Nobel Prize in Medicine Explained

So the Nobel Prize in Physiology and Medicine for 2012 has been announced, but what have the deserving winners done anyway? Here’s a look at the defining achievements that have cemented their place in history.

What’s the Big Deal With Stem Cells?

Sir John Gurdon from Cambridge and Dr. Shinya Yamanaka from Kyoto University have won the prize for their work on induced pluripotent stem cells (IPS), and every biologist has greeted this news with a cheer. Every cell in our body is specialized to perform its own task; that’s why your food goes into your stomach and air into your lungs. However, every cell in our body arises from one single cell. How does this division of labor occur? At some stage of development in the womb, cells undergo a process called ‘differentiation’, which is what tells the cells what functions they will be restricted to performing. What we call ‘stem cells’ are essentially undifferentiated cells, which are enormously powerful simply because they can turn into any type of tissue we want!

Sir John B Gurdon, who first proved that differentiation could be reversed. [Image Credit:]

This differentiation was thought to be one-directional. In 1962, Sir John Gurdon showed that the reverse of the ‘differentiation’ process could be achieved. Cells from a tissue like the skin could be reversed to form ‘stem cells’ that could in turn turn into any type of tissue. He took out the nucleus of an adult frog and injected it into an egg cell of a tadpole (from which the DNA-containing nucleus had been removed). This embryo then grew into a live tadpole, showing that ‘adult DNA’ really could become ‘immature’ again.

Dr. Shinya Yamanaka converted skin cells from mice into embryos that could grow into adult mice. [Image Credit: nobelprizeorg]
Dr. Shinya Yamanaka, in 2006, concocted an actual recipe for this reverse differentiation, and produced IPS cells from the skin cells of mice in this seminal paper. He identified 4 genes that could convert these skin cells into immature yet all-powerful stem cells.

These cells have huge potential in both medicine and research. Brain cells, for example, are notoriously difficult to isolate. Thanks to their discovery, we can produce IPS cells and culture brain cells instead of having to isolate them. While the direct applications to medicine are not yet on the horizon, this technology does hold promises for the future.


Mothers Carry Pieces of their Children—In Their Brain

Did you know that long after you’re born, your mother carries little parts of you in her body? This phenomenon is called ‘microchimerism’, the presence of foreign cells in a tissue or organ. Recent research has now found cells from the foetus in the most distal part of the mother’s body, the head.

Babies’ Cells Migrate Into Mothers’ Bodies

Microchimerism arises during pregnancy when fetal cells move into the mother’s body where they may persist and multiply for a long time. This phenomenon is how the complete sequence of a foetus’s DNA can be determined simply from the mother’s blood. The effects of these cells on the mother’s health, if any, aren’t known. Some hypothesize that these ‘foreign’ cells could trigger off the mother’s immune system leading to autoimmune diseases. Others hypothesize that these cells actually help in the repair of damaged tissues in the maternal body. The kidneys, lungs, liver, lymph nodes and the hearts of mothers have been found to contain their sons’ DNA. Do they also travel to the brain?

fetal DNA in mother's brain
The origins of microchimerism. It is during pregnancy that cells from the foetus enter the mother’s body and may persist for as long as a few decades. [Image Credit: Wikimedia commons]

Looking for Y Chromosomes in Female Brains

Firstly, let’s talk about why ‘son’s’ DNA is mentioned, but not daughters’ DNA lest scientists be accused of sexism. Males contain a copy of the Y chromosome while females don’t. Merely finding a piece of this chromosome in a woman would be sufficient to determine the presence of foreign cells (most likely to be her son’s). On the other hand, to look for a daughter’s DNA, scientist would have to look for very specific differences between the mother and the daughter’s genes.

Keeping this in mind, researchers at the University of Washington in Seattle tested if a particular sequence of DNA in the Y chromosome was found in the brains of women who had sons. 63% of mothers were found to contain this segment of DNA, indicating that fetal cells do, in fact, travel all the way to the brain.

The next time your mother says you’re in her heart or on her mind, you know she means it literally. You can read about this research here.

