Blurred Lines on the Tree of Life

The line of classification that separates the living from the non-living is normally drawn just short of viruses.  Unlike a simple cell or bacterium, a virus cannot reproduce or metabolize on its own – but a virus does have a genome.  And so, although excluded from among the living, it is difficult to include them among the dead.  New findings have now made this line of distinction even more blurry.

In July a team of French and Swedish scientists led by Jean-Michel Claverie and Chantal Abergel announced the discovery of a new kind of virus, and they gave it the epic name of ‘Pandoravirus’.  To say that the Pandoravirus is simply a virus would be an understatement, but it can’t be considered a living cell either.  A virologist at the University of Pittsburg described the discovery of this virus as being “like finding a Sasquatch”.  Indeed, it appears to be the closest thing to a missing link between the periodic table and the tree of life.  Here is why.

Pandoravirus is a behemoth. 

While most viruses are 50 to 200 nanometers in diameter, the Pandoravirus is up to 1000 nanometers across.  This is large enough to be visible in a microscope, which is how it was first observed.  Being microscopic is normal for a microbe, but not for a virus.  The same team of scientists announced the discovery of Mimivirus (400 nanometers) in 2003, followed by Megavirus (750 nanometers) in 2010.  These two viruses were the previous record holders for girth in the virus world.  In fact, Mimivirus was mistakenly classified as a type of bacteria for 11 years.  This error highlights the significance of size with these viruses: they are larger than some bacteria, and the Pandoravirus even measures up to some eukaryotic microorganisms.

Pandoravirus has serious genetic game. 

In simplistic terms, viruses are a bundle of genes packaged inside of a shell of proteins.  So a bigger virus means more space for more genes.  Pandoravirus has up to 2,556 genes – in other words, blueprints for 2,556 different proteins and enzymes.  This level of genetic complexity is on par with some of the more simple living microorganisms that we know of.  For comparison to the average virus, the seasonal flu virus typically has 12 genes, and HIV has 9.

Pandoravirus is a freak. 

Of these 2,556 genes wrapped inside a Pandoravirus, only 7% can be found in any other virus or living organism.  The other 93% are unique genes that have never been seen anywhere before.  To understand how alien this is in genetic terms, consider that about 61% of the genes in a fruit fly also exist in humans, in some comparable form.  Being as how the Pandoravirus appears to have no kin in the world of viruses or on the tree of microbial life, this raises many interesting questions about what its origin may have been. 

Pandoraviruses are probably everywhere.

In the reported findings, those responsible for the discovery of Pandoraviruses actually reported the discovery of two viruses that were similar enough to both be considered part of a ‘Pandoravirus’ family.  This would not be inherently interesting or unusual, except that one was found in a saltwater sediment sample off the coast of Chile, and the other was found in a freshwater sample taken from a pond in Australia (where lead scientist Jean-Michel Claverie just happened to be attending a conference).  Claverie summarized the significance of this serendipity by stating, “The fact that two of them were found almost simultaneously from very distant locations either indicates we were incredibly lucky or that they are not rare. They are probably everywhere.” 

All of this is very exciting for microbiologists and virologists who can’t help but feel as if Pandora has been summoned.  These abnormally large viruses were initially discovered by accident.  But now that there has been a purposeful search for them during the past decade, more are sure to be added to the list.   “We still have more crazy things in store that we expect to be able to publish next year”, stated lead scientist Chantal Abergel.  If this is the tip of a biological iceberg, then there may be cause to consider reevaluating whether or not viruses belong in some domain of their own on the tree of life.  But more importantly, this demonstrates the need to view microbial life as a continuum, where the line between viruses and microorganisms is more blurry than we had thought before (Figure 1).  Without a doubt, it will be very interesting to see what the rest of this iceberg looks like.

Figure 1. The physical and genomic size of the Pandoravirus is compared to that of the smallest representatives found in each of the three domains of life.  The physical size of the Pandoravirus approaches Eukaryotic microorganisms, while genomic complexity exceeds that of some bacteria.

