So that finally puts the autism-vaccination link to bed, right? Wrong. To read some responses in the blogosphere, one could assume that The Lancet had declared war on all humanity. In Natural News, Mike Adams writes that “The Lancet is doing exactly what George Orwell described in 1984 — rewriting history by obliterating scientific truth and removing it from their archives.” In the Age of Autism, Mark Blaxill refers to the General Medical Council’s judgment that precipitated the retraction as “deep and profound censorship”. Now, I have no intention of picking a fight with these people, but what we have here is a failure of logic and some profound cherry-picking of scientific literature. Thus:

1) In 1998, The Lancet publishes a paper suggesting a link between vaccines and autism. The Lancet is right.
2) In 2010, The Lancet retracts the paper. The Lancet is not only be wrong, but corrupt as well.

I want to ask Mr. Adams and Mr. Blaxhill just one question. At what point in the 12 years between publishing an article that confirms your beliefs and the subsequent retraction was The Lancet usurped by Orwellian propagandists?

I suspect the issue here (and I am sure even Mr. Adams and Mr. Blaxhill will agree) is a failure to trust. Some of us choose to trust the medical/pharmaceutical establishments, some don’t. If you don’t have confidence in these institutions, no amount of pronouncements will change your mind. For many, the primary reason to mistrust Big Pharma is that it is profit-motivated. But so are farmers (yes, even organic ones), private hospitals, and the people that make your seat belts. Occasionally they make mistakes and do stupid things but this is not evidence of conspiracy.

If this retraction is a sign of anything, it is of a healthy peer-review process. The Lancet made a judgment, reviewed it, and found it to be in error. It would be great if we were all capable of such logic.

What did the group find?
Kleinfeld’s group devised a technique that uses elaborately-named “cell-based neurotransmitter fluorescent engineered reporters” (CNiFERs for short) to examine how neurotransmitter receptors are activated. CNiFERs are cells that have been engineered to change color when acted upon by a specific neurotransmitter. The group created CNiFERs that responded to acetylcholine and implanted these cells into the frontal cortex of adult rats. When stimulated, the CNiFERs fluoresced to indicate the presence of acetylcholine in the frontal cortex.

Next, the group injected the rats with clozapine and olanzapine – neuroleptic drugs (antipsychotics) that are often used to treat schizophrenia. The implanted cells ceased to fluoresce, indicating that the drugs were blocking the transmission of acetylcholine. In other words, the group could see how neuroleptics were affecting the frontal cortex simply by looking at its color!

Why is this important?
This is very exciting and potentially very important. It is theoretically possible to create CNiFERs that respond to any neurotransmitter and to implant cells in any part of the brain. The mechanisms by which many psychiatric drugs work is largely a mystery, with selective serotonin reuptake inhibitors (SSRIs, used to treat depressions) being a case in point. With CNiFERs, researchers have a potentially powerful tool to understand how biochemical signals are relayed through the brain and the sites where they are active. This may lead to more effective treatments for disorders and lay bare many of the secrets of biochemistry that have been hidden for so long.

Many hours of belly laughs later and I began to feel rather guilty. How terrible it must be to labor through life as Super Mann. How the schoolyard must cackle when Garage Empty is called back to class. For children with truly awful names, life is undeniably tough. Sherwood and Rayback found that these kids are more likely to require psychiatric care and to perform poorly at school. But then again, if you’re called Warren Peace, what kind of parents did you have to begin with?

Even for the majority of us not saddled with monickers such as Infinity Hubbard and Hugh Jass, names can go some way toward determining future success in life. One particularly intriguing set of analyses was conducted by Leif Nelson at UCSD and Joseph Simmons at Yale University. The authors found that individuals with the letter ‘A’ or ‘B’ in theirs initials are more likely to achieve higher grades and attend higher-ranked universities than those with ‘C’ or ‘D’ initials. Similarly, baseball players whose names begin with the strikeout-signifying letter ‘K’ tend to strike out more often. Nelson and Jackson contend that this represents an unconscious drive to produce “name-resembling performance”. Although this particular suggestion may be hard to swallow, one should not ignore the presence of name-letter effects in many walks of life.