Electronics That Dissolve in the Body

Electronics are often bought with one thing in mind—how long are they going to last? A new class of electronics might be on its way to reversing this paradigm. New on the technology block are ‘transient electronics’ that dissolve in water, and importantly, body fluids.

From Use-and-throw to Use-and-Disappear

Researchers at the University of Illinois, Tufts University and Northwestern University have pioneered biocompatible electronics that are both robust and high performance, and also capable of dissolving and thus free of the problems of waste disposal that accompany conventional electronic goods.

The applications of this class of devices could be wide-ranging and important. Starting with medical implants that perform a biological function for a specified duration of time or record biological parameters before being resorbed into the body’s system, and moving to environmental monitors that dissolve and reduce environmental impact,  these ‘transient electronics’ have great potential.

A biodegradable sensor seen to be dissolving in water. [Photo Credit: Beckman Institute, University of Illinois and Tufts University]

How Do They Dissolve?

The key to this invention is the use of ultra-thin silicon sheets which are so thin they easily dissolve. Used together with soluble conductors employing primarily magnesium and magnesium oxide, they offer the raw materials for a wide range of applications. Wireless power coils, radio transmitters and antennae, solar cells and temperature sensors are some devices that have already been constructed.

The engineers have also come up with a way to control the time after which these devices dissolve,  by wrapping them in a layer of silk. It is the structure of the silk that determines the rate of dissolution. The timescales for dissolution can range from as small as a few minutes to days, weeks, months or potentially, years, all depending on the silk packaging.

You can read about this research here.

Feature: How Evolution Can Explain Allergies

Every summer, when I return home for my vacations, I am hesitant about eating food at roadside stalls because, you know, who knows how unhygienic the food there is? In a role reversal that I still find amusingly ironic, my mother would accuse me of being wimpy and shove a plateful of food into my hands. Her logic—if we are over-protective of our immune systems, they will ‘forget’ how to respond when hit by a major infection. Blood them in battle, she said.

I’m still going to hold off from the delicious and teeming-with-microbes sugarcane juice on Indian roads, but as it turned out my mother was on the right track. A variant of her statement does apply in the case of allergies in what has been proposed as the ‘Hygiene Hypothesis’. Did you know that the incidence of autoimmune diseases (allergies being a prime example of these) is much higher in industrialized countries? Exposure to infectious agents in childhood primes your immune system for a more effective immune response as you grow up. Conversely, an extremely sanitized environment (often seen in industrialized countries) during childhood can make your immune system weak, unprepared to face infections and respond to harmless molecules that then become allergens.

Evolutionary Mismatch

How, and why does this happen? The answer lies in an ‘evolutionary mismatch’. Our bodies evolved in an environment which is very different from the one we live in now.

Let’s travel back in time for a little bit. In the first stage of human history, members of our species were hunter-gatherers. Our immune systems were constantly being exposed to a host of microbial organisms and worms. Around 12,000 years ago, we started settling down and took to agriculture. We continued being exposed to microbes, and in fact the sedentary lifestyle led us to being exposed to them for longer periods and increased human-human transmission. And then came the Industrial Revolution, bringing with it sanitation, vaccines and the beginning of the world as we know it. Many of the organisms that our ancestors encountered on a daily basis are now depleted from our present-day environment.

[Image Credit: ucla/ Nature Immunology]

‘The Old Friends’ Hypothesis’

We have grown up in the industrial age, but our immune system has evolved over centuries in the first and second stages of human history. Microbes and worms were so omnipresent that our immune systems learned to tolerate their presence in the body if they were harmless. Reacting to an infection is costly for the body, as we know from the all-pervading weakness we experience after a fever. A wiser route for the immune system was to just let the microbe exist, and simultaneously, the worms evolved to release certain molecules that would down-regulate certain components of the human inflammatory system. In the current environment, our bodies do not contain the micro-organisms that regulated our immune system. Our immune systems thus rise to inflammatory baits in a heartbeat.

It’s still a hypothesis, but there’s plenty of evidence that supports it. Guts of children with allergies have been found to have fewer numbers of a bacterial species called lactobacillus. Another study in Argentina showed that people with fewer worms called helminths have fewer incidences of multiple sclerosis (MS).

