If you’re looking for science-inspired plans tomorrow night…

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Hi everyone!  I had this great plan for my next blog post (which is totally coming next month) but my time has been pretty filled the last few weeks working on slides for a presentation I’m giving tomorrow night – and here’s the best part: it’s a public lecture about science, geared toward non-experts AND it’s streaming free online.  So if you’ve got some free time tomorrow evening (11/12) beginning at 7 p.m., set up camp at your computer and watch the live stream.  I’m the third talk in a series of three talks about RNA (which is a molecule found in your cells).  The first talk introduces the traditional role for RNA as a messenger, shuttling genetic information from DNA into protein; the second talk is about all the other really cool things RNA can do; and my talk will cover how RNA is being designed as a treatment for a variety of diseases, what types of diseases RNA treatments could be used for, and how those treatments might work.

The live-stream is here: https://sitn.hms.harvard.edu/sitn-live/

Or, if you’re a Boston local, feel free to attend in person: directions here.

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Debunking the science behind Ebola infection and treatments

It’s been a busy few months, but fortunately I keep signing up to write articles for Harvard’s student group Science in the News (read: someone else reminds me about deadlines) so here’s a new blog post for you to read.  This time around, I’ve decided to take a step back from the news of the Ebola epidemic to talk about how exactly Ebola infects us, how it causes harm inside the body, and finally how treatments are targeting it.  Hope you learn something interesting 🙂

Ebola Virus: How it infects people, and how scientists are working to cure it

Since the beginning of the current outbreak last May, Ebola has been a near daily news story. Most articles have focused on the public health aspect of the disease in terms of its spread throughout West Africa, attempts to contain it, and efforts to set up viable health care stations near affected areas.  However, most coverage hasn’t devoted much space to the actual mechanics of the Ebola virus – what it is, how it gets into your cells, how it causes the characteristic hemorrhaging and fever, and, most importantly, how researchers and doctors are developing treatments for it.  I’m going to talk more about that in the rest of this post.

How does the Ebola virus infect people?

Ebola virus contains a type of genetic material called RNA, which is similar to DNA and contains the blueprint for assembling new virus particles. Unlike animals and plants, which also use DNA as a repository of information, viruses are not technically alive because they are incapable of replicating without help. In order to create new viruses, the virus must infiltrate a living cell, where it hijacks the host cell’s machinery to fulfill its own goals. In order to get into the cell, Ebola must travel through the cell membrane, which is a barrier that protects the cell from its environment. However, all cells need nutrients, which must have ways of entering the cell; the viruses hitch a ride into the cell via one of these established nutrient-uptake entryways. Ebola virus takes advantage of a non-specific engulfing process called macropinocytosis, which allows the virus to be “eaten” by a wave-like motion of the cell membrane (see the figure below; you can also go here for more details).

Once inside the cell, the virus hijacks the cell’s own machinery to create more copies of itself. Often, this appropriation of the cell’s replication machinery comes at the expense of the cell being able to make all of its own needed machinery, leading to the death of the cell or at least an inability to function properly. After all of the pieces for a new virus have been assembled, the viral pieces “bud” from the cell, using the cell’s own membrane to make a capsule for its safe travel to new cells nearby (Figure 1b).

Ebola Figure

A diagram of how Ebola virus infects human cells. (A) The Ebola virus is enclosed in a package that contains RNA, its genetic “blueprint” for reproduction. (B) Ebola has a protein called glycoprotein that sticks out of its membrane and binds to receptors (in red) on the cell surface. (C) The binding of these receptors triggers a cell “eating” process called macropinocytosis, resulting in the virus being engulfed by a wave-like motion of the cell membrane. (D) Once inside the cell, the virus’ RNA is uncoated, at which point it hijacks the human cell’s proteins to create more copies of itself. (E) Once new viral particles have been assembled, they move to the cell membrane and “bud off,” at which point they can travel to infect new cells (F).

How does this cell-by-cell infection translate to the full-body symptoms of Ebola?