For example, if I am called Lawrence, I am more likely to move to Los Angeles for the simple reason that our names both begin with ‘L’. If I am called Doris, I am more likely to move to Denver. This is known as “implicit egotism” and has been observed in career choice (people named Dennis or Denise are overrepresented among dentists) and choice of partner (people tend to marry those whose first or last names resemble their own). Whatever the reason, there does seem to be more to a name than meets the eye.

For many, this type of social science research only serves to fuel skepticism of the field in general. That said, the impact of broader cultural factors on cognition and cognitive decisions is undeniable. G2C Online is all about how different levels of understanding synchronize to produce human behavior – about how experiences can alter gene expression and neural connections. We receive all our experiences through the filter of culture and history and it would be foolish to underestimate them. That said, I won’t be rushing out to name my first son Aaron Aardvark.

This is the surprising news from a team of researchers are the University of Szeged, Hungary. The researchers made the discovery by analyzing a type of neuron called neurogliaforms. Neurogliaform cells (also called dwarf cells or dwarf neurons) are GABAergic neurons – they release the GABA neurotransmitter (the primary inhibitor in the central nervous system).

Neurogliaform cells are widely distributed in the cortex and are involved in many cognitive functions including attention, language, learning, memory, and perception. All of this was known before the team, led by Gábor Tamás, began their study. What was not fully understood was how neurogliaforms communicate.

The group used electron microscopes to analyze brain tissue, which showed that neurogliaform cells have bushy axons with many branches. They examined the terminals at the end of these axons (axonal boutons) and found that of the 50 boutons studied, only 11 formed synapses. In other words, the majority (approximately 78%) of do not form “classical” synapses. My old neuroscience lecturer would have had a fit! If they are not forming synapses, then how are they communicating?

It would appear that the cells are communicating using a mechanism called volume transmission, where the GABA is diffusing in a cloud through the extracellular fluid. The bushy structure of these neurons would seem to be ideal for this type of signaling. Subsequent experiments by the group confirmed that a single neurogliaform can release enough GABA to inhibit nearby neurons, even when no synapses are present.

Another set of experiments showed that neurogliaforms contain receptors that can detect very low levels of GABA. This suggests that they are purpose-built to communicate among themselves, again in the absence of synapses.

This is truly groundbreaking stuff. Just as Francis Crick’s central dogma of molecular biology has gradually yielded to some unexpected molecular acrobatics, so too the dogma of synaptic neurotransmission must be rewritten. Certainly, synapses will remain the main players, but now there is a little competition on the pitch.

To date, every study that identified practice-related changes in brain structure located these changes in grey matter. Now, for the first time, a paper by Scholz and colleagues in the journal Nature Neuroscience has identified training-induced changes in white-matter architecture. This has important implications for how we understand neurodevelopment.

What are grey (gray) and white matter?
Grey matter is a thin layer (less than half a centimeter thick) that forms the outermost part of the brain. It derives its grey color from neurons and unmyelinated (uninsulated) axons. Grey matter is considered the part of the brain that accomplishes the major cognitive chores – attention, language, learning, memory, perception, and thinking. As such, it was not surprising to discover that when we learn our grey matter changes.

White matter is different. It consists mainly of myelinated axons and does not contain dendrites. It is most commonly regarded as the support structure to the cerebral cortex, and interconnects different brain regions. Hitherto, changes in white matter as a result of learning had never been observed.

What did the study show?
Scholz and colleagues used diffusion tensor imaging (DTI) to measure white matter in 48 individuals (DTI is a relatively new neuroimaging technique capable of penetrating deep into the brain). Half the individuals were placed into a training group for 6 weeks, where the learned to juggle. The other half did no training for the same six weeks. All the participants were scanned before and after training.

Unsurprisingly, the training group showed significant differences in gray-matter density. What will come as a surprise to many is the observation of increased white matter volume in the training group, specifically the area underlying the right posterior parietal sulcus. The control group showed no such differences.

