DNA Origami

DNA origami provided me with the first hint that there might be research worth pursuing outside of physics, which, as a physicist, was a sort of revelation.  The idea behind DNA origami was deceivingly simple, but offered so many interesting questions.  Given our knowledge of DNA, could we use it to make nanostructures?

Most people, at least I like to think that most people, are familiar with DNA’s double helix geometry and that it contains some sequence of four different “units” strung along a sugar-phosphate backbone.  The four units are nucleobases: adenine, guanine, cytosine, and thymine, also referred to as A, G, C, and T.  The bases bind together to form base pairs, A with T and G with C. The binding then connects two strands of DNA to form the double helix (see below).

From http://karimedalla.wordpress.com/2012/11/01/3-3-7-1-dna-structure/

DNA’s functions and forms are very pretty things to consider and I would like to talk about why DNA components form a double helix and how the base pairings work in biological processes and so on, but we’ll stick with the basics for now.  We have four basic units that have preferential binding to one another, all connected by backbone that forms some polymer.  Given this, I’ll ask again: is it possible to fit DNA into other shapes beyond our beloved double helix?

Paul W. K. Rothemund put forth an answer in this paper at Caltech in 2006.  He used a method termed “DNA origami” to fold DNA into various shapes approximately 100 nanometers (think one tenth the width of a human hair) in size.  The method involved one long (~7000 bases) strand of DNA along with many shorter (~32 bases) “staple” strands.  The long strand would fold back and forth along some pattern based on its sequence of bases and the staple strands would help hold the structure together (see below).

From figure 1 of Rothemund, Paul W. K.  (March 16, 2006).  Folding DNA to create nanoscale shapes and patterns.  Nature, 440.  doi:10.1038/nature04586

The DNA still forms the double helix, but the helix itself folds and crosses over and connects with staple strands to form a design.  The variety of possible shapes is large.  For example, see the samples used in the paper shown below:

From figure 2 of Rothemund, Paul W. K.  (March 16, 2006).  Folding DNA to create nanoscale shapes and patterns.  Nature, 440.  doi:10.1038/nature04586

The top two rows are schematics of the design while the bottom two are atomic force microscopy images of the structures themselves.

Not only can we form two dimensional shapes, but we can also make 3d structures as well.  They can have branches or be hollow or or have dynamic parts.  And scientists are developing different methods that will further enlarge the variety of structures we can form!

I was, and am, amazed by the new ideas that such a familiar, ubiquitous molecule inspire.  Something we used to think of as working strictly within cells has applications in drug delivery, imaging, and art.  It’s easy to go overboard and say the possibilities are unlimited.  Given so many applications, it is rather hard to resist the sense of power one might get knowing that one can manipulate DNA to do one’s bidding.  In fact, I might just have found some extra motivation to attend grad school seeing how the title “Professional DNA Whisperer” has a nice sound to it.  Hopefully I won’t get carried away with my new-found power along the way.

Logical Fallacies - Confirmation Bias

Confirmation bias is another one of those logical fallacies that we commit without realizing it.  Confirmation bias is the tendency to pick up on and remember evidence that supports some hypothesis we hold while forgetting everything that might disprove it.

It's not necessarily intentional.  Perhaps you just noticed over the past few days that a lot of your friends with green eyes are scientists.  Then you made the association that scientists have green eyes more often than people in other professions.  Confirmation bias then primes you to remember when you meet another scientist with green eyes.  But if you meet a scientist with blue or brown eyes, the encounter won't seem as significant to you and you will casually forget about it.  It may actually be the case that most scientists have brown eyes, but the green-eyed ones are the ones that catch your attention.

Alternatively, consider looking out over a parking lot and seeing one red car and then another and another and pretty soon you're noticing red cars everywhere you look.  Perhaps you form, consciously or not, the hypothesis "red cars are more popular this year than previous recent years."

