Breast Cancer Awareness Month - The State of the Research

Happy Breast Cancer Awareness Month! In the United States, October has been designated as a month to increase awareness and to raise funds to help accelerate biomedical research in the valiant search for a cure (The actual origins of NBCAM are a little shady, but I won't get into that here).

Figure 1: A pink ribbon, go find and wear one today!

All across the country, charities are organizing walks, concerts, and various other events to get people to donate to the cause and to start meaningful conversations about breast cancer. Every year, 1 in 8 women in the United States are diagnosed with breast cancer and it is estimated that we lose 40,000 women a year to this terrible disease. While these statistics are painful to look at, modern medicine has increased survival rates to levels never thought possible. I am continually encouraged and inspired by the strong women who continue to beat breast cancer every year and it is extremely important that we keep fighting for this cause. Below is a brief summary of what breast cancer is and what is the latest research in the field.

What is breast cancer?

Breast cancer is a disease in which cells in the breast (typically the cells that line the milk ducts) become cancerous. The mechanisms by which cells develop into cancer are complicated and varied and the risk factors that play into your likelihood of developing cancer are equally varied. Many of you have heard of BRCA1 and BRCA2, so called "breast cancer genes", which caused Angelina Jolie to receive a double mastectomy in 2013. This terminology, however, is a little misleading!

Having BRCA1 and BRCA2 is actually normal, as these genes are responsible for repairing damage to DNA (which is one way in which cells can turn into cancer cells). It's when these genes are mutated that cancer can arise. It's estimated that about 5-10% of breast cancers are related to this mutation, which leaves a significant portion of breast cancer cases open to a slew of other causes. Obesity, smoking, environmental conditions; it's all been implicated in potentially causing breast cancer. *Note* The research linking breastfeeding (or not breastfeeding) to an increased risk for breast cancer remains inconclusive.

Figure 2: BRCA1

As I mentioned, survival rates for breast cancer have reached all time highs. Nevertheless, breast cancer is still a significant killer of women (and men!) every year.  It accounts for 25% of all cancers in women and resulted in half a million deaths worldwide in 2012. Recommended screenings for breast cancer are recommended for women over the age of 50, but it never hurts to start performing self exam today!

What is currently being done to treat breast cancer?

Currently, the conventional approaches to treating breast cancer are a combination of therapies used in other cancers, including radiation and chemotherapies. With respect to BRCA1/2, a new class of drugs known as PARP inhibitors are currently in clinical trials that are being in used in patients with the above mutations. PARP1 (poly ADP ribose polymerase) is a protein that repairs DNA damage. Removing this beneficial protein results in the death of cancer cells, which divide so quickly that they rapidly succumb to a lack of significant DNA repair. Your normal cells divide more slowly and have other mechanisms for fixing this damage, so (for the most part). your normal cells remain unharmed via PARP1 inhibition.

There are also a few anti-angiogenesis drugs currently being tested in the clinic. As you can imagine, tumors require significant amounts of energy and nutrients to grow. One way it accomplishes this is through angiogensis, which is a process that leads to the creation of new blood vessels that lead to the tumor itself. If you can block this, you can effectively "starve" the tumor!

Lastly, there are some drugs known as HER2 inhibitors being tested in the clinic as well. HER2 (human epidermal growth factor receptor 2) is a receptor that sits on the surface of cells. When this receptor is in overabundance, it tends to lead towards certain types of aggressive cancers, so drugs currently developed are trying to destroy these receptors.

All of these treatments are very promising and are creative attacks on cancer mechanisms. This is a very brief summary of the sort of therapies that are being developed around the world; there are many other interesting treatments that are constantly being investigated, both in the clinic and in the laboratory! While we will always have to live with cancer as a part of our lives, I am confident that with continued research we will be able to reduce cancer from a high-level threat to a minor inconvenience.

The OTHER Nobel Prize

Earlier last month, the 2014 Ig Nobel prize awards were given out to scientists pushing their respective fields in unimaginable directions. You're probably more familiar with the Nobel Prize, which is presented to individuals who have significantly increased our understanding of the world around us. What then, are the Ig Nobels, you may wonder?

Figure 1: Alfred Nobel, chillin' like a villain (who just invented dynamite)

The Ig Nobel Prizes were established in 1991 to highlight research that "makes people laugh, then think". These awards are usually pretty hilarious; you'll understand what I mean when you see some of the winning projects for this year!

Biology: "...documenting that when dogs defecate and urinate, they prefer to align their body axis with Earth's north-south geomagnetic field lines." Public Health: "for investigating whether it is mentally hazardous for a human being to own a cat." Art: "for measuring the relative pain people suffer while looking at an ugly painting, rather than a pretty painting, while being shot [in the hand] by a powerful laser beam. " Arctic science: "For testing how reindeer react to seeing humans who are disguised as polar bears."

