Stem Cells (written for the KidsKnowIt network)

Cell Differentiation (Specialization)

Cell differentiation is the process where cells acquire a new identity. This allows the cell to perform more specialized roles in the body. Almost all cells in the body differentiate from stem cells.

Image 1 (large): <https://www.istockphoto.com/photo/3d-illustration-of-transparent-cells-with-nucleus-on-purple-background-gm877371150-244844464>

As you go about your day, take a moment and consider all the jobs your cells are doing. Your neurons in your brain are responsible for your thoughts and feelings. Your heart cells pump blood throughout your body. Your skin cells defend your body from invaders. It takes a lot of work to keep you healthy! But where did all these cell types come from? How does a cell figure out what job it needs to do? As with many things in biology, it all starts with stem cells.

Stem Cells

A stem cell is a cell that can renew itself. This means that when the stem cell replicates, its "daughter cell" is identical to the parent cell. A stem cell must also be able to generate a more differentiated (specialized) cell. How does a stem cell know whether to produce another stem cell or a more differentiated cell? A stem cell receives its instructions from the environment around it. The home where a stem cell lives is called the stem cell "niche". Signals from the niche will inform the stem cell what sort of cell the organ needs the most!

Image 2 (small): <https://en.wikipedia.org/wiki/Stem_cell#/media/File:Stem_cell_division_and_differentiation.svg> <This diagram shows the decisions a stem cell may make. In purple are the stem cells. They may make more stem cells, or decide to make a more differentiated cell (in blue). These differentiated cells can go on to become more specialized (yellow cells).>

Stem cells are present in nearly every organ in our body. When our organs need new cells, stem cells divide and replenish the organ with fresh cells. For example, when neural stem cells divide, they make a choice. They can make more stem cells, or they can create more differentiated cells like neurons. In the bone marrow, stem cells create differentiated cells you need to make blood.

Every cell that you look at has the same DNA. What makes cells different from one another is which genes are turned on in the DNA. A liver cell, for example, will only turn on liver genes. A skin cell will only turn on skin genes, and so on! 

Very early stem cells have a lot of flexibility in what genes they turn on and off. As they differentiate, they be more selective in what genes are turned on. For example, a neural stem cell will turn off the genes for many other cell types. This leaves only the "neural" genes activated. The more differentiated a cell is, the more specialized its set of "active" genes will be.

Aging

Image 3 (small): <https://www.istockphoto.com/photo/comparison-portrait-of-beautiful-woman-with-problem-and-clean-skin-aging-and-youth-gm921677406-253090358> <Aging results in many changes to our body.>

If stem cells can produce differentiated cells that our bodies need, why don't we live forever? Why do we age? These topics are under intense investigation in the lab. Scientists theorize that as time goes on, our stem cells become damaged. When enough damage occurs to these stem cells, they are no longer able to sustain themselves. If our stem cells are exhausted, then no differentiated cells can come from them! That is bad news for organs. A lack of stem cells means that there are no more healthy cells to replace damaged ones. Over time, this will cause an organ to keep functioning.

More Great Resources

How cells become specialized - AmoebaSisters - https://www.youtube.com/watch?v=t3g26p9Mh_k

Cell differentiation - Nature - https://www.nature.com/scitable/topicpage/cell-differentiation-and-tissue-14046412

Cell differentiation - Microscope Masters - https://www.microscopemaster.com/cell-differentiation.html

By Francis Aguisanda

Landslides (written for the KidsKnowIt network)

A landslide is mass wasting event where soil, rocks, and other debris fall down a slope. Landslides come in many different forms! Rock flows and mudslides are common types of landslides.

 Insert photo 1: (large photo) <https://www.istockphoto.com/photo/landslide-erosion-caused-of-earthquake-and-heavy-rain-gm804402298-130443761>

What causes landslides?

If you looked at a mountain or hill in the distance, what would you notice? Both of these features have sides that are sloped. If you stood at the top of a mountain and dropped a stone, it would roll down the mountain until it reaches the bottom. What keeps the side of a mountain together? Usually, the ground on a slope is strong enough to withstand the force of gravity. Over time, natural process like weathering and erosion, can make the ground on a slope weak. Landslides happen when this ground no longer stable. When the ground loses stability, gravity will pull it down the side of the slope. 

Insert photo 2:(small photo) <https://www.istockphoto.com/photo/asphalt-cracked-road-collapsed-by-landslide-gm805467796-139020935><The ground next to this road became unstable, which led to a landslide.>

Weathering is when rocks, soil, and minerals are degraded by the effects of weather. How can weathering weaken a slope? One form of weathering that can degrade rocks is called frost weathering. If water enters the cracks in a rock and the weather is too cold, it will freeze. Water expands when frozen, so this force can crack the rock even more! If this happens several times, the rock can fall apart and lead to a weakened slope.

Erosion is when a surface process moves material from one location to another. Water and wind are two processes that can do this.Imagine that the mountain in our example was next to a river. Over time, the river may remove enough of the ground under the slope to make it unstable. This could lead to a landslide!

A landslide must be triggered before it can begin. Sometimes, this process is very slow. The slow weathering of rocks may itself be a trigger. In other cases, an abrupt event will trigger a landslide. For example, an earthquake could shake any loose material on a slope and start a landslide.

What are different types of landslides?

Landslides come in four varieties: flows, falls, topples, and slides. Landslides are classified based on how the material in a landslide moves.

For example, a flow occurs when material moves down a slope in a way that resembles a liquid. One major subtype of flow landslides are called a mudflows. Mudflows are caused when large amounts of water make the ground too heavy. This water usually comes from a heavy rainfall or melting snow. Some mudflows are slow, but many move quickly. That is because the water makes the ground flow like a liquid. Mudflows are extremely dangerous. They can travel as fast as a car on the freeway!

