Filling Cabbies’ Heads with ‘The Knowledge’

In a post here, back in January 2010, I mentioned some research that had been done on London taxi drivers, who in order to be licensed have to master the (very) complex street layout of the city, and pass a demanding test called “The Knowledge“., a process that can take several years.  The research found that taxi drivers had visible differences in the brain structure known as the hippocampus, relative to the typical person.  That study, though, did not tease out the origin of the difference; in particular, it did not show whether the taxi drivers were different because of their work, or if people with the differing brain structure were more likely to succeed as taxi drivers.

Some new research has now shed some more light on this question, according to a post on the “Wired Science” blog at Wired.   In the new study, published in the most recent issue of Current Biology [abstract], two researchers from University College London, Eleanor Maguire and Katherine Woollett, tracked a group of 79 trainee cab drivers, and 31 control subjects.  At the beginning of the study, brain images taken of the participants showed no differences in structure, in the hippocampus or elsewhere.

Three to four years later, 39 of the original trainees had successfully acquired The Knowledge, while 40 had been unsuccessful.  Studies of the trainees’ brain structures at that point showed an increase in gray matter in the posterior hippocampus for the successful trainees.  Neither the unsuccessful trainees nor the control group showed any significant change.  It also appears, according to a press release from the Wellcome Trust,  which funded the research, that acquiring the new information and skills came at a price.

On the memory tasks, both qualified and non-qualified trainees were significantly better at memory tasks involving London landmarks than the control group. However, the qualified trainees – but not the trainees who failed to qualify – were worse at the other tasks, such as recalling complex visual information, than the controls.

It is still possible that the successful trainees had some inherent advantage that led to their success, but it does appear that the observed brain changes are directly related to the process of acquiring The Knowledge.  It is also not clear at this point just how the changes take place; however, this is another piece of evidence that the adult brain is. potentially,  considerably more malleable than was once thought — and that has to be good news for all of us geezers everywhere.

More News from Inner Space

I’ve mentioned here before the ongoing research on the menagerie of micro-organisms that call us home; the National Institutes of Health is sponsoring the Human Microbiome Project, which is attempting to identify and classify these organisms (which outnumber our own cells by about 10:1), and their roles.   Many of these microbes inhabit out digestive systems, and play a beneficial role in aiding digestion and producing certain micronutrients.  Research has shown that a delicate balance is maintained between these microbes and the immune system.   Disruption of this balance can lead to some serious health problems; some research even suggests that changes to the microbiome can affect mood, via the central nervous system.

A recent article at Ars Technica reports on some new research that uncovers an additional mechanism that helps maintain the intestinal equilibrium between microbes and the immune system.

Cells in the gut sense when the bacteria get too close, and produce a peptide that kills some of them off when they do. This keeps the space around the cells of the small intestine free of bacteria, which in turn keeps the bacteria from setting off a full-blown immune response.

The primary function of the small intestine is the absorption of nutrients and minerals from food; its inside surface is covered with small, finger-like projections (called villi), which increase the effective surface area available to absorb nutrients.  This surface has no intrinsic protection from the very large number of bacteria present in the intestine; the study, which was published in Science [abstract],  attempted to discover why there is not, in general, a full-scale immune system response.

The mammalian intestine is home to ~100 trillion bacteria that perform important metabolic functions for their hosts. The proximity of vast numbers of bacteria to host intestinal tissues raises the question of how symbiotic host-bacterial relationships are maintained without eliciting potentially harmful immune responses.

Th researchers found that the innate immune system — that “generic” part of the system that recognizes common features of bacteria in general, rather than specific organisms — uses a signalling protein (called MyD88) to regulate the production of an anti-bacterial protein (called RegIIIγ) that acts to maintain a bacteria-free zone around the surface of the intestine.

Here, we show that RegIIIγ, a secreted antibacterial lectin, is essential for maintaining a ~50-micrometer zone that physically separates the microbiota from the small intestinal epithelial surface.

This image shows the separation; the blue projections on the left are the intestinal villi, and bacteria are green.  (Image by Shipra Vaishnava and Laura Hooper.)

This is still not the whole story, because the bacteria-regulating protein (RegIIIγ) is only effective against some bacteria (gram-positive organisms).  There is presumably another pathway that keeps gram-negative organisms in check, but that is yet to be elucidated.

How Bugs Fight Drugs

Although antibiotics have been an enormous boon to human health, providing successful treatments for a variety of bacterial infections that had been killers for millenia, their use creates selection pressure that leads to the evolution of antibiotic-resistant strains of bacteria.  I’ve written here before about the emergence of new strains of resistant organisms; often, these are first discovered in a clinical setting, when they make someone sick.