The Application of Sunscreen Advice

In spite of being a part of the high school graduating class of 1997, I occasionally forget the proverbial commencement advice of Mary Schmich, which was made popular by Baz Luhrman two years later in his song ‘Everybody’s Free (To WearSunscreen)’.  But since moving to Arizona 7 years ago, I have taken the part about sunscreen to heart:

“The long-term benefits of sunscreen have been proved by scientists, whereas the rest of my advice has no basis more reliable than my own meandering experience”. 

True indeed.  But perhaps not as simple as it used to be.  As I reached the bottom of yet another tube of SPF 30 this summer, I did some shopping around to find a replacement.  Options abound these days.  There is a whole gamut of SPF values to choose from.  How much UV-A vs. UV-B does one need?  And what about active ingredients?  Much of the marketing is lost on the average consumer.  So here is my attempt to demystify some of the science behind the labels.

UV-A and UV-B

Once upon a time in 1665 England, a 23 year old Isaac Newton proved with a prism that the colors of the rainbow are components of sunlight (and NOT artifacts of the prism).  What we have learned since then is that light exists as a wave (while also being a particle, but we won’t get into that for now), and depending on how big the wave of light is (wavelengths), we get different colors.  And there are wavelengths of light that go way beyond and before the small rainbow of ‘colors’ that we can see.  This is where UV light fits in – it is how we classify a range of invisible wavelengths of light that come just before the wavelengths for ‘violet’.  First UV-A, then UV-B.  If this sounds confusing, then hopefully Figure 1 will be worth another 1000 words of explaining.  Anyway, there is a tradeoff between UV-A and UV-B in terms of sun protection: UV-B is more damaging, but UV-A is about 20 times more abundant.  This is because our friend the ozone layer filters out most of the UV-B (and thankfully all of the UV-C, so we don’t need to discuss that as long as we stay on good terms with the ozone layer).  And so in a nutshell: since both UV-A and UV-B can cause skin damage and cancer in their own ways, a good sunscreen should protect against both (i.e., ‘broad-spectrum’).

Figure 1. A part of the wavelength spectrum of light. UV-A is designated as the range between 315-400 nm, and UV-B is 280-315 nm.  Visible wavelengths manifested as colors are between about 400-700 nm.

Active Ingredients

There are basically two types of sunscreen: those with organic active ingredients, and those with mineral (or inorganic) active ingredients.  Sometimes the former is referred to as ‘sunscreen’ while the latter is dubbed ‘sunblock’.

Unlike when applied to foods, the term ‘organic’ in the context of sunscreen simply means that it is carbon based.  The active ingredients in this class of sunscreen will contain molecules with seemingly abstract names like octocrylene, octyl methoxycinnamate, octyl salicylate, and oxybenzone to name a few.  Octocrylene tends to be the most common, and it is represented here in Figure 2.  The others are similar.  See all the carbon atoms?  The ones with double bonds are important here.  These act like a net to filter or ‘screen’ out UV sunlight by absorbing it.

Figure 2.  The octocrylene molecule, also known as 2-ethylhexyl 2-cyano-3,3-diphenyl-2-propenoate.  Hydrogen atoms are not shown.  UV is absorbed by double bonds between carbons, particularly in the rings.

Mineral sunblocks work in a more intuitive fashion.  These are creams that contain microscopic metallic particles that are either titanium dioxide (TiO₂) or zinc oxide (ZnO).   In principle, the metallic particles in sunblock creams work together to reflect, or ‘block’, UV sunlight the same way as those large reflective car sunshades do.  Because they reflect the light, titanium and ‘zinc creams’  appear white rather than clear when applied.  But this is changing.  The metallic particles are getting smaller  – small enough to be considered sub-microscopic nanoparticles (less than 100 nanometers in diameter).  Nanoparticles are so small that they tend to absorb light like the molecules in organic sunscreens do, rather than reflecting it.  Consequently, nanoparticle creams now can also appear clear when applied.  Because nanoparticles are new and quickly becoming more common in sunblocks (and other cosmetics), some concerns about their safety have been raised and are worth noting.  But bear in mind that other concerns exist regarding some active ingredients in organic sunscreens as well.  For now it has been established that the general benefits of using any sunscreen far exceed any specific risks.