Insert photo 3 (small photo) < https://www.istockphoto.com/photo/terrain-landslide-gm694963436-128448079> <This mudflow caused a tree to collapse>

A fall happens when some soil or rock detaches from the side of a steep slope. Once it hits the side of a slope, it makes its way down by rolling or bouncing. 

A topple happens when when a mass of soil or rock falls forward out of the slope. As an example, imagine yourself standing flat on the floor with your back against the wall. Imagine that the wall is the slope of a mountain and you are the ground covering it. If you slowly lean forward away from the wall, you would fall flat on your face! That is exactly what happens in a topple landslide. 

Imagine that you put down a carpet on the side of a very slippery slope. What would happen when you let go? The carpet would slide down to the bottom. The carpet is still fully intact - it just moved positions. This is what happens in slide landslides.The top surface of a slope detaches and slides down. When this happens, the ground that slid down remains intact.

Other Great Resources

Landslides 101 - USGS: https://landslides.usgs.gov/learn/ls101.php

Landslides - National Geographic: https://www.youtube.com/watch?v=mknStAMia0Q

Types of Landslides - eSchoolToday: http://eschooltoday.com/natural-disasters/landslides/types-of-landslides.html

And so it begins...

I love science fiction. As both a Star Wars fan and a scientist, I often find myself daydreaming of what the future holds for both technology and mankind. As we continue to progress as humans, we will inevitably hit numerous ethical speed bumps (or speed mountains) along the way to becoming the most advanced species in the universe.  Want to get to Mars? Live forever? Cure all human disease? All of these things sound great, but these advancements are always tied to some pretty hard choices.

Figure 1: Sometimes the choice won't be this easy! The answer is cake, by the way.

A few months ago, I blogged about how genetic engineering has the potential to help cure a variety of human diseases. I also mentioned how thought leaders in the genetic engineering space proposed that a moratorium be held on any attempts to use such technology to edit a human embryo. Well it seems like that those requests were ignored, as a study was recently published in Protein and Cell attempting to correct the gene that causes beta thalassemia in embryos. This disease results in misshapen hemoglobin, the component of your blood that carries oxygen. Misshapen hemoglobin leads to anemia, so you can see why someone would want to cure it! In the above paper, 86 embryos were used in an attempt to correct the mutation. They used CRISPR/Cas9, a very clever system discovered in 2012 that has the ability to hone in on specific regions of DNA, cut out the gene in question, and replace it with a different one. Only a small number correctly replaced the mutated gene with a normal copy, and the process also generated mutations in other unintended parts of the genome.

Let me be very clear here. The researchers (at least, to my knowledge) never intended to implant these embryos into an actual womb. As controversial as this study was, it actually provides us with important confirmation of what we already suspected - we simply need to learn more about how gene editing technologies like CRISPR/Cas9 work before we can hope to use them in an actual embryo. The success rate for this paper was pretty small. The success rate if we want to start using this routinely? 100%.

This technology has the potential to rid the human race of a whole host of genetic disorders, but the fact that we are still extraordinarily naive about how exactly such technologies will behave in an actual embryo cannot be understated. The majority of scientific institutions throughout the world seem to agree with me, with over 170 companies, patient groups, and research institutions stating that a moratorium is necessary. Nature and Science, two of the world's most influential journals, rejected the paper due to its ethical dubiousness.

Just as choosing whether or not to pursue such research will always remain a difficult choice, it is inevitable that this sort of research will continue to be attempted. It doesn't matter if 1000 research centers say that it is dangerous - it only takes on lab. The argument can certainly made that unless we try these techniques in actual humans, we'll never truly know if they work or not. There is only so much that you can do in a laboratory before one needs to make the scientific leap. This leap has been taken many times throughout the history of science, and it's always fraught with the unknown.

Take, for example, Edward Jenner. His name may not be familiar to you, but his invention of the vaccine has saved millions of people around the world. How did he discover this? He inoculated the 8 year old son of his gardener with pus from a person with cowpox, then challenged him with the virus. This worked beautifully, but it certainly seems a little ethically questionable, don't you think?

Figure 2: Edward Jenner advising a farmer to vaccinate his family

Of course, we know better now. We have better informed science, and we have better models upon which to test our ideas. So when will we see the successful correction of a mutation in a human embryo? Only time will tell, but I can guarantee that it'll happen sooner than you think!

Transduction, s'il vous plait?

As most of you are aware, I work for the National Center for Advancing Translational Science (NCATS) here in Rockville, MD. We often talk about translational research at the office - how it works, how we can improve on it, and how we can use it to make people healthier. But what is translational research? The vast majority of biomedical research in the United States is known as basic research. This research seeks to understand the fundamental mechanisms that govern life - how genes are regulated, what proteins influence biochemical pathways in the body, and so on and so forth. I think that this research needs relabeling, as basic seems to imply a lack of complexity (at least, that's what it sounds like to me!). The word fundamental would probably be more apt here, as this research is absolutely critical to applied research. Applie research uses the information gathered in basic research to create new therapies for humans, such as new medical devices or new drugs. The process by which knowledge is transformed from basic to applied research is known as translation, which is the challenging topic that my institute focuses on.

This is certainly easier said than done. As you can imagine, a vast amount of basic research is performed around the world every year, yet the rate at which we develop new therapies is much lower. 200 billion USD was spent on research and development last year ($90 billion in the US) alone in the life sciences, while thousands of scientists work around the clock to figure out new ways to tackle problems in human health. Do you know how many drugs were approved by the FDA last year? 41. Forty. One. This is actually much higher than the 21 per year that the FDA averaged over the past decade.

Okay, let me be a bit transparent here. That figure is of novel drugs approved, which means that the drugs were completely brand-spankin' new. This would be in contrast to repurposed drugs, which are drugs that have already been developed by can now be used for another disease. But even if that number of drugs were in the hundreds, it is still abysmally low relative to the amount of money that we put into research. What gives?