Ebola virus is characterized by a variety of symptoms, beginning with fever, headache, and muscle pain, followed by vomiting, diarrhea, and internal bleeding. Upon entering the body, the virus targets specific cell types, including liver cells, cells in the immune system, and endothelial cells, which line the inside of blood vessels. Once inside the cells, one of the proteins made by the virus is called Ebola virus glycoprotein. The glycoprotein can disrupt cell adhesion, so that cells have trouble sticking to each other and to a scaffold called the extracellular matrix, which in healthy tissue helps to hold the cells together. The loss of cell adhesion is detrimental to any solid tissue, and by infecting blood vessel cells, the virus causes the vessels to become leaky, leading to hemorrhaging and internal bleeding.

By targeting liver cells, the body’s ability to clear toxins out of the bloodstream is compromised, and by infecting the immune system, whose cells travel everywhere in the body, Ebola has an opportunity to increase rapidly its area of infection. Over time, infection of cells throughout the body can cause organ failure, while fever, internal bleeding, diarrhea and vomiting can cause severe loss of electrolytes, blood plasma and fluid. Ultimately, organ failure and shock caused by the internal bleeding lead to death.

What is the science behind treatments in development?

Researchers are exploring several avenues for treating Ebola. Many drug companies are developing vaccines, although none of these vaccines is ready for full-scale production, or even approved for human treatment. These vaccines use non-virulent portions of the virus, injected into the body, to teach the immune system to recognize the Ebola virus and defend your body against it in the event of a true infection. Although the vaccines would usually be months or even years away from approval, emergency protocols approved by the World Health Organization have determined that this epidemic warrants the use of unapproved drugs and vaccines, so cautious plans are being made to expand access to Ebola victims.

A second treatment being developed uses small fragments of genetic material called “small interfering RNAs” (siRNAs). These small pieces of RNA are designed to match specific pieces of the virus’ RNA. Just like two pieces of Velcro sticking together, when the siRNA encounters the corresponding viral piece of RNA, it sticks to it. Once stuck to the siRNA, the viral RNA cannot be used to create new Ebola particles, thus slowing the replication of the virus. The FDA has recently approved siRNA therapy for use in the current outbreak.

Another treatment which has been used for several health-care workers who became infected with Ebola virus involves the use of antibodies. Antibodies are large, Y-shaped proteins that are designed to recognize and neutralize foreign objects in your body, such as bacteria or viruses. Currently, the most well developed drug is called ZMapp, which is a cocktail of three antibodies. The antibodies have a “lock” on the tip of the Y that recognizes a specific “key” – in this case, a specific portion of the Ebola virus glycoprotein described in the previous section. Once bound, the antibodies neutralize the glycoprotein, which subsequently keeps the virus out of the cell. So far, data about its efficacy in humans has been inconclusive, as the patients did not all receive the drug at the same point in the course of their disease, nor did they receive the same levels of medical care. ZMapp or other similar drugs are important as tools to treat already infected patients during an outbreak, but unlike a vaccine, they do not confer lifelong immunity to the virus. This ultimately means that exploring both vaccines and drug treatments may be the most effective way to combat Ebola.

Even if experimental drugs can be scaled up to have large enough quantities to treat the current epidemic, the traditional methods of treatment will continue to be paramount for saving lives. In order to stave off shock from loss of blood and fluids, patients in health-care facilities can be given infusions of blood, fluids and electrolytes to help their bodies remain stable while fighting the virus. In the immediate future, the major challenges in bringing this epidemic under control will continue to be a focus on its containment, coupled with an influx of health-care facilities and experts capable of delivering the best care possible in onerous conditions.

Global Warming/Climate Change editorial

Good afternoon, readers.  As usual, it’s been too long since a blog update – what can I say, graduate school is apparently a large time commitment.  But I’ve written an editorial about the effects of climate change in developing nations, so if you’re interested in learning about climate change outside our borders (with some implications included for our own future here in the USA) follow the link to the Harvard Science in the News website and read on!  As a teaser, here’s the figure from the article, which highlights some of the challenges that countries will face as the temperature continues to rise throughout the globe.  Happy July!

http://sitn.hms.harvard.edu/flash/2014/climate-challenges-developing-nations/Climate change figure

Brown Fat: Burning Body Fat Instead of Storing It

How do animals stay warm in the winter?  I don’t know about you, but I personally like the southern migration solution – avoid the problem altogether.  For those animals that don’t (or, like most of us, simply can’t) head south for winter, other common solutions are to grow a thick fur coat and/or add a layer of fat to insulate the body.  Fat can indeed insulate the body, helping to keep it warm, but there are actually two types of fat, and only one of those types is good for insulation.