For the full list of the winners, check out the Ig Nobel's website at http://www.improbable.com/. I've always wanted to win a Noble prize, but I think that I'd settle for an Ig!

For those of you who are curious, the actual Nobel prizes should be awarded within the next few weeks, with the prize in medicine or physiology coming in on the 6th. Expect a post an explanation of the winning science!

Why flies?

As most of you are probably aware, I did the vast majority of my research in college on Drosophila melanogaster, the common fruit fly. At about 2.5 mm in length, you've probably seen them hanging around trashcans snacking on whatever they can find! As you can probably imagine, having to justify why I did research in flies to both family and friends proved to be very tiring. Why don't I work on something real, like cancer research (spoiler alert - this can also be done in flies)?

Figure 1: Drosophila melanogaster

All around the world, thousands of researchers spend countless hours and millions of dollars studying the intricacies of these little guys (they're kind of cute, right?). In her first speech on her domestic policy plan during the 2008 elections, Sarah Palin famously scoffed at the idea of fruit flies ever being used for the public good:

http://www.youtube.com/watch?v=HCXqKEs68Xk

In her defense, the leap from flies to humans seems pretty extreme. How can any information about people be extracted from a bug? The answer to this question (and the answer to many other questions biology) can be boiled down to one thing: evolution.

Thousands of years and hundreds of speciation events later, we as humans are related to many other critters in various ways. As it turns about, about 75% of known human disease genes have matches in the fruit fly genome and 50% of protein sequences in flies are also similar in humans. This allows us to study many diseases relevant to us without experimenting on actual people. You know, ethics and stuff. This is also why we continue to do research on other model organisms, such as mice or rats. Fruit flies also carry many other advantages, such as:

1. Their cost of care and culture is low

2. They have rapid generation times, allowing us to study many generations of flies within a relatively short amount of time.

3. They have only four chromosomes, making genetic analysis much simpler

And many many more. There have been three Noble prizes awarded to fly research and the use of our little friends in the laboratory has lead to discoveries in fields ranging from neuroscience to developmental biology. So before you think of fruit fly research being frivolous, remember that the alternative would be experimenting on YOU!

Using stem cells to treat cancer?

Cancer is a very interesting disease. As I mentioned in a previous blog post, its ability to mutate into countless different forms means that generating effective ways to combat it is no small task. Researchers and physicians usually have to be pretty creative with how they approach treatment- no one drug will help every patient! A very interesting review coming out of Nature talks about a very interesting new way in which scientists are approaching this problem. As was reported by several laboratories, it turns out that stem cells have the natural tendency to migrate towards tumors. Using this principle, biologists are beginning to hijack these stem cells to deliver a wide variety of different things. Here is a brief summary of some of the therapies discussed (for the full story, check out the paper that I linked above!

Figure 1: A colony of stem cells!

Strategy 1: Delivering Therapeutic Proteins

There are many proteins out there that can be used to cause the spontaneous death of cells. One of these proteins is called TRAIL; it binds to a protein called death receptor 4 (ominous, I know!) and causes apoptosis, which is the cells way of destroying itself. By navigating directly to the tumor, stem cells are able to deliver these noxious proteins directly to the cells they wish to kill while sparing the surrounding tissue!

Strategy 2: Stem Cell Mediated Suicide Therapy

In this treatment, stem cells migrate to the tumors of interest and convert a previously harmless drug into one that is pretty nasty! By doing, this the stem cell sacrifices itself while simultaneously preventing the risk of it going on to divide into different things. This also means that dangerous drugs will only appear at the tumor site - if the drug manages to escape and go somewhere else, it won't be toxic because it hasn't been converted any stem cells!

Strategy 3: Nanoparticle delivery

One of the biggest difficulties in getting drugs to their targets is the body's own immune system. Your innate defense system is pretty potent (which is a very good thing!), but it also means that drugs are recognized as foreign entities and are quickly destroyed. To get around this, scientist have begun to surround drugs in nanoparticles, which your body doesn't identify as being a bad thing. This "Trojan horse" method allows your therapeutic of choice to sail past the defenders and make it to the end zone. Touchdown!

Figure 2: What your stem cell friends look like delivering nanoparticles. Close enough, right?

Strategy 4: Oncolytic Virus delivery

Oncolytic viruses are viruses that selectively destroy the rapidly dividing cells characteristic of cancerous tumors. However, the delivery of such viruses is difficult due to the same hiccup described in strategy 3: avoiding host immune defenses. The ability to "hide" within a stem cell allows the virus to remain inconspicuous until the moment is right!

Figure 3: A schematic of the therapies discussed above. Pretty snazzy! Picture courtesy of Nature Reviews Cancer.

