as at HHMI's prestigious Janelia Farm Research Campus in Virginia.

Specifically, Robert is widely known for his studies into how genetic information stored in DNA is copied (transcribed) into RNA, which directs the production of proteins inside cells that are essential to life. He devised a way to isolate the individual components of the cell involved in transcription and recreate this complex, highly regulated process in a test tube. Advances in technology have also enabled Tjian to purify rare sequence-specific transcription factors, which bind to DNA at specific sites and regulate the expression of genes, and to isolate the genes that encode these important transcription factors.

His work has provided new insights into the molecular mechanisms that underlie various human diseases and conditions, including Huntington's disease, cancer, diabetes, and infertility.

Robert has also been actively involved in training a new generation of molecular biologists who are poised to answer new questions generated by today's scientists. "It gives me great pride to have guided so many students into medical careers, and to watch my students and postdoctoral fellows develop into first-rate scientists," says Robert.

In addition to spearheading HHMI's formidable medical research initiatives as Institute president, he is also committed to advancing the Institute's long commitment to science outreach to students. Says Robert: "HHMI is committed to funding education programs that excite students' interest in science. We hope that these programs will shape the way students look at the world -- whether they choose to pursue a career in science or not."

Robert was born in Hong Kong, the youngest of nine children. His family fled China before the Communist Revolution and eventually settled in New Jersey. Known as a voracious consumer of scientific information and data, Tjian famously talked his way into the biochemistry laboratory of the late Daniel Koshland as a Berkeley undergraduate - even though he had never taken a single course in the subject.

Robert went on to receive a Bachelor's degree in Biochemistry from Berkeley in 1971 and his Ph.D. from Harvard University in 1976. After completing a post-doctoral fellowship at the Cold Spring Harbor Laboratory with James Watson, he joined the Berkeley faculty in 1979 where he later assumed a variety of leadership roles, including serving as Director of the Berkeley Stem Cell Center, and the Faculty Director of the Li Ka Shing Center for Biomedical and Health Sciences. He is a member of the National Academy of Science and has received many awards honoring his scientific contributions, including the Alfred P. Sloan Prize from the General Motors Cancer Research Foundation, and the Louisa Gross Horwitz Prize from Columbia University. He was named California Scientist of the Year in 1994.

Click here for more information.

carlyo Tue, 11/05/2013 - 12:04

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USA Science & Engineering Festival

X-STEM

biochemistry

DNA

Howard Hughes Medical Institute

Extracting Genetic Material

cagapakis — Tue, 15 Jun 2010 15:15:54 +0000

Extracting Genetic Material

The first (and sometimes 3rd, 12th, 25th, 134th...) step of any genetic engineering experiment is often extracting DNA from some organism or another. While novel gene synthesis technology will likely make this procedure obsolete, these days it's still most economical to do it by hand. Extracting DNA from fruits like strawberries has also seen a popular resurgence thanks to groups like DIYbio, with instructions for making DNA shots available online for a fun and nerdy party activity. Today my iGEM team extracted RNA from strawberries and oranges to isolate the genes responsible for strawberry allergy and orange flavor as BioBrick parts.

We extracted RNA instead of DNA because many plant genes contain introns, which are pieces of DNA that don't end up in the final protein sequence. By isolating the RNA, which already has these bits spliced out, we can get just the sequence that codes for the protein we're interested in. The procedure is pretty similar either way--chop up and homogenize some of the fruit tissue (using liquid nitrogen!!!), add soapy, salty water to break up the cell membranes, precipitate the genetic material using alcohol, and then isolate and wash the DNA or RNA. I'm used to doing this with yeast or bacteria, and it was a lot of fun to play with food in the lab today!

cagapakis Tue, 06/15/2010 - 11:15

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As a structural biologist, this is something I rarely get to see -- I typically only work with genes that have been conveniently inserted into a high-production plasmid. What is your strategy for isolating the desired gene from the pooled RNA? Do you intend to create a whole cDNA library, or do you have primers for specific PCR from a reverse-transcribed product? Did you have to create an RNAse-free zone in your lab for this?

We made a cDNA library by doing a reverse transcriptase reaction with oligo-dT primers that bind to the poly-A tail of the mRNA. Somewhere in there is hopefully the cDNA of the template we want! We probably should have made an RNAse-free zone, we just tried to be as sterile as possible, we'll see how it worked when we try the PCR later this week!