Sun Protection Factor (SPF)

Ever since sunscreen manufacturers began placing a cryptic value on their products in the 1960’s as a means to quantify how much sunburn they prevent, the SPF values of various products have been perpetually escalating.  Neutrogena finally broke triple digits in 2009 by offering the first SPF 100 sunscreen in the U.S.  At this point, the FDA decided that things were getting ridiculous and stepped in to propose that, among other things, we stop counting SPF beyond 50.  Why?  Unfortunately, in order to understand how SPF values are quantified you practically need two semesters of calculus and a philosophical understanding of Zeno’s Paradox.  But check out Figures 3 and 4 instead.  You’ll notice that the amount of UV that is unblocked by sunscreen becomes increasingly insignificant anywhere beyond about 30.  So when you are at the beach and you notice that your friend’s sunscreen SPF is twice as high as yours, relax.  As long as you are using at least SPF 30, you’ll be just fine.  Although a higher SPF would in theory last longer, this is not always the case in practice due to variables such as application, water, sweating, and variations in quality from product to product.  So in conclusion, just remember to apply and reapply – or cover up!

Figure 3.  A plot representing SPF values vs. the percentage of UV rays blocked.  Because the increase is exponential and not a linear relationship, the difference between SPF values becomes increasingly insignificant.

Figure 4.  The significance of SPF can be viewed in this manner as well.  While it is true that SPF 30 permits twice as much UV to pass through as SPF 60, this perspective can be deceiving if percentages are not taken into account.

Vaccines, Autism, and the Scientific Method

Disclaimer: As with other articles posted in this blog, several of the links will lead you to the original research articles as they are found on the websites of their respective publishers.  I feel it is important to provide citations that direct people to the purest source of information that is available.  Unfortunately, many journal publishers cannot allow free access to the public of full articles, so the links may allow you to see only the abstracts in some cases.  Full articles can be purchased, or accessed via university networks that have a paid subscription with publishers.

Prologue

It is a well-known axiom in any science that ‘correlation does not imply causation’.  Because coincidences run rampant in nature and in life, focused efforts must be made to extract the effect with its true cause from a mess of random concurrences.  This is where the scientific method comes in (Figure 1).  

The observation of simultaneous events may lead one to hypothesize that one causes the other.  But, before any solid conclusions can be drawn there is a prerequisite step: Experimentation.  This is the inconvenient step; the one that requires meticulous planning, long drawn-out trials, repetition, peer-review of the results, and funding.  

This step was bypassed by some during the early 2000’s in their zeal to hop to the conclusion that vaccines cause autism.  But 13 years later, some new results are in from a very broad study designed to probe the alleged vaccine/autism link.

Figure 1. The fundamental scientific method, shown left.  The box on the right shows how faulty theories can be drawn  from conclusions that have no experimental basis and incidentally no results to support them.

Observation

First, we go back to 1998 when the correlation was most ostensibly observed.  Andrew Wakefield was at the time a doctor and medical researcher specializing in bowel disorders at the London Royal Free Hospital School of Medicine.  

In the prestigious medical journal The Lancet, Wakefield was the lead author of a published observation that 12 children (11 boys, 1 girl; ages 3 - 10) were all diagnosed with autism-related behavior abnormalities by parents or physicians after receiving the measles-mumps-rubella (MMR) vaccine.  It was noted that 8 of these children had a confirmed onset of behavioral abnormalities within 1-14 days following vaccination.  All 12 children also were found to possess gastrointestinal disorders.  

Wakefield’s work was funded by the UK Special Trustees of Royal Free Hampstead NHS Trust and the Children's Medical Charity.

Hypothesis

In consideration of the fact that rates of autism were on the rise (and continue to be) following the introduction of the MMR vaccine in 1988 in the UK, a hypothesis appeared to become self-evident.  As stated objectively in Wakefield’s paper:

“We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.”

The ‘environmental triggers’ referred to here is the MMR vaccine.  So, to paraphrase the hypothesis: ‘12 kids that were once normal now have bowel problems and autism, and we think these issues might be correlated, and there is a possibility that both could be caused by the MMR vaccine’.  This was a fair observation worthy of further investigation, based on the data presented.  The authors conservatively added:

“We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described. Virological studies are underway that may help to resolve this issue.”