But as you may note from the the title of the review, Stem cell-based therapies for cancer treatment: separating hope from hype, not everything is as simple as it seems! The field of stem cell research is still relatively young; thus, there are still a myriad of problems with using stem cells in humans. These issues are too long to list here (contact me if you wish to discuss!), but always take any new revolutionary treatment with a grain of salt. I, however, remain incredibly optimistic that we will circumvent these challenges and that stem cell therapies will soon become routinely used in the clinic!

Antibiotics, a most powerful double-edged sword

When we are sick, our first instinct is normally to reach for the closest pill or to pay a visit to our local pharmacy. In an age and culture where we expect immediate gratification, it is very tempting to find the solutions to all of our medical problems in a convenient little drug. Now before I discuss the main topic of this post, I am in no way endorsing forgoing medication. Modern medicine is a wondrous thing, and we have been extraordinarily successful at creating longer and happier lives via pharmaceuticals. That being said, the use of antibiotics is something that deserves some extra special attention! But first: what is an antibiotic?

Figure 1. Microorganisms. Many are good, some are bad!

An antibiotic is defined as an agent that either kills or inhibits the growth of a microorganism. Common antibiotics include penicillin and tetracycline and can operate in wide variety of ways. Some antibiotics kill bacteria by degrading their cell wall, while some interfere with the bacteria's key enzymes. The discovery of the first antibiotic is a very interesting story which I will spotlight in a later post!

These antibiotics are normally pretty effective at wiping out an infection. Most people after taking their first pill feel pretty great after 5-7 days. Super effective!

As powerful as these pills are, bacteria are very crafty little critters. As soon as one bacterium (out of millions of other little guys) develops a resistance to a drug, they are able to pass on this resistance to their fellow bacteria. Pretty soon, you've got a population that laughs in the face of the drug you just took.

Figure 2. Simba is ambitious, so are microbes!

Well, why can't we just use a different antibiotic when one becomes resistant? While this is a plausible solution, there are only a finite number of antibiotics currently in existence. If we have bacteria that are resistant to all of these, we're toast! So needless to say, it's in our best interest to limit the rise of these so called "superbugs". Here are three ways in which you can help make sure this happens:

1. Finish your course of antibiotics!

When you are prescribed antibiotics by your physician, you are given a series of pills which you must take on a regular basis. Many people feel fine after a few days of medication, so they stop taking the pills. This is would be a critical error, as you may leave small populations of bacteria left in your system who now have a chance to acquire immunity. Don't give them a fighting chance! Is taking four more pills really that much of a hassle?

2. Know that not everything can be cured by an antibiotic!

As I mentioned earlier, we are often very quick to turn to the cure that works the fastest. Remember that many things that make us ill are caused by viruses, and will not be affected in any way by antibiotic treatment. Below is a wonderful table from the Mayo Clinic that summarizes some differences between diseases caused by viruses and bacteria. A study recently published in Pediatrics found that there are about 11 million instances in which antibiotics were inappropriately prescribed to patients. Yikes!

3. Sharing is not caring!

If you follow the first two rules above, this shouldn't be an issue! I have seen an alarming amount of people over the years giving leftover antibiotics to their friends and family because they feel ill. The overuse of antibiotics plays a large role in allowing them to learn what all of these medications are and develop resistance. So before you go around asking for antibiotics, remember that their use should only be under the supervision of a physician!

Science is good, smart science is even better!

What is Ebola?

One of the most frightening headlines emerging in the media within the past few months is the current Ebola outbreak in West Africa, which has claimed over 2200 lives at the time of this post. With the outbreak continuing to worsen, I've decided to give a (very) brief primer on what Ebola is, how it spreads, and what is being done to contain it!

1. What is it?

The term Ebola virus actually refers to five different species of virus, all of which cause a disease known as Ebola hemorrhagic fever. The virus is named after the river near which it was discovered in 1976 in the Democratic Republic of the Congo. All viruses are infectious agents that require a host to survive and can infect all forms of life, including bacteria! When the virus enters a host, it invades the cell by attaching to proteins known as receptors on the cell surface. It then penetrates the cell membrane and uses the host cell's own machinery to produce viral proteins. These proteins then leave the cell, destroying the host cell in the process. This leads to a cascade of cells dying and causing a massive immune response, which results in the symptoms mentioned below.

Figure 1: Ebolavirus

Ebola hemorrhagic fever has several key symptoms, including headache, severe muscle pain, diarrhea, vomiting, stomach pain, and unexpected bleeding or bruising. Of those infected with Ebola, only about 47% survive, which is pretty terrifying!

Figure 2: Ebola symptoms, according to the CDC

2. How does it spread?

Ebola spreads via contact with blood or the bodily fluids of an infected animal. It is not known to spread via the air. Ebola has been known to infect animals such as bats, gorillas, chimpanzees, and pigs and normally resides in these animals as a natural reservoir. Virus transfer from a live animal to a human is unlikely except in cases where a human has either handled the animal carcass or eaten the meat.