Oooh, making biobricks from eukaryotic genes hmm? Although the orange flavour genes could be very interesting ones too biobrick. Wish them the best of luck from me!

Expanding the Genetic Code

cagapakis — Thu, 18 Feb 2010 18:10:24 +0000

Expanding the Genetic Code

Almost every living thing shares an identical genetic code, with three nucleic acids in an RNA sequence coding for a single amino acid in the translated protein sequence. While there are 64 three-letter RNA sequences, there are only 20 amino acids and degeneracy in the code allows some amino acids to be coded by multiple codons. Chemists and synthetic biologists in the past few years have been working to expand this genetic code, with unnatural nucleotides that can be incorporated into DNA and RNA sequences and unnatural amino acids that can expand the chemical functionality of proteins. These amino acids can add chemical groups that are not usually present in proteins to create new biochemical reactions, or to create more stable bonds inside the protein for enzymes that are more resistant to harsh environments. Because each three-letter RNA codon already is matched to a specific amino acid, it's very difficult to incorporate these unnatural amino acids into proteins of live cells. Some researchers have mutated one of the "stop" tRNAs in E. coli (there are three codons that tell the ribosome to stop, each corresponding to a different tRNA molecule that will terminate the amino acid chain) so that instead of stopping translation it inserts the unnatural amino acid instead. A cell with each of the "real" stop signals in the genome mutated to one of the other two stop codons would be a perfect "chassis" for using one of these unnatural amino acids.

But what if instead of mutating individual tRNAs, you could make a whole parallel genetic code in a living cell? An awesome paper in this week's Nature makes progress towards this goal, by using directed evolution to design a ribosome that reads four letter codons instead of the normal three. With a four letter code, you could potentially program 256 different amino acids, to create altered proteins or entirely different biological polymers. For a lot more detail on how the researchers went about "reprogramming the code of life" check out the webcast of a presentation by the senior author, Jason Chin.

Expanding the genetic code to include unnatural biological building blocks is an interesting problem for synthetic biology. Most synthetic biologists aim to recombine natural systems in unnatural ways, making new connections between existing or slightly modified proteins to create a new function. Using different chemical building blocks has the potential to create totally new chemistries with fascinating implications for how we understand and use living systems. An editorial in the most recent issue of New Scientist addresses some of the typical concerns that arise with any new synthetic biology technology:

This is a fundamental advance that could lead to new drugs, materials and energy sources. But tampering with life's operating system will inevitably raise safety concerns - and it's true that we have no way of predicting the fallout of this work. Synthetic biologists need to confront openly and honestly public fears that they are "playing God". If such deeply felt concerns go unanswered, the huge potential of this breakthrough could come to naught.

Designing unnatural amino acids can seem, well, unnatural, but most research in synthetic biology is primarily about better understanding how natural living things work. Moreover, realistically, we can't change all that much without wrecking proteins and killing the cell. It is very hard to predict how a protein will fold from just looking at the protein sequence (with today's computer technology it's impossible for more than a handful of amino acids), and when you throw in unnatural amino acids with different chemistry it gets even harder. Unnatural amino acids may become gradually incorporated into research of how proteins fold and how they function chemically.

In many ways, the use of unnatural nucleotides and amino acids in laboratory strains of bacteria has the potential to actually create safer synthetic systems. Unnatural amino acids have to be chemically synthesized and supplied to the cell in the growth medium, thus preventing the cells from being able to grow in the wild if they were to escape. More importantly, wild-type cells would be unable to "read" the synthetic genes in a cell with an expanded genetic code, so any gene transfer between engineered cells and natural cells would make protein "gibberish" (most random protein sequences don't actually fold in the cell, and thus would not lead to any new function). Instead of simply relying on the hand wave-y argument of "lab strains are already probably unfit for survival in the wild", these sorts of "failsafe" systems may soon be feasible to ensure environmental health and safety for all new biological designs.