Have you ever volunteered for a walk to help fund medical research? Maybe you've donated some money here and there to foundations promising to accelerate research. If you've been in either of those scenarios, I'm sure you've felt frustrated that it seems like the amount of energy and money that we spend trying to cure diseases usually results in very limited results.

In the end, it boils down to one thing: it's really really really really really really x 1000 difficult to move an idea found in the laboratory to the clinic. So difficult in fact, that my institute was founded on the very premise of solving this as a systematic problem. Once we can solve this problem, we will be able to utilize the vast wealth of basic research that scientists around the world have spent their entire careers on. As the Isaac Newton once said, "If I have seen further it is by standing on the shoulders of giants".

Before I let you go, I'm going to spoil the ending a little. Despite the sort of dreary tone this blog post holds, I am infinitely optimistic that we will only continue to improve the way in which we discovery new drugs and develop new medical interventions. Costs will go down, precision will go up, and most importantly, the quality of life for sick patients around the world will soar. But before we can cross the quagmire that is translation, we're going to need some supplies. What makes translation so difficult? Where do we need to improve on? This is what I'll be discussing in the next few blog posts, so stay tuned for more!

Achoo! How drugs saved my life.

I've been over winter since about mid-January, so when March 20th rolled around I was more than happy to greet the new season. Cherry blossoms, warm weather, and warm rain showers. Best season ever, right? WRONG. WRONG. WRONG. WRONG.

I love most of spring as much as the next guy, but when those pollen counts start ticking higher and higher my body begins a heavy revolt. I start to sneeze, my nose runs, my eyes itch, and my mind starts to become overwhelmed. It heavily affects my ability to focus and is an overall huge hindrance to my productivity - not good when you're working in a lab! For today's post, I'm going to focus on something that has kept me from having a meltdown over the past few weeks - antihistamines.

Figure 1. This is why I don't like going outside. Yuck!

When you experience and allergy attack, be it hives or a runny nose, your body is mounting an immune response to a perceived threat. My immune system, for example, hates cats, grass, and trees. When it detects bits and pieces from these things in the form of dander and pollen, it ramps up the production of antibodies against these allergens. These antibodies then bind to cells called mast cells which contain large amounts of histamine. Once released, this histamine causes a variety of the symptoms you normally associate with an allergic response. For example, these antibodies can bind to mucous membranes in your nasal cavity, leading to a histamine release which causes sneezing and nasal congestion.

Antihistamines work by blocking the receptors that recognize histamine, resulting in a reduced immune response. The earliest antihistamines developed, also known as first generation antihistamines, were not very specific to the histamine receptor. This lead to some undesirable side effects, including drowsiness thanks to their ability to cross the blood-brain barrier into the central nervous system. This is why if you've taken one of these medications (i.e. Benadryl, ChlorTrimeton), you may have had to avoid driving! Because of this side effect, some modifications to these first generation antihistamines are used to treat insomnia (i.e. ZzzQuil).

Then came the second generation antihistamines, which were much better at targeting their intended histamine receptors and only crossed the blood-brain barrier to a small extent. These "non-drowsy" medications include Claritin, Allegra, and Zyrtec. Despite being in the same class of antihistamines, all of these different medications have varying chemical structures and potencies. Your results may vary!

Finally, one of the most popular classes of allergy medications in recent years has been the nasally administered corticosteroids, which includes Flonase and Nasacort. These nasal sprays work in a slightly different way than the above medications and aren't technically antihistamines. These corticosteroids bind to glucocorticoid receptors in the nasal passages, which are important in downregulating immune activity (inflammation).

In my experience, Flonase has worked the best for me. Each person is different, however, and may require different regiments of allergy prevention medications to be effective. For more information, go see your doctor! In the meantime, I'm going to go back into the lab, happy and heavily medicated.

Don't touch my embryo!

In a recent commentary in Nature, leading scientists in the field of genome editing warned against altering the genetic code of human embryos. The authors claim, and rightly so, that it is likely that we will see a great number of studies in the near future that have attempted to edit the embryo at the molecular level. With the advent of very advanced gene editing techniques, we have the power to alter the expression of genes at will, or knock them out completely. Okay, that's probably a gross oversimplification, but you get the picture!

via Shutterstock

The reasoning behind pursuing this technology makes sense. If a patient has a deleterious gene mutation that causes cancer, for example, just remove the gene and insert a healthy one. Easy, right? Indeed, this technique has been performed repeatedly in cells in vitro (in a test tube, glass dish, etc) and in some model organisms such as monkeys, but human beings are whole other ballgame. And as you can imagine, nothing in biology is quite that simple. Editing one gene could affect its interactions with other genes or edit the wrong genes, and these ramifications may not become apparent in entire humans until its too late.

Ethical conversations like this one are extremely important to the advancement of science. Just as our science should be used to inform the public, the public should be used to inform our scientific decisions. I am a very strong proponent of research into genetic modification, as these tools will be immensely powerful in combating the diseases of today and tomorrow. I also acknowledge, very strongly I might add, that this technology is in its very early infancy. Will changing the DNA of an embryo cause untold changes in the developed human? Yes? No? Maybe? The truth is that we just don't know for sure, and it will likely require years of intense research to find out the answer to that question.

I think it's very tempting for scientists to march forward with a disregard for what is ethical - we, of course, possess the technical knowledge to pursue such endeavors. To dismiss the ethical risks that are usually paired with scientific advancement, however, would also risk losing the trust that the public places in the scientific community. Thus, it is immensely important that these processes are transparent and that we are able to engage the public  in an active conversation, no matter the outcome.

