Babies. Some picture a cute little thing with fat little toes and fingers, an innocent smile and huge eyes. Others picture a tiny little devil that cries at the most inconvenient of places. Such as during flights. And then there are those that picture babies as perfect hosts; large objects with loads of resources with weak defence systems.

Pathogens. I am talking about pathogens.

All microbes (although I can speak of conviction with viruses, since I know these the best) love a good baby. It’s immune system is not just underdeveloped, but it is naive, meaning it does not have the immunity that develops from repeated infections. Additionally, the final nail on the coffin is that the immune system is, in fact, Th2 biased.

The adaptive immune system is comprised of two major players: T cells and B cells. B cells are responsible for producing antibodies, which help in long term protection against pathogens. T cells are more complicated, and have many different roles, which have separated into classes termed: Th1 (for T helper 1), Th2, Th9, Th17 etc. Of these, Th1 and Th2 type responses were the first ones identified. Th1 immune responses are formed to actively kill the microbe or infected cell, and result in inflammation and our feelings of fever. Th2 responses however, target pathogens that are not present inside the cell, but outside in our blood— like parasites. In some cases, Th1 and Th2 responses can be thought of as opposites: Th2 responses are required to reduce the damage created by Th1 responses; while Th1 responses are required to actively destroy pathogens that the Th2 response simply keeps at bay. An overwhelming Th1 response results in large amounts of cell death and inflammation: think what happens when a severe infection like avian flu kicks in; while an overwhelming Th2 immune response results in asthma. Thus, a balanced Th1:Th2 response is ideal.

I previously mentioned that babies have immune systems that are Th2 biased. Despite the risk of susceptibility to infection, or the risk of asthma, there is a reason for this. Fetuses formed in the mother are constantly exposed to “foreign” proteins: that of the mother. Th1 responses such as inflammation would be bad for the fetus at this stage: indeed mothers with a history of spontaneous abortions have higher Th1 cytokines (immune effector proteins) in their bloodstream than mothers without a history of abortions. Additionally, once the baby is born, nearly all cellular processes, including the development of organ occur rapidly in the infant. An inflammatory response at this stage could damage these fledging organs, and potentially destroy certain cells that are crucial for development. There is also some evidence that an excess of certain innate protein activator (TLR2 agonist) can cause brain damage in baby mice.

Given this, evolution has selected for Th2 responses in young babies, and this is enforced through many stages of the immune response: both innate and adaptive. This period is short lived though: the baby immune system develops rapidly and by 6months to a year of age, the immune system is capable of almost mounting a balanced Th1-Th2 response.

Which brings us to Respiratory Syncytial Virus. Children who are most at risk are those born ore-term, and peak of infection (ie the age at which most kids are infected) is 5-6 months of age. This means RSV swoops in, enjoys the Th2 bias (or possible enhances it), replicates and gets out. And the baby having asthma is collateral damage. Not personal at all.

All is not lost however. Research has shown that a babies immune system is capable of mounting a Th1 immune response. It just requires a strong kick up the rear— something certain adjuvants (substances used to enhance the activity of proteins) are capable of doing. However not many of these Th1 inducing adjuvants are licenced yet, hampering our ability to create vaccines against viruses such as RSV that thrive on, or indeed encourage this inbuilt Th2 bias.

The battle between pathogen and the immune system is probably the longest ongoing war on earth. Organisms a small as bacteria to ones as large as blue whales have viruses that infect and cause great harm. Until recently, the microbes had the upper hand. With the advent of vaccines, hygiene, antibiotics and nutrition, we thought we had managed to get a little ahead of the microbes. And then something like RSV comes along— no treatment, no vaccine, silent, deadly and affecting babes in the cradle— to remind us that our battle against pathogens is far from over.

If I were a virus, I think I’d like to be Respiratory Syncytial Virus (RSV).

What is that, you ask? Exactly my point.

Our lungs are the only organ in our body that is exposed to the filth of our environment. Because of this, our lungs have to fight off bacteria, viruses and pollutants, and yet try to function normally to help us breathe. 

Asked to name a respiratory virus, our mind immediately jumps to influenza, the big daddy of viruses that affect our lung. Yet, there is a virus that infects more infants throughout the world (in developed and developing countries), that nearly all of us have been infected by at least once by the age of 1 year,  that we have no vaccine or treatment for, that our body is unable to develop long lasting immunity to, and that kills more elderly individuals than influenza. That virus is RSV, and yet, is but a blimp in our collective consciousness.

I will admit, I am partial to this virus. I work with it for my PhD. My aim is to study how infections with RSV early on can cause asthma.

Oh right. I forgot to tell you. If you are hospitalised with RSV infection as a kid, you have a higher likelihood of getting asthma as you get older. Influenza on the other hand? Can’t cause asthma.

See why I said I’d like to be RSV if I were a virus? Infectious, and yet staying under the radar.

There are a number of ways by which we think early life infection can cause asthma, and I might go into those in a later blog post. But one of the coolest suggestive mechanisms, was published by Nandini Krishnamoorthy, at the University of Pittsburgh and her colleagues in Nature Medicine in September, 2012.

 They started with the knowledge that in mice, any allergen, if given with TGFbeta (an important cytokine) to a baby mouse through its mother’s milk, then the baby mice develop tolerance to the allergen: by this, I mean that these baby mice will not have an asthmatic reaction to the same allergen as they get older. However, baby mice that received milk without the allergen would develop asthma if they saw the allergen later in life. This process is mediated by a subset of lymphocytes called T regulatory cells (Treg), which are important for tolerance and preventing autoimmune diseases.