Stopping the spread of the virus in the current outbreak has been difficult for many reasons. First, adequate medical supplies and personnel have been scarce in the regions hit hard by the virus, leading to international calls to raise the amount of support for such humanitarian efforts. The virus spreads best when humans (both living and dead) are in close proximity to one another, which usually happens in these overcrowded facilities. Second, it is thought that a major way in which the virus spreads is due to local burial practices, including washing the body of the diseased (the key here is direct contact!). Lastly, there are plenty of cases of Ebola denial in which some deny that the virus even exists. Such claims range from that the virus is a complete hoax to the Ebolavirus being an invention of the West!

Many people grew concerned when we decided to bring back an American physician afflicted with Ebola for treatment back here in the United States. In fact, Donald Trump raised a salient point (sarcasm here, folks) that sending aid into Africa is risky, as our troops will return home "infected". Right.

It's important to note that the reason this virus is spreading so quickly isn't necessarily due to how deadly it is; it has more to do with health disparities in Africa. Healthcare officials weren't concerned with bringing Dr. Sacra back home because we have more than enough facilities to keep the virus contained and to keep hospital staff safe.

3. How do we stop it?

This is a pretty difficult question to answer, although a recent escalation in support from the White House will certainly help to curb the epidemic. According to the World Health Organization, we would ideally stop Ebola transmission within 6-9 months and prevent its international spread. While the report itself is 27 pages long, it boils down to the following: strike fast, strike wide, and strike hard. With models predicting thousands of new cases in the coming months, it is imperative that the international community band together to stop this malady from spreading around the globe. What is perhaps the most difficult thing about fighting Ebola is that we need to gain victories on the cultural and information front as well. Once we spend the time educating those most likely to be affected about the dangers of Ebola and how to halt its advance, curbing its spread should be much easier. A threat to human health is a threat to global health, but I am confident that this outbreak is causing many to stand up and fight the good fight!

For more information visited the World Health Organization's website at www.who.int.

Schizophrenia - More than meets the eye

Schizophrenia. The word tends to conjure a wide range of images, from hearing voices to extreme paranoia. Symptoms of schizophrenia are diverse and include false beliefs, paranoia and unclear thinking. You may have been introduced to the disorder in the film A Beautiful Mind, where mathematician John Nash is diagnosed with paranoid schizophrenia. Figure 1: A self portrait of a person with schizophrenia

Schizophrenia is obviously much more complicated than what is portrayed in the movie, but until recently we understood very little about it's biological basis. Researchers from the Washington University in St. Louis have recently discovered that schizophrenia is actually a collection of eight different disorders, each with a unique genetic profile. This is very exciting, as this new outlook on schizophrenia will allow psychiatrists to tailor more focused treatments to patients with specific subsets of the disorder.

I think that it's very common for us as humans to desire a simple association between a disease and its cause. With the advent of cheaper forms of genetic sequencing, it is quickly becoming clear that many human disorders (both mental and physical) have very complex genetic causes. Personalized medicine, or using each person's unique genetic signature to craft patient specific treatments, is something that I think will quickly become the norm in modern healthcare within the next few decades.

Remember: our knowledge of many diseases often represents just the tip of the iceberg! There is still so much to learn, which makes science a very exciting frontier to explore!

For more information on schizophrenia, take a look at this primer from the National Institute of Mental Health.

A recovering ozone layer: A lesson in long term investing from Mother Earth

Many of you out there are probably aware of that one of the most dramatic effects of releasing pollutants into our atmosphere is the destruction of the ozone layer, which would allow harmful ultraviolet radiation to reach our planet. Thankfully, after 30 years of legislation and environmental campaigning, it appears that the ozone layer is recovering! This brings us to two important lessons for today:

1. What is ozone? And what made it disappear in the first place?

Ozone is a form of oxygen made up of three oxygen molecules instead of two. It naturally forms in the stratosphere (a layer in Earth's upper atmosphere) through interactions between ultraviolet radiation and normal oxygen. The accumulation of ozone at this altitude is a good thing, as it prevents these ultraviolet rays from hitting us in the face! I don't know about you, but I'd rather not increase my risk of skin cancer.

Figure 1. The sandwich that saves our skins

On the other hand, ozone can also be a bad thing. At ground level, ozone forms from the interaction of pollutants such as oxides of Nitrogen (NOx) and volatile organic compounds (VOC). This is a bad thing, as breathing in ozone can reduce lung function. Yikes!

  In the 1970's, it was discovered that chemical compounds called chlorofluorocarbons (CFC)s reacted with atmospheric ozone and destroyed it, leading to the so called "hole in the ozone layer". You may be familiar with a more proprietary CFC produced by DuPont called freon. After this realization, leaders around the world signed a document called the Montreal Protocol, effectively phasing out CFCs. It took 30 years, but it seems like the ozone is finally rebounding!