I encourage you all to read the original commentary hyperlinked above. Keep an eye out for an increasing debate in the field of gene editing - it's going to get very interesting!

Vaccine Update - plasmapheresis time!

Long time no update! A few days ago, I was informed by the study team that I had  either the highest or second highest (they wouldn't specify) immune response to the experimental Ebola vaccine. As such, they are interested in harvesting the antibodies that my body has generated for use in a potential transfusion to a patient suffering from an Ebola attack. I'm glad my white blood cells are such active little guys! Side note: the data this decision was made on was based on an analysis of my blood conducted in December. The analysis takes a while, so rather than wait to see what my blood has looked like over the past few months the team decided to go ahead and retrieve my plasma now. Using premade antibodies provides an Ebola patient with an extra leg up on the disease. Antibodies are used by the body to discern which things in the body aren't supposed to be there (antigens), so having antibodies against Ebola allows an Ebola patient's immune system to recognize the virus faster and mount a defense of its own. This is how ZMapp worked, which was a monoclonal antibody produced in a tobacco plant that was given to a few of the earliest health workers returning from Africa with Ebola.

To get this process started, I underwent what is known as a plasmapheresis. This is when the staff at the clinical center harvests my plasma, which is the "liquid" part of the blood and is the part that contains all of the antibodies that I have against Ebola. About 55% of your blood is made up plasma. This plasma is then split into different parts and frozen, ready for use should the need arise. A small portion will also be used for further research.

You may have friends who have had this procedure done before - it's not that uncommon! In essence, my blood is removed , spun in a centrifuge, the plasma is removed and the remaining components of the blood are returned to me. The apparatus looks something like this:

Figure 1: The plasmapheresis process. Note that my red blood cells, white blood cells, and platelets are returned to me with the addition of some saline to make up for fluid loss.

And my procedure looked something like this:

Figure 2: The fairly large needle in my arm is able to both draw and return blood, no second needle necessary!

Figure 3: The resulting plasma and the fantastic nurses at the NIH Clinical Center!

All in all, it was a very pleasant experience! The only side effects that people tend to experience is a feeling of faintness, similar to what you would feel during a typical blood donation. The machine also circulates an anticoagulant through the blood, which ensures that the blood doesn't gunk up the system. The anticoagulant can cause tingling in the lips and fingers, but I didn't have any of that. The bed I was in had a memory foam mattress and I was given copious snacks upon the completion of the collection. I'll start with giving three times - the protocol itself allows for up to 20 collections. Hopefully my nurses aren't tired of me by then!

The 40 million dollar placenta

Well, more like placentas. Last year, the National Institutes of Health announced that it was embarking on a new research program studying the placenta. Today, it also announced that $41.5 million would be earmarked for research projects within the program. The policy wonks reading this are probably thinking who the hell would pay so much taxpayer money learning about the placenta? Don't we have better things to research? As with most things within biomedical research, the true value that research brings needs to evaluated with your critical thinking caps on! *I was going to put a picture of a placenta here, but I refrained from doing so for the sake of my readers with sensitive stomachs!*

The placenta, according to the National Institute of Child Health and Human Development, is one of the least understood organs. You're probably aware of its vital role for the fetus: it allows the fetus to feed, remove waste, and receive gases critical to normal growth. We normally look at the placenta indirectly via ultrasound and blood tests, and we can also examine the tissue after birth has occurred. How the placenta changes throughout pregnancy is still a bit of a mystery, so by investing research in this area the NIH hopes to glean new information of how the cells grow and adapt to support the developing fetus.

Why is this important? As I've stated above, the placenta is critical in maintaining the health of the child, so if anything were to go wrong in proper placental development it could lead to potentially life-threatening conditions in the womb. These conditions, including gestational diabetes and preeclampsia (high blood pressure during pregnancy) can lead to miscarriages or premature deliveries. A greater understanding of this critical organ will hopefully gives us the ability to better prevent these tragedies from occurring in the future.

The Epigenome

Today, a slew of very important research papers were published in the journal Nature describing a pretty incredible feat of science - the sequencing of the epigenome (well, mostly). Most of you are probably more familiar with the sequencing of the human genome via the Human Genome Project. Led by the National Institutes of Health (NIH), this endeavor mapped all of the genes in the human body and concluded in the early 2000's. The implications of this new knowledge were pretty huge! From a better understanding of the genetic basis of cancer to more personalized drug therapies, scientists gained a very important milestone in the difficult journey of learning how our bodies work.

Today, we gained another milestone through the sequencing of the epigenome, which are the modifications on the genome that affect which genes are expressed in a given cell. Think for a moment of how diverse the cells in your body can be - some can fire electrical signals to send messages throughout the nervous system (neurons) while some are engineered to produce that insulin that controls your blood glucose (beta cells in your pancreas). The genetic material in these cells, no matter where they are, is exactly the same, give or take the occasional mutation here and there. What makes the cells different from one another are what genes are turned on and off, which is partially controlled by your epigenome.

Figure 1: The epigenome controls which genes are "unwound", revealing their information to your cells. ADAPTED FROM ILLUSTRATION BY SIGRID KNEMEYER, PREVIOUSLY ADAPTED BY LAUREN SOLOMAN

This $300 million project, again supported by the NIH, was quite challenging to say the least! With the human genome project, scientists only had to worry about one genome. The epigenome, however, differs from cell to cell, making any attempts to sequence it pretty onerous. This makes sense, as the epigenome is essential for defining an individual cell's identity! The efforts mentioned above sequenced about 111 different tissues, with more to come in the future.

So in the end, why does this matter ? Our knowledge of the epigenome will allow us to notice smaller differences between people at the molecular level, which can lead to a better understanding of what causes human disease. For example, scientists may reexamine patients with cancers caused by genetic mutations and ask themselves "what role does the epigenome play in this disease?". With insight from the now-sequenced epigenome, they may discover that certain genes are inappropriately turned "on" in cancer patients, leading to therapies that target those specific genes.