The cells most people think of when picturing fat cells are storage centers for fats, and they have one big blob of fat that takes up most of the space in the cell.  These are the pesky type of fat cell that most of us wish would disappear from our mid-sections.  Due to their storage of a large droplet of white-colored fat, these cells look white under a microscope, so they are called white fat cells.

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The other type of fat cell has a totally different role in the body, and it is also pretty important for staying warm in winter.  These are brown fat cells, and they burn fat instead of storing it.  That’s right: there are cells in your body that are capable of burning fat without you even needing to get off the couch and go for a run.  Unfortunately, scientists don’t fully understand how these cells are turned on, so don’t give up on your resolution to exercise just yet.

Now you may be wondering why cells that burn fat could help you stay warm in winter, since it seems counter to our belief that extra fat helps keep the body warm.  Brown fat cells actually do one better than mere insulation.  They burn fat to generate heat, thus enabling a body to stay warm even in winter.

I mentioned that white fat cells are white because of the huge fat droplet in the cells; brown fat cells look brown under a microscope.  This is because they have tons of mitochondria, which are brown in color, thus making the whole cell look brown.  Mitochondria are basically the power plants of our cells, churning out a molecule called ATP, which is the battery used to power everything your cell does.  It makes sense that a cell needing lots of energy would have lots of mitochondria, such as a muscle cell.  But why would a cell that generates heat need a lot of “batteries”?

The answer turns out to be unexpected: the cell isn’t using the mitochondria to make ATP.  Usually, mitochondria use the energy gleaned from breaking down fats, sugars, or carbohydrates to build ATP.  In brown fat cells, that energy is dissipated as heat instead.  When your body is cold, the brain activates brown fat cells to start burning heat, and it sends signals to the white fat cells to release some of their stored fat.

Due to their ability to burn fat, brown fat cells have huge promise for combatting obesity.  If researchers can figure out how to activate brown fat cells in a healthy, controllable manner, treatments could be developed to aid people with weight loss.  Also exciting is a series of discoveries about “beige” cells.  It may be possible to convert white fat cells into brown-like cells, thus decreasing the number of fat-storing cells while simultaneously increasing the number of cells that burn fat.

While it may be a few years before brown fat cell weight-loss programs are a reality, there is a silver lining: every time you head out into the polar vortex and lament how cold you are, you can be comforted by the fact that your brown fat cells are burning some fat to help keep you warm.

Ease into 2014 with a little science!

Happy new year everyone!  In continuing my resolution to get back into blogging, here’s the first post of 2014.  It’s less basic-science focused than usual to ease us all back into the groove.  Since it was published online at the Science in the News Flash, you can read the full article here (I suspect they like keeping track of viewcounts and if you read it on my blog they won’t know you read it!).  Here’s a picture to peak your interest:

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If this sneak preview wasn’t enough, here’s the brief synopsis: the full article is about stem cells, which are basically “young” cells capable of “growing up” into any kind of cell in the body.  These cells have huge promise for medical and basic research, since they could be used to cure spinal cord injuries, grow organ transplants, and tons of other things.  Unfortunately, as with any rapidly advancing technology, there are important ethical considerations for the public and scientists to keep in mind – should treatments be offered before clinical trials test whether they are safe?  Is there a conflict of interest for doctors who claim only to want to treat patients with untreatable diseases but charge large sums of money?  Read more about these and other debates facing the stem cell field over at the Flash – and if you are feeling interested/ambitious, keep reading, since the Flash has a whole special series on stem cells and there are several other articles of note in this publication.

My article: http://sitn.hms.harvard.edu/flash/2014/never-an-easy-answer-the-ethics-of-stem-cells/

Explore the rest of the issue: http://sitn.hms.harvard.edu/category/flash/

Why do mammals commit to monogamous relationships?