2. The environment is worth it.

When the protocol was signed, it generate a pretty sizable negative response from the CFC industry, including DuPont. They claimed that the science "wasn't conclusive" and that government regulation on CFC emissions would kill jobs. Sound familiar? Of course, neither of these things proved true and it's estimated that we've prevented millions of cases of skin cancer because of a global ban on CFCs. The point here is that while the economic benefits of environmental protection may be difficult to see in the short term, the global health gains are potentially immense. So before we pick a path that will put more change in our pocket, perhaps we should consider solutions that add more years to the lives of our children instead.

After all, what would Captain Planet do?

http://www.youtube.com/watch?v=VcJI87u3DoQ

UPS - It's not just for packages!

Happy Monday internet! I hope you all are having a great start to the week - I know I am! The Lasker Foundation announced today that the recipient of the Albert Lasker Basic Medical Research Award would be awarded to Dr. Kazutoshi Mori from Kyoto University and Dr. Peter Walter from the University of California, San Francisco for their work on the unfolded protein response. This award, often known as the "American Nobel", is one of the highest awards that can be given to a scientist.

Figure 1: Living that science life

The unfolded protein response, or UPS, is an important process that cells carry out to maintain their internal environment. For any protein to function properly, they must be folded in a specific way. To put this in another way, imagine a nail buried halfway into a block of wood. If I gave you a saw and a hammer, both of the same weight, which would you use to pound the nail into the wood?

Even if you had no idea what a saw and hammer were typically used for, you would probably discover quite quickly that the hammer is an ideal tool for driving that nail further into the block. One of the cardinal rules in biology is that structure dictates function. Your proteins are the same way - they must be folded and shaped in a way that best suits their eventual function. But if proteins are folded improperly, this is a bad thing. In reference to the previous example, if the hammer head was forged in such a way that it resembled a cork screw, it would certainly not be able to do its job very effectively!

Figure 2: Yikes.

If your hammer factory was producing hammers in such a fashion, you'd probably want to halt the production of the faulty hammers, get rid of the faulty hammers you already have and hire someone a bit more competent to create better hammers! The goals of the UPS are the same:

1. Stop the translation or new proteins 2. Degrade misfolded proteins 3. Increase the production of chaperones, which are proteins that assist in protein folding.

How each of these steps occur and are regulated are beyond the scope of this post, but just remember: your cells are always hard at work making sure that you are healthy and happy! So the next time you're feeling like you don't want to get out of bed on a Monday morning, just remember that your cells have been hard at work all night so that you can tackle your week!

For more information on how to tackle difficult production situations, please see the following educational film produced by Ball et al. in 1952.

http://www.youtube.com/watch?v=8NPzLBSBzPI

Francis, what exactly do you do...?

Many of you have asked what I've been up to since I graduated from George Mason in May, so I thought I'd dedicate this post to my fellowship and what projects I've been working on! As of June 2nd, 2014, I have been a research fellow at the National Institutes of Health, the US government's main agency responsible for biomedical research. The NIH is comprised of 27 different institutes and centers, including the National Cancer Institute (NCI) and the National Institute of Allergy and Infectious Disease (NIAID). In particular, I work within the National Center for Advancing Translational Sciences (NCATS), which focuses on solving problems related to translating the knowledge generated in basic research laboratories into human therapies.

I'm involved with NCATS' Therapeuetics for Rare and Neglected Diseases program (TRND), which studies diseases with very small patient populations. Not only do these diseases lack enormous patient advocate organizations (such as the American Heart Association), they tend to get very little research funding because there is almost no opportunity for profit. After all, with the average therapeutic costing billions of dollars and years to develop, why would a pharmaceutical company want to pursue something that it would never make a buck on?

Of course, that's an extremely oversimplified explanation of a complicated problem. In fact, many firms have dedicated research programs for rare diseases. Improving this scenario by advocating for innovations in the drug production pipeline (a more detailed description of this will follow at a later date) is critical, which is where we come in.

As of today, I'm working on some drug discovery projects related to the following: X-Linked Creatine Transporter Deficiency (CTD), Pulmonary Alveolar Proteinosis (PAP), and a side projected related to Amyotrophic Lateral Sclerosis (ALS). I'm really loving what I do, and I'm so thankful to have this unique opportunity to work on critical problems facing human health. While I certainly miss my flies, working with human cells is a whole new adventure!

For more information, check out this video:

http://www.youtube.com/watch?v=iYd5zxvF4HQ

Feeling hot hot hot

If I were to walk outside of my office, I'm pretty certain it would feel like something between the surface of the sun and the fires of Mount Doom. According to the Capital Weather Gang, it feels like 98 with humidity and is easily one of the hottest days this year for the DC metro area. Between you and me, I think I'll spend most of the day in our walk in refrigerator. Figure 1: Washington, DC.