Given this, Krishnamoorthy et al exposed new mouse moms to an allergen called OVA derived from eggs, so that these allergens are passed onto their pups through breast milk. These pups, when they were older, did have any asthmatic symptoms when exposed to OVA. However, the same pups, when infected with RSV virus and then exposed to OVA, developed severe asthmatic symptoms. Somehow, virus infection of these mice was breaking tolerance to the allergen, and causing disease.

How does the virus do this? Turns out, infection with the virus changes the nature of the cells in the lymph nodes of these tolerised pups, so that the Treg cells present are now Th2 expressing-Treg cells, rather than normal Treg cells. Th2 type immune responses have been shown to be crucial in mouse and humans for the development of asthma, and RSV’s ability to push Tregs down the Th2 path causes these cells to break their normal roles, and push towards asthma in mice.

What does RSV get out of this push towards an asthmatic-Th2 immune response? Both mouse and human babies (and probably babies of other species) have an immune response that starts off as Th2 biased. The reason this happens is because the alternative, a Th1 inflammatory response, while great for fighting off viruses as adults, also causes damage to normal cells and this would be bad for a still developing young baby. RSV has learnt to exploit this chink in our immune armour, and predominantly infects young children when their immune systems are still developing and are Th2 biased. This way, the virus can infect and replicate, before the Th1 immune response of our bodies evolve and stop the virus in its tracks. Additionally, there is some evidence that RSV actively induces a Th2 response, in order to carry along its merry way. Therefore, the virus doesn’t try to actively cause asthma— rather, it is the nature of our immune system, along with the viruses’s innate desire to live and replicate, that drives our immune system to develop asthma.

Not all kids who are infected however, get asthma. Why this happens, is a whole other mystery. Welcome to science.

Reference:

Krishnamoorthy et al. Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma. Nat Med. 2012 Oct;18(10):1525-30. doi: 10.1038/nm.2896. Epub 2012 Sep 9.

Bats are the stealth bombers of the animal kingdom. Equipped with radar-like echolocation, the dark form of the bat allows this creature to stay in the shadows before launching into attack on its unsuspecting prey. Scientists are now increasingly interested in bats for the biological payloads they carry: these include highly pathogenic viruses such as Ebola, rabies, and SARS.

After rodents, bats are the second most numerous mammal species on earth. The increasing interaction between bats and humans might be due to mankind’s need for more land, bringing him closer and closer to the jungle. What allows bats to harbor viruses highly lethal to humans, with no overt signs of illnesses is an important question in public health. Surprisingly, the answer may lie with one of the most characteristic features of the bat: its ability to fly.

There are two major families of bats: the old world fruit bats and the echo-locating (predominantly-) insectivorous bats. In a paper published in Science on January 25^th, Guojie Zhang and colleagues at the Beijing Genomics Institute, University of Copenhagen and Australian Animal Health Laboratory, describe a study where they compared the genomes of two wild bats: an Australian fruit bat (Black flying fox) and a Chinese insectivorous bat (David’s Myotis), with the genomes of a number of other mammals, including humans and rhesus macaques. Comparing genomes helps researchers identify how certain genes differ in bats and other mammals. These differences can help identify genes responsible for the evolution of certain features, for instance, flight in bats. Researchers now know that bat flight requires a lot of energy, which led to the selective evolution of genes involved in metabolism. This however raises another problem. Increased metabolism releases free radicals, which can cause DNA damage. To cope with this DNA damage, Zhang’s group found that bat genomes had selectively evolved a number of DNA repair genes.

DNA repair plays an important role in the immune system’s ability to fight pathogens. While looking for genes involved in the bat’s immune system, the researchers found one gene involved in both DNA repair and the immune system.

This discovery led the researchers to hypothesize that the consequence of bat’s evolution of flight may have led to changes in bat immunity.

More interestingly, Zhang and his colleagues identified major differences in genes of Natural Killer cells between bats and the other mammals. Natural Killer (NK) cells play hugely important roles in our immune system’s fight against viruses such as Ebola, SARS and HIV. Both bat genomes in this study lack the same NK cell genes that the other mammals had. This could mean that bat NK cells react to viruses differently. This is important, because most disease we see in humans after viral infections is due to our immune system’s battle against the microbes. Comparing how bat and our NK cells react to viruses could help us understand why bats don’t get sick from these highly dangerous viruses, but we do.

While Zhang’s work is thought provoking, there is still much left to be understood. Is there a causal relationship between bat flight and immunity, or are the links found just correlation? Rather, the differences in NK cells that these researchers found might be more interesting. Studying these differences between bats and humans could provide us with new drug targets that reduce the effects of an overzealous immune response. Tantalizingly, bats enjoy a longer life span than animals of similar size, and this may be due to their unique immunity. Only time will tell if the bat immune system holds the secret to our fountain of youth.

References:

1.         Zhang, G. et al. Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity. Science 339, 456–460 (2013).

So is this anti-vaccine drivel targeted towards the vaccines themselves? Or distrust to the companies that make these vaccines? 

There’s a saying allegedly attributed to Stalin that “the death of one man is a tragedy, the death of a million is a statistic”.

Nearly all of the anti-vaccine arguments I’ve seen online include parents talking about the one kid of theirs that they know suffered because of their vaccination. Definitely a tragedy. But what about the millions that did not suffer from the vaccination? That were then protected against infection?