But how do you know the current number of red cars is greater now than in previous years when you hadn't been paying that much attention to it before?  Once you form your hypothesis, you can't just assume it's true. You have to take in all the evidence and weigh it as appropriate.  Well, you do if you actually care enough to make a systematic survey of eye color frequency across professions or car color fluctuations over time.  If you don't feel like putting in the effort to properly test your hypothesis, then you will just have to let it go.

Confirmation bias doesn't just come up when you notice details that may suggest a trend.  It is also possible to have a pre-existing notion that you never bother to question or might not even be aware of and from there, collect bits of "evidence" that support your idea.  Think of politics in the United States.  From an early age, our parents tend to teach us to identify with one party or another without really understanding what either one represents or does.  When we finally start to pay attention to politics and current events, it is so easy to remember all of the ridiculous statements and ideas made by the opposing side and so very hard to admit to yourself that they might not be 100% insane when, on occasion, they utter something reasonable.

Beyond a certain amount of conscious manipulation of a hypothesis or set of evidence, confirmation bias turns into something more like cherry picking or ad hoc rationalization.  As always with logical fallacies, the best way to avoid confirmation bias is to be aware of its existence.  Recognize when you are unintentionally ignoring evidence that is contrary to your beliefs or assumptions and remember that if you want to come to a significant, well-substantiated conclusion, you have to weigh all the supporting evidence against all the contradictory evidence.  If you don't, then all you are left with is a spurious anecdote and that's nothing to base a winning argument on.

Theory and Experiment

One of the most elegant things in science is the interplay between experiment and theory.  The experimenters find some relationship in the data they collect and the theorists come up with a model or explanation that fits the data.  The model makes specific predictions and the experimenters design ways to test the predictions.  The experimental results give the theorists something new to incorporate into their theories and the whole process goes on in a lovely self-correcting way.

I found a visual that brilliantly describes the way theory and experiment go together.  I've seen it in a lot of places, but I believe it is from Reddit user KTR2.  Enjoy:

Logical Fallacies - Post Hoc Ergo Propter Hoc

Do you not only want to be able to dismantle your friends' arguments, but also be able tell them the name of every mistake they make in their reasoning?  Then you should learn about logical fallacies!  Knowing about logical fallacies not only helps you avoid making your own logical errors, they give you a chance to teach everybody around you how to be less stupid!  Logical fallacies:  Learn about some today!  Guaranteed to make your friends and coworkers respect you even more*!

Lucky for you, I just happen to be writing about a logical fallacy right now, one known as "post hoc ergo propter hoc."  Literally translated as "after this, therefore because of this," post hoc ergo propter hoc is almost a sort of temporal periedolia.  Our brain notices that some action B happened after some other action or circumstance A and decides that this means A caused B.  It finds a pattern in time that can be used to explain something that happened and possibly predict when or if B will happen again.

I expect post hoc ergo propter hoc is responsible for a lot of superstitions, such as those followed by athletes.  If you had one of the best games in your life after a losing streak, you might ask yourself what was different before that winning game.  Maybe you ate some chicken and rice and all the other nights you had been eating beef and potatoes.  You might get it in your head that it was the chicken that caused your luck.  After that, there is no reason to risk not eating chicken.  Confirmation bias, the tendency to remember evidence that supports your beliefs rather than evaluating all evidence equally, helps here too.  You eat chicken before every game.  The games you win, you keep in your mind as evidence that chicken causes your to win.  The games you lose are forgotten.

Post hoc ergo propter hoc has some more serious effects than determining Wade Bogg's athletic ritual.  Doctors vaccinate children against measles, mumps, rubella, whooping cough and other diseases when the child is about 12 months old and again around the time the child enters preschool or school.  Autism diagnoses often come around this time as well.  The post hoc ergo propter hoc conclusion that the vaccines caused the autism can be a comforting thought when there is still much unknown about the condition.  But as Jenny McCarthy's crusade against vaccines demonstrates, such a conclusion does far more harm than good. Of course, Andrew Wakefield's fraudulent paper which "demonstrated" a link between vaccines and autism is also to blame, alongside other factors, for leading people to believe this false conclusion.  But now that you know we are prone to the post hoc ergo propter hoc fallacy, do try to avoid it.  I'd prefer it if polio and typhoid fever didn't make an epic comeback.


