The Global War against Super-bugs - Where a simple cut can kill...

Antibiotic resistance occurs when bacteria evolve and antibiotics no longer work in the people who need them to treat infections.

The post-antibiotic era looms and it's time to sound the alarm. A nightmare report by the World Health Organization (WHO) warns we are officially running out of drugs for the hardiest of harmful bacteria. This serious threat is no longer a prediction, it is happening right now all over the world and can affect anyone, of any age, in any country.

Bacteria naturally evolve to develop drug-resistance. But the problem is accelerated by the misuse of antibiotics, and once bacteria evolve resistance, there are few new ones to fight them.
One of the biggest barriers to confronting drug-resistance is the lack of data. For example, hospitals, where antibiotic resistant bacteria thrive, aren’t required to report outbreaks. And there’s no global consensus on how to track or report infections. The WHO report is the first effort to gain a full picture of drug-resistance. It found the problem is global and in some countries resistance is already at “alarming levels”. In the U.S. alone, ~$30 billion a year (and growing) is spent on infected patients. The WHO aims to find better ways to track antibiotics in people and food-producing animals, which are among the major consumers of antibiotics.

Antibiotics are one of the miracles of modern science that allow us live longer and healthier. But they've been taken for granted and abused. Unless we take significant actions in producing, prescribing, and using antibiotics, the implications will be so devastating that Cancer and Climate Change will be afterthoughts of human health. The general public can help on the "use" side of the equation by using antibiotics only when prescribed, completing the full prescription (even if you feel better), and never sharing antibiotics or using leftover prescriptions. Health workers can help the "prescription" side by enhancing infection prevention and control in hospitals, and prescribing the right antibiotics only when they are truly needed.

My research focuses on identifying new targets in bacteria for the antibiotic "production" side of the equation. The current antibiotics that are slowly losing the battle primarily target and inhibit the synthesis of DNA, RNA, protein, and the cell wall. These processes are essential for bacterial growth. To develop more effective antibiotics, alternative drug targets are needed. I study transport systems that are found in almost all bacteria, but are absent in humans, making them prime drug targets to combat antibiotic-resistant bacteria. The tranpsport systems are required for DNA inheritance, cell division, metabolism, cell motility, and biofilm formation. These essential processes are required for pathogenesis. In the long-term, my research will allow for the development of an arsenal of antibiotics that stop bacterial growth and infection.

If we do not address this issue now with vigor (and funding!), a simple knee scape can once again be considered potentially fatal. The wording of the report is alarming, “The problem is so serious that it threatens the achievements of modern medicine” and “Far from being an apocalyptic fantasy, [it] is instead a very real possibility for the 21st century.”

For a better grasp of the severity of the situation, I recommend watching FRONTLINE's report Hunting the Nightmare Bacteria.

Our Bacterial Selves

 

   

 

 I start many conversations with "There are 10 times more bacterial cells than human cells living in us and on us. We are more bacterial than human." 

 

But as newborns, we come into this world sterile. It is by passing through the vaginal canal that provides our first dose of bacteria, called lactobacillus. Right out of the gates, bacteria gifts us with the ability to digest our mother's milk. 

 

That's day one. How does bacteria help us for the rest of our lives?

 

Scientists have studied bacterial DNA from healthy individuals and found 10,000 DIFFERENT species of bacteria. To put that number into perspective, many probiotics boast on having 10 to 20 species. Lame.

It's time we learn more about our "bacterial selves".

 

Studying our bacterial selves has only recently been possible as a result of the genome revolution (See post below). Cells from our mouth, genitals, gut, nose, skin, and even belly button have been sequenced. Strikingly, for every human gene there are 360 bacterial genes. I find this both exciting and frightening. Imagine going to a mechanic who only knew how 0.2% of a car worked.  Now replace that mechanic with a doctor, and replace that car with you!

 

For better or for worse, funding is largely given to scientists that study what's killing us. Cancer and pathogenic (bad) bacteria or viruses always take center stage and a good chunk of funding. The 10,000 bacteria that make us who we are have been watching from the peanut gallery.

