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.

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!"

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.

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?

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!

I'M SORRY

Alright, so I've been totally dropping the ball lately regarding the content on this blog...I PROMISE I'll write things up over the weekend and have all new things ready for you by next week! I recently got put on a project at work that is intended to find feasible therapies for Wolman disease, a disorder in which your cells can't metabolize cholesterol properly. I'm hoping to eventually write this up for a publication, so I'll be somewhat sparing of the details of the project...when I can divulge more, I will!

In other Francis-you're-kind-of-a-scientist-now news, I started my first induced pluripotent stem cell cultures yesterday, which I'll be further differentiating into other forms of stem cells such as neural and mesenchymal stem cells. This is my first experience with handling stem cells, so I'm pretty stoked to get the ball rolling on this project. Unfortunately, it means I'll have to be at work to take care of them every day (including weekends) indefinitely, but at least I'll be working on a pretty sweet project. Cool stuff! Here's a picture of the little guys: aren't they adorable?

Figure 1: Those large clumps of cells are stem cells! The smaller bits floating around are debris/dead cells

Have a fantastic, science filled weekend!

P.S. Did you hear the Philae lander that landed on that comet determined that the water present was different from that found on earth? Full disclosure: the water (also known as heavy water) found on the comet was only different in that it had an extra neutron - the structure was the same. Heavy water is found here on earth  (contrary to many news headlines that I've seen lately), but it's much rarer than regular water!

In the pursuit of a cell-fie: Part 2

2014 has been one of the craziest years for science. We even landed on comet, for God's sake! Needless to say, this year has been pretty kind to the biological sciences as well, with some key innovations being made in the pursuit of an artificial cell. So sit back, relax, and let's go over some key innovations that have been made this year! You've got to move it move it

Researchers this year from Technische Universität München published a pretty cool paper in Science where they constructed artificial vesicles that could move on their own. Pretty amazing! To achieve this, they coated the inner surface of the vesicles with proteins called microtubules, which are the proteins that allow your cells to move (they also provide structure in what is known as the cytoskeleton. They also added motor proteins called kinesins that move microtubules, pushing the little cells forward. Of course, the energy molecule ATP was also added as fuel and BOOM! We have movement!

Figure 1: A high resolution photo of the artificial cell! Via TUM

And here's a cool video of the cells moving:

http://www.youtube.com/watch?v=Rc3Ss30z1Os

Part 3 is just around the corner! See you all in a few days!

In the pursuit of a cell-fie, Part 1

Have you ever taken time to look up at the night sky and gaze in amazement at the web of stars in the sky? Nature has the uncanny ability of inspiring a sense of wonder and awe when you sit down and wonder, "Gee, how does it all work?" I would argue that you'd probably get that same sense of wonder if you sat down and thought about the endless list of processes and reactions that your body has to undergo everyday just to keep you alive. There are about 37.2 trillion cells in the human body, with thousands of different functions represented in the various tissues. That's 372 times the number of stars in the Milky Way! When you consider that these cells must all interact with one another and look out for their own survival, you can see why constructing a completely artificial biological organisms would be pretty challenging!

Figure 1: The Milky Way

To make this task more feasible, scientists for many years have been trying to start with the cell, the smallest functional unit of life. Biologically speaking, a living cell must meet certain criteria that are rather difficult to fulfill artificially.  These are listed here:

1. Homeostasis: A cell must be able to regulate its own internal environment

2. Metabolism: A cell must be able to turn chemicals into energy

3. Adaptation: A cell must be able to response to stimuli from the environment and response appropriately

Stretch goals:

4. Reproduction: A cell must be able to replicate itself

5. Organize: Ideally, artificial cells would eventually organize themselves into more complex things like tissue and organs

6. Grow: Through metabolism, cells should be able to grow in size (or at least replicate to make the organism bigger)

Figure 2: The goal - are you up to the challenge?

If I gave you a laboratory and some supplies, could you do it? It certainly seems like a herculean task! Thankfully, researchers around the globe are hard at work to make such technology a reality. The journey to create an artificial cell dates back to the 60's, where Thomas Change at McGill University created a cell with an ultrathin membrane made of nylon and other crosslinked proteins, which contained a slew of things such as hemoglobin and various enzymes.

In the 1970's, this technology was revamped to make a completely biodegradable cell, and in 2011 researchers at Harvard University reported creating the first fully synthetic cell membranes.

The genesis of synthetic cell membranes marked an important step in crafting a fully artificial cell, but the issue of an artificial genome (collection of genetic material) still remained. Artificial DNA synthesis has been around for a while (I'll cover this in another blog post), but it took until 2010 for researchers at the J. Craig Venter institute to create a cell with a fully artificial genome. I'll spare you the minute details, but workflow of the experiment is as follows:

1. Design a genome on the computer.

2. Synthesize that genome artificially. In the case of the above experiment, the genome of a bacterium known as Mycoplasma mycoides was designed on the computer and crafted.

3. Insert the genome to a different cell. The researchers transplanted the M. mycoides genome into a different bacterium, M. capricolum.

4. SUCCESS!

Their M. capricolum began only producing protein products from M. mycoides, proving that their genome switcharoo was a success. The cells were even able to replicate, a triumph for the field! So as a proof of concept, humans can design fully functional artificial genomes. Done and done!

Note, however, that although the genome is artificial, we are still relying on the native bacterial machinery to translate those genes into proteins. Ideally, every part of these cells would be completely manmade, but it's clear that our foray into the creation of artifical life is having some success! In recent years (especially in 2014), huge advancements have been made in these other areas of cell creation. To see how biologists have figured out how to make cells move and carry out their own reactions, check out part 2 of this blog series on Monday!

Nature, improved

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

Figure 1: Obligatory futuristic depiction of your DNA!

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

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

Linking autism and the genome

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

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

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

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

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

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

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

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

Sensationalism in Science: Is this for real?

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

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

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

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

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

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

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

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

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

Is this for real?

What goes in an Ebola vaccine?

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

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

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

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

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

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

Ebola vaccines and pipelines: Where are we now?

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

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

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

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

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

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

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