I wonder what would have happened if these anti-vaccinationists were as vocal during the small pox mass vaccination era. We might still be afraid of getting small pox now. And that is a disease far far more scarier than diptheria or measles.

Furthermore, how do you convince someone that vaccines are safe, when there seems to be a general mistrust towards the manufacturers- ie big pharma themselves? Ben Goldacre’s book, Bad Pharma is a brilliant read on how drug companies have hidden or manipulated the data from a number of drug clinical trials. This book is sure to give the anti-vaccinationists fuel to their argument that vaccines are bad, and that all pro-vaccinationists are paid by pharma companies and the government.

And this is unfortunate, because the current anti-vaccine movement may be a manifestation of the outcry towards Big Pharma. How do you trust a vaccine, when the people that make it are hanged for their misrepresentation or important clinical trial data on drugs? 

The biggest sufferer in between this battle of politics, economics and society is the vaccine itself- a product formed out of scientific know-how and created by scientists for the main purpose of preventing illness. In addition to children of course, who are at most need of these vaccines because of their immunological immaturity.

Source- Vaccine Truths

The leading killer of humanity, and indeed of most species on earth has not been war or famine. Rather, the cause of death has been infectious disease. Infectious diseases have altered the nature of species, controlled the success or failure of organisms in a given environment, and indeed, been crucial to the evolution of a myriad of organisms itself. The bubonic plague, which ravaged medieval Europe and killed a majority of the populace, resulted in the selection of a certain group of people with genotypes that now happen to confer resistance to HIV.  Such pandemics are common- more recently, the Spanish flu epidemic of 1918 resulted in over 50 million deaths the world over, and the SARS and swine flu epidemics of the past 10 years are still fresh in our minds.

Despite these recent epidemics, we have been more successful in the past few centuries in reducing infectious disease deaths, as well as preventing life long disfigurations that are characteristic of certain infections. A number of factors have contributed to this success- the establishment of sewage draining systems, the discovery of antibiotics; but the most controversial of these developments has been the discovery of vaccines.

Modern vaccines are a far cry from the first vaccines we created. Indeed, the first vaccine- Edward Jenner’s small pox vaccine was the similar looking cowpox virus isolated from the pustules of a person infected with cowpox. These early vaccines, including Pasteur’s rabies vaccines and more recently, the formalin inactivated vaccine against Respiratory Syncytial Virus have had unfortunate side effects- including life long disability and death. But the success of many other vaccines- polio, small pox and measles vaccines for example, have established the importance of these early life innoculations in preventing what would otherwise have been severely debilitating diseases in children. Unfortunately, vaccines are thought to be the victims of their own success.

The rise of the anti-vaccine movement in recent years has flummoxed researchers and vaccine policy makers. Why would parents refuse to vaccinate their infants against diseases such as polio that could cause lifelong disability? Why refuse vaccines against diseases that have previously had high mortality rates in young infants? Why not receive a vaccination that could significantly reduce the development of cancer in later years? The anti-vaccine movement was encouraged by the Wakefield paper, which correlated the Measles-Mumps-Rubella vaccine with the development of autism. Wakefield’s data could never be replicated, and investigative inquiry showed obvious financial biases in Wakefield’s data, and his papers were subsequently retracted. Despite this, the anti-vaccine movement has continued unabated, and recent outbreaks of measles and whooping cough have been linked to intentionally unvaccinated children.

Key points in the history of the anti-vaccine movement.

Jenner’s cowpox innoculation to prevent small pox was not the first attempt at trying to stop this highly pathogenic virus. Since time immemorial, variolation, or injecting tiny doses of live small pox virus from an infected person to uninfected people was used to prevent severe disease by small pox. Lady Mary Wortley Montagu imported the concept of variolation to the UK in 1702, and despite some success, the treatment may have been as dangerous as the disease itself. In between then and 1796, when Jenner described his cowpox vaccine, a number of physicians had given cowpox to humans and successfully preventing small pox. Jenner’s treatment involved scraping the pus of a cowpox blister on a milkmaid and giving this to a young boy. Jenner then variolated the kid, and observed no disease. His vaccine had worked! Jenner was responsible for popularising vaccinations, introducing the scientific study of vaccinations, and indeed coming up with the term vaccine (vacca, latin for cow).

Fears of vaccination date back to Jenner’s cowpox vaccine. The Anti-Vaccine Society in the UK famously published the following caricature of  ” The Dangers of Cow Pock [sic]” drawn by the pre-eminent caricaturist of the time, James Gilray in 1802.

In the 1800s, a number of laws were passed in the UK requiring compulsory vaccinations. In 1853, a law that made vaccinations compulsory in infants less than 3 months and fines for those who did not get vaccinated resulted in wide-spread riots throughout England. This led to the formation of the Anti-Vaccine League. An 1867 law resulted in vaccinations being compulsory upto the age of 14, and the Anti-Compulsory Vaccination League was formed to oppose this “infringement of personal liberty and choice”. Extremely vocal, the league’s publications inspired other movements in Europe, resulting in dramatic decreases in vaccinations and a concurrent increase in small pox. By 1898, a new law was passed which removed penalties for not vaccinating, as well as allowed certain parents  who did not believe vaccination was effective to obtain a certificate of exemption.