 

Healthy bacteria equals a healthier you, and scientists are studying how to enrich the good guys, while minimizing the impact of bad ones. Imagine a house party where every time a crasher tries to join in, the host uses mustard gas.  The crashers are killed, but so are your invited guests. In later parties, the crashers get wise and bring masks. Now everyone dies, except for the evolved party crashers. When we get an infection, we drop antibiotic bombs on the bacterial party in our guts; killing the good guys that brought the keg, chips, and dip. By learning more about the good bacteria, we can start treating infections with snipers instead of bombs.

 

So what do our bacterial selves do? The easier question might be what don't they? Alterations in our bacteria have been linked to Crohn's and irritable bowel syndrome. That may not come as a surprise, but links are also being made to our behavior, depression, allergies, and many, if not most, inflammation-related diseases.

 

One of the key goals of the study was to find the key bacteria in all healthy individuals. Shockingly, it turns out that different people have different microbial communities, and so do different body parts on the same person! Not a single species was universally present across all volunteers. This suggests different bacteria can do the same jobs. We have to find out what those jobs are. What causes the bacterial diversity? Age, gender, weight, diet, geography, genetics, the tenancy to lick door knobs? These and more likely play a role.

 

Sequencing an individuals bacteria again after several months showed the same bacterial communities. This means our bacterial selves are unique, but stable over time. I can easily imagine a future where a visit to the family doctor will literally involve a "gut check".  When you are young and healthy, your stool sample will be used to grow, dry and store your bacterial selves in pill-form. You'll then be able to rePOOPulate your gut for the rest of your life and whenever you want - after a dose of antibiotics, traveler's diaherra, or any other illness.

The Human Microbiome Project Consortium, “Structure, function and diversity of the healthy human microbiome,” Nature, 486: 207-214, 2012.

Flu 101

Vaccine or no vaccine? That is the question.
Whether 'tis nobler in the mind to suffer the symptoms of flu,
Or to take arms against a sea of viruses,
And by opposing, end them.

We make this decision every winter, but often with misinformation. The number of reported flu cases is exploding and we aren't even near peak flu season.

Let's put the question into context. Last year's flu season was mild for two reasons: (1) The circulating flu strains were the same as the previous two years. That means if you got the flu or the vaccine even in 2009, you were likely still immune from the strains of last season. (2) Scientists do a bit of guess work to decide on which strains to vaccinate against based on the ones currently circulating and the ones expected to circulate in the next season. The degree to which a vaccine matches the circulating strain determines its effectiveness. Last year, the vaccine was an excellent match. Go science!

So what about the 2012-2013 flu season? The strain, H3N2, is new and aggressive. But fortunately, this season's vaccine protects against H3N2. Scientists guessed correctly once again! If you got the flu shot you have a strong chance of not getting the flu. But as with every flu season, false information circulates just as fast as the virus. As a result, conspiracy theories and "vaccine-hesitancy" still looms and they are serious health problems in Canada and the US.

Flu shot myths are rampant, so I thought it would be fun to discuss my favorites: 

"The flu shot gave me the flu!"
Impossible! Sorry, but the science is strong on this one.  You are not given a live virus in the vaccine. You are given dead or attenuated virus that cannot replicate. There are three main reasons why you may still get the flu after the shot: (1) It takes two weeks for the vaccine to become effective.  That means you are still vulnerable to infection for a couple weeks after injection. (2) As I mention above, scientists have to guess at what strains to defend against. Sometimes they are way off the mark and the shot is only 0 to 50% effective. Even when a good guess is made, as they did this season (and last), the vaccine effectiveness is still not 100%. It is more like 60-90% effective. Therefore you may still be vulnerable. (3) There are plenty of other flu strains that are not defended against in the shot and there are other viruses that give flu like symptoms. 

"The flu shot is a government and pharmaceutical conspiracy to make money"
I never understood the logic on this one.  Yes, pharma companies make big money and yes, the government saves big money. But did you ever ask why? Because it works! Kids go to school, thousands of work hours are saved, the few hospital beds we have stay open for those who need them, and most importantly, less people die from a preventable infection.