This caution was appropriate considering that the sample size was small (12 cases) and the study involved no controls (children not exposed to the vaccine, or children not diagnosed with autism) for comparison.  Because the diagnosis of autism usually happens early in life, as do vaccinations, controls would be indispensable for proving a casue/effect relationship.  Otherwise one could just as well declare that Flinstones Vitamins are the cause of autism and/or gastrointestinal irregularities.

Retraction

The publication of Wakefield’s paper caused a stir as people mulled the impossible choice between protecting their children from infectious diseases, or protecting them from autism.  

Inevitably, a few chose to abstain from vaccinating their children.  A few years later, an increase in measles cases began to emerge in the UK.  In light of this, 10 of the 12 authors on Wakefield’s 1998 paper clarified their position by issuing a formal ‘Retractionof an Interpretation’ in a 2004 publication of The Lancet:

“The main thrust of this paper was the first description of an unexpected intestinal lesion in the children reported….We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.”

While these 10 authors attempted to distance themselves from a proposed hypothesis that was mistaken for a conclusion among a small segment of the general public, one author was conspicuously absent from this statement: Andrew Wakefield.  

The journal responded in the same issue by reporting that an investigation was carried out and focused on the methods used in the 1998 study and found no ethical violations.  However, six years later, not only was this statement of support retracted by The Lancet, but the entire 1998 paper was retracted:

“Following the judgment of the UK General Medical Council's Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al are incorrect, contrary to the findings of an earlier investigation. In particular, the claims in the original paper that children were "consecutively referred" and that investigations were "approved" by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record." 

Statements by the editors in the media were far less diplomatic than this carefully worded retraction.  Serious aspersions were cast by journalists and others in the scientific community.  Conversely, a few publicly defended Wakefield amidst the kerfuffle that ensued.  

Andrew Wakefiled lost his medical licence, but responded by telling his side of the story in a 2010 book, and continues to stand firmly by his original hypothesis.

By 2011, the World Health Organizahtion (WHO) sternly urged Europeans to vaccinate their children in response to 26,000 recorded cases of the once rare measles.  90% of those cases had not received the vaccine.  

The Centers for Disease Control (CDC) issued similar warnings in response to much smaller outbreaks that followed in the U.S., where the disease was previously considered to be practically eradicated.  Clusters were observed in highly populated cities, as well as in Minnesota and Utah.

Experimentation

Going back now to 2000, an elaborate study designed to investigate vaccines as a cause for autism was initiated in by Frank DeStefano and colleagues at the US Centers for Disease Control (CDC), which funded the study.  

This study involved a much larger sample size as well as controls: 256 children on the autism spectrum, and 752 without autism were included in the study.  All children received some level of vaccination.  The control subjects were matched for comparison to autistic subjects according to the child’s age, gender, and managed care provider.  The children were 85% male.  Data on these children were compiled retroactively from the records of three separate managed health care providers.  This data included the types and amount of vaccines each child received, when they received them, and when they were professionally diagnosed with autism.  Data for 24 separate vaccines were included in the study, including MMR.  At the time, many of these vaccines contained thimerosal as a preservative – a compound that has caused concerns due to its mercury content.  The care providers examined the children for autism during the vaccination period at the points of 3 months, 7 months, and 24 months.  Comparisons were made among children with and without autism, and how much of which vaccines they received, when they received them, and when the onset of autism symptoms began.

Results and Conclusions

The data was meticulously combed through over the course of the following years, and correlations were probed.  The results were published in an April 2013 issue of the Journal of Pediatrics, with charts and graphs showing that an increase in exposure to vaccine immunogens does not correlate to an increase in autism diagnosis.  Accordingly, the following succinct conclusion was stated:

“We found no evidence indicating an association between exposure to antibody-stimulating proteins and polysaccharides contained in vaccines during the first 2 years of life and the risk of acquiring ASD, AD, or ASD with regression.”

This conclusion is corroborated by several earlier studies that have been published elsewhere in the scientific literature.

Epilogue

Uncertainty is a sentiment that any disciplined scientist must learn to be comfortable with.  It is the gap between questions and answers that compels research to keep moving forward.  