Our bodies are thus not adapted to the environments we live in, leading to this kind of a mismatch. In context of public health, it is not feasible to think of returning to the environments of our ancestors, nor is it feasible to think of infecting allergic patients with 50 hookworms that would downregulate the immune response. However, learning more about the symbiotic  mechanisms between our ‘old friends’ and our immune systems could help design more effective therapies towards autoimmune disorders.


Microbes, immunoregulation and the gut

Old Friends Hypothesis

How Parasites can trick your immune system

Could Your Genes Tell You Why You Hate Cilantro?

The next time you make a face at the cilantro (coriander in certain parts of the world) on your plate, you can blame your genes. A genetic component for the intense dislike of cilantro has been found.

Before you get outraged by the thought of studies performed on culinary preferences, responses to cilantro has been thought of as interesting for quite a while. There are polarizing reactions to it, with some people comparing its taste to soap. On the other hand, it continues to be used generously in South Asian and Latin American cuisines. This even prompted the New York Times to publish an article called ‘Cilantro Haters, It’s Not Your Fault’.

The distinct flavor of cilantro is because it contains a class of molecules called aldehydes. It was thus hypothesized that differences in proteins that can detect these molecules—called receptors—could be responsible for the strong variation in response to the herb. Now, researchers at the sequencing company 23andMe have used genome sequences of 14000 Europeans to hunt out a genetic cause.

Cilantro (also called coriander) is commonly used in many cuisines across the world. Different populations, however, often have sharply contrasting perceptions of its taste.

‘Crowdsourcing’ Data

This research was part of a larger group of projects under 23andMe, which could be called crowdsourcing. In this process, the company sequences people’s genomes and provides genetic analysis. Clients willing to participate in 23andMe’s research are then asked to fill up a questionnaire about various traits that might be genetic, for instance, whether they think cilantro has a ‘soapy’ taste (another example could be eye color). The company then uses this data for their analysis. In this experiment, they found that one varying position in the genome—called a single nucleotide polymorphism (SNP)—was found to be associated with the way people think cilantro tastes. To put it another way, people who detest cilantro were much more likely to have one version of this SNP as opposed to people who like it, who are more likely to have another version.

Having found this SNP, they realized that it lies within a cluster of 8 olfactory receptor genes, genes involved in the perception of smells. This could thus be a strong candidate gene responsible for the divisive response to cilantro.

However, this SNP only explains a very low percentage of the variance in the trait. What does this mean? Ideally, we would expect to be able to predict a person’s response to cilantro based on the SNP she has. However, that is not the case, only 1.5% of the variance in the trait can be explained. This could be because there are multiple genes that act together in determining cilantro response (and they have only managed to capture one of them), or that only a small amount of cilantro response is actually genetic. Thus, in the latter case, even a significant SNP cannot significantly affect cilantro detection. This study was only performed on a European population, studies capturing a greater diversity could yield further answers.

You can read about this research here.

Speaking Out Your Fears Helps You Face Them

If the results from a recent psychological experiment are to be believed, the saying ‘’Face Your Fears’ might just have to be changed to ‘Blurt Your Fears’. Researchers at the University California, Los Angeles, have found that saying your fears before facing them actually reduces the fear itself.

Fooling Yourself into Being Less Scared

Similar to other actions that intentionally regulate emotions, such as distraction, it has been increasingly believed that giving an emotion a label, either in verbal or in written form, can help downregulate it. This downregulation is not merely at a superficial level. Brain regions that are involved in emotional processing are actually found to be less active when an emotion is labelled as opposed to when it is not.

Speaking out your fears may help you face them. [Image credit:]

Is Labeling One’s Fear Better than Distracting Oneself or Rationalizing Away the Fear?

Scientists decided to apply this in a real-world context, by testing how different groups of people could change their fear of spiders (arachnidophobia). Participants were divided into four groups—each of which had to face a tarantula. The first group, called the ‘’affect labeling’ group, had to state their fear before they went closer to the spider. The second group, called the ‘reappraisal’ group, had to vocalize something neutral (and definitely not negative) about the spider and their emotions towards it, something that would prime them to think less negatively about how they approached the spider (for example, “Looking at the spider is not dangerous for me”). The third group was the ‘distraction’ group in which participants had to describe furniture in their room. Participants in a fourth ‘control’ group did not vocalize anything. Participants from all groups were again exposed to the spider a week following this test.