Keep an eye out for more developments in this field - they're going to be pretty monumental!

What is love? (Baby don't hurt me)

"Do you believe in love at first sight, or should I walk by again?" - Unknown When I sit at my local coffee shop to work on planning experiments, about 15-20% (rough estimation) of the patrons around me appear to be on dates. Fresh off the heels of Valentine's Day, a thought passed through my head that I thought was pretty intriguing - what is love?

Figure 1: Wall-E and EVE. This post may not apply to robots.

Emotion is a classic topic in science that has been somewhat difficult to explain over the centuries. As a biologist, my first instinct is to boil down such a complex social phenomenon into its individual physiological components. The difference between happiness, sadness, jealousy, anger, and everything in between is simply the way in which the electrical signals in your brain coordinate the release of neurotransmitters, like dopamine and GABA. Some see this perspective as rather dull, but I think it's really quite beautiful!

When you see someone very attractive, what happens to you? Your heart begins to race, you start to feel very warm, and it seems like everything surrounding the object of your affection fades into the background. What explains this fixation? A fascinating review in the Journal of Sexual Medicine focused on this specific topic. With the use of advanced technologies, we can better visualize the physiological basis behind that warm and fuzzy feeling you get when you see someone you're interested in!

Ortigue et al. differentiate between two types of love in the review I've hyperlinked above. The first is known as passionate love, which is the sort of love you have towards a significant other. The second is compassionate love, which is the love you might feel towards a good friend or a family member. By using a device known as functional magnetic resonance imaging (fMRI), scientists can see how blood flow throughout the brain changes when these types of love are experienced.

In one study, scientists allowed participants to view images of their respective partners for about 17 seconds, while taking a peak into their brain via fMRI. They found that blood flow was significantly increased in areas of the brain associated with reward and euphoria, including areas of the brain that are also associated with euphoria-inducing drugs like cocaine. Activity was also shown in areas involved in memory. Simultaneously, blood flow was decreased in areas of the brain associated with anxiety and fear, such as the amygdala. These are also the areas of the brain that are highly active in humans who experience emotional stress, like a bad break up. A second study found that the reward centers of the brain are also stimulated when participants were shown the name of their significant other. How romantic!

Bartels and Zeki in 2004 performed a similar study, but this time they were seeking to further understand compassionate love. The experimental design was similar to the one above. In this case, the participants were all mothers who were shown pictures of their children. The researchers found significant activity in an area of the brain known as the periaqueductal gray matter (PAG), an area of the brain that is involved in pain suppression during intense emotional experiences, such as childbirth. Activity was also shown in areas of the brain associated with higher cognitive processing.

The same author has also discussed the idea of "love at first sight", which about 58% of Americans believe is a real phenomenon. As it turns out, when you look at someone who you find extremely attractive, 12 different areas of the brain work together to release a whole host of different neurotransmitters within 0.2 seconds of visual contact. Just think about that - within a fifth of a second, your brain is able to tell you "Wow, this person is incredible!" as opposed to the person to their left or right. Whether or not this feeling of intense emotion is actually "love" is a debate that continues to rage on today. What does this scientist think it means? From a biological perspective, it goes something like this:

"Ah, this person looks like they have good genes. Probably would make strong, healthy offspring. Proceed with mating."

In short, your brain is capable of generating very different feelings of love depending on the situation. It's a pretty incredible system, isn't it? Of course, why some people trigger strong feelings of love over others is a lengthy subject and probably too much for the scope of this blog. So when the next time you see your significant other (or that cute barista working the espresso machine), think about how hard your brain is working to say, "Hey buddy, time to make your move!"

In Memoriam: Dottie Thomas, a story of scientific love

About a month ago, Dottie Thomas died at her home in Seattle, Washington. She was 92. You probably aren't familiar with Dottie Thomas or her life, but you may be familiar with her work! Along with her husband (and Nobel laureate Don), she was an integral part of the team that proved that bone marrow transplantation could cure leukemia and a host of other blood related disorders. I couldn't possibly detail her life history as well as this summary by Diane Mapes, but here is a summary of a life of love and science.

Figure 1: Cells of the blood, which come from stem cells in the bone marrow

Imagine it. The University of Texas at Austin, 1940. A rare snowstorm finds its way to the Lonestar state and shuts down campus for the day. A young Dottie Martin, a freshman journalism major, takes part in a campus snowball fight and nails a senior chemistry student in the face. That man was Don Thomas, who she would fall in love with and marry in 1942. They were married for 70 years until his death in 2012.

Throughout her life, she relented tirelessly with her husband Don at the University of Washington to show that bone marrow transplantation could be a highly effective treatment. She served as the chief administrator for the Clinical Research Division at the Fred Hutchinson Cancer Research Center for 15 years and was a devoted scientist, editor, and mother. Their research has saved thousands of people around the world, and her husband went on to win the Nobel prize in Physiology or Medicine in 1990.

"They were incredible workaholics - working 80 and 90 hour weeks -- but they were also incredibly good parents. Mom always had time for us no matter how busy she was. She went to the PTA meetings. She did the macaroni art." -Dr. Elaine Thomas, Dottie's daughter

The procedure mentioned above removes bone marrow from a healthy donor and gives it to someone without healthy bone marrow. Bone marrow is very important, as it contains very important cells known as hematopoeitic stem cells. These are the cells that will eventually transform into the cells in your blood. Having healthy stem cells is the key to having healthy blood cells! The treatment can be used in patients with leukemia, lymphoma, and other disorders of the bone marrow.

