Nature, improved

The vast majority of you who read my blog are probably aware of my obsession (a strong word perhaps, but apt) for science: wake up, eat, science, sleep, repeat. As a result of both curiosity and my natural tendency to wander the internet, I tend to focus my energies on learning things within a specific area due to an article I read or something of that nature. I call these "kicks", and for the next few blog posts I'm going to introduce you to a recent obsession of mine: synthetic biology.

Figure 1: Obligatory futuristic depiction of your DNA!

For centuries, humans have had to operate within the confines of nature. Want to cure your fever? Find an herb. Want to have bigger cows? A combination of careful breeding and finger crossing should do the trick! Now when we're faced with a problem (say, why don't we have better cancer-fighting enzymes), we are presented with a third option: make it up. We now have the power to craft our own custom DNA, create new cells, and effectively "edit" life as we know it.

Will these technologies be known to history as man's triumph over the universe, or will they be our downfall? I'll leave that for the ethicists to decide, but you can't deny that these technologies are pretty interesting! So stay tuned for some background into synthetic biology and where our technologies are at in 2014. You don't want to miss it!

Surviving Thanksgiving

Without a doubt, the most troubling (and usually hilarious) comments I hear about science happen around the Thanksgiving table. Whether it's your crazy uncle from out of state or your neighbor's grandma, Thanksgiving small talk tends to erupt into a storm of nonsense. "Global warming? Yeah right - did you feel how cold it was yesterday?"

"You know, the government actually does have a cure for cancer. They just want to help fuel the pharmaceutical industry"

And so on and so forth. To help you prepare for such encounters, here are a few of my favorite videos/infographics summarizing some key scientific concepts. Happy eating and safe travels!

1: The top 10 things you need to know about Ebola, via the CDC

2. This FANTASTIC video explaining climate change from Veritasium

http://www.youtube.com/watch?v=OWXoRSIxyIU

3. This video explaining the fundamentals of evolution

https://www.youtube.com/watch?v=hOfRN0KihOU

4. Top 10 things to know about stem cell therapies

5. Preparing for landing on Philae

https://www.youtube.com/watch?v=AvkPFXdpOQQ

6. And finally, and perhaps most importantly: what happens when you eat too much?

http://www.washingtonpost.com/posttv/c/embed/168a5c54-73e6-11e4-95a8-fe0b46e8751a

Linking autism and the genome

With the dawn of advanced genetic sequencing and the completion of the Human Genome Project, science is rapidly trying to dissect the genetic causes for a wide variety of human disorders. Some of the most perplexing human disorders fall on the autism spectrum, which includes things such as autism and Asperger syndrome. Disorders on the autism spectrum are characterized by deficits in social/communication skills, repetitive behaviors, and cognitive delay (in some cases). Researchers have desperately been trying to link particular genes to autism spectrum disorders (ASD) for many years, as successes in this field may potentially lead to promising therapies. While this problem has certainly been daunting, scientists recently reported in eLife that they have made an interesting connection between a gene called SEMAPHORIN 5A (SEMA5A) and ASDs.

Before I talk about SEMA 5A and it's role in the brain, I want to briefly emphasize the sheer complexity of your brain. The human brain is certainly one of the most fascinating structures in all of nature, with 80-100 billion neurons making 100 trillion connections to process thousands upon thousands of thoughts a day. Everything from your thoughts on the meaning of life to whether or not you want to wear a coat outside can be reduced to a collection of neurons firing together. That's pretty wild!

Figure 1: Your body has to coordinate the formation of BILLIONS of these neurons!

As you can imagine, the way in which these neurons connect with one another (these connections are known as synapses) is very tightly controlled. Exactly how this is done is the topic of a lot of research labs around the country (including the lab I worked in as an undergraduate) and is a very fascinating area of research.

SEMAPHORIN 5A is known as an autism susceptibility gene, which are genes that are associated with high risks of developing ASDs. SEMA5A is a protein that controls the formation of dendritic spines, which are projections from dendrites, the part of the neuron that receives input from neighboring neurons.

Figure 2: A comparison of neurons when the SEMA5a gene is deleted. Focus on the two red boxes: the red box on top is when SEMA5A is present, and the red box on the bottom

The difference is pretty dramatic, and mice with SEMA5A deleted gained many of the behavioral characteristics that humans with ASDs have. The exact reason why an increase in dendritic spikes causes behavioral abnormalities is still not very clear, unfortunately.

I know what you're thinking - so what? Why does this matter? While it may seem like the knowledge gained from this paper seems somewhat limited, keep in mind that this gene, in conjunction with many other genes, are required for a properly functioning neural circuit. If we can understand what genes go awry in different diseases, we are one step closer to fine tuning therapeutics to target those specific genes!

Rough.

If you recall, I mentioned that there was a possibility that I would receive the placebo in my clinical trial, which is just saline. Well, it looks like I actually received the vaccine... As the day went on yesterday, my joints started to feel really achy. Hips, knees, and lower back. At one point during the night, it felt like someone had tied my legs to a truck and told it to drive off - ouch! My temperature also hit about 101.6 degrees, which is a pretty good fever. What's worse is that my raging fever alternated with strong chills, so I had to adapt to feelings ranging from hellfire to Arendelle.  I know this is for the good of humanity and whatnot, but there were definitely points last night where I thought to myself, "Damn, was this worth it?".