Our Bodies Show Different Responses From Our Minds

The skin conductance response test (SCR) was used as one indicator of emotional arousal while approaching the spider, so as to reduce subjectivity. It was found the the degree of this arousal (representing fear) decreased much more in participants of the ‘labeling’ group as opposed to all other groups, i.e., participants who had stated their fear of the spider showed the greatest reduction in this fear response a week later. Interestingly, none of the participants said they felt less scared when they were asked to self-report their fear, it was just that their bodies responded less…fearfully.

The authors propose that this result is similar to those achieved by being in a state of mindfulness, which is also associated with reduced activity in the regions of the brain involved in emotional response.

Thus, speaking out your fears might just be all you need to face them more easily. You can read the published article on this experiment here.

Curing the Inability to Smell in Mice

‘Anosmia’ is the inability to smell, which is more harmful than it sounds, primarily because it could lead to a tendency to eat less, often leading to starvation and weight loss in mice. Anosmia can be caused by a number of factors, one of which is ciliopathy—when there are problems with the tiny protuberances on sensory cells called cilia. Among other cells, these cilia are found on the neurons that function in odor perception, and serve as ‘antennae’.

Image Credit: University of Michigan Health System

Scientists at the University of Michigan have treated mice that had genetic defects in a protein IFT88, which causing them to have no cilia across the body. They injected a common virus into these mice carrying DNA with the normal version of this gene. As the virus inserted itself into the genomes of these mice, they started producing cilia and their feeding patterns were found to change considerably. Moreover, the mice showed a 60% increase in body weight. “By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants,” says postdoctoral fellow and first author Jeremy McIntyre, Ph.D.

This is only a starting point for ciliary disorders, primarily because a mutation in IFT88 in humans is fatal, and does not cause the same defects as in mice. Thus, though this research has some way to go before it could be extended to humans, it shows promise in treating olfactory diseases that are genetic and due to malfunctioning cilia. Moreover, cilia perform important functions in diseases that aren’t just related to smell perception. Polycystic kidney disease and a disease called retinitis pigmentosa in the eye also result from a problem with the cilia.

You can read about this research here.

Good at Maths? Your Brain Communicates Better

Have you ever wondered why you are decent at Mathematics? Well, it isn’t just because of wonderful Mrs. Gunderson who taught you in high school. It’s because certain parts of your brains have more ‘wires’, or neurons, connecting them.

Division of Labor—Recognizing Quantities and Computing Are Done by Two Different Halves

There is a region of the brain called the parietal cortex  that performs the role of numerical cognition. Additionally the left and the right halves of this cortex perform different parts of this activity. While the right parietal cortex primarily processes quantities, i.e. this half confers an intuitive sense of the magnitudes of numbers and their relationships, the left half performs numerical operations. What has remained unknown is how these two halves work together while we perform arithmetic that requires the functions of both halves.

The parietal cortex is the outer art of the parietal lobe. [Image Credit:]

Greater Neural Crosstalk Improves Arithmetic Ability

Researchers at the University of Texas and the University of Michigan used functional MRI to image the brains of 27 adults and found that the neural connectivity between the left and the right parietal cortex increased in each of these individuals when they were given mathematical problems to solve. Individual participants who were faster at performing the arithmetic tasks (subtraction in this case) were found to have greater connectivity between the two halves, whereas no such correlation was found between speed of computing and activity within each half. This implies that the speed at which we compute depends to some extent on how fast numerical quantities and operations transmit between the two halves of the cortex.

Before some of us rush to place the blame for our mathematics grades on our genes, it should be noted that the brain is remarkably plastic. The more we work on something, the better the brain becomes at it. The neural structure of our brains might be a result of extensive mathematics practice rather than inherited. This study therefore reflects the mechanism, and not the cause of arithmetic ability. Thus, you might just have to thank Mrs. Gunderson for your enhanced neuronal structure after all.

You can read about this research here.