The anti-vaccine movement in the US arose from the movements in the UK. William Tebb, a leading anti-vaccinationist visited New York and founded the Anti-Vaccination Society of America in 1879. Over the next few years, this movement led to the formation of a number of splinter societies that were able to repeal compulsory vaccinations in a number of US states. Thus, far from being a recent phenomenon, the anti-vaccine movement can trace its origins back to the founding of the modern vaccine itself. The increase in media coverage, as well as the freedom of opinion that the internet allows simply gives anti-vaccinationists a louder voice.

What do anti-vaccinationists fear?

The modern small pox vaccine is a far cry from the original one Jenner created. Rather than taking out the virus from pustules of people infected with cowpox, the vaccine that was used the world over was the live form of cowpox, that was used to vaccinate people. Small pox was finally eradicated in 1976. This remains, the only example where complete eradication of a virus has been achieved. Other viruses, such as polio still exist in small pockets of the world, and recent outbreaks have been linked to a lack of vaccination.

Given that the small pox vaccine was the live virus, it is inevitable that there would be some adverse reactions. While most of us would have been able to generate a strong enough immune response to the virus, those of us with immune deficiencies, or pregnant women were recommended against getting the vaccine due to its inherent side effects, which include, in those susceptible, full blown infection with cowpox.

The antigenic component of the vaccine (ie the protein or other particle derived from the virus or bacteria that tricks the immune system into responding and generating a memory immune response against the protein and thereby, the parent microbe that it was derived from) can be of various kinds: live-attenuated (live, but weakened so only replicates a little), inactivated (live, but cannot replicate), antigen alone (certain proteins from the surface of the microbe) and more recently, the DNA or RNA that encodes for certain proteins of the microbe. This list is also in order of severity of side effects to those with weakened immune responses, with live attenuated having higher risks than proteins or DNA. No new vaccine uses a live virus similar to the small pox vaccine- rather, any virus that is present is either inactivated or highly attenuated.

Like nearly all therapies, a certain level of risk is inevitable. Infact, many of our anti-viral therapies- drugs that are given after a serious infection have similar chemical structures to our DNA and RNA building blocks, and thereby prevent viral replication by incorporating into viral RNA. A certain amount is also incoporated into our own DNA or RNA, thereby increasing the risk of cancer and/or other side effects. Other drugs work by directly activating our inflammatory response. A vaccine may just be far safer.

Components of a vaccination include an adjuvant, which helps triggering a stronger immune response, and agents such as formaldehyde (for inactivating the microbe), thiomersal (a mercury derived compound that acts as a vaccine preservative). The National Vaccine Information Centre, an anti-vaccine group with a title masquerading as a source of scientifically correct information on vaccination lists these and other ingredients of vaccines, such as bovine protein albumin, egg protein, MSG in bright red circles rather than numeric terms, thereby increasing the confusion of people looking for knowledge. For instance, the amount of mercury in the annual flu vaccine is marked by a red circle many fold bigger than the circle representing influenza antigens. What this would tell the uninformed is that far more mercury is present in vaccines than the active antigen, thereby resulting in severe disease than the flu itself.

The seasonal flu kills between 3000-49000 people in the US. On the other hand, deaths from the flu vaccine were miniscule. The Vaccine Adverse Events Reporting System (VAERS) collects adverse events after vaccination as reported by vaccinees. In the 2011-2012 year, VAERS data reported an increase in febrile seizures in infants under 2 years of age after receiving a vaccination. Febrile seizures in young infants are caused by fevers, and an increased risk after influenza infection (4-9% of young infants with influenza infection have febrile seizures). VAERS also reported upto 90 cases of Guillian-Barre syndrome (GBS). Amongst the many decades of seasonal influenza vaccinations, only the 1976 vaccine was linked with increased risk of GBS. GBS arising from influenza vaccinations are rare, and probably account for 1 in every million vaccinations, which is significantly lower than the actual epidemiology of GBS (1-2:100,000).  It should be noted, that VAERS data is primarily from vaccinees themselves, which means that it could be biased much more research is needed on any of the adverse events that are noted from these data sets. The VAERS therefore could be equivalent to a wikipedia for vaccine adverse events.

The thiomersal fears arose from the fact that the preservative contains mercury-as ethyl mercury. Thiomersal is a preservative, and prevents growth of bacteria and/or mold in vaccine bottles. Most toxicity studies on mercury however were conducted with methyl mercury. Comparing ethyl and methyl mercury is as futile as comparing ethanol (which is in all of our alcoholic drinks) and methanol (which can cause blindness or death). Despite no correlation between thiomersal and side effects, the FDA has regulated that no vaccine licensed after 2001 should contain thiomersal. The use of single dose bottles (one dose per bottle) and the nasal influenza vaccine do not contain any thiomersal. Only multi dose bottles (ie many doses in one bottle, so the constant use may increase risk of microbial growth) contains small amounts of thiomersal. 