"The flu shot causes...Autism, Guillian-Barre Syndrome (GBS), Allergic reactions, death, etc."
Millions of research dollars have been put to waste to conclusively show Jenny McCarthy and Jim Carrey that vaccines do not cause autism. There is also no increased risk for GBS. All flu vaccines are made by injecting virus into chicken eggs and the amount of egg protein in the vaccine is extremely low. But those who react to eggs severely should see an allergist before receiving a vaccine. There is less than a 0.1% increased risk of febrile seizures in kids. To put that number into context, 1 in 25 kids normally experience at least one febrile seizure in their lifetime and it is typically not life threatening.

H3N2 is aggressive. It is spreading early and fast, and it is only going to get worse in the coming months. But it's not too late. If not for your own health, think about your co-workers, friends, kids, and family members that have to breathe your air. Think of it as a gesture of courtesy. 18 children have already died in the US and that is just the reported number. The actual number due to complications is actually much larger.

Vaccine or no vaccine? As always, the decision lies with you.

On a personal note, my wife and I got our shots as we do every year. We both had the usual sore arms and drowsiness that lasted the day.

Do you already have the flu? Would you like to see who gave it to you? Or perhaps who you gave the flu to? There's an app for that! "HELP I HAVE THE FLU" app searches the profiles of your friends to see if they have used the terms cough, fever, flu, etc...
Finally a good reason to be on Twitter and Facebook!

HAPPY NEW YEAR!!!!

Science's Next Top Supermodel?

The naked mole-rat may save us from brain damage, pain, cancer, and even aging
 

 

Sure these dirt-dwellers look like a part of the male anatomy with buck-teeth, but their attributes only go up from there (pun?). They survive long periods without oxygen, show insensitivity to pain, and unlike related mice that live 2-4 years, the naked mole-rat lives into its 30s. For humans, that would be a lifespan extension of ~ 400 years. Not impressed? Well they also don't get cancer....ever.

Oxygen Smoxygen

Our brains are damaged after just 3 minutes of oxygen deprivation. This is a concern for heart attacks and strokes, where blood supply to the brain is interrupted. Brain tissue of the naked mole-rat remains functional three times as long as brain tissue of mice, and when oxygen is restored, the brain recovers. With their claustrophobic environment of underground tunnels they've evolved to contend with low oxygen and high carbon dioxide levels. Naked mole-rats protect their brains using the same strategy as infants. Infant humans are more tolerant to oxygen deprivation than adults, and calcium is the culprit. Normally, calcium in our brain helps memories form. But the balance is delicate: too much calcium is damaging. When our brains are oxygen starved, they no longer regulate calcium entry, resulting in too much calcium and brain damage. Researchers discovered that calcium channels in infants close during oxygen deprivation, protecting the brain from calcium overdose in the womb, where the baby gets much less oxygen. After birth, however, oxygen is plentiful, and these channels are replaced by ones that open in response to oxygen deprivation, often leading to cell death. Naked mole-rats retain "infant-style" calcium channels even as adults, which explains their resiliency. These findings provide a new strategy to help victims of heart attack and stroke: design a drug that quickly increases the number of infant-style calcium channels in the brain. This could provide valuable protection during a time when the supply of oxygen-rich blood is stunted.

Are you a man or a mole-rat?

I recently went on a whiskey distillery tour and the guide asked me to stick my nose in the fermenter and take a whiff (Fermentation: Sugar = CO2 + Delicious Alcohol). I jolted up with my nostrils being pricked by a thousand horseradish-tipped needles. High levels of CO₂ can be painful to the eyes and nose due to the formation of acid on the surface of those tissues. A less sadistic experience is the feeling of burping through one’s nose after drinking a coke. Mole-rats are completely insensitive to this and other irritants. The nerve fibers that respond to irritants are less sensitive in naked mole-rats. Importantly, these fibers are responsible for the pain people experience after an injury. Surprisingly, naked mole-rats have these fibers everywhere, but they do not make the neuropeptides usually released because of a gene defect associated with relaying the message of pain. A greater understanding of how this type of pain processing is altered in naked mole-rats has significant implications for the treatment of chronic pain in humans.