I, for one, am not looking forward to hopping back into my car after work! But this got me thinking - how hot does it get in a car in this kind of heat?

According to Jan Null, adjunct professor at San Francisco State University, the average sedan (when it's 90 degrees outside) can get to 124 degrees within 30 minutes and 133 degrees within an hour. To put that into context, the record for the hottest temperature ever recorded on planet earth was 134 degrees at Death Valley National Park, California. To combat these insane temperatures, most people recommend opening the car windows a tad to allow some of this hot air to escape. But does this really work?

In a study published about a decade ago in Pediatrics, McLaren et al. found that cracking your car windows does not significantly reduce the maximum temperature reached or the rate at which these temperatures increase. So there you have it - that tip your dad told you about opening the windows slightly doesn't work. The solution? Park your car in the shade! That direct sunlight is a major reason why the temperature rises so quickly in your car.

Figure 2: A raging inferno enclosed in a small, metal box

And under no circumstances should you ever, EVER leave a living creature inside a vehicle for an extended period of time, especially in this sort of weather! Stay cool, my friends!

How am I supposed to breathe with no air?

For many of you who experienced cicadapalooza, you probably remember these little guys hanging out on every tree for miles:

Figure 1: AHHHHHHHHHH

Well, these bad boys are the exoskeletons of cicadas, which they remove before maturing into adults. This process is called molting, and is essential in the lives of organisms that wish to "outgrow" their current form. Crazy, right? As it turns out, the story ends up getting a little crazier...

In a paper recently reported on by Science published in Freshwater Science, researchers from North Carolina State University and the Strout Water Research Center looked at the molting process in mayflies (Cloeon dipterum). They found that this process is, unfortunately, very stressful for our insect friends!

Cloeon.dipterum

Figure 2: Cloeon dipterum, the most common mayfly in the British isles.

When these mayflies remove their exoskeleton, they also shed the interior lining of their respiratory system. This would be the equivalent of you shedding your lungs...yikes! When the biologists measured the oxygen consumption rates during this process, they found that while this inner lining was being replaced, the mayflies actually held their breath for approximately 45 minutes before beginning to breathe again.

Significance? As global temperatures begin to rise, insects will begin to molt more and more. All of those periods of extreme oxygen deprivation may be harmful, but the jury is still out on whether or not holding their breath for this long actually causes tissue damage.

In the end, just be glad that you don't have an exoskeleton to shed!

Will we ever cure cancer?

One of the most common complaints that I receive at my kitchen table (and at numerous family gatherings) is why we haven't come up for a cure for cancer. If we can put a man on the moon, surely we can fight a disease that has been around for centuries, right? Well, as you might imagine, it's not that easy!

A very interesting study published in Nature Communications that recently came out of Kiel University is making quite a stir. In short, the study established that evidence of cancer can be found in organisms that are extraordinarily high in the evolutionary chain, suggesting that cancer has been around since the dawn of time and that it may ALWAYS be a part of life.

So is curing cancer even possible?

Figure 1. Cancer cells from a human prostate

I think that its important to rethink what we mean when we say "cancer" and critically look at the nature of the beast. The word "cancer" is an enormous umbrella term, encompassing over 200 different types of cancer. Each of these different types of cancer could have multiple unique pathways that contribute to their manifestation, and that these cancers can invade every organ in your body. Eradicating cancer as a global health problem would mean finding  treatments to combat hundreds of molecular pathways. That's a lot of chemotherapeutics!

It's also important to note that when one thinks of cancer, they usually think of it running in someone's family. As it turns out, only 5-10% of cancers are related to inherited genetic mutations; the remaining are due to environmental factors. And when I say environmental factors, I mean everything. Stress. Diet. Viruses. Pollution. Solar radiation. Smoking. The list goes on and on!

There are 7  billion humans on this planet. Curing cancer would involve having treatments for every mechanism of cancer, for every type of cancer, and that are compatible with each person's unique genetic make up. So will we ever live in a world without cancer?

Probably not. However, we will one day live in a world where cancer becomes so easily treatable that it will be effectively eradicated, which is still a very promising vision of the future!

I have come across some very interesting new research on cancer therapies that I will be publishing within the next week. There are thousands of scientists around the world who work tirelessly to find a cure, and I remain INCREDIBLY optimistic that we will one day beat cancer. Every single time.

Coffee 101: What's an Arabica bean?

I usually like to come in to work at least 30-45 minutes early so I have a chance to brew a nice big cup of coffee. By the time my morning ritual is over, I have energy coursing through my veins and I am officially wide awake! I feel energetic, inspired, and ready to tackle any scientific problems that are thrown at me. Move over Darwin - Francis is ready to make history! When I picked up my can of coffee this morning, I noticed a small phrase towards the bottom of the can: "100% Arabica Coffee Beans". What is arabica, and are there other beans? Fear not reader, yours truly did some sleuthing to find out!