And it definitely was! As sudden as the symptoms began, they left without a trace. I woke up this morning feeling great and my fever had completely abated. I went for my regularly scheduled appointment and blood draw and my nurse said I was good to go! If my case is at all similar to the other patients in my cohort, I should be in the clear for the time being. I'll be receiving a booster shot of the vaccine in about a month, so I'll let you know if it's any better the second time around! At least I'm theoretically immune to Ebola, right?

Have a stellar weekend!

My adventures as a clinical trial patient!

Today, I was dosed with an experimental vaccine for the Ebola virus known as VSV-EBOV, produced by a company called NewLink Genetics. Before I go on with my post, here are a few disclaimers. 1. This vaccine DOES NOT contain, nor did it ever contain, Ebola. I will AT NOPOINT receive Ebola. Thus, there is no risk of contracting Ebola.

2. My participation in this study is completely voluntary and is in no way related to my work at the National Institutes of Health (NIH).

3. I am not contagious in any way, shape, or form with Ebola. While this vaccine does take advantage of a different virus, the only way you could catch it is by kissing me. Sorry ladies!

As I've blogged about before, there are currently only two vaccines in clinical trials for the Ebola virus, with several more in active development. For more information regarding the composition of the vaccine, check out my previous blog post. If you aren't inclined to read the whole thing, here is the basic idea:

1. The vaccine contains a virus known as the vesicular stomatitis virus, or VSV. VSV infects farm animals such as cattle, horses and pigs. The virus cannot reproduce in healthy humans, although it may cause some very mild flu-like symptoms.

2. This virus has been engineered to produce a glycoprotein that belongs to Ebola. While the virus itself is not Ebola, this small component is enough for the body to produce an antibody response as if I was infected with Ebola.

3. Now that my body has been primed in this manner, I (theoretically) should be immune to future Ebola infections. Don't worry, this won't ever be tested!

The purpose of this phase in the study is to determine if the vaccine is safe in humans. While VSV has been used in many other clinical trials (safely, I might add), the vaccine must have unique data in order to proceed with clinical development. This study is a double-blind study, which means that neither myself nor the research team will know whether or not I've received the actual vaccine or the placebo (just saline). That being said, here is an overview of what happened to me today!

"A Phase 1 Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of Prime-Boost VSV Ebola Vaccine in Healthy Adults"

Step 1: Arrival

Last week, I was screened at the NIH Clinical Center for things such as HIV and Hepatitus, which would have disqualified me from participating in the study. Those results came back negative (phew), which gave the team the green light for me to continue forward! I arrived at the NIH at around 7:30 this morning, and after having my car searched I entered the actual Clinical Center for my appointment.

Figure 1: The NIH Clinical Center, America's Research Hospital

The NIH Clinical Center (or Building 10, as it's known around here) is a very interesting place! The Center itself is not your average hospital - it doesn't provide services such as labor and delivery or other basic services you would expect at your local hospital. Designed as research facility, the Clinical Center contains more than 1,600 laboratories that are manned by over 1200 physicians, scientists and dentists. I genuinely felt fortunate to be at the Clinical Center as a healthy volunteer. Many of the patients here have very rare or undiagnosed diseases, which really cemented how important the continuation of medical research is for me. I made my way up to the clinic to begin my appointment, passing by countless families, patients and scientists alike.

Step 2: The Visit

As soon as I arrived at the clinic, I was ushered into an examination room where my case manager gave me a general physical exam. After he confirmed that I was healthy, I was sent down to phlebotomy for a blood draw and urine collection. Remember that the purpose of the vaccine is to generate antibodies against Ebola, so this blood draw is intended to be a "baseline" measurement.

The nurses here are professionals - I've never had an easier time giving blood! I blinked and it was all over. The nurse who took my blood told me that she had been in the same spot for about fifteen years - I guess practice really does make perfect! All in all, they took 66 milliliters of blood split into about 15 different tubes.

Figure 2: That's a lot of blood!

While I was in the phlebotomy department, the Clinical Center's pharmacy was busy making the vaccine. There are no stockpiles of this vaccine lying around (at least, not in Maryland), so it has to be made fresh every time I receive a dose!

Step 3: Injection

I returned to the clinic and received the vaccine. Nothing too crazy here. Pokey thing goes in, stuff is injected, pokey thing comes out. Easy! I initially felt a little soreness around the site, but nothing more painful than I've received with other routine vaccinations. Note that out of the 13 people in my cohort, 3 will receive a placebo vaccine, which contains only saline. It's entirely possible that I received a placebo - I won't know until the study is over!

I stuck around for about an hour just to make sure I didn't have any, err, dramatic responses to the vaccine. Thankfully I didn't and was able to return to work right after my visit!

Figure 3: The diary card I'll be using to monitor my symptoms.