Formaldehyde is another component of some vaccines. In high concentrations, formaldehyde (or formalin, the aqueous form of formaldehyde) is used to preserve body tissues. At lower concentrations, formaldehyde is used to fix cells- notable in laboratories for further experimental assays. Formaldehyde acts by crosslinking proteins, thereby preventing the virus from actively releasing its genomic contents and replicating. Formaldehyde is present in the seasonal influenza vaccine, in order to inactivate the virus and ensure it does not replicate in vaccinated people, while inducing a protective immune response. While formaldehyde is a known carcinogen, it has been shown to be essential in the synthesis of purines and pyrimidines, which form the backbone of our genomes. The level of formaldehyde in our bodies has been estimated to be 2.5 micrograms/ml of blood, which means even in the smallest of infants, the total amount of formaldehyde is more than that present in vaccine formulations (which at most, is 0.1mg) 

At times, the level of misinformation is astronomical. Most information on vaccines and vaccine safety comes from the primary care physicians, and the case for vaccines isn’t helped if the physician is Dr Robert Sears, America’s best known pediatrician. Rather than saying vaccines are bad, Sears claims that the vaccination schedule in infants, as proposed by the American Academy of Pediatricians and the CDC is wrong and crowds the infant with a host of vaccines. Sears proposes an alternate schedule, that relies on infants being vaccinated multiple times over their first 5 years of birth, rather than being vaccinated early on, which is when a majority of infections occur due to the immaturity of the immune response. Sears goes further in his best selling book, “The Vaccine book: Making the Right Decision for your Child”, and states that parents should hide their infants in the herd; ie rather than vaccinate their children and risk vaccine-related diseases, parents should hide in the herd of vaccinated infants, so that the unvaccinated kids don’t contract any disease. This is flawed on many levels: While there is truth to herd immunity, delaying vaccinations (as he proposes) as well as informing people of the hiding tactic prevents parents from discussing or understanding the risks it entails for kids. If many of the herd are unvaccinated, but continue to act like they are, the levels of vaccine preventable illnesses will certainly rise since herd immunity has not significantly thinned. Sears also comes off as condescending; he claims he alone has understood the true nature of vaccinations, that the vast legions of medical students and doctors don’t understand the risks of early life vaccinations. It doesn’t help that Dr Sears is an engaging personality, and appearing on the Oprah show can definitely boost one’s perception in the public’s eyes, even if the thoughts are scientifically wrong and potentially dangerous.

Another issue that arises out of the anti-vaccinationists camp is that “Natural infection is better than vaccination”. A few chickenpox parties have been hosted through facebook, where uninfected kids are allowed to interact with infected kids so that natural immunity may occur. Chicken pox is mild enough for kids, so the infection is cleared. However, chicken pox can cause severe infections in pregnant mothers and is highly dangerous for the developing fetus. Additionally, the body never really clears the chicken pox virus- Shingles, the adult form of chicken pox arises when the virus reactivates, following treatments for cancer or immunosuppression, or simply when the immune response starts to weaken as people age. Additionally, chicken pox in adults is more dangerous than an infection in children, and can lead to severe complications such as pneumonia, hepatitis and secondary bacterial infections.

Conclusions:

It is a sad state of affairs that people trust celebrities such as Jenna McCarthy, Rob Schneider and Jim Carrey on the dangers of vaccines rather than the huge amount of scientific evidence that exists on vaccine safety. The anti-vaccine movement is not restricted to the US alone- although polio has been eradicated in the US, it still exists in a number of countries because of vaccine fears of a different kind- that the vaccine is secretly a sterility measure. There are other dangerously hilarious myths about vaccines- for instance that HIV arose out of the monkey cells used for to create the polio vaccine for instance.

It is unfortunate that these anti-vaccinationist movements have stronger media strategies than that of the pro-vaccine movement. Jenna McCarthy and Dr Sears have been on Oprah, and the NVIC recently put up public billboards extolling the dangers of vaccination. I’m not saying that there should be a war- that pro-vaccinationists should take to the streets and rally. Rather, ensuring that the right information reaches the ears of the people directly would be a good place to start. Government regulations that ensure compulsory vaccinations could be another step- some US states have made vaccination exemptions harder but there is still a long way to go. Perhaps there is a need for public debate on the importance of vaccines; for vaccine scientists and doctors to discuss the benefits of vaccine directly to the people rather than be condescending in their approach. In the 1800s, after small pox vaccination levels dropped in certain parts of Europe, a new wave of small pox rose that resulted in a dramatic increase in the number of vaccinations. Vaccinations then stayed high until small pox was eradicated over the 20th century. It is possible that there are people who have never seen polio or measles, and thus do not know of its life-altering disability or severity. Similarly, influenza is currently seen as a mild infection that leaves you in bed for a week at the most. Most people hardly know of how severe influenza epidemics can be- claiming that the 2009 outbreak was an “epidemic” may have been overkill by head honchos at WHO, but their fears arose from the greatest epidemic in recent times- and one that most people hardly know about. 

The Spanish flu of 1918. In the midst of the first world war, an influenza epidemic took hold of the world and killed over 50 million people the world over- more than the number of people that had been killed in all the wars of the past century. Populations were ravaged, entire communities decimated, and entire cities becoming ghost towns. Imagine what these people would have given for a vaccine against that pathogen.

The above example was not given to scare people into getting any vaccines- rather, the sole purpose was to show that infections that we may laugh at, that we believe are mild inconveniences are only so because their worst has past back in our evolution. 

The current anti-vaccination movement is dangerous if it continues unabated. Already, there is an increase in vaccine-preventable disease outbreaks in a number of countries across the world. In a way, perhaps these small outbreaks may goad policy makers to ensure mandatory vaccinations for all, but at what cost?

Or maybe it is time for war. To ensure that the anti-vaccinationist movement is stopped. We need billboards. We need celebrities. Maybe we should get Justin Bieber to convince the world that vaccines are necessary- that the benefits far outweigh the risks.

References:

Wolfe RM and Sharp LK. BMJ, 2002. For the history of the anti-vaccine movement.

Offit PA and Jew RK. Pediatrics, 2003. A summary of the components of vaccines and their uses.

Offit PA and Moser CA. Pediatrics, 2009. An article countering Dr Sears alternative vaccine schedule.