*Your results may vary.  Please use your well-informed understanding about how to construct logical arguments responsibly.  The Uraniborg blog and its writer do not condone condescension and general irritating know-it-all-ness.

Order of Magnitude Estimations

A few years ago, I thought I would pursue a career in cosmology. To prepare for such a trajectory, most of my electives during my first few years of college involved astrophysics. My interest has since switched to biophysics. The transition was less difficult than I expected. Many of the basic ideas used in astrophysics carry over the biophysics, including the use of order of magnitude estimations.

Some particular students complain that order of magnitude estimations aren't accurate or precise enough. That we must know every fundamental constant to at least 17 places after the decimal or else we're failing as scientists. In reality, order of magnitude estimates are a good tool to give you an idea of what scale you're working with. Is the Earth 100, 1000, 1000000000 kilometers in radius? Are there hundreds, millions, trillions of bacteria in my gut? What is a reasonable amount of concrete to order for my construction project? 10 pounds, 100 pounds, more?

Working with orders of magnitude also allow you to simplify your calculations so you can focus on how the variables interact with each other. What happens when the radius of a marble falling through a liquid is very big, orders of magnitude bigger than the other variables like the viscosity and density of the liquid? What if it is small? In what range does the density of the liquid affect the marble's behavior more than any other variable? How do I scale these variables to apply them to the problem of a submarine moving through water? You don't need to calculate precise constants or results until you're ready to look for small details, confirm the numerical prediction of a theory, or design and build whatever you're planning. Of course, if you're an engineer, please, please don't stop at order of magnitude estimations when designing your bridge. But for astrophysicists and biophysicists, order of magnitude calculations can provide useful insight into the problem at hand.

For a quick example of an order of magnitude problem, I will estimate how many human cells and how many bacteria cells are in the human body solely from prior knowledge. However my prior knowledge includes some things I learned in class. To even out the playing field, I will just say that there are 2 kilograms of bacteria in the average human gut and an E. coli cell has a volume 1 cubic micrometer. Now we can begin.

Start by thinking about the average mass of an adult human. Are we ~10 kilograms, ~100 kg, ~1000 kg? Our answer is in the 100 kg range. We can get more accurate than that if we want to, but it probably won't make a difference. Trying using 70 kg instead of 100 kg if you want to check for yourself.

At some point in elementary school, you probably learned that about 2/3 of the human body is made up of water. That leaves us with 1/3 of 100 kg or 33 kg worth of human cells in the human body. Note that I didn't bother subtracting out the 2 kg of bacterial cells that I mentioned at the start of the problem. That's because 100 - 2 = 98 which is more or less equal to 100. Once again, if you don't trust me, I encourage you to substitute 98 for 100 and see how much the answer changes.

I don't know the mass of the average human cell, but it's not too difficult to make a reasonable guess. First I will estimate lower and upper bounds for the size of a human cell. I said earlier that an E. coli cell is about 1 cubic micrometer. Human cells are larger than E. coli cells, so 1 cubic micrometer is my lower bound. For the upper bound, I will consider the volume of an onion skin cell, since I remember looking at them under microscopes in high school. Let's say they have a volume of 100 cubic micrometers. Then we can take the square root of the product of our bounds to get a sort of weighted average. The result of sqrt[(10^-19) cubic meters * (10^-12) cubic meters] is about 10^-16 cubic meters.

We have an estimate for the volume of the average human cell. By assuming that the cell is mostly water and therefore has the density of water, we can determine the mass. Multiply our volume by the density of water to get (10^-16 cubic meters) * (1000 kg / cubic meter) = 10^-13 kg. Then to find the number of human cells in the body we multiply like so: (33 kg) * (1 human cell / 10^-13 kg) = 10^14 human cells in the body, approximately. Check the results using 98 kg and 70 kg instead of 100 kg. Doesn't make much of a difference does it?