For the next year, I will be monitored for any adverse reactions to the vaccine. This includes regular visits the clinic (which means regular blood draws) as well as monitoring my symptoms via a diary card and thermometer. I'll be updating you all on how I'm feeling, as well as with more information regarding the status of the vaccine and it's implications in the fight against Ebola!

Sensationalism in Science: Is this for real?

For some people, reading over science headlines in your local paper or favorite website can be a little scary. With articles talking about "3 parent babies" and the emergency of a new "stupidity virus" infecting half of our population, it's easy to think that we have entered bizarre futuristic world where mad science runs unabated. Is this really what's going on? Today, we're going to talk a little about journalistic sensationalism and why it harms the conversation gaps that we're trying to bridge between scientists and the general public. I'm not saying there isn't any truth to some of these crazy titles. 3 parent babies do technically have genetic material from three people. The so-called stupidity virus does slightly reduce some aspects of cognitive function in humans. These two stories, however, are much more complicated than their headlines may have you believe. I'll talk more about the above two stories in more detail in a future post, but the point is that you can't really convey the subtleties of a new technologies or discoveries in a sentence. In reality, you should be prepared to critically evaluate and engage every headline you see, science or not. There is usually much more than meets the eye!

A few days ago, I saw a post entitled the "9 Disgusting Things the FDA is Letting You Eat" pop up on my Facebook feed. What scandal! If we can't trust the FDA to keep crazy things out of our food supply, how can we trust going to the grocery store ever again? As with most posts of this nature, the truth is really that frightening. Let's dive into a few examples.

Figure 1: Keep out of my pantry, big scary government!

The very entry lists "sawdust" as the first FDA approved disgusting additive. It then goes on to talk about how the actual additive is known as cellulose, which is derived from wood when used in food. So why isn't this a bad thing? Cellulose is an incredibly important polymer that makes up the cell walls of plants. What else has cellulose besides wood? Every plant on Earth. Whether your body receives cellulose derived from wood or from celery is moot, as your cells cannot tell the difference between the two. Harmful? Hardly.

Another post lists "human hair and duck feathers", which probably just sparked horrific memories of you finding a hair in your lunch back in middle school. The post goes on to talk about how the real additive is L-cysteine, which is removed from hair and feathers. Here's an image of what L-cysteine looks like, and what your body sees when it is added to your food:

Figure : The ever terrifying L-cysteine. Gross, right?

L-cysteine is an incredibly important and common amino acid in the human body and is present in a wide variety of things. As with the "sawdust above", we arrive at a common theme that characterizes many food-based science articles. Regardless of where the L-cysteine came from, your body won't be able to tell the difference. A molecule is a molecule is a molecule, any way you slice it. Harmful? Of course not!

Another axiom to keep in mind (especially important in food science) is that disgusting doesn't mean harmful. Just because the source of a particular amino acid or vitamin may sound gross doesn't mean it's bad for you!

In the end, many of these articles aren't really so scary after all. Sensationalism is used to grab a reader's attention, but it's usually very misleading and in the case of articles about scientific information, reckless. It's the responsibility of both journalists and scientists to make sure that any discussion we have with a reader is frank and honest. Until we get to that point, expect plenty of misleading articles and topics to gain a lot of attention and traction in the coming years. So the next time you pick up your paper or open your favorite website, make sure you ask yourself:

Is this for real?

What goes in an Ebola vaccine?

On my last post, I talked about the current state of Ebola vaccines and how close we are to getting them into patients. Today, I'll chat a little bit about how the Ebola vaccine actually works! Let's focus on one of the two vaccines in Phase I clinical trials right now, produced by a company known as NewLink Genetics and the Canadian National Microbiology Laboratory.

Figure 1: Professor Adrian Hill, Director of the Jenner Institute, and Chief Investigator of the trials, holds a phial containing the Ebola vaccine at the Oxford Vaccine Group Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)

In general, the purpose of a vaccine is to prepare your immune system to respond to a particular virus. Your body has the incredible ability to remember pathogens (any infectious agent) that it has encountered in the past, so by giving your immune system a "heads up", it's ability to knock down the virus goes way up.

There are a few ways to accomplish this. Some vaccines are inactivated vaccines, which means that the virus is completely killed before it is introduced into a person. The viruses for rabies, smallpox, and the flu are made in this way. Some vaccines are also attenuated, which means that the virus is live, but was raised in a way that disables its ability to become virulent. Lastly, a vaccine may feature a protein subunit of the virus in question, but not the entire virus. This would be the equivalent of giving a bloodhound a piece of a criminals clothing. It's not the actual criminal, but it's close enough for the purposes of recognition!

The NewLink Ebola vaccine (known as VSV-EBOV) is a combination of the last two types of vaccines. It features an attenuated virus, although it is NOT the Ebola virus. Instead, the scientists used a virus known as vesicular stomatitis virus (VSV), which causes flu like symptoms in farm animals. This virus has been genetically engineered to express one of the Ebola proteins, thus giving your immune system a chance to recognize what Ebola looks like and produce the antibodies that will eventually fight if off. Clever, right?