The Technology Review has a recent article describing a new approach to understanding the evolution of antibiotic resistance.   Developed by Professor Robert Austin and his research group at Princeton University, the method uses a specially constructed microfludics chip to provide a range of nano-scale environments for bacteria.   The chip contains more than 1,000 tiny hexagonal chambers, interconnected by tiny slits.  A nutrient solution is allowed to flow along one side of the chip, and a solution of the antibiotic ciprofloxacin along the other.  This produces a range of environments in the chip’s chambers, with gradients of nutrients and antibiotic.   This allowed the researchers to observe how the evolution of resistance took place as a function of the local environment.

One of their observations was that developing resistance did not require a great deal of time, even considering the short duration of bacterial generations.

Austin and colleagues began to see resistant strains emerge within five hours. After 10 hours, the resistant strains  were populating even the most Cipro-saturated chambers

What is perhaps more interesting is that, when the experiments were repeated, the same pattern of mutations and evolving resistance was observed.

The researchers also discovered that the evolution occurred predictably. Every time they ran the experiment, they got the same result, with the same four resistance-conferring mutations emerging over and over again.

If this result holds true, it could be of great value in drug development; potentially, drugs could be designed to block the emergence of resistance.  The same technique could also be used to study the evolution of beneficial bacteria, and Prof. Austin hopes that it may also be useful in understanding how some types of cancer cells become resistant to chemotherapy agents.

Dr. Watson Will See You Now

Today’s edition of the Washington Post has an interesting article,by Martin Ford, on the potential application of IBM’s Jeopardy!-winning Watson technology in medicine.   You will probably recall that medical diagnosis was mentioned prominently by IBM as a potential practical use of Watson’s technology. On September 12, IBM and Wellpoint, the largest medical benefits company in the US by membership, announced an agreement for the joint development of medical applications.

The article points out some of the areas in which Watson could provide real assistance to medical personnel, based on its ability to process huge amounts of information in unstructured, natural language documents.

Watson could churn through millions of case histories to learn what diagnosis is likely to be correct and what treatment would be the most effective. The system could almost instantly process medical textbooks, electronic medical records and the latest published research, illuminating obscure links among studies in seemingly unrelated specialties. Watson could someday be a standard diagnostic tool. Its ability to make sense of a universe of data would be far beyond that of any person or team of experienced physicians.

Watson’s ability to process enormous amounts of information will come in handy; it has been estimated that the overall body of medical knowledge doubles in size about every five years.  A more efficient, and less error prone, method of assimilating the flood of new information might help check the ongoing escalation of health care costs.  Combined with the growing  use of electronic medical records, the system could help spot unusual conditions, or rare but serious drug interactions.

Mr. Ford also points out that, if Watson can establish a track record as a diagnostician, it might help alleviate a projected shortage of physicians, especially in primary care. Some medical practices already use physician’s assistants to help them care for more patients; a system like Watson might make this a lot more common.

The article also touches on the threat that systems like Watson might pose to some sectors of the economy.  I’ve mentioned before the idea, suggested by the late computer science and AI pioneer, Joseph Weizenbaum, that intelligent systems might devalue routine mental labor, just as the Industrial Revolution devalued routine physical labor.  (I wrote about a proposal to use Watson in marketing not long ago.)   As with other disruptive technologies (genetic engineering comes to mind), there is, in some sense, no turning back. The knowledge of how to build Watson can’t be unlearned; the genie can’t be put back in the bottle.  To the extent that humans possess intelligence beyond that of machines, we will need to use it to make wise use of our discoveries.

[Martin Ford is the author of The Lights in the Tunnel: Automation, Accelerating Technology and the Economy of the Future; he also writes the Econfuture blog.]

Mood-Altering Bugs Inside

I’ve mentioned here before the ongoing research on the menagerie of micro-organisms that call us home; the National Institutes of Health is sponsoring the Human Microbiome Project, which is attempting to identify and classify these organisms (which outnumber our own cells by about 10:1), and their roles.   We’ve also seen that disruption of the normal microbial population of the digestive tract can cause some serious health problems.

The Science Now site has a report that some new research suggests that changes in the digestive system’s microbiome can affect how the brain works.  It has been hypothesized that neurological functions might be affected by toxins produced by bacteria, or by the effect of microbes on the immune system, but this new work seems to suggest a more direct effect.