Mother-in-Law, Daughter-in-Law Conflict Led to Evolution of Menopause

One evolutionary quandary that has plagued biologists is the existence of a menopause in women—the time after which a woman loses her ability to reproduce. Why would females of a species stop reproducing? What is the evolutionary advantage to this? Wouldn’t it be better for a woman if she could keep producing offspring and thus propagating her genes for as long as possible? In fact, menopause is relatively uncommon in animals, though it has not been widely studied.

Grandmothering Effect and Other Hypothesis

One hypothesis that has been proposed to explain this is the aging effect. As women age, they are more likely to develop mutations that they pass on to their children. Stopping their ability to reproduce could help protect the species from defective mutations. Another hypothesis is the ’Grandmother effect’. If older women use their resources to help bring up existing off-spring instead of creating new ones, the additional resources given to a child increases its fitness.

A research team has used data from a pre-industrial Finnish population to test these hypotheses. Since the 17th century, the Lutheran church has collected a register of all births, deaths and marriages in Finland. The researchers had access to three generations of 5 Finnish populations.

This age-old conflict runs deep enough for evolution to have acted upon it! [Image Credit: towntopics]

Mothers-in-Law Compete with Daughters-in-law, But Not With Their Daughters

Their most interesting result was that when a mother-in-law and a daughter-in-law had children within two years of each other, their off-springs had significantly smaller lifespan by up to 66%. This suggests that competition between in-laws have led to menopause evolving as an adaptation. On the other hand, when a mother-daughter pair had children within two years of each other, no reduction in children’s ages were seen.

A woman shares no genes with her daughter-in-law, and her grandchild only shares 1/4th of her DNA as opposed to her child (which has ½ of her DNA). Thus, there is no co-operation between the two during child-rearing leading to reduced fitness of all the off-spring. It is interesting to note the contrast when mother-daughter pairs bear children simultaneously and show no competition. The authors suggest that in-laws fought over resources for their children instead of co-operating as mothers and daughters might do.

Modeling this data, the authors of this research have proposed a combination of factors that lead to the evolution of menopause. The first is the grandmother effect, and the second is the avoidance of reproductive conflict between mothers-in-law and daughters-in-law.

You can read about this research here.

Another Reason to Hit the Sack— Humans Can Learn While Asleep

Sleep is a state of being characterized by a lack of consciousness. But are we capable to perceiving sensory stimuli while we are asleep, or we totally oblivious to the world around us? It is known that humans can strengthen previously acquired memories during sleep, but it is not known if we can actually take in new information.

If a Skunk Passes By While We Sleep, Would Our Brain Know It?

Researchers at the University of Israel decided to test the assimilation and acquisition of new non-verbal information during sleep. It is known that we respond to unpleasant smells by producing shorter sniffs, and to pleasant smells by longer, deeper sniffs. The research team used this information to create a unique test. While participants were asleep, they paired odors with musical tones, i.e., an odor-tone pairing was created with the tone being separated by the odor by at least 1 second. To ensure that these were being detected by the participants, their sniffing behavior was studied, and it was ensured that their sniffs were shorter when unpleasant odors were being presented. They also ensured that participants did not wake up in response to these odors; participants who did wake up within 30 minutes of the experiment were excluded from the analysis.

Sleeping might be less wasteful that you thought. [Image Credit: wikipedia]

Upon waking up, the same participants were presented to the tones alone, and it was found that the tones which were paired with unpleasant odors induced a shorter sniffing response in the participants. Moreover, they were unaware of the experiments that had been conducted while they were asleep. This shows that their brains could process at least two things—odor processing, and association of tones with odors while sleep. This shows that our senses are definitely at work while we sleep!

What, and How Much Can We Take In While Asleep?

These participants only learned a simple non-verbal response. More studies will have to be conducted to determine the extent to which we can learn during sleep. Head researcher Anat Ariz says, “There will be clear limits on what we can learn in sleep, but I speculate that they will be beyond what we have demonstrated.” Though it is unlikely that we can learn all our Algebra by listening to recordings while we are asleep, this research could have implications in treating addictive disorders, for example, by using conditioning that pairs addictive drugs with a negative connotation. As Arzi says, perhaps the best way to cure such disorders might be learning at a level of non-awareness.

You can read more about this research here.