So far, the safety of this vaccine is being tested in humans, with hopes of ramping up production and sending the vaccines into West Africa!

Ebola vaccines and pipelines: Where are we now?

With the Ebola virus raging on in West Africa, scientists and clinicians around the world are racing to develop feasible treatments and vaccines. Here in the United States, there are currently two vaccines in Phase I clinical trials here at the National Institutes of Health. But what does that mean in terms of development? Are we close to deploying these therapies in Africa? To illustrate the typical path of development for drugs, here's a little graphic produced by Nature Drug Discovery:

Figure 1: The drug development pipeline. Note that the Ebola vaccines are currently in Phase I studies!

As a side note, the NIH center where I work focuses on the stage just before Phase I, which is preclinical development. As the title implies, Phase I-III trials are conducted in human patients in the clinic. Briefly, here is a summary of the three different phases:

Phase I: Safety. In this phase, the vaccine is given to healthy individuals to determine if the vaccine is safe in humans and to establish what doses are safe. The virus in question is NOT given to the patient in this phase - this is simply to test if the vaccine by itself is safe.

Phase II: Efficacy. In this phase, the vaccine is given at full therapeutic dose to patients with the virus to determine whether or not it is effective. There are plans in motion to send doses of the vaccines to West Africa for this purpose.

Phase III: More efficacy! In this phase, the trial is expanded to a much larger amount of participants in a final determination of biological effectiveness.

These trials normally take years to complete, but due to the desperate need for therapeutics the "typical" pipeline is being greatly enhanced. The Phase 1 trials are underway, so hopefully GlaxoSmithKline and NewLink Genetics (the two companies with intellectual property rights in the vaccines) will be able to finish the entire pipeline as soon as possible. I'll go into more details as to how the current vaccines work in a few days, but keep an eye on the news to see if any new experimental drugs pop up!

An alternative to antibiotics?

I blogged a month or so ago about the worldwide danger of rising antibiotic resistance - can you imagine going to the doctor with a bacterial infection and not having any feasible medications available? A very scary scenario! Recently, researchers from a Swiss biotech startup published a paper in Nature Biotechnology about a potential new strategy in fighting bacteria, all without using antibiotics. Score one for science! The key to this solution is the creation and injection of liposomes, which is a collection of lipids that closely mimics a cell membrane. These liposomes are engineered to "soak up" the toxins released by bacteria, which are primarily used to combat your immune system. Once these toxins are out of the way, your immune system can sweep up the remaining infection!

Figure 1: An example of a liposome!

Of course, this assumes that your immune system isn't compromised in any way. As many physicians have pointed out, it's likely that this technology won't completely replace antibiotics, but they may be used in conjunction. For example, administering these liposomes to patients who are suffering from system shock due to toxin overload, but require a fair amount of time for the full identification of the bacteria. These liposomes could buy them precious time!

Perhaps the greatest benefit for this therapy may lie in its ability to provide us with an alternate mechanism to antibiotics. Remember, the enemy is great in number but our arsenal is limited! Don't fire 'til you see the peptidoglycans of their cell walls!

Global Climate Change: The fight for our future

Earth. Isn't it beautiful? Rolling hills, deep blue oceans, and lush rainforests. If you take some time to step back and marvel about the wonder that is our home, it's pretty obvious that we'd like for our Earth to remain the way it is. Nourishing, full of life, and full of wonder.

This past weekend, the Intergovernmental Panel on Climate Change (IPCC) produced The Synthesis Report, a 116 page report detailing the results of nearly a year of comprehensive research performed by the panel. This research centered around a few key features: why climate change is happening and what can we do to stop it. A huge number of scientists and policy experts contributed to the findings (which are far too long to list here), but here are a few key points to focus in on:

1. "It is extremely likely that more than half of the observed increase in global average surface temperature from 1951 to 2010 was caused by the anthropogenic increase in greenhouse gas concentrations and other anthropogenic forcings together"

2. "Without additional mitigation efforts beyond those in place today, and even with adaptation, warming by the end of the 21st century will lead to high to very high risk of severe, widespread and irreversible impacts, globally"

3. "Climate change will amplify existing risks and create new risks for natural and human systems. Risks are unevenly distributed and are generally greater for disadvantaged people and communities in countries at all levels of development. Increasing magnitudes of warming increase the likelihood of severe, pervasive, and irreversible impacts for people, species and ecosystems. Continued high emissions would lead to mostly negative impacts for biodiversity, ecosystem services, and economic development and amplify risks for livelihoods and for food and human security."

I could really go on and on, as even the summary of the findings is 40 pages long. While the findings request daunting amounts of change to the way in which we interact with the other, I think it's important to note there there are many ways in which we can significantly slow down the effects of climate change.

I feel for environmentalists, I really do. From losses on Capitol Hill to seeing problems exacerbated by climate change snowball out of control, I imagine it's pretty easy to feel a sense of despair!

As I detailed in a previous blog, however, fighting the good fight will lead to victories. Human-induced climate change stands to affect everything we hold dear: biodiversity, water availability, global economic security, and so on and so forth. To slow down climate change is to save animals from perishing. It means ensuring that rural communities will have a little extra water on which to survive. Perhaps most importantly, it means that we are giving our children another shot to get things right. What lesson are we teaching future generations if we decide to give up because the goal seems too far away? Too impossible?