For the full story on the life of Dottie Thomas, click on the hyperlink above. In the meantime, I encourage you all to enter yourselves into the national bone marrow donation registry at http://bethematch.org/. 360 people a day are diagnosed with cancers of the blood - will you be someone's cure?

What does it mean to have three parents?

I commented on this briefly in a blog post some time ago, but this topic has seen a resurgence in the media lately. This past week, the British House of Commons voted to allow for the creation of a baby made with the genetic material of three people, so called "three-person babies". Not surprisingly, this has some people up in arms over the ethics of such a procedure, as well as its implications for the future of genetic modification. I even saw someone call it "letting the gene out of the bottle". Clever! In true Kitchen Table Science fashion, I'm going to give you a brief overview of what this technology is and what is it meant to correct. Just the facts ma'am, just the facts!

1. The Mitochondria

You may remember from high school that the mitochondria is the powerhouse of the cell, responsible for the majority of energy generation for your body. You may also remember that it, in fact, has its own genetic material independent of the rest of your genome. The reasoning behind this is theoretical and may be discussed in a future post, but know that the DNA present in your mitochondria comprises less than a tenth of a percent of your overall genetic code. Its 37 (versus the remaining 20-25,000 genes in your genome) genes do not influence anything related to appearance, intelligence, or anything along those lines.

2. Mitochondrial disease

As with all genes, your mitochondrial DNA is susceptible to mutations. These mutations can cause a family of disease known as mitochondrial diseases. Symptoms of these diseases vary wildly and include poor growth, muscle weakness, and poor coordination. Since your mitochondria process DNA separately from the rest of the cell, you can theoretically correct for mitochondrial disease by replacing the damaged organelle with a healthy one in the embryo. The healthy mitochondria would continue to be passed down to the cells in the developing embryo, ensuring that all cells in the fully formed human will have good mitochondria. Below is a great graphic from the Human Fertilization and Embryology Authority on how this works:

Figures 1 and 2: Proposed methods for correcting mitochondrial genetic abnormalities

So is this safe and/or ethical? Technically speaking, yes, the resulting child will have the genetic material of three different people. Calling the donor of the mitochondria a "parent" though is a pretty big stretch, considering how little of the DNA contributed will actually affect the rest of the body. It is impossible to predict whether or not something will be completely safe when it comes to procedures like this - only time will be able to tell us that.

I'll leave it for you to decide whether or not society should proceed with this technology. My opinion? This presents an exciting new way to correct for some devastating diseases, and am I certainly looking forward to seeing how this technique evolves in the coming months!

Precision Medicine

At 11:00am today, Barack Obama announced a $215 million endeavor known as the Precision Medicine Initiative. That may seem like a large price tag (it is), but let's briefly highlight what the initiative includes and why it's important for science: 1. $130 million will go to the National Institutes of Health (NIH) to develop a voluntary cohort of research volunteers (at least a million) for a long term study on overall health. This initiative is intended to measure everything, from eating habits to data on exercise to the composition of their genomes.  These huge cohort studies have already been established in the UK and Japan, so it's about time that we pursued it here in the United States.

Such studies are very important. Although time consuming and pricy, data like this will help solve important questions regarding the effect of different lifestyles on the body. It'll also help scientist analyze how large of an effect your genetics has on your different aspects of your life. For example, let's take that group of 1,000,000 people and follow them throughout their life. Down the line, if we noticed that 10,000 become morbidly obese, we can look to see if there are any genetic components that these people have in common that would predispose them to such a state. The possibilities are pretty much endless with huge data sets like this - and if the data remains largely accessible, it'll be a huge boon to scientific research.

Figure 1: Let's take a closer look at this, shall we?

2. $70 million wil go to the National Cancer Institute (part of the NIH) to map "genomic drivers" in cancer and apply this knowledge to developing treatments.

Cancer is a very tricky disease. Unlike diseases that are caused by a specific mutation or other agent (such as a bacteria), cancer can be caused by a huge variety of genetic mutations. Our understanding of what mutations cause what cancers is still in its infancy, so great knowledge in this field will hopefully lead to smarter therapies.

The idea of precision medicine has been here for a while now, but newer technologies has been making advances in this area more of a reality. One of the largest problems in treating any disease is that not a single person on this earth is the same, especially on the genetic level. Prescribing the same dose of the same drug for thousands of people with a similar disease seems kind of silly, doesn't?

Precision or personalized medicine seeks to address that problem by tailoring treatments to the individual patient, based on their individual genetics and needs. Efforts in understanding the subtle nuances that govern each disease will help us know what to look out for in people, which will hopefully lead to more effective treatments!

P.S. The remaining cash in this initiative will be used to set up the databases/data transfer agreements that will make generating this much data possible!

The humanity of it all

Every now and then, I like to take a step back from my workload and put everything I'm doing into perspective. I think that it's incredibly easy for us to lose sight of our purpose when all you feel like all you're doing is running from one task to the next (which is pretty overwhelming, I might add). This practice of asking myself, "Why are you doing this? Why does this matter?" helps me see the value in the things that I do on a daily basis. Earlier today, I was working on some stem cells from a patient who had Wolman disease, which is a fatal genetic disorder where your cells lose the ability to degrade certain fats. Out of curiosity, I did some research on where the cells exactly came from. I scrolled down the screen, looking at information related to specific mutations. Eventually, I came to some lines that really struck me:

GENDER: Female AGE: 4 months (At sampling)

Wolman disease is fatal in infants - they usually die within 6-12 months of being born, which means that this patient probably died just a few months later. These cells aren't just cells - they were somebody's baby girl. Someone's daughter that was taken far too soon. Somewhere in the world are two parents who spent time calling relatives, excited over the prospect of a new life. Two parents who went shopping for baby shoes, baby clothes, and baby bottles. Two parents who had to hear the devastating news from their doctor, that their little girl wouldn't make it to her first birthday. And as painful as this story is, it is not unique. It happens every day, in every country around the world. And it's unacceptable.