Autism is a question that deserves answers, and it would be comforting to believe with certainty that we have found them.  However, this does not yet appear to be the case.  Because the works of science are often communicated in a language that many don’t speak, people often must accept or reject them as an act of faith.  It is my intention and hope that such faith in scientific methods can be perfected by making the works more accessible.   

In writing this post, my bias was obviously in favor of the work that I am familiar with that was presented here.  But all conclusions are subject to dialogue.  If you are aware of peer-reviewed reliable scientific research that does demonstrate a cause/effect relationship of vaccines and autism, by all means post it in the comments.  Thank you!

HIV's Penicillin Moment?

In 1979, an immunodeficient 5 year old girl died in a New Jersey hospital.  Baffled by their inability to administer any successful treatments from 6 months of age, the doctors had nothing left to do but perform an autopsy and carefully record the results.  Four years later, retrospective consideration of the child’s medical history and the mother’s lifestyle appeared to be consistent with the epidemic that had emerged in the meantime.  This may have been the first recorded fatality of a person who contracted HIV via birth.  Now, 34 years later, it appears that there may be a hope for newborn infants similarly afflicted.

On March 3 this year, an announcement was made at the 20^th Conference on Retroviruses and Opportunistic Infections: A two year old child appeared to be functionally cured of AIDS.  To elaborate more plainly, a woman with HIV who never received treatments during her pregnancy gave birth to an infant who was consequently HIV infected.  Treatments began directly with the infant 30 hours after birth – which is the moment when transmission of HIV from mother to child often occurs.  The decision was made to treat with a more aggressive combination of drugs than infants are usually given.  However, the series of treatments was halted prematurely and unexpectedly by the mother, who abruptly left town much to the frustration of the doctors.  This aberration in the treatment procedure proved to be an unexpected breakthrough.  When the mother finally returned with her baby, a relapse of HIV in the absence of treatment was expected.  Instead, the virus was physically undetectable – only traces of HIV genes could be detected.  This observation may have been a penicillin moment – if the mom had continued the prescribed treatment process as usual, the doctors may have not realized that a functional cure could be possible rather than the expected decades of treatments intended to keep the virus at bay.

In first-world nations, in the year 2013, newborns with HIV are rare.  The diagnosis is often made with the mother during pregnancy and preventative treatments can be effectively administered before birth.  But diagnosis doesn’t happen this way in less developed regions where HIV has a more ubiquitous presence and health clinics do not.  This is where this discovery matters the most.  The details of exactly how the cured 2 year old was treated are not yet available, but will likely be published soon.  From there, attempts will be made to reproduce it using the same combination of drugs, at the same point in time, etc.  Time will provide data, data will provide conclusions, and conclusions will provide parameters for future experiments that can refine the practice.  We will probably hear about this again.  Until then, here is a look at three common classes of HIV drugs that are often used in combination and how they work.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

All viruses are essentially genes packaged inside a ball of proteins.  In the case of the HIV virus, the genes are in the form of RNA.  If DNA is like a zipper, then RNA is like one side of that zipper.  In order for the zipper to be useful, you obviously need both sides.  And so the HIV virus also has an enzyme packaged inside of it along with its genes.  That enzyme is called reverse transcriptase, and its job is to convert the virus RNA into DNA after infection by completing the other half of the ‘zipper’ with compounds called nucleotides (the modified form of nucleosides).  Nucleotides are the elemental components of DNA and RNA, and they are abundantly found within any cell.  Once the DNA has been produced, the virus blueprints are copied en masse within the infected cell and the production of millions of new HIV viruses begins.  NRTIs are compounds that are similar enough to natural nucleotides to be used by the reverse transcriptase enzyme, but different enough to prevent the production of useful DNA (Figure 1).  These drugs inhibit the replication of HIV genes at the point of the reverse transcriptase enzyme function.