(via New Scientist)

cagapakis Thu, 02/18/2010 - 13:10

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Synthetic RNA Switches

cagapakis — Tue, 26 Jan 2010 14:03:10 +0000

Synthetic RNA Switches

Today in my searches for the hot new trends in synthetic biology, I found a news article from Science Daily with an intriguing title: "Scientists Achieve First Rewire of Genetic Switches." Rewiring genetic switches sounds pretty neat, but this headline was intriguing to me first of all because it's kind of late to the party--in fact one of the first papers in modern synthetic biology back in 2000 was about engineered genetic switches: "Construction of a genetic toggle switch in Escherichia coli". When I looked more closely, the article wasn't about this kind of transcriptional switch though, but about an RNA-based control mechanism, the riboswitch. Riboswitches are parts of messenger RNA molecules that fold up on themselves in such a way that they can turn the expression of the gene they belong to on and off, depending on whether there is a small molecule bound to the RNA structure, first described by one of my college biochem professors, Ron Breaker. Riboswitches that respond to all sorts of metabolites control the activity of a lot of different genes, and many people have worked on engineering riboswitches and other synthetic RNA aptamers that will bind many different kinds of molecules. I'm curious to read the paper that the news story refers to and to see how their work differs or improves on previous engineering (the paper won't be published until next week, I'll add the link when it goes live), but in the meantime it got me thinking about how cool RNA engineering is and all the cool synthetic biology that people have done with RNA molecules.

Engineered RNA is very versatile for controlling gene expression because RNA is a dual function molecule; RNA can carry a code, like DNA, but unlike DNA, that code can also cause folds and bends in the RNA sequence that create shapes that can perform enzymatic activities like binding chemicals and binding to and/or cleaving RNA or DNA. Engineered RNA sequences can be programmed to bind to an mRNA gene transcript, preventing it from being translated into protein and becoming active. These RNA aptamers can be designed to change shape when they bind a specific small molecule, rapidly falling off the gene and activating expression.

Figure 1--Schematic of synthetic RNA aptamers for control of gene expression from my review article:
More complicated gene expression control switches have also been programmed into the mRNA sequence of synthetic genes, allowing for more complex control of gene expression in response to multiple different input chemicals. These riboswitches have different "arms" that can each bind to different molecules, and depending on how they are designed, will work together to make different logic gates, requiring both, neither, or either one of the input molecules to cause gene expression.

Figure 2--Synthetic RNA Logic Gates from my friend Patrick's review article:

Methods for artificial evolution of synthetic riboswitches that bind to arbitrary small molecules have been improving in the past few years and there are now hundreds of different sequences that can be used in these kinds of synthetic applications. Different combinations of these riboswitches in addition to other control systems, as well as switches that respond to different and crazier molecules can be used to make increasingly complicated synthetic genetic circuits, with all kinds of crazy applications from medicine and gene therapy, biotech and metabolic engineering, to better understanding of the basic science of gene control.

cagapakis Tue, 01/26/2010 - 09:03

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What if everything you thought you knew about the genome was wrong?

sporte — Tue, 24 Mar 2009 16:25:54 +0000

What if everything you thought you knew about the genome was wrong?

For the past few months, the shake-up that began with Next Generation DNA Sequencing has been forcing me to adjust to a whole new view of things going on inside of a cell. We've been learning things these past two years that are completely changing our understanding of the genome and how it works and it's clear we're never going back to the simple view we had before.

What's changed? The two most striking changes, to me at least, are the new views of the way the genome is put together and what the cell does with the information.

They just don't assemble chromosomes like they used to.
I used to think things like structural variations in our chromosomes were relatively uncommon. And, I wasn't the only one. I can even find those kinds of statements in some pretty recent genetics texts.

But, I was wrong and so was everyone else.

Copy number variations (CNVs) are regions of DNA where sequences, of variable lengths, have been duplicated or deleted. There are more CNVs, and more inversions, where a piece of DNA has been flipped around, and translocations, where bits of DNA have moved from one chromosome to another, than we would have ever expected.

It's not that we didn't know these structural variants existed, it's just that we (or at least I) always thought about these variations in the context of disease. When I learned about inversions, translocations, or copy number variations in genetics; it was because there were genetic diseases associated with these changes. Some cases of Down Syndrome for example, can occur when a piece of chromosome 21 is copied and pasted onto chromosome 14 Other well-known translocations are associated with certain types of cancer. Chronic myelogeneous leukemia can occur when bits of DNA are exchanged between chromosomes 9 and 22. In another more recent case, a copy number variation has been associated with autism susceptibility.

Now, we know that translocations can occur without producing some kind of genetic disease. Like inversions, deletions, and duplications, our new ability to scrutinize the genome is making it clear that individual genomes vary more than we ever knew.