Now, a new study suggests that gut bacteria can even mess with the mind, altering brain chemistry and changing mood and behavior.

To test for an effect, John Cryan, a neuroscientist at University College Cork in Ireland,and a group of researchers from McMaster University in Canada, fed laboratory mice a broth containing Lactobacillus rhamnosus, a benign bacterium.  The particular species was handy, but is also of potential interest because other bacteria from the genus Lactobacillus are common in probiotic preparations.  Compared to a control group of mice that received broth without the added bacteria, the treated mice showed lower levels of stress and anxiety.

Mice whose diets were supplemented with L. rhamnosus for 6 weeks exhibited fewer signs of stress and anxiety in standard lab tests, Cryan and colleagues report online today in the Proceedings of the National Academy of Sciences [abstract].

The research team found some evidence that the effect was due, at least in part, to a change in the receptors for GABA [gamma-Aminobutyric acid], an important inhibitory neurotransmitter.

In the brains of the treated mice, the researchers found changes in the activity of genes that encode portions of the receptor for the neurotransmitter GABA. GABA typically dampens neural activity, and many drugs for treating anxiety disorders target its receptors.

The researchers also found that, if the vagus nerve, a major channel for sensory data from the gut to the brain, was severed, the effect did not occur, providing further evidence that the central nervous system was being affected directly.

How all this works is still a considerable puzzle, but it is another reminder that all of our bodily systems are connected in many different ways.

The MedicalXpress site also has an article on this research.

More on Triclosan

I’ve written here before about triclosan, an antimicrobial agent used in soaps, toothpaste, deodorant, mouthwash, other cosmetic products, and household cleaning supplies.  There have been some suggestions that widespread use of triclosan  may contribute to the development of antibiotic resistant bacteria; the chemical is also suspected, based initially on data from animal experiments, of being an endocrine disruptor.  The FDA is currently reviewing the safety of triclosan; the results of the review were originally scheduled to be released in April of this  year, but have been delayed.

The New York Times recently published an article on the ongoing triclosan controversy.  As I mentioned earlier, it is present in a very wide range of products, and there is also evidence that exposure to it is growing.

It is so prevalent that a survey by the Centers for Disease Control and Prevention found the chemical present in the urine of 75 percent of Americans over the age of 5.

Triclosan does have one antibacterial application for which the FDA has given explicit approval: there is evidence that its use in toothpaste helps to prevent gingivitis.  The safety concerns are mainly focused on its broader uses, especially in anti-bacterial soaps.  These are advertised as being more effective, hygienically, than ordinary soap, but there is no real evidence that this is true.  The FDA has a fact sheet, Triclosan: What Consumers Should Know, which says:

At this time, FDA does not have evidence that triclosan added to antibacterial soaps and body washes provides extra health benefits over soap and water.

A study conducted at the University of Michigan School of Public Health also concluded that plain soap was just as effective.  Many people are, nonetheless, persuaded by the advertising; the “anti-bacterial” soaps account for about half of the $750 million market for liquid soaps in the US.  (Some of the success of the advertising may be rooted in history.  In the early 20th century, there was a theory that washing hands was effective because the combination of water and the emulsifying properties of soap somehow disrupted the cell wall of bacteria.   We now know that most of the hygienic benefit comes from the physical removal of bacteria from the skin.)

The industry claims that there is no “real” evidence that triclosan might be harmful.  Calling for more, or a different kind, of research, has become a standard tactic taken from the tobacco industry’s playbook.

Brian Sansoni, spokesman for the American Cleaning Institute, said the evidence against triclosan was hardly convincing and that the chemical had been used safely in consumer products and in hospitals for decades.  “You would think after heavy use in hospital settings over several decades it would have shown up by now,” Mr. Sansoni said.

This is one of those plausible-sounding arguments that is really fairly specious.  Triclosan has only been in general use since the early 1970s; unless the effect were enormous, which no one is claiming, it would not “show up” unless someone looked for it. The FDA, for its part, is now saying that it is unlikely to have results from its review before next year.

My own conclusion is that, since I have seen no evidence that these anti-bacterial products provide any benefit, and since there may be some risk, they are not worth using, especially since they cost more than plain old soap.  I suspect part of their appeal is due to a variety of magical thinking.  It took me a while, quite a few years ago, to develop the habit of carefully washing my hands whenever I came home, and before preparing food, for example.  Rather than doing the work required to develop the habit, many people may find it easier to buy something that has the miracle ingredient that will fix everything.