Sorry it’s been so long…graduate school gets busy sometimes.  But in honor of the rapidly approaching new year, I’ll be blogging regularly again.  To get us all started, here’s an article I wrote a few weeks ago for Science in the News, a student-run organization dedicated to explaining the science behind news articles that pertain to scientific breakthroughs.  Anyway, it occurred to me that I might as well share it here.  Happy reading!

Our culture generally assumes that human beings are a monogamous species, with two people committed to one another for a long-term relationship.  Scientifically, the existence of monogamy seems counter-intuitive.  One of the principles of evolution is that all animals want to maximize their reproductive success.  Parents want their genes to be passed on to the next generation, and having more offspring increases the likelihood that progeny will survive into adulthood, thus increasing the prevalence of the parents’ genes in the next generation.  It is therefore advantageous for males to mate with multiple females in order to increase their chances of siring healthy offspring.  Particularly for mammals, where females have long gestation and lactation periods during which they are unavailable to mate again, it would to be to the male’s advantage to move on to a new mate, leaving the female to raise the offspring alone.  How, then, could any species have developed monogamy, if bonding with a single female counteracts the advantages of mating with multiple females?

It’s easier to explain this phenomenon for some species than for others.  Birds, for example, are overwhelmingly monogamous, and scientists reason that this is because both males and females can participate in caring for the eggs and feeding the hatchlings – the equitable division of labor gives males a reason to stick around.  Male mammals can’t help with the gestation of a fetus or the feeding of a newborn; nevertheless, around nine percent of mammalian species are monogamous.  Our closest relatives on the evolutionary chain are even more likely to be monogamous: up to a quarter of primate species live in male-female breeding pairs.

Overriding the desire to spread genes around with multiple mates

Many factors may have contributed to the development of monogamy in mammals, but there are three prevailing theories (see the figure below).  One theory postulates that males stick around after mating in order to protect their progeny from being killed by rival males.  These rivals kill the existing progeny, which don’t have their genes, so that the females will be ready to mate again more quickly.  This “infanticide” practice allows the new male to pass on his own genes.  An alternative theory, called the “discrete range” theory, is that males were forced into monogamy because competition and food availability forced females to live far apart, so that it was impossible for males to control more than one female.  A third theory predicts that the advantages of paternal care select for monogamy because the extra care and protection provided by a second parent increases the survival rate of their offspring.  Unfortunately, it has proven difficult to determine which theory was the primary force in developing monogamy.

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There are three main theories for how evolution evolved in mammals. The risk of progeny being killed by rival males may have encouraged males to stay and protect the female/offspring (A). Alternatively, females may have lived too far apart for polygamy to be sustainable, forcing males to stay with a single female (B). The addition of paternal care allows offspring to grow healthier and smarter, which may have selected for monogamy (C).

Two recent studies attempted to lay this debate to rest, but the question will have to remain unanswered for a while longer – they reached different conclusions.  A study led by Dieter Lukas at the University of Cambridge in England focused on 230 primate species (monkeys, gorillas, chimpanzees, etc.).  The lab identified which species practice infanticide, which species have females living in discrete territories, and which species are monogamous.  They then used computer modeling and statistical analysis to reconstruct the most probable evolutionary history of these three traits (more on how this works in the next section).  Based on their findings, they concluded that infanticide most often precedes a switch from polygamy to monogamy, while the distance between females (whether they lived in discrete ranges) did not correlate strongly with monogamy.  These results lead them to conclude that the primary force behind developing monogamy was the need to protect offspring from infanticide, since its practice usually corresponded with a development of monogamy.

The other study, performed by Opie et. al. at University College London, based its analysis on more than 2,500 mammals (nearly half of all mammalian species).  They, too, classified each species as monogamous or not, noted whether females live in discrete or overlapping territories, and whether males practice infanticide.  They concluded that almost every time monogamy evolved, it was in species in which females lived far from each other.  They further analyzed just the primate subsection of their data, again finding that it supported the hypothesis that discrete female territories, and not infanticide, drove the development of monogamy in species that practice it today.