Why is this important?
In most neuroscience textbooks, white matter is given scant consideration, especially when it comes to learning. Changes in dendrites – dendritic growth – generally hog the headlines as hallmarks of neurodevelopment. When we learn, dendritic branches (little tree-like protrusions that spurt out from our neurons) form new synapses and build the connections that help us remember. White matter has no dendrites, so clearly there is something else going on.

The authors suggest that electrical activity in axons (as the result of learning) may regulate myelination in axons. Similarly, gross changes in the axon – the diameter or packing density – may be the cause.

Whatever, the reason, the white matter is changing. This is very important and promises to elevate the status of white matter as a correlate of neurodevelopment. Moreover, the countless MRI and fMRI studies that associate grey matter changes with everything from Internet use to the acquisition of wealth may only be telling half the story.

MRI techniques are not able to penetrate white matter, and is is quite conceivable that the myriad of studies that focus on the cerebral cortex are missing something. Researchers and educators take note – white matter really does matter!!

Ribosomes are molecular machines composed of RNA and protein that perform the critical function of translating messenger RNA (mRNA) into protein. In other words, they transform the genetic code from a static list of instructions into dynamic entities that constitute life. As the Nobel Foundation’s announcement eloquently put it, “they build and control life at the chemical level.”

In a tour-de-force of atomic chemistry, Ramakrishnan, Steitz, and Yonath used X-ray crystallography to locate each of the several hundred-thousand atoms that make up the ribosome and generated 3-D models of antibiotics binding to the structure. These models promise to spur the development of new antibiotics, which are so critical to modern medicine. Ultimately, they will have a critical impact in reducing suffering and mortality worldwide.

Check out our ribosome game here.

Venkatraman Ramakrishnan was born in India in 1952. He is the Senior Scientist and Group Leader at Structural Studies Division, MRC Laboratory of Molecular Biology, Cambridge, UK.

Thomas Steitz was born in Milwaukee in 1940. He is the Sterling Professor of Molecular Biophysics and Biochemistry and Howard Hughes Medical Institute Investigator, at Yale University.

Ada E. Yonath was born in Israel in 1939. She is Director of the Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly, at Weizmann Institute of Science, Israel.

Charles Kuen Kao will receive half the Prize for laying the foundations of the modern fiber optic industry. In 1966, he calculated how to transmit light signals over long distances using glass fibers. To that point, traditional materials had only been capable of transmitting signals over short distances (i.e. 50 feet). Kao’s discovery demonstrated how to send signals over many miles. Four years later, the first ultrapure glass fiber was built, increasing signal transmission by an order of magnitude of several thousand. Today, optic fibers are everywhere, and fuel Internet technologies that allow us to receive video, images, and sounds in microseconds. His discovery has had a profound impact on how creating the digital age.

Smith and Boyle's invention laid the foundation for the digital age

The second part of the award will be shared between William Sterling Boyle and George Elwood Smith for inventing CCD technology, most widely used to transform light into electric signals. CCDs are the apparatus that drive digital cameras by creating digital images from light signals. They were pioneering by Boyle and Smith in 1969 while at AT&T Bell Labs.

The award is also a nod toward the Nobel Prize’s best-known recipient, Albert Einstein, who won in 1921 for theoretical work on the photoelectric effect.

Charles Kao was Director of Engineering at Standard Telecommunication Laboratories, UK until 1996. He is a British and US citizen.

William Boyle was Executive Director of Communication Sciences Division, Bell Laboratories until 1979. He is a Canadian and US citizen.

George Smith was Head of VSLI Device Department, Bell Laboratories until 1986. He is a US citizen.

In a recent review of autism research, Brent Bill and Daniel Geschwind (Current Opinion in Genetics & Development Volume 19, Issue 3, June 2009, Pages 271-278) survey the latest advances in tackling autism spectrum disorders. As is explained in the review, pinning down traits and genes is extremely difficult for mental illnesses which involve aspects of cognition that are still only just beginning to be understood.