And this is a previously written one as well.

In many ways, smoking your first joint is an integral part of growing up. Whether peer pressure sucked you in, or you just wanted to try something new, marijuana use is skyrocketing among the youth, with 4% of students in grade 10 and 6.6% of students in grade 12 using marijuana daily in 2011.  Marijuana, venerated in movies and by rappers, is the world’s highest consumed illicit drug, due to the preconception that the drug itself is harmless. Indeed, anecdotal tales abound amongst us all about the friend of a friend who was stoned throughout his classes and still got A grades. Recently a report in the Proceedings of National Academy of Sciences (PNAS) on persistent marijuana and IQ decline cause a large number of science journalists to jump on the article, politicians to look down their glasses, wag a finger and say “I told you so” and potheads the world over to go “Duuuuuuuude”.

The study in question arises from New Zealand, and describes data obtained from participants of the Dunedin study, which followed 1037 individuals from their birth (in 1972/73) until they turned 38 (2011/2012). To study the effect of marijuana use on their mental processing abilities, these individuals were given an IQ test at the age of 13- hopefully before they had the chance to smoke up – and then regularly for nearly 20 years at the ages of 18, 21, 26, 32, and 38.  At every test, persistence in use was measured, until the final test at the age of 38. What the authors saw was that persistent use by adolescents, ie having been found to have used marijuana in 3 or more of the ages where IQ tests was administered, resulted in the highest IQ drop of up to 6 points compared to those who have never done the drug (who actually increased in IQ by 0.8 points). Similar IQ drops were seen in other users as well, although not to the same levels as persistent users. In those adolescents who had managed to get over their dependence, their IQ levels never recovered to pre-marijuana levels; a similar decrease was not seen in users who only started using marijuana after they became adults (age 18+). The reason this study received so much attention was due to the large number of youth studied, as well as strict ways to ensure no confounding variables- such as other drugs/alcohol dependence, as well as controlling for years of schooling. While it can be argued that IQ is not an ideal measure of one’s intelligence-indeed factors such as wealth, height and proper food are correlated with higher IQs- the authors mention that persistent adolescent users also have decreased attention and memory in daily life settings.

So what does this all mean? Is the use of marijuana bad? Was that first joint we smoked in high school to impress a girl affecting our chances at getting into grad school now?  As with all science, data involving such human subjects pose a real problem in coming up with a definite conclusion. A number of questions can be asked- was the wealth of the participants controlled in the study? Wealthy adolescents can buy more weed, but wealth also correlates with a higher IQ. Where does that leave us? Were other extraneous conditions- such as family life and/or depression controlled?  The data from the adult groups only has about 50 participants in all compared to the initial 1037 participants, suggesting marijuana persistence might be more rare than expected.

One thing is certain. The brain of the adolescent already has a lot of things to take care of- puberty or navigating high school for instance. While biologically, it is possible that marijuana or other drug use could cause changes, much more research in this field is needed before jumping to any conclusions. Not that such trivial details would stop our politicians.

References:

1)   Johnston LD, O’Malley PM, Bachman JG, & Schulenberg JE. (2012). Monitoring the Future national survey results on drug use, 1975-2011. Volume I: Secondary school students. Ann Arbor: Institute for Social Research, The University of Michigan, 760 pp.

2)   Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS, McDonald K, Ward A, Poulton R, & Moffitt TE (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. PNAS 2012 Aug 27.

Previously published in http://blogs.mcgill.ca/ossstudents/

Photo source: www.marijuana.com

So this one is a little old, but I want to keep all my work in one place.

This is another piece I wrote for the McGill Tribune. Also the first time I interviewed someone!

Humans are a complicated bunch. We all have different hopes and aspirations, likes and dislikes, dreams and realities. We like to think of ourselves as the most complicated and advanced species on this earth.

Given this presumed complexity, the results of the Human Genome Project—a massive effort to record every sequence of human DNA, and a precursor of the ENCODE project—showed a pitiful number of protein coding genes, which came as a surprise.

The Human Genome Project was expected to demonstrate that humans have a huge number of genes in our DNA, but as it turns out, we have only about 21,000 protein coding genes. Drosophila, the annoying little flies that hover over our overripe fruit, have 15,000. Daphnia, a water flea barely visible to our eye has 31,000. So what makes a human so complex?

The Human Genome Project was intended to uncover the blueprint of our species—the instructional manual that would tell us who we are and how we work. Disappointingly, the information discovered was incomplete; the project gave us only the index page of the human instruction manual. These 21,000 genes that set us apart account for little more than one per cent of our entire genome. The remaining 99 per cent  is often referred to as ‘junk.’ Identifying a role for this ‘junk DNA’ was the task undertaken by the ENCODE (Encyclopedia of DNA Elements) consortium.

The ENCODE consortium, formed soon after the publication of the Human Genome Project, includes 32 research groups and 440 scientists. ENCODE published their work in 30 journals earlier this month.

One of the key findings of the ENCODE project was that a large portion of our genome has a functional role—as high as 80 per cent, though some believe this number is exaggerated. According to critics, the real proportion of our genome that is functionally active is around 20 to 30 per cent.

Nevertheless, this functionally-active portion of our genomic expanse is encoded for multiple regulatory sites, thereby controlling the production of the previously identified 21,000 genes.

“Think of these regulatory sites as switches,” Daniel Tessier, vice-president of the Technology Centres at McGill University and Genome Quebec, said. “The Human Genome Project gave us a two-dimensional version of the human genome, while ENCODE gives us a three-dimensional version of our genome. We now know the regulatory hotspots that control our protein coding genes.”