They don't use the information the same way any more either

Our genetics texts used to present this nice simple picture of the way gene expression worked. We had a region of DNA called a "gene," the information from that gene was copied, producing a molecule of RNA. If that RNA contained the information for making a protein, it would be sent out of the nucleus into the cytoplasm, where the ribosomes would read the information and build a protein. Two steps, nice and sweet.

But the real picture is turning out to be much more complicated.

We used to be satisfied with three types: tRNA, ribosomal RNAs, and the messenger RNA that codes for proteins. But now, every experiment seems to be finding more and more kinds of RNA. Now, we've got ribozymes, telomerases, RNAs involved in splicing, micro RNAs, small RNAs, long non-coding RNAs, and everywhere you look there's some new kind of RNA with some unknown kind of function.

What's brought about this change?

We're being forced to change our view of the world because of the new technologies. In earlier years, we were look able to look at the genome by using Sanger sequencing to determine the order of bases in the DNA, and the transcriptome, by using either Sanger sequencing to look at the RNA molecules produced in a cell or microarrays or SAGE to look at small parts of RNA molecules. None of these methods were comprehensive enough to really gave us the whole picture.

It's a brave new world.

sporte Tue, 03/24/2009 - 12:25

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Genetics & Molecular Biology

genomics

Next Generation DNA sequencing

Next Generation DNA sequencing

A lot of these new ways of looking at the genome were apparent about three or four years ago with the advent of high density genomic microarray technology such as ROMA. That is certainly when I realized the genome was more complicated than expected.
It has taken years, however, for the new picture to filter down to biologists in general.

I really dislike sensationalist "articles" like this. Not much content and giving the wrong impression to boot. No, not everything we know is wrong. It is like after just using whole number calculations you finally discover fractions - it is a whole new field which makes it more complicated and expands your understanding. But it doesn't invalidate what you know about whole numbers.

To anyone familiar with evolution and the RNA world hypothesis it doesn't come as a big surprise how involved RNA is either. That had already become very apparent when the structure of the ribosome was solved and it was shown that rRNA does not have a structural role supporting the proteins in their function, but that the proteins have a structural role and rRNA is the catalyst.

Don't worry Markus, later posts will have more detail.

I forgot to mention all the changes in our views of alternate splicing, alternate transcriptional start sites, multiple promoters, much more extensive RNA editing, and alternate polyadenylation. It's a taken some time for all the new bits of information to form a more comprehensive picture.

Even when you suspect that things might be more complicated than before, it's different when you start seeing the data.

It is the article I have issues with, not the biology.

Statements like "EVERYTHING WE KNEW IS WRONG" are not just sensationalist but plain simply wrong and undermine the credibility of science. A credibility which has been built on facts over hundreds of years. This article was pointed out to me by a layman (I didn't know this site before). How is a layman supposed to know that this article is , well, crap? How often do you thing creationists cite articles like this as evidence that Science got it wrong?

You write a blog. You think you have something to say. Then shouldn't that something be worth saying?

I don't think I will be coming back to read more.

The comments you've received on this post are fascinating. Expressing a bit of enthusiasm for new information that forces an adjustment to your previous understandings is not the same as sensationalized distortions meant to propagandize a particular worldview. Please do not take the feedback you've so far received as evidence of failure to communicate effectively. I think that you have. The new information is fascinating and highly representative of the way scientific understanding progresses. Such understandings aren't set. They aren't unchanging for all time. And they aren't complete as is. Not to everyone's taste, but certainly exciting and challenging for a great many, you and me included.

Hoping to read your next installment.

Reminds me of what happened in physics over decades: I grew up learning that atoms were made up of protons, neutrons, and electrons. Many years later quarks were added to the description, and now today we have a mind-boggling 'particle zoo' that numbers in the multi-dozens even at the most fundamental level of matter. The original conception may not be entirely 'wrong' but it missed so much of the complexity that it might as well have been! And it should be expected that undiscovered complexity is even more inherent to the biological arena than to the physical. We remain at an incredibly primitive level in our understanding of genetics, subject to much change.

Very much agree with Arj and Greigos (and therefore disagree with Markus' harsh criticism): one has to be indeed careful how one puts into words such paradigm shifts that happen from time to time in various fields of science. It is clearly hard for a layman to understand how such drastic changes in our understanding do not completely invalidate the interpretations that were reached before, based on earlier (and less detailed) knowledge. Yet I agree with you very much that many of us had to (some might still have to!) quite radically reset our thinking about genome structure and genetics in general. Interesting times indeed!