Is Joan Rivers a Mole-Rat?

With a recorded lifespan of 32 years, they are the longest-lived rodents known, and remarkably, they are in good health for most of their lives. At an age equivalent to a human age of 92 years, naked mole-rats show unchanged levels of activity and metabolic rate, sustained muscle mass, fat mass, bone density, cardiac health, and brain function. They delay the onset of aging and compress the period of decline into a small fraction of their overall lifespan. These findings of sustained good health are turning current theories of aging on their head. For example, the widely accepted "oxidative stress theory of aging" attributes our decline in function to damage caused by reactive oxygen species. In much the same way that oxygen causes your car to rust, cell membranes, proteins, and DNA are also damaged. Over time, we "rust", which causes our bodies to slowly malfunction. Surprisingly, naked mole-rats also show high levels of rust at an early age, yet cellular function is not impaired. Another aging theory is that the length of an organism’s DNA ends (telomeres), is a marker of aging. As our cells divide, the ends of our chromosomes get shorter and shorter, eventually chewing into genes required for cellular function. But the naked mole-rat has short telomeres, similar to those of humans. Thus, the telomere theory is unlikely to explain their longevity. Where's the fountain of youth?!

Rat for the cure

The naked mole-rat doesn't get cancer. Scientists have blasted these critters with cancer causing radiation and no tumors develop. Some real jerks even altered their DNA to produce aggressive tumors. Again; nothing! But the jerks did notice something intriguing. The cancerous cells didn't die, they just stopped dividing. It seems as though the naked mole-rat is very good at recognizing abnormal cells, neutralizing cell overgrowth, and repairing DNA. The genome of the naked mole-rat has unveiled novel insights into why they are impervious to cancer. Given that cancer is one of the largest contributors to mortality in elderly humans, these cancer prevention pathways may contribute substantially to the longevity of naked mole-rats.

They sure are ugly, but we are slowly recognizing the beauty from within. Research on this fascinating animal will do so much. If I'm ever saved from brain damage, pain, cancer, or even aging because of these critters, I'll be the guy in the naked mole-rat mobile with the naked mole-rat tattoo on the way to PetSmart to buy a dozen naked mole-rats....to be my pets!!!

Your Genome for the low price of $999!

For $1,000 bucks, you can get your entire genetic code and its secrets. And it's only getting cheaper!

The machine itself takes up as much space as a printer, it does an entire genome in a single day, and costs only $100,000; making it affordable for medical practices.

For now, research labs will be the main customers, to obtain the complete genome sequence of people with cancer or autism, for instance, to seek out a disease's underlying genetic causes and ways to treat it.  In the very near future the door will open to people who are not ill.

The Data Deludge Revolution?

One problem is that the costs only start with the actual sequencing. The cost of understanding the sequence will be much, much higher. For example, in one study the sequencing cost $48,000, but because it found 2.6 million DNA misspellings and 752 other genetic glitches, it took a few hundred thousand dollars worth of labor to understand what the sequence meant. My wife is currently working to improve data quality when sequencing cancerous tumors.

It would take a genetic counselor roughly 5 hours to explain what a typical genome means, further adding to the true cost. If you want me to recommend a job for your kids?

GENETIC COUNSELLING!! We do not have nearly enough to meet the need if sequencing becomes widespread. Will doctors pick up the slack? 90% of patients trust their physician to explain genomic data to them, and 90% of physicians say they don't feel comfortable explaining genomic data...MDs, go figure.

The genomic revolution has arrived! And herein lies the crux of the matter.

Will you want to know?

You'll know if your baby will have a genetic disease, such as autism. In some instances the disease will be curable. In others, you'll know the dreadful future of this baby. Will you want to know?

Babies will certainly be first in line for sequencing. The US and Canada already screen newborns for at least 29 genetic diseases. But we need to be careful how we utilize this information. Do you tell a newborn's parents his apoE status? That is, whether he has the form of a gene that raises the risk of Alzheimer's disease? Will you want to know?