If there's one thing I want you to take away from reading my blog, it's that anything is possible. Anything. This isn't Francis standing on his soapbox (okay, maybe it is), but if you have your doubts, I encourage you to read the reports. Because, as is true with most things, the truth lies in the science.

Spooky science!

On this All Hallows' Eve, I've decided to spotlight one of the oddest (some would say creepy) experiments ever conducted in the biology. I hope you enjoy! Around the year 2000, researchers at Stanford were experimenting with an idea called parabiosis, which is a technical term that refers to the joining of two separate organisms into one larger organism. In the case of the Stanford lab, researchers joined the circulatory systems of two mice, one old and one young, and the results were quite extraordinary...

Figure 1: A simple schematic of how the experiment was set up!

The group, led by stem cell biologist Amy Wagers, found that when blood from younger mice was coursed through the veins of older mice, the older mice had high amounts of myelin regeneration. The myelin sheath is a material that coats the neuron and is essential for proper neuronal function. This same setup has also been shown to heal cardiac and liver tissue in aging mice. But what causes this improvement?

The same lab eventually identified a protein called GDF11 that is the probable cause of these miraculous events. When injected intravenously, GDF11 has been shown to reduce thickening of the heart, allowed for faster muscle recovery, and even increase the sense of smell in laboratory animals. It's thought that GDF11 works by increasing the activation of stem cells.

While this experiment may seem like mad science, its implications for human disease are quite large. Giving a natural protein such as GDF11 to the elderly may be safer than current drugs and do wonders in slowing down the aging process!

Okay, so the story isn't quite as scary as that of Countess Elizabeth, who was known to bathe in the blood of her victims in an attempt regain her youth. But you can't deny that's it's just a little bit spooky! Happy Halloween!

Figure 2: Happy Halloween! Love, the creepiest villain in history

Interpreting science 101

Alright, so I've talked a lot about increasing communication between the scientific community and the rest of the world, but how can we actually do that? As I pointed out in a previous post, increasing such communication is a two way street. Over the next few months, I'll be periodically introducing some basic tips on how to critically examine everything, from scientific papers to your local election advertisements! One of my favorite concepts in interpreting data was taught to me a very long time ago. In fact, this axiom is something I carry with me pretty much every day. ARE YOU READY?! Repeat after me...

Correlation does not imply causation.

Ah, isn't that beautiful? Believe it or not, applying this statement to anything you see on television or read in a newspaper will help you determine whether or not the claims they announce are true. To explain what this sentence means, I present an excellent example of this reasoning as described by the Simpsons:

Figure 1: Simpsons lessons are the best lessons!

Let's apply this concept to a different, more science oriented setting. Say your aunt gives you a new herbal tea, with the intention of curing your cold. If your cold goes away after drinking the tea for a week, did the tea cure your cold? Not necessarily! The cold could have resolved itself on its own, or you may have taken another medication that treated it! Correlation does not imply causation.

Alright, one more example. Let's say you're sitting in your car during traffic, and you're really hoping that the light will turn green. In desperation, you scream to yourself, "WILL YOU JUST TURN GREEN ALREADY?!" The light turns green. Did your screaming cause the light to change? Audience, now's your chance to write down your answer!

If you said no, you've clearly been paying attention! Correlation does not imply causation.

When you look at a news article, scientific or otherwise, you should always ask yourself two questions:

1. Do I believe that the claims made in this piece true? 2. If yes, how do I know they are true? If no, how do I know they are not true?

While correlation does not imply causation won't directly answer either of those questions, it's a great way of pumping the breaks and realizing that arguments or claims may not be as crystal clear as the author may want you to believe.

At the risk of having this post grow too long, the take away message is this: just because two events happen at the same time doesn't mean they influenced each other! Keep this point in mind and I will guarantee that your likelihood of getting bamboozled by some ridiculous claim will go down by at least 70%!

Hijacked!

First, a big "thank you" to all of you who have joined in reading my blog! I appreciate all of your support and I sincerely hope you enjoy exploring science with me! With the recent outbreaks of Ebola in West Africa and the isolated cases in the United States and the rest of the western world dominating headlines, your fears over the emergence of this and other viruses have probably increased quite dramatically in the past few weeks! But how can a virus, considered nonliving in the world of biology, become so dangerous? As you may have guessed based on the title of this post, it all lies in the ability of the virus to hijack your cells. Deception, cunning, betrayal. A viral infection has all of the makings of a great spy movie!

As I was sipping my coffee this morning and scanning the headlines, I spotted a very interesting paper published in Science that described how Influenza A virus (IAV, which kills between 250,000 and a few million people very year) uses your own cells against you. To illustrate how this all works, here's a schematic created by the team at Science about how the virus gets into your cells:

Figure 1: Influenza A getting to work! Sneaky sneaky!