I had a genomics grant turned down several years ago because I had a partial sequence of a genome that was closely related to another and had found several significant rearrangements. They essentially said I didn't know what I was doing. A few years later and nobody would've questioned my results.

This is an excellent summary of the startling sea changes that have occurred even since I took undergrad genetics, and that was just 3 years ago.

I am curious not so much about the content of this information but rather about how it is dynamically and spatially organized. Especially interesting to me are the many ways in which the establishment and dynamic changes of the gut microbiome could be programming our immune systems and thus overall health. There is already evidence that specific microbiota are strongly implicated in the development of inflammatory bowel disease.

I'm looking forward to the rest of the series.

Thanks everyone,

I do plan to write more about these new developments, but first, I have to post some assignments for my class....

A few weeks ago I had on my hands a New Scientist magazine stating "Darwing is wrong". I understood immediately the rethoric of the statement and actually have to say that the article was really well written and interesting. But there was immediate reaction from creationist in the UK celebrating that a prestigious scientific magazine was in their side nearly recognising their victory. That is why, although rather harsh, I understand Markus' point and concern. I have to say though that the article is interesting and I share the idea as to how new technologies and changing how we use to see the molecular world. The pioneers, like Einstein in physics, were not wrong, but they had wished having access to the technologies available nowadays.

While I also think you raised some very interesting points I'm a bit puzzled that you didn't even mention how much our understanding of epigenomics has grown and how this changed our view on how cells work, how inheritance works and therefore even how evolution works.

Krakonos: I would have, but I was pressed for time. You're right, our ability to identify all the methylated positions in a genome has certainly increased our understanding.

Fast sequencing and informatics are finally giving us a view of the hard drive of life. We are also getting closer to understanding the mechanism of evolution and development.
As each new shRNA or RNAi CNV or randomly conserved sequence is elucidated I see it as the uncovering of the ancient mechanism that got life going and evolving eons ago. Dawkins wrote about a Blind watchmaker but I believe the watchmaker devolped or evolved a kind of biochemical sight.

In this sense understanding the exact path we took from slime to cell is looking more and more like the key to nearly everything in biology and medicine.

I was talking to one researcher recently who showed me some data about prostate cancer risk being directly related to the path cells take from stem cell to tissue. In short to understand how the cancer develops they have to understand how specific tissues evolve.

My idea and it's probably not unique to me is to look at the analogy of cooks and recipes in a good restaurant.

You see an organism which wants to survive evolutionary forces is like the cook in nice restaurant. Most of the clients come to get the dish that they love but they also want to see something new. So most of the menu is a standard recipe but the cook has to put out experiments to see what the market likes. Now when the customers really like something the cook has to freeze the recipe and put it with the standards. The question in biology is how does variation get frozen when it's good?

Most people think it's all just natural selection acting on the whole organism each time a mutation happens but if that was the case it is unlikely we would have ever evolved beyond the complexity of a single cell like a bacterium. Also the process of evolution probably isn't driven by random mutation (changing single bases in the DNA) and then selection. Rather nature is like a good chef working with complex ingredients -- it moves and rearranges whole chunks of of already "evolved" DNA around. The reason is that random changes of single bases is too slow to have produced the changes we see in nature. In fact they are so rare that you can use them to date the divergence of races and species.

So for evolution to work there has to be some equivalent of a master chef at the heart of the evolutionary process that does "experiments" by moving bits of DNA around and there has to be the equivalent of a restaurant manager - the person who hovers around in the back and looks to see which new recipe is worth keeping and turning into a new standard. In evolution genes that are important are often "conserved" that is they are the same across a whole host of species. Well it turns out that large stretches of DNA that don't seem to code for anything are also conserved and the mechanism of what conserves them or lets them vary is going to be an important factor in understanding how evolution works.

What does this have to do with the new confusion in genomics in Sandra's post? I think we are just getting our first look at the chef and the restaurant manager at work even though most of us track them by watching the waiters and bussboys.

The talk about a "master chef" is getting us into dangerous territories, I think. Maybe I shouldn't feed the trolls, but we should really stick to evidence based science here.
To make it short: No, there is no evidence of a "master chef". Nice try though.