You'll know your chances of getting a variety of different diseases, such as alzheimer's or cancer. Will you drastically change your quality of life to prevent these diseases?  Will you live an entire lifetime worried, but well? Will you get the disease anyways!? Will you want to know?

Insurance companies and businesses may one day get a hold of your code. Can you get a discount on insurance with an impecable genetic code? Can you get insurance at all with a code plagued with error? Will Tobacco, drug and even food companies focus their marketing to those that show a susceptibility to addiction?

What if the information becomes public? Will a first date involve a comparison of eachothers genetic makeup? If you're incompatible for producing healthy offspring, do you stop from getting to know someone that could have been your, for the lack of a better term, soul mate? Will you want to know?

EVERYONE carries genes that predispose them to more than one serious or lethal disease. Bioethicists are only beginning to study how that knowledge might affect someone's decisions, from marrying or having children to saving for retirement.

The cost of sequencing will continue to plummet. A "zero-dollar genome" is already forseable, making it likely that it will be a part of routine clinical care.

And here is my microbe spin. There are more bacterial cells in you and on you then there are human cells. What about their DNA? Welcome to your METAgenome! Soon you will know the sequence of your human cells and all the bacterial cells that make you, you! There are many mysterious and still unnamed genetic diseases that are linked to the genetic makeup of your bacteria, and this information will soon be available for solving these riddles.

How to access your right brain without a stroke

Below are two TED videos that explain the functions of the left and right brain. I've emailed them before and you should view them before reading further:

1) A concise explanation of the left and right brain. http://www.ted.com/talks/iain_mcgilchrist_the_divided_brain.html

2) A neuroscientist descibes her own brain function while having a stroke!http://www.ted.com/talks/lang/eng/jill_bolte_taylor_s_powerful_stroke_of_insight.html

The message of both videos is that the right brain has a lot to offer: imagination, creativity, abstract thinking, happiness, living in the present. The left brain on the other hand can be argued as more important for survival. It gives context to the present. It recalls your past. It predicts your future given a choice your about to make. It also provides extreme focus for specific tasks. Due to its importance, the left brain is the ruler of both sides.  If your left brain is the heavy-handed type, you might not be using your right as much as you'd like!

So the question remains: How do you access the right brain to provide a richer life?


This thought was echoed by my buddy Nick who replied "A scientist telling an accountant to stop using the left brain...never thought I'd see the day. Let me know if you figure out how to access the right without having a stroke!"

Some recent and controversial research has already found clues to answer Nick's question...Psilocybin! Otherwise known as the active ingredient in magic mushrooms.

Clinical trials show that a single dose provides an enduring but positive personality change in the majority of patients. The drug increases an individual's sense of "openness". What's more, the positive personality shift can last more than a year! How does this relate to your right brain? Remarkably, this study shows that psilocybin can strengthen imagination, abstract thinking and creativity in general. All attributes associated with the right brain.

So it turns out mushrooms can really make you a "Fun Guy"....lame.

Scientists believe that psilocybin could have therapeutic uses in the future. For example, current studies are underway to see whether the hallucinogen might be useful in helping cancer patients cope with the depression and anxiety that often accompany the disease.

I want to emphasize that I am not trying to encourage drug use! The research needs to be replicated and studies on dosage, downsides, and long-term side effects are obviously needed.  But having said that, please take a look at the graph below:  

Mushrooms are one of the least harmful drugs out there. Also notice how our most dangerous drug is the most socially acceptable - Booze.


Before I'm officially labeled a hippy, I want you to answer the next question honestly. After knowing that heart disease, diabetes and obesity are North America's greatest killers, where do you place Salt, Sugar and Fat on this graph?
(or even wheat for that matter: http://www2.macleans.ca/2011/09/20/on-the-evils-of-wheat-why-it-is-so-addictive-and-how-shunning-it-will-make-you-skinny/)
I'm frequently reminded of the quote from Shakespeare's Hamlet "There is nothing either good nor bad, but thinking makes it so."