Thinking about this really made me realize how important it is to realize the humanity of science. For the past few months, working with these cells was just a routine. Come in, feed, experiment upon. Now when I put them under the microscope, I think about the family that had to suffer from this loss and how important it is that we continue to work to make these diseases things of the past. It's my team's responsibility to make sure that her cells are a gift to the world, and that they contribute to finding a cure for dozens of other little infants around the globe.

The humanity of it all is really humbling, and it's why I'm so in love with what I do.

STOP EATING LUNCH AT YOUR DESK (Please)

If you’re like the majority of Americans (two in three, to be exact),  you either don’t take a lunch break or you usually spend your lunch sitting at your computer. You wander over to the office freezer, heat up your Lean Cuisine, and quietly sit back at your desk to finish that report you were working on. Sounds thrilling, right? Now that 2015 has rolled around, it’s time to make a new commitment to your health and to your office mentality: stop eating lunch at your desk!

Figure 1. This guy. Don't be this guy.

You’re probably thinking, “But Francis, I can’t afford to take the time to sit outside for lunch. My boss is breathing down my neck to get all of this work done!” Be that as it may, taking the time to sit with coworkers or leave the building during lunch actually increases your productivity and improves cognition. In fact, researchers at Humboldt University in Berlin found that those who chose to go out for lunch with coworkers had increased sensitivity to detecting subtle changes in facial expression, indicating  an enhanced perception of minute stimuli. Want to be on your toes at your next meeting with that big client? The science shows that going out may be your best bet.

Of course, this doesn’t necessarily mean that you need to eat at a restaurant to get these positive benefits. After all, I’m sure that your New Year’s resolutions include a fixed budget! The key here is to move to a different location and to socialize with others. I’m sure you’ve all felt that mid-afternoon slump in your desire to get anything done and this is a great way to combat that.

And if that wasn’t enough to convince you, eating away from your desk may actually result in you eating less. This is due to a phenomenon known as “distracted eating”. Your brain needs about 20 minutes from the start of your meal to receive signals from your stomach saying, “Hey, I’m full!” If your attention is focused on something else, making a presentation for example, your brain may not release the signal until sometime after you should have stopped eating.

So there you have it. Take the time to sit outside or in your cafeteria, socialize with your colleagues, and get ready for a more productive you. The science is on your side!

Leap seconds??

One of the things that I love the most about science is that we are constantly seeking to improve on the status quo. "If it ain't broke, don't fix it" assumes that the object in question is already perfect, and we all know that that isn't necessarily the case! Once upon a time, before the 1950's, we based the passage of time on the rotation of our planet. This was about 1/86,400th of the average solar day. If this seems totally arbitrary to you, you'd be correct! It seemed like a good idea at the time - a day should always take the same amount of time to pass, right? It turns out we were wrong; due to the Moon's gravitational pull, the Earth's rotation is slowing down at a rate of about 1.7 milliseconds per century.

In the post 1950's era, time is now based on the atomic clock, which defines a second as "the duration of 9,192,631,770 periods of the radiation corresponding to the transition between the two hyperfine levels of the ground state of the caesium 133 atom". We don't need to get into the nitty gritty details about what this means, but know that this is a way more precise means of measuring time. However, because we were on the old method for so long, we've been behind the true time for many years now. To correct this, we occasionally add a "leap second" to the year to make up for this difference.

Figure 1: FOCS1, a swiss atomic clock

So in the end, who the hell cares? Assuming our species exists in the universe for many millennia, we would eventually lag behind significantly in time in comparison to the "true" time, so we might as well fix it now. Hyper accurate time is also important in having accurate electronics and other devices that base their calculations and actions on time. Fixing these time differences can be a lot trickier than what I've described here, so for more information check out this wonderful post by The Conversation.

So on June 30th of this year, rejoice! You'll get a brand new, shiny second to enjoy. What will YOU do with your second?

Science and the Social Media Revolution

Whether we like it or not, humans born from around 1982 to the year 2000 will forever be labeled as millennials, myself included. When you think of a millennial, I'm sure there are a myriad of different stereotypes that pop into your head! For example, author David Burstein notes that we carry our own brand of unique idealism and are very conscious of causes for social justice. Others say we are a pretty optimistic bunch of folks compared to our parents. But the most pervasive commentary on my generation is that we are population of narcissistic individuals, driven largely in part by what has been known as the social media revolution.

Figure 1. Social media and science are a match made in heaven!

I'll freely admit that I fall under the category of "social media obsessed twenty something". I've got it all: Facebook, Twitter, LinkedIn, Instagram, Google +, Ello, WordPress, and so on and so forth. To those who choose not to plug in to social networks, spending time looking at your friend's vacation photos or pinning cool ways to reuse old shoes on Pintrest may seem like a total waste of time, and it indeed does seem to really put a damper on our work productivity. Just think about it: for every minute that goes by, over a hundred hours of content has been uploaded on YouTube. Over 350 million photos are uploaded to Facebook every day, and Twitter users worldwide send half a billion tweets per day. Who has time for all of that content?

While this may seem like an energy sink, you've got to admit that there is significant power in the social network. It has heavily influenced everything from political elections to armed uprisings around the globe, and it seems like it has reached its tendrils into every facet of human existence. This is no different for science, and I think that we are witnessing a beautiful collision between the two seemingly different worlds.

I've spoken before about how important it is that science communication be a part of our everyday lives. Scientists will never bring down the ivory towers surrounding their fields until the flow of information from academic to laymen is so fluid that the line between them ceases to exist. With the advent of social media, we possess the immense ability to easily reach out to huge groups of people (such as you, dear reader!) simultaneously. We can share our ideas, explain our research, and show the whole world what we are doing to make it better.