The preliminary data from the ENCODE project was first published in 2007. Since then, advances in techniques and tools have enabled researchers to further delve into the vast expanses of our genome. The work involved investigating how the four nucleotides: A, C, T and G—the backbone of our DNA—form regulatory sequences that interact with other sites of our genome.

The work published this month arises from studies on multiple laboratory cell lines, “the appropriate model system,” according to Tessier, “since we can’t really go around sampling humans.” The work of the ENCODE project is far from complete, and the next steps will involve human samples.

“For instance,” Tessier said, this would involve “taking two different biopsies from a person suffering from cancer, so that we can compare and contrast changes in the regulatory regions, and how these relate to the development of disease.”

Tessier said that work such as this could lead to personalized medicine.

“In 10 years, we might all have a little chip in our health care cards that holds our personal human genome sequence,” he said. “Personalised medicine is a buzzword right now, but it is what the future holds. This work sets the foundation for the future, similar to how we are now enjoying the fruits of technology that were created a couple of decades ago.”

There is some criticism leveled at the ENCODE consortium, notably on their broad definition of ‘functional’ that resulted in the large figure of 80 per cent. Additionally, according to CNN, the ENCODE project has already recieved over $288 million in funding. Given the amount of work left to fully map out the three-dimensional structure of our genome, completing ENCODE could be costly. Despite these drawbacks, researchers argue that the data coming out of this project are fundamental to understanding the true nature of our genomes.

“The Human Genome Project was an endeavour similar to putting man on the moon,” Tessier said. “It is just as elaborate, extravagant and forward thinking.”

This month’s deluge of data on the ENCODE project is only the beginning; there are still an infinite number of questions to be asked about the vast universe that lies in each and every one of our cells. The ENCODE Project puts us on the cusp of an incredibly exciting phase in our understanding of the human species.

Photo credit: http://www.flickr.com/photos/publicenergy/

http://mcgilltribune.com/?p=15641

Here’s an article I wrote for the McGill tribune on a science policy conference held at McGill.

So I want to be a science writer. Probably just like everyone else doing a Ph.D. I could go into the usual “I’ve always liked science” and “I’ve always wanted to be a science writer, but I dislike such rhetoric. There’s a reason I want to be a science writer. I just don’t know what that reason is. 

Recently, I m finding it harder to pen thoughts into words. Something about writing is also a muscle that requires a constant workout. Drawing parallels, I bike to work. The first time was torturous. But slowly, a few months in, it started getting easier. Now I dont feel like puking when I bike up the hill that takes me to my lab. 

I’ve heard its harder to write about yourself than about something or somebody else. I guess talking about myself is a good way to get some practice writing. Lets see how that goes.

Note- this blog write up is simply a connection between brain and fingertips. No preparation. No research. Nothing.

I dont think its necessary to have been top of your class to be decent at graduate studies. Heck, I think the average of all my grades from middle school to the end of my masters has been about 75%. So what am I doing here?

Simple. Curiousity. Actually scratch that. Boredom. Or self-diagnosed ADD. I find it hard to focus on a certain thing for too long, because far too often, there’s something else out there that is far more interesting. Respiratory Syncytial Virus? Oooh cool- it infects babies, can cause asthma, mouse models… oh man that Ebola sounds pretty cool no? Infects monkeys, upto 80% mortality, bleeding from every orifice… hey, science writing sounds like fun. Maybe consulting? Life science consulting sounds like a blast- there’s traveling, money- hmm, science policy. Decisions! Power!

And that is a sampling of all the mental leaps I’ve made in the last 6 months. 

So where does science writing come into the picture?

One thing that I’ve realised about me, and took me nearly 25 years to do so, is that I m curious. I like reading about different things. I am constantly looking for that “Hooly shit that was so freaking cool”. Rather than focussing to the extremity on one subject, I have a burning desire to learn about a lot of different things. And this is where my science writing aspirations fit in. Hunting for the “ooh cool!” aspect. And describing it. Reading about many different subjects. And talking about it. 

And this, I think is the reason I want to be a science writer.

And what do I want to write about? That is still under mental processing. All I know is I want it to be different.

All of us in science have a story of why we got here. Some started off as drug addicts. The others as geeks. And some just fell in. The #iamscience and related tumblr have all their stories. Many of these stories have one thing in common. An early interest in science. Indeed, a number of people state that they “loved (certain field), love it now and always will”.

Good for you!

For instance, biology. You always loved biology. You played with animals growing up, and had a number of pets, yada yada, and now you are a zoologist. Or a paleontologist. But what about those of us that like immunology now? Or viruses? We didn’t start out playing with B cells in our backyards, infecting our pet dogs with snot we collected from ourselves to see how sick little Jimmy got. Rather, we liked the idea of science, the idea of experimenting, the idea of putting things together to see what happens. And this inherent curiosity is the not the sole prerogative of those who would one day suffer through grad school, but one that took us through childhood. When the world was our toy. Like the time we could put a magnifying glass over an ant. With the sun behind it. Or the time random shampoos and soaps we found in the bathroom that when mixed and drunk could potentially give us superpowers. Somewhere along, as we grew up, we gave up on random experimenting and slotted into more traditional pathways. The few of us that still found joy in experimenting ended up in science. Where we couldn’t do things willy-nilly, but had to follow the scientific method. And ask questions with real answers. No more could we ask if wearing a cape would make us fly (it won’t) or whether ants could swim (they cant), but we had to ask if viruses can suppress natural killer cells (sometimes) and whether quantum transitions occur in trapped antihydrogen atoms (err…what?). No more were we funded by mommy’s kisses or stuff we stole from around the house, but from taxpayers money. And boy, do we have to be responsible.