The role of prior knowledge (bias) in affecting these studies’ outcomes

Although both teams used similar experimental approaches, they reached dissimilar conclusions.  The differences may come down to the details in the way they defined their data and set up the statistical analyses.  Both teams used a statistical technique called “Bayesian inference.”  This method is used to determine how true a hypothesis is based on a particular set of data.  This method provides a mathematical way to combine new evidence with prior knowledge, rather than depending on the evidence alone.  For example, imagine that you want to know the weather without checking your phone or going to the window.  You predict that it is rainy, sunny, or snowing.  You are then presented with evidence in the form of a picture of your front yard covered in snow.  Based solely on this evidence, you could decide that it is snowy outside; however, you also know it is July and you live in Boston, so your prior belief in the probability of there being snow outside your window in July is very small to begin with, making it highly unlikely that it is snowing, regardless of the pictorial evidence.  Bayesian inference provides a way for you to include that prior knowledge in the mathematical analysis.  In both of the monogamy studies, the scientists involved framed their hypotheses and defined their data based on prior knowledge.

However, it’s important to recognize that prior knowledge is inherently biased.  For example, the two research groups didn’t classify mating systems exactly the same way: one group strictly defined each species as either monogamous or polygamous, while the other group classified species that practice both living styles into both categories.  These differences may have influenced the conclusions reached in each study.

Evolution of human monogamy: a mystery for another day

Lukas et. al. also included humans in their analysis, and claim that their conclusion about infanticide driving monogamy could apply to the existence of monogamy in human societies.  However, it may be too soon to apply these studies to humans.  It’s important to note that while the majority of humans live in monogamous relationships, it is by no means the only type of relationship practiced.  Some societies allow men to have several wives, and there are examples of cultures where women marry several husbands.  The practice of monogamy with short- or long-term sexual relationships with someone outside the marriage is also relatively common.  Interestingly, the more closely scientists study “monogamous” animal species, the more examples they find of sexual liaisons by both males and females with mates outside of their monogamous pairing – these extramarital relationships may be more evolutionarily likely than previously thought.   Another consideration is that these studies focus on the males’ choices, but the females’ choices, particularly for humans, may also have played a role in the evolution of monogamy.  Future studies will be needed to determine which of these factors were important for human monogamy.  However, scientists who study humans will also have to consider something that is less prevalent in animal species: culture.  The importance of culture in driving the formation of monogamy cannot be overstated – human culture is an enormous force in shaping many aspects of our lives.  Ultimately, the evolution of monogamy in human societies is likely a combination of several or all of these forces.

Implanting Fake Memories – No Longer Total Fiction

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(Photo credit: Wikipedia)

In this week’s edition of science found around the web, I’ll feature this article from the New York Times about implanting mice with false memories.  The unreliability of memory is well known.  For example, my sister and I are pretty close in age, and we sometimes have to get verification from our mother about something we think happened to one or the other of us in childhood – my sister will remember something as happening to her, only to find out that it actually happened to me (or vice versa – my memory’s just as bad as hers when it comes to what happened to whom growing up).

While there’s still a great deal of work to be done in understanding the brain, memory formation, and how false memories can end up being remembered as true, scientists have begun to probe these questions.  For full details, read the article (link below), but the gist is that scientists at MIT stimulated the section of a mouse’s brain that was associated with a happy, safe place while simultaneously delivering a shock to the mouse (which would create a negative memory).  When they returned the mouse to the happy, safe location, it tensed up in fear – as if it remembered being shocked in that place, even though the shocks had been delivered in a separate location.  Sure, this study doesn’t address why human memory is so fallible, but it’s a step toward understanding how these discrepancies might occur.  And either way…it’s pretty awesome to think about being able to implant fake memories.  But don’t worry – science is still a long way from being able to create an entire set of memories and implant them in a person’s head a la Total Recall.  Fortunately, that particular technology is still situated solidly in the realm of science fiction.

Original article: http://www.nytimes.com/2013/07/26/science/false-memory-planted-in-a-mouse-brain-study-shows.html