Let's start at the very beginning! The virus, shown in yellow, is engulfed by your cells via a process known as endocytosis. Once the virus is enveloped in an endosome (the bubble like structure that results from an object being ingested), the virus begins to increase the acidity within that environment. This increase in acidity results in a fusion of the virus with the endosome, which marks the beginning of Influenza's grand escape.

The goal that the virus is pursuing is to inject its payload into your cell's nucleus. This payload includes things such as viral enzymes and RNA, which the host cell (you) will use to produce viral DNA and viral proteins. This is very clever, as your cell will just assume that genetic material in the nucleus needs to be converted into proteins. At this point, the virus has won! But as you can see from the image above, the virus is enveloped in its own shell that must be broken in order to deliver these things into the nucleus.

To make that happen, Influenza A waves around a little protein called ubiquitin, which is actually a signal your cells used to determine what things need to be degraded. Once your cell sees this signal, it sends proteins to go after the virus in an attempt to degrade it, which was the focus of the paper mentioned at the beginning of this post.

Now here's when things start to get a little mysterious! In the same vein as your favorite murder mystery, there is a span of time in this process that we just can't seem to account for. Experimentally, the authors have shown that something happens in between the recruitment of degradation proteins and the breaking of the viral shell, but we aren't sure exactly what that is. But whatever mechanism that the virus is taking advantage of to break itself free, it will likely become a very promising drug target.

No breakage = no payload delivery = no infection. Virologists, start your engines! The search is on!

*Author's note* Ebola is also an encapsulated virus; thus, it must also break free of its shell to deliver its payload. To what extent it uses the above mechanism performed by its brethren remains to be seen!

"Talk science to me"

Okay, maybe those aren't the exact words that Poison sang 27 years ago, but it was the easiest segue I could think of into the topic of this blog. This post is going to be a little different from past ones, where I've highlighted interesting stories or developments in the world of science. Rather, I'll be focusing on the very reason why I started Kitchen Table Science in the first place: communication.

Figure 1: This is me (somewhat aggressively) promoting neuroscience!

Yesterday, I read a very interesting article from the Huffington Post that compiled quotes from various politicians who have shied away from talking about scientific topics. Their general excuse?

"I'm not a scientist!"

This is essentially the equivalent of covering your ears and saying "la la la la la I don't hear your facts". But who is at fault here? I, and many others in the scientific community place a lot of the blame on ourselves. Science is a wondrous thing, built on the backs of giants and heavily invested in by your tax dollars. We work hard to better our collective understanding of the world around us and it's only fair that we bring everyone along on that journey with us. Can I get an amen?!

If you're reading this blog, you've probably already spent some time browsing the internet, be it Facebook or Twitter. My challenge to you, dear reader, is to find a news article in the sciences, read it, and discuss it with a friend. Do you have a friend with diabetes or cancer? Are you curious as to why the leaves seem to be changing slower or faster this year? As detectives Mulder and Scully would say, "The truth is out there!".

My dream is that everyone, including our elected officials, will one day be able to critically discuss and analyze findings emerging from laboratories around the world without having any advanced training. I want to see these discussions being started at your water cooler at work, or over a lovely meal at your kitchen table. You shouldn't need to be a scientist to talk about stem cells or climate change. After all, can we not debate literature without being novelists? Or discuss world affairs without being a diplomat? If your answer to the above two questions was "of course we can", then let's chat!

Increasing public engagement within the scientific community has been a struggle for a long time, but the advent of the internet and social media is making it easier and easier to disseminate knowledge to everyone. While we'll always work to improve our skills, I am making it my personal mission to be the best communicator of science that I can be.

On a side note, let's also stop trying to put spin on science for personal gain when spin isn't necessary. I'll never understand perverting science to bend to one's own agenda; but then again, I'm not a politician!

Figure 2: Not a politician...yet? Photo courtesy of Sean Hickey Photography

Detecting cancer, one CTC at a time

In honor of breast cancer awareness month, I've been scouring science headlines around the internet to find really interesting, clever, and unique approaches to fighting all sorts of cancer. I stumbled on some fantastic research this morning that really piqued my interest; I hope it does the same for you! The early diagnosis of cancer makes a dramatic difference in the prognosis of patients. Take, for example, breast cancer. Below is a chart showing 5 year survival rates of breast cancer patients relative to the stage at which the cancer was diagnosed:

Figure 1: The 5-year relative survival rates among breast cancer patients

The contrast between Stage I and IV survival is pretty stark, as you can see! The cause of this jump is a phenomenon known as metastasis, which is cancer's ability to spread its tumors from the primary site to remote organs. In fact, the majority of breast cancer fatalities occur due to these remote tumors (in the bone, liver, etc) rather than solely cancer in the breast. This is a defining feature of Stage IV cancers.

Detecting these metastatic tumors has been a challenge, but recent advances have allowed scientists and clinicians to detect circulating tumor cells (CTCs) in the blood. This allows us to study and monitor cancer in a noninvasive manner, which is critical in ensuring that the cancer treatment process is as painless as possible. Aceto et al. published a paper in Cell describing a very interesting discovery in the nature of these cells. As it turns out, the cells that are the most successful in establishing remote tumors travel in clusters, rather than in isolation.