When it comes to eye color, even a 5 year old can tell you that someone has green, blue, or brown eyes. If we wanted to be a bit fancier, we could imagine that with a chart and camera, we could put eye colors into dozens of systematic categories. But measuring and evaluating the cognitive defects that characterize autism (impaired social behavior, language deficits, repetitive behavior, ect.) is far more challenging.

That is not to say that defining where along the autistic spectrum an individual is an impossible task, but that it is as yet still somewhat imprecise. After all, can you imagine characterizing other complex cognitive traits, humor for example? How funny is a particular comedian? Maybe there is funny or unfunny, but what is the difference between Jerry Sienfeld funny and Victor Borge funny?

Difficulty in characterizing the traits of autism also hampers the high throughput techniques that have made finding genes for other simpler illnesses much more effective. As mentioned in the paper, increases in orders of magnitudes of subjects in some studies have not yielded the desired results, and further increases in subjects will be needed. This is not to mention the further confounding fact that traits which appear similar on the surface may have vastly different genetic causes. After all, if you were looking at humor, and only counted something as funny based upon someone laughing, would that really tell you a lot the difference between Three Stooges funny and Woody Allen funny?

Despite these challenges, there has been progress in identifying some areas of the genome that may have a significant role in autism

Carol Greider isolated the Telomeric Gene while at Cold Spring Harbor Lab

What is a Telomere?
A telomere is a region (or cap) of repetitive DNA at the end of every chromosome that basically protects the chromosome from deconstructing. Telomeres are an important element of the cell cycle – after every round of cell division, telomeres get shorter to the point where they no longer exist (and the cell is then destroyed).

What is Telomerase?
Telomerase is an enzyme that works against this type of shortening – it replenishes the chromosome by adding DNA sequence repeats to telomeres regions. It is particularly important during prenatal development, where it buffers against cell-instability and aging. When we mature, telomerase “switches off” in virtually all tissues, ensuring the cell will only complete a certain number of divisions (e.g. 20-70) before dying. The switching off of telomerase is important process in cancer biology – unrestrained dividing (i.e. cell immortality) is a classic hallmark of the cancer cell.

How was the discovery made?

With Joseph Gall, Elizabeth Blackburn pioneered the discovery of telomeres

With a lot of hard work! In 1978, Blackburn and Joseph Gall, then at Yale University, published a landmark paper, identifying telomeres paper as a repetitive chain of six-nucleotide sequences that comprised the chromosomes’ end. In a number of studies in the 1980s Blackburn and Szostak confirmed that these repeats stabilize chromosomes inside of cells and also predicted the existence of the telomerase enzyme.

Blackburn moved to the University of California and recruited Carol Greider as a graduate student. In what the Lasker Foundation described as a “tour de force of biochemistry”, Greider purified the telomerase protein and demonstrated its enzymatic activity. Greider moved to Cold Spring Harbor Laboratory, where she achieved the ultimate milestone of isolating the RNA gene that encodes for the telomeric template.

The award recognizes importance of telomeres and telomerase to understanding the fundamental properties of the cell and cell-division. Telomeres and telomerase are important components of aging and cancer research.

Blackburn, Greider, Szostak, and Gall are currently based in the University of California, San Francisco , Johns Hopkins University School of Medicine, Harvard Medical School, and the Carnegie Institution respectively.

Physiology and Medicine…

The main contenders: Elizabeth Blackburn, Carol Greider, and (possibly) Jack Szostak
The discovery: Telomeres and telomerase
The verdict: Strong favorites

Carol Greider

Blackburn, Greider, and Szostak are well-known in biology circles for discovering telomeres and telomerase. A telomere is a region (or cap) of repetitive DNA at the end of every chromosome that basically protects the chromosome from deconstructing. Telomeres are an important element of the cell cycle – after every round of cell division, telomeres get shorter to the point where they no longer exist (and the cell is then destroyed).

Telomerase is an enzyme that works against this type of shortening – it replenishes the chromosome by adding DNA sequence repeats to telomeres regions. It is particularly important during prenatal development, where it buffers against cell-instability and aging. When we mature, telomerase “switches off” in virtually all tissues, ensuring the cell will only complete a certain number of divisions (e.g. 20-70) before dying. The switching off of telomerase is important process in cancer biology – unrestrained dividing (i.e. cell immortality) is a classic hallmark of the cancer cell.