Arabica coffee beans originate from a particular species of coffee plants known as Coffea arabica. Most commercial coffee growers and coffee connoisseurs alike consider arabica beans superior to those of the next most widely cultivated species of coffee, Coffea canephora (also known as "robusta" beans). It's estimated that arabica beans make up about 80% of all coffee produced in the world. These two plants grow in very different environments which causes significant differences in the chemical composition of the beans and their flavor profile.

Figure 1. Arabica berries and beans                                 Figure 2. Robusta berries and beans

Robusta beans grow at a lower altitude and contain double the amount of caffeine that their arabica cousins have. As a result of their immense caffeine content, they are much easier to grow as they are resistant to pests and disease. In fact, robusta beans are significantly cheaper than arabica beans due to their different growing requirements. So why aren't these more widely consumed? It's all about the flavor!

Arabica beans are known for their extraordinary depth of flavor when roasted, whereas robusta beans have a rather harsh flavor profile. They produce very strong, bitter notes which are used by some coffee brewers to either use as filler in lower-end blends or to add a depth of flavor in espresso, where bitterness is already expected.

So there you have it folks - if you're hardcore, you'd probably get the most caffeine for your dollar with robusta beans. While I agree that arabica beans have much more complex flavors, never be afraid to push society aside and just drink what you think tastes wonderful! Because, as Taylor Swift would say:

If You Sprinkle When You Tinkle

One of the things that I love about science is that it's often incredibly bizarre, which often makes for the most interesting table conversations! As I was scanning the most current issue of the Proceedings of the National Academy of Sciences (which is one of the most highly respect journals in the scientific community), one paper in particular popped out at me: "Duration of urination does not change with body size".

Francis, you've lost your mind. Urination? Really? Someone funded this?

Before you cast judgment, let's delve a little into what these researchers at the Georgia Institute of Technology looked at.

Patricia Yang et al. used a combination of high-speed videography and flow-rate measurements to discover whether or not the size of a mammal influences the rate at which it empties its bladder. There were a plethora of images and videos, which I will spare for the sake of decency. There were several fun facts and findings listed in the paper, a few of which I've summarized here:

1. An elephant's bladder, at 18 liters, is nearly 3,600 times large in volume than a cat's bladder which can only hold 5 milliliters.
2. Most small mammals (Less than 3 kg) take between 0.01-2 seconds to urinate, while larger mammals take about 21 seconds.
3. The peak pressure in your bladder is consistently measured 5.2 kPas, or about 1 X10^-6 pounds per square foot.
4. Larger animals tend to have continuous bladder streams, while small animals tend to urinate in small droplets

Figure 1. These animals take the same amount of time to pee!

So then why do smaller mammals take just as long to empty their bladders than larger mammals? Don't they have less volume to release? As it turns out, all of this can be explained via basic physics. As you would imagine, larger animals contain larger urethras, the part of the body that carries urine from the bladder to the outside world. These longer urethras have greater hydrostatic pressure driving the flow of liquid forward, allowing for high flow rates. The narrower urethras of smaller animals causes urine to only exist in small drops due to high viscous and capillary forces. Liquid tends to slow down in narrower pipes because more of this liquid is interacting with the interior of the pipe. In contrast, large pipes also have liquid interacting with the interior of the pipe but this leaves the majority of liquid to flow in the middle at maximum velocity.

Figure 2. Laminar flow. Note the faster flow is towards the center!

You're probably experienced this phenemonan in rivers in streams. If you step into a river, you'll note that water is moving pretty slowly near the shore. But if you were to walk directly into the water, you will notice that the water is moving much faster in the middle of the river. This is called laminar flow. Pretty snazzy!

In summation, all mammals above 3kg empty their bladder in 21 +/- 13 seconds. This is incredible, as this same rate is applicable for animals as small as a cat to animals as large as elephants. So in the end, who cares? What's the significance?

Based on the average time it takes to urinate, the average mammal spends about two minutes a day urinating. Given that this is such a small proportion of a mammal's day, it likely does not influence reproductive fitness, or the ability for an organism to pass on its genes (especially in comparison to activities such as eating and sleeping). The newly found significance in the geometry of the urethra, however, may play a role in more important activities such as ejaculation. This knowledge may also be used to find urinary problems in animals and in biological-based hydrodynamic systems.

Remember that all science is significant, you may just need to adjust your perspective!

ALS: The disease behind the challenge

Unless you've been living under a rock, you're probably well aware of the ALS Ice Bucket Challenge. This social media campaign has stormed the internet, flooding newsfeeds from Facebook to Twitter. In this challenge, a person "challenges" their friends to the ice bucket challenge (pouring ice water over your head) or they have to donate $100 to the ALS Association. If you scour the internet hard enough, you may even be able to find my attempt...