Most importantly, we have the ability to start conversations. I don't think science should ever possess a "I say, you listen" mentality. The greatest exchanges of understanding and of knowledge often come moments of disagreement, and while these disagreements can often come in the form of distasteful comments on YouTube videos, I do think that we would be doing the right thing if we embraced social media with open arms. This is certainly easier said than done - the majority of scientists don't use common social networks to promote a great understanding of their science. With new kids on the block such as yours truly coming onto the scene, we will hopefully see that shift significantly in the coming decade.

If you have a science background, I challenge you to explore the different ways that you can use social media to talk about your research with the world. Engagewith others and facilitate discussions. Most importantly, remember that science is easily distilled but should never be diluted. Practice communicating your message in a clear, concise way without losing the core ideas that you're trying to convey. It's not easy, but practice definitely makes perfect! If you don't have a science background, I challenge you to go follow a few science oriented accounts on Twitter (I hear @ATPandMe is a great one), like some pages on Facebook, and make an honest effort to learn something new and have a little fun. The more you integrate the sciences into your personal social media machine, the more routine our conversations about the world around us will be.

Consider this blog my attempt at using these incredible technologies to further those conversations, #NoFilter needed!

A little vaccine update

Last week, I received a booster dose of the VSV-EBOV Ebola vaccine that I've blogged about before, and I'm happy to report that I had no symptoms this go around. This is a pretty stark contrast from when I got my first dose...a 101.6 degreefever and terrible joint pain make for a pretty miserable evening!

Figure 1: A picture of the vaccine, isn't it cute?

Since starting the trial, a few bits of news regarding this particular vaccine have come out. An article from NPR a few weeks ago noted that a vaccine trial in Switzerland using the same vaccine noted increased joint pain in their patients, leading them to stop the trial. I also had pretty significant joint pain, but our trial here at the NIH is trucking along pretty nicely. Huzzah!

NewLink Genetics, the company that produces the vaccine, was also awarded a $30 million grant today from the US Department of Health and Human Services (HHS) to manufacture and develop the vaccine in collaboration with pharmaceutical giant Merck. The NIH also announced that they will initiate further phases of the clinical trial next year. Keep your eyes and ears out for updates on how this story evolves!

This is important, Dr. Oz

Happy Saturday! As a scientist, I'm trained to have a healthy balance of skepticism and open-mindedness. It seems like my skepticism proved to be correct about a certain television physician, who I've considered a bizarre mouthpiece for pseudoscience for some time now. When I would first catch Dr. Oz on TV, I was optimistic. An educated, eloquent physician discussing important health topics to millions of Americans - what could go wrong? This seemed like the perfect medium to communicate real information on real health issues.

Unfortunately, I was mistaken. From promoting "faith healing" as a means for curing miracle ailments to peddling strange energy practices such as Reiki, Dr. Oz has a track record of spreading misinformation. My feelings were confirmed by a paper published in the British Medical Journal (which, you know, has actual scientific information) that determined that almost half (46%) of the claims on Dr. Oz's show over the course of 40 episodes were shown to be either refuted by modern medical science or completely baseless.

This is a huge shame - I would like to think that Dr. Oz is a good person and genuinely cares for his viewers. I always assume the best in people, I suppose. All I'm asking is that the team behind the Dr. Oz Show fully examine the scientific claims they are making or disclose that many of the supplements on their show have not been proven to have any health efficacy.

Full disclosure: if you believe in things like psychic communication and dream interpretation, more power to you! This is a free country, and you should be able to believe in what you want to believe in. But when you begin claiming that these things have clear medical benefits when they have been proven to be useless, that's when things can get dangerous. The power to influence medical decisions is immense and, in my opinion, should only be used when the science is sound.

So the lesson for today is to always critically examine all claims. Just because someone has a fancy background and speaks well doesn't mean what they're saying is the truth!

Case and point:

http://www.youtube.com/watch?v=LI_Oe-jtgdI

Synthetic enzyme, weight loss miracle

Obesity is a huge problem worldwide, costing our healthcare systems billions of dollars every year. The World Health Organization estimates that about 1.2 billion (yes, billion) people around the world are overweight, and among those between 200-300 million are clinically obese.

Figure 1: Obesity in America, courtesy of the New Yorker

Obesity is a tough health problem because it's existence can exacerbate a whole variety of other medical disorders. From type 2 diabetes to cardiovascular problems, the list is pretty large. Curing this epidemic would not only mean a healthier world, it would remove a huge burden on our hospitals as well. Well it seems like that cure may be upon us thanks to some obesity researchers from the Helmholtz Diabetes Center in Munich, Germany!

In a recent paper published in Nature Medicine, investigators have created a pretty incredible weight loss drug that reduced weight in laboratory mice by a third while preserving their lean muscle. Their strategy was a classic tour-de-force of synthetic biology: inspired by nature, improved by man.

There are three enzymes involved in this story: GLP-1, GIP, and Glucagon. The first two enzymes are used by the body to help control appetite and blood glucose levels, while the last enzyme is used to increase glucose in the blood. While increasing blood sugar may seem like a bad idea, it actually does assist with burning fat. In obese patients, the ability to respond to these enzymes is dampened. This is also why losing weight after being overweight for a while can be quite difficult - your actual biochemistry changes to make it tough!

Strategies using these enzymes individually have had limited success, so to circumvent this biologists engineered a molecule that displays characteristics of all three. As you can see from the graph below, the results are pretty remarkable.

Figure 1: A chart showing weight loss in mice. The black line is the control while each other line represents a different form of the drug. The most dramatic loss is seen when the highest concentration of drug was used!

So there you have it, yet another way in which synthetic biology is changing our lives. While we have yet to see this drug used in human patients, I think it's safe to say that we should be seeing more news out of this team in the near future!