*For those of you wondering how this ties in with microbes. 
Mushrooms are fungi. Fungi are microbes.

MERRY CHRISTMAS!!!

Climate Change

Today I deviate from microbes to another topic that deserves attention - climate change.

A study that started in 2009 by University of California physics professor Richard Muller has found the earth is warming. This has been shown a thousand times over so why is this study important?

1) Professor Muller WAS a climate change denier
2) Funding for the study was provided by the Koch brothers - Republican, Tea-party supporting, billionaire US industrialists that lobby against man-made global warming.
3) Several years ago, there was a media storm concerning a scandal called "Climategate", in which the emails of climate scientists were hacked and posted online in an effort to expose supposed data manipulation that exaggerated the planet’s warming trends. Leaders in this firestorm of ridicule, were FOX news and professor Muller.

"Climategate" received several hours of media attention.  How much did the new findings receive? Less than 30 seconds on MSNBC and CNN, and ziltch on FOX. This is the problem. The public still thinks there is a debate because the only source for their science info is the media, who created and sustain an imaginary conflict that hasn't existed in the scientific community for decades!

Let me hit you with some real stats. 98% of scientists agree climate change is real. Of those, 95% agree that it is man made (1). Therefore, I refuse to blog about the "debate" on climate change. Doing so would suggest there is one. Let me just say that the evidence for man-made climate change is irrefutable, but deniers have been clever in misrepresenting the data.  This link explains a few examples very clearly: http://www.fool-me-once.com/

Another problem seems to be the term "Theory". Some say climate change and evolution are ideas not fully accepted by scientists because we call them theories.  For scientists the term "theory" is an accurate description of the natural world.  For example, gravity is a theory.  If you don't believe in gravity, please float away!

What I've been immersed in recently is the psychology behind the denial. I can sum up why it's hard for a denier to accept a well-supported but opposing view in three points:
1) Confirmation bias, 2) Goalpost shifting and 3) False equivalence.

Confirmation bias is the unconscious tendency to favor info that confirms your own preconceptions.  For example, after reading "95% of scientists believe in man-made climate change", how did you recieve that info?  If you believe in climate change, you might say "Ah ha! climate change is real and I'm right!". If you are a denier, you might say "Wow, 5% of scientists are also deniers.  Therefore climate change must be a huge conspiracy with 95% of all scientists in on the scam!".

Goalpost shifting is when you rework your position to fit the evidence after the fact. An obvious example is the religious fanatic Harold Camping who predicted the rapture in the 90's, and then on May 21st, and then on Oct 21st, and then on...you get the picture. Many climate change deniers said they'd accept whatever Professor Muller found. But after Muller switched opinions, the deniers say he was brainwashed by those crazy climate scientists and the data was manipulated.

False Equivalence is to equate two things without taking into account the underlying differences which make the comparison completely invalid. A perfect example comes from the media attention towards climate change.  Although 95% of scientists and an overwhemling number of publications (over 10,000) have shown strong evidence to man-made climate change, the media still gives roughly equal attention to scientists who express views that climate change is caused by humans (53%) as they do to those who say it is caused by nature (47%).

So with all this said, will the false debate on climate change ever end?  No way.

Deniers have built elaborate arguments and rationalizations that they can't let go of, even in the face of direct factual refutation. They claim their views are based on science, but clearly take politicized positions and attack climate scientists (scientists in Australia have to work under high security because of death threats and vandalism to their property). The emotional tone itself reveals that these attacks on science are motivated attacks.

Muller's data won’t change anything. It is just fuel for the fire. No scientific result, of any kind, is going to end the imaginary debate in the public arena (it ended long ago in the scientific arena). There is only one way to make deniers go away. We need climate change policy. When that day comes, the debate becomes irrelevant. The deniers still won’t buy it. But they will have ceased to matter, even politically, and the media and audience will have to move on.

                                          Galapagos Islands

(1) Anderegg, William R L; James W. Prall, Jacob Harold, and Stephen H. Schneider (2010). "Expert credibility in climate change". PNAS)