Non-nucleoside Reverse Transriptase Inhibitors (NNRTIs)

As with NRTIs, the target of NNRTIs is also the reverse transcriptase enzyme.  The difference is in how they block the function of the enzyme.  As implied by the name, these compounds are not false surrogates for nucleosides like NRTIs.  These compounds instead bind directly to the reverse transcriptase enzyme near the active site, which is to say where the enzyme chemistry happens.  Once bound to the enzyme, the chemistry is inhibited and the entire function is blocked (Figure 1).  The end result is that HIV genes cannot be replicated.

Figure 1. NRTI and NNRTI drugs interfere with the function of the HIV reverse transcriptase enzyme in two different ways.

HIV Protease Inhibitors

Further on down the line of HIV infection, another enzyme called HIV protease comes into play.  After the RNA of HIV is converted into DNA by the reverse transcriptase enzyme, the cell’s natural enzymes use the HIV DNA as a blueprint for producing a long ‘poly-protein’.  ‘Poly’, because it is a series of distinct HIV proteins (or enzymes) that do not become functional until they are severed from one another.  This is the job of the HIV protease enzyme – it cuts the ‘poly-protein’ up into its constituent proteins, which thereafter assemble to become a slew of newly formed viruses ready to spread their infection.  HIV protease inhibitors are compounds that work in the same way as the non-nucleoside reverse transcriptase inhibitors.  They bind to the HIV protease enzyme where the chemistry takes place, rendering the protease enzyme without function (Figure 2).  The result is that new virus particles (Figure 3) are never assembled because their individual components are all tied up together in a useless string of proteins.

Figure 2. HIV 'poly-proteins' are cut into constituent proteins by HIV protease.  Protease inhibitor drugs block this process.

A variety of other drugs are also used to suppress HIV by other mechanisms.  As we know, this is difficult to do and the virus tends to find ways around it.  And so we have learned that combinations of drugs are usually necessary to plug all the holes.  What we may learn from the case of this HIV-free 2 year old is that it is apparently much easier to plug those holes immediately after the infection takes place.

Figure 3. Simplified anatomy of HIV, assembled from the products of cleaved 'poly-proteins'.

Antarctic Life Finds a Way

As we ponder the possibility of life existing on other planets, we have recently expanded our understanding of the parameters that define how life can exist on our own planet.  After years of planning and preparation, an American team of scientists have now drilled through 800 meters of ice to tap into a confined lake in Antarctica in search of life.  On January 28, they announced that they had found it. 

We don’t know yet exactly what ‘it’ is, but ‘it’ has microbiologists and astrobiologists really excited right now.  This is not as much because Antarctica is a cold place as it is because this particular lake is an isolated place.  Most of life thrives within some sort of ecosystem where the existence of one organism depends on the existence of an extensive network of others – the ‘great circle of life’, if you will.  Usually this can be traced back to a plant or other organism that gets its energy from sunlight.  But a lake that has existed in darkness under a sheet of ice, undisturbed for thousands of years (until we poked a hole in it) is cut off from most of that.  But inevitably, ‘life finds a way’.  Or to be more specific, metabolism finds a way.  Metabolism can be loosely defined as the way that an organism makes energy from what it consumes.  It usually involves a complex series of chemical reactions that begins with some form of outside energy that is not inherently useful.  For instance plants metabolize carbon dioxide and sunlight energy via photosynthesis to produce ATP and carbohydrates – chemical forms of energy that all living things rely on.  So the big question here is, in a cold, dark, confined, really salty lake, devoid of oxygen and limited in biodiversity, what sources of energy are available to sustain any kind of life?

Carbon dioxide

We often think of oxygen as being necessary for life, but this is because it is essential for our life as human beings and we are therefore biased.  Actually, quite a few organisms outside of the animal kingdom do perfectly fine without oxygen.  But carbon is essential – being as how all life forms on earth are carbon-based life forms.  For such, carbon-dioxide is often the breath of life.  As an example, a group of microorganisms called Methanogens consume carbon-dioxide and hydrogen gas, and expel methane (natural gas).  Methanogens do this by the chemical reaction in Figure 1.  But don’t let the simplicity of the reaction fool you.  The reaction proceeds through six intermediate steps that are catalyzed by ten different enzymes.  Methanogens live deep in the soil where decomposition takes place; or in the intestinal track of another organism where digestion takes place.  It is unlikely that they would be in the Antarctic lake, as they tend to avoid salty environments.  But if they did, then the next question would be: ‘Is anything consuming the methane?’. 