As silly as this may seem, you can't deny that it has definitely sparked conversation and has raised more than 79.7 million dollars since July 29. Incredible!

But what exactly is ALS, and why is it so devastating? Join me as we explore the biology behind Lou Gehrig's disease!

Part 1: The Basics: What is ALS?

Amyotrophic Lateral Sclerosis, or ALS, is a progressive neurodegenerative disorder that affects the motor neurons in your brain and spinal cord. Essentially, motor neurons are cells in your nervous system that control your muscles. These are the same neurons that allow you to chew your food and shove your way into metro cars during rush hour! Below is a little schematic of what they look like:

The structure on the left hand side of this picture is known as the soma, or the cell body. In neurons, electrical signals originate at this point and travel down the axon in the center of the neuron! When the impulse reaches the end of the neuron, it causes the muscles that it's associated with to contract. In ALS patients, these axons begin to contract, causing the muscles to lose their association with the motor neuron.

When muscles aren't stimulated, they tend to waste away. This process is called atrophy. You may have heard of atrophy ocurring in the legs of patients who have been in a wheelchair for an extended amount of time. In cases like these, the idea is the same: If you don't lose it, you'll lose it! This leads to eventual paralysis of several parts of the body.

About 25% of ALS cases are what is known as bulbar onset. These patients begin to lose control over their voluntary muscles their head and torso, leading to difficulty breathing and speaking. The remaining 75% of patients are known to have limb onset ALS. These patients begin to notice symptoms in their arms and legs before the disease spreads to other parts of their body. It's estimated that 30,000 people in the United States at any given time suffer from ALS, which is why attention to this terrible disease is so important.

ALS is fatal - after disease onset (which normally happens after the fourth decade of life), most patients succumb within 3-5 years.

What causes ALS? Is it genetic, or does it happen spontaneously?

Unfortunately, we don't know a lot right now about what causes ALS. Of all ALS cases, 10% are related to a genetic mutation and are known as familial ALS (fALS). The remaining 90% of cases are sporadic cases of ALS (sALS). It's very possible that some patients who fall into the sporadic ALS category have a previously unidentified genetic mutation, or a genetic mutation that those with fALS have that spontaneously occurred.

How close are we to a cure?

This is always a tough question to answer!  Organizations such as the ALS Association and the Northeast ALS Consortium are sponsoring a wide variety of clinical trials with potential ALS treatments. The process by which treatments pass through the usual hurdles to come to market is long and arduous (I may write about this in the future), so even these treatments have the possibility of failing and going back to square one. It’s really easy for small successes in the clinic to be overblown in the media, so I’m always conservative on estimates for this. While I can’t put a timeline as to when we’ll have a viable treatment for ALS, what I can say is the rate at which we are learning more about ALS is greatly increasing! At the risk of making this post overly heavy, if you wish to discuss these particular discoveries, just shoot me a message!

So remember, always hope. Know that there are hundreds of brilliant minds all around the globe working towards a cure, and that one day, we will live in a world where treating ALS is as routine as getting over the common cold.

"Hope lies in dreams, in imagination, and in the courage of those who dare to make dreams into reality." - Jonas Salk

Why science is the greatest thing on Earth. Period.

"Francis, you go on and on about biology. Is it really that great?"

I often say that science is the greatest thing on Earth,  usually to the groans of my friends who reside in other fields. But do you know what I love the most about science? The fact that everyone, in their own way, is a scientist. What do I mean by that, you may ask?

Our good friends at Merriam-Webster define science as the following:

sci·ence

noun \ˈsī-ən(t)s\

: knowledge about or study of the natural world based on facts learned through experiments and observation

That definition (granted, there are many others, but I think this one is pretty good!) means that nearly everything we do can be considered a science. The barista that made you your cappuccino this morning? Scientist. The plumber who spent an hour figuring out how to fix your pipes? Scientist. The cleaning person who had to figure out how to empty every trashcan in the building before closing? Scientist.

Figure 1. A barista blurring the lines between art and science

Science, at its core, is a way of thinking. When you take in observations of the surrounding world, apply a few sprinkles of logic and execute a plan, you've just performed a bit of science yourself! Thus, the only thing that makes "natural" scientists (i.e. biologists, chemists) different from accountants, dancers, and florists is simply what problems we choose to apply our logic too. Our days are filled with "everyday science", ranging from cooking your dinner to evaluating whether or not the telemarketer on the phone is trying to scam you out of fifty bucks.

Science is about asking questions and questioning everything. Science is about being curious and not being afraid to travel down the road less traveled on. Science is about finding something that lights a fire in you that burns like an inferno, so hot that it makes you want to spend your whole life pursuing, understanding, and embracing it.

YOU are a scientist, and life is one giant experiment. That's pretty freaking cool.