Figure 2: A schematic showing CTC mediated tumor establishment. Credit: Aceto et al. 2014

These cells express a protein called plakoglobin, a cell adhesion protein which presumably allows the cells to remain in contact with one another until they reach their destination. Traveling in this way seems to provide a protective advantage, as the scientists also noted that solitary tumor cells suffered much higher rates of cell death. Patients with high levels of this protein in their cancer cells had a much shorter metastasis-free survival time.

Researchers hope that with this new knowledge, our monitoring of cancer patients will become much more effective. For example, if a clinician notices that levels of plakoglobin and/or clustered CTCs are rising in his/her patient, that may call for a more aggressive treatment regimen. It may also warrant a closer examination of the genetics of these clusters, as metastatic tumors are notorious for having different genetics than their parent tumors, which may partially explain why some chemotherapies eventually stop working.

For more information, check out the full paper in the first hyperlink above. The more you know!

Ebola - Some Key Messages

With fear of the spread of Ebola rising around the world, I think it's always helpful to reassure ourselves with the facts. So here are just some key statements (according to WHO) to keep in mind when reading the news!

1. Ebola is most infectious in the blood, feces and vomit of those infected with Ebola. Some levels have been detected in semen, urine, and breast milk. Data regarding the presence of Ebola in saliva and tears is inconclusive, and the virus may only be present in saliva during the latest stages of infection. Lastly, Ebola has never been found in human sweat.

2. Ebola is not an airborne virus, and there is no evidence to suggest that viruses can radically change their mode of transmission.

3. That being said, there is a difference between airborne viruses and viruses spread via sneezing/coughing. The term "airborne" refers to the ability of the virus to remain virulent when in suspension in the air. If someone with Ebola sneezes directly on you, that is the direct transfer of virus particles from within that patient to you via projectiles.

4. Ebola can be transmitted indirectly (i.e. touching surfaces with Ebola), although this risk is low and can be mitigated via disinfection.

I'm not saying that these statements mean that Ebola is not a threat in the United States. As was shown in Dallas, it is clear that we have the infrastructure to contain the virus, but we are at risk only when basic protocols are breached. In addition, "no evidence" does not necessarily mean it couldn't happen. After all, science has shown us crazier things before!

Just remember these facts when discussing Ebola with your friends. Knowledge is power!

Losing your vision? There's a cell for that!

I feel like I wake up every morning and experience the same few things: a hot cup of coffee, a cold bowl of cereal and an article describing some breakthrough in stem cell technology. Yesterday was certainly no different, as a paper published in the journal Lancet described an exciting study by researchers from several institutions regarding the treatment of disorders of the eye.

Figure 1: Dr. Steven Schwartz, the lead author on the above study

The scientists injected cells derived from human embryonic stem cells (hESCs) under the retina of patients in the study. These patients suffered from two diseases that lead to vision loss: age related macular degeneration and Stargardt macular dystrophy. They found that more than half of the patients improved their eyesight, which is pretty remarkable considering that it was extremely unlikely that their vision would have improved on its own. More importantly, however, was that none of the patients showed adverse reactions to the cells!

A common question I get about these therapies is as follows: if we have supplies of stem cells and if they work fairly well in animals, why aren't we using them to cure humans? The biggest roadblock for the use of stem cells in the clinic is a lack of data regarding safety. Consider this: stem cells are naturally programmed to grow into all of the cells that your body needs. As you can imagine, many scientists are concerned that reimplanting these cells into our bodies may lead to cancer, which can be loosely defined as the out of control growth of a population of cells. A robust rejection of the cells by your immune system is also a big concern!

Without a doubt, this study is an important landmark in the field of stem cell biology. Now that we've proved (at least, early on) that these cells are safe, you'll probably see many more innovative use of stem cells in human trials very soon!

Curing Diabetes, one stem cell at a time!

I've blogged about the power of stem cells before, most recently regarding their use as a potential treatment for cancer. I cannot overestimate the utility of these cells; just think, these guys can transform into any cell in the human body. That's a pretty crazy thought. Lack a particular organ or gland? We can make that for you!

Figure 1: These human stem cells were plated using a printer. Credit: Dr Will Shu / Biofabrication

As you can imagine, the therapeutic potential for research in stem cell biology is massive. I would not be surprised if the routine use of stem cells in the clinic becomes as common as an antibiotic prescription.

Case and point: Some very brilliant (and creative) researchers at the Harvard Stem Cell Institute, led by Dr. Douglas Melton were able to cure type 1 diabetes in rats using insulin-producing cells that were created from stem cells. Type 1 diabetes is a disease in which the beta cells in your pancreas, the cells that make insulin, are attacked your body's immune system. Insulin is a hormone that allows your cells to control the level of glucose in the blood, so those who suffer from diabetes have volatile blood sugar levels.

This is a massive step forward in the field, as the majority of current diabetes interventions involve patients monitoring and injecting extra insulin when necessary. Some excellent automated devices have been made to this effect, they clearly lack the advantage of using insulin produced natively in the body. Were this therapy to move into people, suffers from type 1 would no longer have to rely on any sort of injection system to deliver their insulin. Very exciting news!