Figure 1. Metabolism of carbon dioxide by methanogens.

Hydrogen

Hydrogen is but a proton orbited by an electron, but even the simplest element in the universe can be used for energy by microorganisms.  There are a few bacteria that have a very special enzyme called hydrogenase that enables them to essentially split molecular hydrogen (H2) into its constituent electrons and protons, and use the resulting separately charged particles for energetic purposes.  The reaction is easier said (Figure 2) than done, and great efforts are underway to understand the chemistry well enough to reproduce it artificially.  Hydrogen would be inherently present in any aquatic environment, and this could be an initial energy producing step in the metabolism of something in an Antarctic lake.

Figure 2. Splitting of molecular hydrogen by the hydrogenase enzyme.

Minerals

Beneath the icy surface of Antarctica and at the bottom of the hidden lakes, is terrestrial land – just like every other continent.  And with that comes minerals, which can be used to sustain life in spite of their obvious non-biological nature.  There are a handful of bacteria that scientists call ‘chemolithotrophs’, which is a fancy word for ‘chemical-rock-eaters’.  In other words, these bacteria can derive the energy they need for metabolism from elements such as sulfur and iron that are present in minerals.  Again, specialized enzymes make this possible by shuttling electrons and harnessing their energy.  Because minerals are usually deficient in the necessary carbon, these bacteria often subsist on carbon dioxide as well.  These microorganisms can feed on a variety of minerals and are found in diverse environments, from hydrothermal sea vents to less isolated Antarctic lakes.  It is very likely that these newly reported Antarctic bugs are some type of specialized ‘chemical-rock-eater’ related to those found elsewhere in Antarctica.

In time, the American researchers will perform a genetic analysis so that they can classify these microorganisms and give them a place on the tree of life.  This will lead to further understanding of their metabolic nature.  Meanwhile, two other teams of scientists are in the process of performing similar experiments on other lakes that are buried deeper under the Antarctic ice sheet and incidentally more isolated.  If they find anything, it will be interesting to compare, and then wonder about the possibility of similar microbes existing in similar environments, within our own solar system.

MERS-CoV: A virus is born

Update: In May 2013 the virus was offically named 'MERS-CoV'.  At the time of this writing, EMC/2012 appeared to be the most official name for the virus, so that is reflected here in the text. Thus, 'EMC/2012' in the text of this article is the same as 'MERS' or 'MERS-CoV' as it will be referred to in the media and literature from now on (31 May 2013).

Viruses are everywhere.  For every species of living organism on the planet, there are probably multiple viruses that can infect it.  There are even a few viruses that infect other viruses.  The Darwinian combination of random mutation and natural selection is exploited by viruses more rapidly than by their hosts, keeping them one step ahead in the race of adaptation.  The result is often new strains of an already existing virus, which can sometimes hop from one species and into another.  Case in point, this past fall the World Health Organization (WHO) reported the identification of a new human virus that has been fatal in over 50% of those unfortunate few who have been infected so far.  This virus was named EMC/2012 and it is a particular concern to the WHO because it is a coronavirus.  That is the same family of viruses that SARS emerged from a decade ago.  By comparison, SARS was fatal in 11% of the 8,422 cases in which it was identified.  And so how is EMC/2012 different and how is it similar to SARS?  Exploring this question can help gauge the probability of a new pandemic.