There are some amongst us though, who eschew the idea of breaking down the real world into its tiniest in order to study its phenomenons. Those amongst us who would rather study how a chinstrap penguin poops or how mallard ducks have homosexual-necrophilic tendencies. Proud recipients of the Ignobel awards. While we might scoff at their research and their conclusions, we still learn something from them. And its fun. And isn’t that what the childhood me thought being a scientist was all about?

FUN SCIENCE! (source)

Boring science. (source) 

In honour of those true intellectuals, who continue to live their childhood perception of what science is meant to be, I present 4 research conclusions that have won the coveted Ignobel awards.

1) Make important long term decisions when your bladder is full (1). However, controlling your bladder to prevent micturition (ie peeing) results in cognitive decline (2). 

Turns out there is a large body of work on visceral control. Most of these studies however involve hunger or sex, and not much work has been done on the urge to pee. Therefore the first group decided to study whether increased bladder pressure and controlling your urge to micturitate (ie pee) would represent spillover into other domains of brain function. For instance, the researchers showed that test subjects (students who were given course credit for participating) were better at foregoing the immediate award (in this case 16$ tomorrow) for the delayed award (30$ 35 days later) if they really had to pee. Given that the current generation is often thought of wanting instant gratification rather than delayed awards (like our parents supposedly did), it means that we need to start holding our pee in rather than voiding it the minute our bladder started to get full.

Or just make life decisions after drinking a lot of water.

Can’t decide? Drink a LOT of water and then come back.  

The second group, however looked at something quite different. They argued that controlling the urge to pee requires an excess of the brain’s resources, that these individuals in fact show a cognitive state equal to someone with low levels of alcohol intoxication or a person who hasn’t slept in 24 hours. Not to fear though. Voiding yourself (appropriately of course) brought back your brain to normal pre-bladder full levels, giving you back all your cognitive abilities.

2) That the stereotypical bearded scientist is in fact a bad one (3). 

The common stereotype of a scientist is of a bald, bearded old person. With glasses. And behind a pile of paper dating back to the beginning of time itself. And while these are potential areas of Ignobel research, the one that has been studied by a group in Maryland back in 1967 was that bearded men posed a significant hazard in a microbiological lab setting. 

To test this, the reseachers sprayed either Serratia marcescens or Bacillus subtilis onto the 73 day old beards of volunteers, and had two time points- 30 minutes (to mimic accidental spill and immediate washing of the beard) and 6 hours (unknown spill and leaving for home ). In an extremely detailed methods section (perhaps so we could replicate their experiments?), which included 4 different shearing methods and two different wash methods, the authors were able to obtain and grow bacteria from both time points from volunteers who did not wash their beards. They also concluded that washing a non-bearded face got rid of more bacteria than a beard that was washed. 

But this doesn’t mean that the bacteria could infect someone. Right? In order to test for contagiousness of the beard, a mannequin head was given a sterilised human hair beard sprayed with Newcastle Disease Virus (NDV), which infects birds. In an experiment  that would get PETA up in arms, the researchers took baby chickens, took them by the neck, held the chicken’s head into the beard of the mannequin and stroked the beard for 5 minutes, after which they were left in a cage to see if they got infected. They also sprayed beards with botulinum toxin and exposed the beard to guinea pigs. Some animals did get sick, meaning your bearded scientist friend could potentially kill you if you greet him by sticking your head in his beard. And holding it there for 5 minutes.

Bioterrorist.

3. Verbose literary manuscripts presented by individuals to artificially enhance the perception of intelligence by one who has undertaken to visually pursue said palimpsest results in a lack of academic advantage present to the author (4)

Or

Stop using big words for no reason.

This one is more up our alley. Admit it. You’ve used bigger words more often than necessary to impress a professor. Or maybe just used complex vocabulary to get higher marks. Or impress a girl. According to a study from Princeton, the more complex the text, the less intelligent you are perceived to be. Even though the ability to use complex words correlates with higher SAT scores and overall intelligence.This correlation was observed irrespective of the quality of the text, or the pre-perceived intelligence of the writer. I could go on about why and how, but I hear being succint is good. Makes me seem smarter.

4) Why not consider sword swallowing as a hobby? (5)

Things I learnt from this article: 1) There actually is a Sword Swallowers’ Association International . And 2) To be a sword swallower, you have to swallow a sword that is atleast 2 cm wide and 38 cm long. Swallow knives? Too bad, you don’t count. 3) There is no correlation between the length of sword you can swallow and your height. 

What are the side effects? Sore throats when you’re learning the trade. Or if you swallow swords too many times a day, or get distracted while swallowing. The occasional cut that leads to bleeding. However, the authors say sword swallowing is safer than than iatrogenic perforations, which have a mortality of about 10% (6). Ie an endoscopy. Performed by doctors.

Conclusion:

Dangerous!

The list goes on. Have a case of the hiccups? Being frightened doesn’t help? Try a digital rectal massage. Dislike New York city’s attempt at banning soft drinks? What about Coca Cola washes that can help kill sperm?! 

This year’s Ignobel awards are happening at Harvard University on September 20th. If you have an extra ticket, let me know. I’d love to go.