To find the number of bacteria cells in the average human body, first find the mass of an E. coli cell using the same assumption as above that its density is equal to that of water. The result: 10^-19 cubic meters * (1000 kg / 1 cubic meter) = 10^-16 kg. Then 2 kg * (1 bacteria / 10^-16 kg) leads to 10^16 bacteria in the human body. There are more bacterial cells than human cells in the human body!

Searching online for answers about how many human cells and how many bacterial cells are in the body gives values close to the ones estimated here. Where "close" means possibly one of two orders of magnitude off. But what's a couple of orders of magnitude between friends, eh?

How Our Brains Trick Us - Near-Death Experience Sensations

Scientists also research the causes behind near-death and out-of-body experiences.  The scene has been described many times: a patient in a hospital reports a floating sensation, seeing a dark tunnel and a bright light, and being able to look down on his own body from above.  Part of the mechanism that causes such sensations can come from heart failure and oxygen starvation in the brain.  These conditions cause the pupils to widen which causes the patient to see bright light and also perceive objects in his peripheral vision as blurry.  Consider going to the eye doctor and getting eye drops that make your pupils widen.  Your vision will get blurry.  I, for one, often needed to have my mom read me the book I brought to stave off boredom in the waiting room.

The dark part of the tunnel experience occurs due to lack of blood flow to the eyes.  The first thing to go during oxygen starvation is sight.  Many people have experienced this while fainting.  First their vision starts to fade out, followed by their hearing, and then their consciousness.  Additionally, the way blood flows through the eyes means that the edges of the retina start to fail before the center, hence tunnel vision.  As a result, tunnel vision is reported most often in cases involving oxygen starvation and not during other near-death experiences.

Floating, flying, and travelling sensations can be caused by the effects of oxygen starvation on muscle fibers.  They may send incorrect signals to the brain, the brain may make mistakes interpreting these signals, and the patient may be convulsing.  The involuntary movement and inability to interpret stimuli accurately lead to a feeling of motion.  The sensation of seeing a bright light at the end of a dark tunnel and then watching that light get bigger as the pupils widen can also evoke motion.

How Our Brains Trick Us - Waking Dreams and Alien Abductions

I'm a little behind on posting as I spent last semester abroad in Copenhagen.  December was my last month in Denmark so I had to work on my finals and get ready to come back to the States, but I'll make up for it.  I need to keep up my writing practice!

This painting:

is known as The Nightmare and was painted in 1781 by Henry Fuseli. The image is representative of what it is like to have a waking dream.  Waking dreams can be related to, but are not necessarily the same as, lucid dreaming.  While lucid dreaming, the dreamer is supposed to be able to control the dream.  He or she is in a state of being aware enough to realize that they are dreaming and can make decisions regarding the dream, but not aware enough to wake him or herself up.  A waking dream involves waking up in a panic, feeling paralyzed, and often sensing something sitting on your chest or in the room with you.  More often than not, this "presence" is perceived as malevolent.  I had one waking dream back in high school and that was enough.

The reason people experiencing waking dreams feel paralyzed is because they are paralyzed.  After we fall asleep, our muscles are paralyzed so we can't hurt ourselves too much.  During a waking dream, we regain consciousness without regaining motion in our limbs.  I wonder if this is the opposite of sleep walking, in which we regain control of our body, but our mind doesn't wake up.  I'll have to look into it.

With your muscles somewhat stuck, it's more difficult to breathe than usual.  People used to believe that some spirit or creature was sitting on the chest of the dreamer, as seen in The Nightmare.  It is pretty easy to make the jump from "I've been paralyzed and I can't breathe" to "there is something trying to hurt me."

In fact, this may be how people end up believing they've been visited, or even abducted, by aliens.  Culture plays a large part in the appearance people give their visions.  Centuries ago, the presence was thought to be a spirit or witch.  Now aliens are more popular.  The most common type of alien abductions reported change over the decades as pop culture descriptions of aliens and UFOs change too.

Stress is supposed to be a cause of waking dreams and sleep paralysis, as is sleep deprivation, so I think I will go to bed now.  Good night!