There are at least 29 classified (and dozens more yet to be classified) kinds of coronaviruses, which can infect a variety of mammals and birds.  Prior to 2002, only 2 of these were known to infect humans, and only with mild respiratory consequences.  However in November of that year, clusters of severe pneumonia cases were identified in people living in the Guangdong Province of China, and then Hong Kong.  Heightened concern led to urgent research, which in turn revealed the cause to be a third, previously unidentified human coronavirus.  By the time this suspect was identified as the SARS-virus, it had already fled to other parts of Asia, Europe, and North America with some ensuing fatalities.  But within 1-2 years, SARS had faded away and the face-masks began to come off.  Gone, but not forgotten, heavy research continued to address where SARS came from and how it became transmissible.  Incidentally, by 2009 two additional coronaviruses were found to be milling about the human population and causing colds, but we never knew about them because we never had a serious reason to look for them.  But last year a reminiscent series of events developed.  In June 2012 a man was admitted into a hospital in Saudi Arabia with severe pneumonia.  Eleven days later he died before the cause was known.  The following month another patient was found with similar symptoms in Qatar, and eventually became severely ill.  Thanks to further investigation, thorough documentation, and the keen eyes of healthcare workers, the two dots were connected and the World Health Organization announced in late September that the two cases were caused by the same pathogen – this time not SARS, but an unknown coronavirus.  Within a little over a month the successful isolation of the virus in laboratory cell cultures was reported, and it was named it EMC/2012.  And then by December the complete genome was sequenced.  In the meantime, 7 more people were found to have contracted the virus in the middle-east, with four more of them being fatal.  In time, EMC/2012 will probably be confirmed in other cases, but for the moment it does not appear to be widespread, and may not be overly transmissible among us humans.  Analysis of the EMC/2012 genome shows that it appears to have evolved from coronaviruses in the bat population.  Although some uncertainty lingers, there is significant evidence that the SARS virus also slipped into the human population from similar coronaviruses circulating in bats.  So, why bats?  Bats make up about 20% of all mammalian species, and about 40% of all mammals in Hong Kong are bats.  A large diversity of bats equals a large diversity of mammalian coronaviruses.  And many bat species adapt well to urban environments, which brings them in close proximity to human populations.

In order to understand how a bat virus can suddenly become a human virus we need to get to know viruses on a physical level.  Viruses are composed of biological components, but are not quite living themselves.  They are the undead, the zombies of the biological world.  Like a riddle wrapped inside an enigma, they are genes wrapped inside of proteins.  The proteins determine what they will infect, and the genes determine the proteins once the infection has taken place.  To elaborate on this concept, the genes may be DNA or various forms of RNA depending on the virus.  All proteins are continuous chains made of 20 possible amino acid links.  Analogous to how programming code determines computer software, the genetic code of DNA or RNA determines the sequence of amino acids for the proteins as they are synthesized within the cell.  Each amino acid is a like a small compound with inherent properties: some are positively charged, some are negative, and some have no charge; some are polar, some are non-polar; some react to pH, some don’t.  A smaller protein of say, 100 amino acids, would have (in theory) 20¹⁰⁰ possible arrangements of those amino acids.  That amounts to a lot of variability in terms of the physical nature of each possible protein as a whole.  Thus, many possible protein shells allows for many possible viruses.

Coronavirus diagram showing the arrangement of spike (S), membrane (M), and nucleocapsid (N) proteins around a core of RNA genes.  Some coronaviruses may also have a hemagglutinin-esterate (HE) protein in the lipid membrane.  Small envelope (E) proteins can also be present in small amounts on a mature virus.

As for the coronavirus family, RNA is used for their genetic transfer, which is encased inside of a double shell constructed mainly of 3 or 4 distinct proteins.  One of these proteins is called (S) for “spike” because it protrudes from the virus, and this is what determines what type of cell the virus will stick to and infect.  Because (S) is usually about 1300 amino acids in length, this allows for considerable variability in the amino acid makeup among coronavirus “spike” proteins.  When a virus infects a cell, it is taken apart, and its foreign genes are copied over and over again.  But like a document that has been photocopied or faxed too many times, the fidelity is poor.  This means an abundance of mutations, and not all of the new ‘baby’ viruses will be genetically identical to their ‘parent’ virus, for better or worse.  So how many mutations need to occur to generate a new virus?  This can depend on a lot of factors, but the arrangement of amino acids on the ‘spike’ protein on EMC/2012 is 64-67% identical to the two bat viruses from which it is believed to have emerged from.  This demonstrates another complexity: often new viruses are the result of a species being infected simultaneously by two similar viruses, creating the opportunity for a genetic swap meet.  It is impossible to predict the epidemiological path that viruses will take, being the marauding mutants that they are.  But for now it appears that we can reasonably hope that EMC/2012 was just a blip on the radar.