In 2006, Blackburn, Greider, and Jack Szostak shared a Lasker award for “the prediction and discovery of telomerase”. The Laskers are the US equivalent of the Nobels, and frequently anticipate future Nobel Prize winners. As such, they have to be considered serious contenders for the gold medal.

In 1978, Blackburn and Joseph Gall, then at Yale University, published a landmark paper, identifying telomeres paper as a repetitive chain of six-nucleotide sequences that comprised the chromosomes’ end. In a number of studies in the 1980s Blackburn and Szostak confirmed that these repeats stabilize chromosomes inside of cells and also predicted the existence of the telomerase enzyme.

Blackburn moved to the University of California and recruited Carol Greider as a graduate student. In what the Lasker Foundation described as a “tour de force of biochemistry”, Greider purified the telomerase protein and demonstrated its enzymatic activity. Greider moved to Cold Spring Harbor Laboratory, where she achieved the ultimate milestone of isolating the RNA gene that encodes for the telomeric template.

Nobel Prizes can only be shared by a maximum of three people. If the award is given for the discovery of telomeres and telomerase, then Blackburn and Greider are the strongest candidates. If there is to be a third recipient, then Joseph Gall (Carnegie Institution and Johns Hopkins), who pioneered the original work with Elizabeth Blackburn, might be also be considered a contender. He did not share their Lasker award in 2006, but did win the Special Achievement Award that same year.

Blackburn, Greider, Szostak, and Gall are currently based in the University of California, San Francisco , Johns Hopkins University School of Medicine, Harvard Medical School, and the Carnegie Institution respectively.

The contenders: John Gurdon & Shinya Yamanaka
Their discovery: Nuclear reprogramming (stem cell research)
The verdict: Too soon?

Gurdon and Yamanaka are well-known for their work on stem cells

Gurdon and Yamanaka shared the 2009 Lasker Award for Basic Medical Research for pioneering the process (nuclear reprogramming) for turning adult cells into stem cells. Gurdon rose to prominence in the 1950s observing that nuclei from adult cells, when transferred into eggs, assumed embryonic features. This discovery demonstrated that adult cells retain all their genes and can be re-programmed. In 2006, Shinya Yamanaka achieved this feat, creating pluripotent (undifferentiated) stem cells from adult fibroblasts (connective tissue cells) in mice. In 2007, his team created pluripotent stem cells from human adult fibroblasts. Nuclear reprogramming techniques have significant potential as cancer treatments and many other therapeutic fields.
With the Nobel Prizes, there is typically a significant time lag between the discovery and the award. Yamanaka is odds-on to get an award at some stage but 2009 is probably too soon.

The contenders: James Rothman & Randy Schekman
Their discovery: The mechanisms behind vesicle transport
The verdict: Good contenders

Rothman and Schekman pioneered research into vesicle transport

Again, an uncontroversial choice of two former Lasker Award winners. Rothman and Schekman won the Basic Medical Research Lasker Award in 2002 for discovering the machinery that drive vesicles, the tiny sacs that transport signaling molecules within cells. This process is critical to virtually every physiological function.

Rothman is based in Yale University. Schekman is a biologist at the University of California, Berkeley.

Physics…
Thomson Reuters recently published a list of leading contenders, based on primarily on citations. They include:
Akir Aharonov, Chapman University
Michael Berry, University of Bristol
Juan Ignacio Cirac, Max Planck Institute for Quantum Optics
Peter Zoller, University of Innsbruck
John Pendry, Imperial College of Science and Technology
Sheldon Schultz, University of California San Diego
David R. Smith, Duke University

Check back for our Physics update next week.

Chemistry…

Again, I will defer for now to Thomson Reuters. Potential winners include:

Michael Gratzel, Swiss Federal Institute of Technology
Jacqueline Barton, California Institute of Technology
Bernd Giese, University of Basel
Gary Schuster, Georgia Institute of Technology
Benjamin List, Max Planck Institute for Coal Research

Watch this space!