As with all things, remember to take this research with a grain of salt. I don't want to sound like a debbie downer, but the jump from treating animals to people can be quite tricky. For example, researchers still need a way to ensure that any implanted cells remain unharmed by your immune system. Another challenge is the origin of the cells: the cells used in this study were derived from embryos, which remains a controversial source. Melton and his colleagues are investigating ways to generate beta cells from induced pluripotent stem cells, which is a way to make stem cells without relying on an existing embryo.

All in all, I think this story represents a win for a science and a huge leap forward for patients everywhere!

Rare Disease Spotlight - Kabuki Syndrome

If you're at all familiar with Japanese art or have been fortunate enough to visit Japan's theater scene, you're probably seen someone with Kabuki-style make up. This iconic style is characterized by dramatic, thick highlights around the eyes on top of a snow white background.

Figure 1: Some examples of Kabuki make up

In 1981, researchers from the Kanagawa Children's Medical Center in Yokohama, Japan identified a rare genetic disease that they subsequently reported on in The Journal of Pediatrics. They called the disease "Kabuki syndome", due to similarities between the appearance of the afflicted with the make up styles described above.

Figure 2: A child with Kabuki syndrome

Only 1 child in 32,000 births are diagnosed with Kabuki syndrome each year and they suffer from variety of congenital defects, ranging from hearing loss to growth deficiencies. The disease was only discovered about 30 years ago, so we lack any significant information regarding life expectancy, but there is no current indication that this disease shortens lifespan.

As with many rare disorders, the advent of robust gene sequencing techniques greatly assisted geneticists who were interested in Kabuki syndome's root biological causes. In 2010, Sarah Ng and colleagues reported that the disease was due to a mutation in a gene called MLL2. But what does this gene do? To fully explain, let's dive into a short biology lesson!

Imagine your cell. Small, healthy, and unassuming. Now, imagine a small speck in the center of that cell, about 10% of its total volume (this is normally around 6 micrometers, or six millionths of a meter). What you are now visualizing is the amount of space available for your cells to pack in all of the genetic information required to code for your entire body, which would be about two meters long if you stretched it end to end! How does your body cram all of that material into such a small space? From the perspective of the cell, it approaches this problem in the same way you would if you were packing clothes into a suitcase for a trip. The key is the way in which you pack everything!

As it turns out, DNA is wrapped very tightly around proteins called histones, which are then wound tightly around each other to form structures called chromosomes. Below is a nice illustration of how that all works:

Figure 3: Packing in the DNA!

Pretty incredible, right? As I mentioned earlier, Kabuki syndrome involves a mutation in a gene called MLL2. This gene codes for a type of enzyme called a methyltransferase, which is an enzyme that affects how tightly some of the DNA in your nucleus is wound up like in the picture above. This is important, as the DNA must be relaxed for it to be translated into proteins. When the DNA is wound up tight around histones and in chromosomes, your cells can't take a look at them because they're all covered up!

Thankfully, most of the medical issues associated with Kabuki syndrome can be helped with modern medicine. While we can't cure genetic disorders yet, science is also providing us with interesting solutions to these tough problems!

And the Nobel goes to...

Most people adamantly follow their favorite sports team or skim through People magazine to predict who the next Oscars will go to, but the Nobel Prizes will always remain my Super Bowl/Academy Awards/World Cup! On October 6th, the Nobel Assembly announced the winners of the Noble Prize in Physiology or Medicine, which in my opinion (contrary to many others - the rest of them are great too!) is the coolest prize in town. So who won, you may ask?

Figure 1: Ice cold, BA knowledge smiths

The above team won for "for their discoveries of cells that constitute a positioning system in the brain". Many have been calling this the brain's "internal GPS". But what are these cells, and how do they work? Let's take a brief look at their prize winning research:

In 1971, John O'Keefe noticed something very interesting when he peered into the hippocampus of rats in his laboratory. When the rats would walk around the cage and stand in a certain place, certain neurons were activated. When the rats would move somewhere else, different neurons were activated. It became clear that the rat was building an internal map of its surroundings, which was quite easy to visualize by just looking at which neurons were firing. He called these neurons place cells, as they play a fundamental role in allowing the animal to understand where it exists in three dimensional space. Cool stuff! Note: this hasn't really been shown in primates yet, although I think it's safe to say that we also have a similar system!

Drs. Moser and Moser (they're married, isn't that adorable?) found that in a nearby part of the brain, the entorhinal cortex, certain neurons are activated when a rat runs over a particular spot in space. These spots constitute a grid that develops in this cortex, effectively forming a coordinate system that the rat can use to position itself. Hence, an internal GPS!

These discoveries show that even in processes that seem infinitely complex, science can always (eventually) tease apart the underlying mechanisms by which these processes occur. With initiatives like BRAIN here in the United States, I look forward to seeing the other secrets of the brain that continue to be unlocked!

*Bonus* Here's a wonderful graphical summary of the prize created by our friends at the Nobel Foundation put together! Illustration by Mattias Karlén.