Believe or not, this blog post is about statistics, the human brain and common sense

Believe or not, this blog post is about statistics, the human brain and common sense.

I like statistics, I am just not very good at it (don’t you dare tell anyone!). Thank God for software packages! However, you may have the best statistical program and that is very good, but you must also have a reasonable working knowledge of what the statistics in an experiment mean, as well as a good measure of plain common sense to properly understand a given scientific work.

Not so long ago, a blog entry in The Guardian presented an excerpt of a 2009 paper*. The title of the blog post was: “How many neurons make a human brain? Billions fewer than we thought“, and in a subtitle it stated that we seem to be about 14 billion short.

The “top of the head” (pun absolutely intended) figure for the number of neurons in a normal human brain is 100 billion, reported in many textbooks, etc, but strangely enough the putative primary literature for this number is nowhere to be found. Fair enough. Now, I have not read the paper yet because it is behind a paywall. I sent an email to the senior author to try to get a reprint, but the information in the abstract (which is freely available) is enough to make my point for now, and I will of course update this post accordingly as soon as I read the paper. In the meantime, in Azevedo et al., they found that the average number of neurons in humans is close to 86 billion. From that perspective, yes indeed, we seem to be missing 14 billion neurons. Don’t panic!

The blog that reported these results said that the experiment was done by determining the number of neurons by an interesting cell counting method that I will not discuss here. Anyway, four brains were used, all from men, with an age range from 50 to 71 years. Here lies the first red flag; brains shrink with age; moreover, the rate of shrinking is surely affected by genetics and environmental factors. The second red flag: the sample number (4) is rather small.

Even more importantly, I am going ahead and predict what my wife will say about this post when she sees it tomorrow (she is peacefully sleeping by my side right now): “Of course they got a lower neuronal average, they used MALE brains!”

But I digress…

The third red flag: the abstract reports 86.1 +\- 8.1 billion neurons. This means that the actual number of neurons (the range) can be as little as 78 billion or as high as 94.2 billion (perilously close to the accepted figure, gasp!). Now, how significant are these results, statistically speaking? We do not know whether that value (the one after the +\-) represents the standard deviation, the standard error; the 95 % C.I. etc. We also do not know the p-value of the comparison against the 100 billion figure or the statistical method used (look these things up, they matter).

I want to clarify that I am not critisizing the paper. In fact, if find it quite interesting, that is why I want to read it!

Rather, I feel kind of annoyed when I read reports (like in the blog post) implied to be factual without the relevant information to reach a proper series of conclusions. It may well be that the 86b figure is significant and it tells us something about our brain, it may as well not, but we will not know which one it is with incomplete information.

The paper also presents a rather interesting observation about non-neuronal cells or glia. The “Common Wisdom” seems to be that glial cells are about 10 times as numerous as neurons. But in the paper and other related work, they seem to be found at roughly the same number as neurons. Now THAT’S interesting, and I hope to discuss it some other time.

In the meantime, I will keep using my neurons and try not to think about whether I have 80 or 100 billion of them.

——–
The paper:
*Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain.
Azevedo FA, Carvalho LR, Grinberg LT, Farfel JM, Ferretti RE, Leite RE, Jacob Filho W, Lent R, Herculano-Houzel S.
J Comp Neurol. 2009 Apr 10;513(5):532-41.

http://www.guardian.co.uk/science/blog/2012/feb/28/how-many-neurons-human-brain

Petition for open access of government-funded research

A group of people at access2research.org put together a petition to the Obama administration to require that any taxpayer-sponsored research be open-access, this is, to make such research available to the public free of charge. More details are found here.

The White House website for this petition can be found here.

The goal is to have 25,000 signatures. I am # 23,482!

Angel Falls

If you like science fiction and fantasy or if you have children who do, you may want to check the debut novel of a good friend of mine. It is intended for younger readers, but it can be enjoyed by all…

You may find it here or here.

I am reading it and so far, so good! I will post an Amazon review of it soon. Thanks!!!!

On really BIG numbers

When I give my introductory neurobiology lecture, I usually try to impress upon my students how really complex the human brain is. It is very easy just to say “the brain is made of about one hundred billion cells, called neurons”…

If I just say that, I will get the most inexpressive blank faces you would ever see. I know this from experience… You see, all of us talk about millions; for many people nowadays, 1 million dollars is not a huge amount of money anymore (it is for me… (:-)…). So, with the economy and all that, we are used to talk of billions, and even more. However, have you ever thought exactly how much a billion of anything is?

Let’s suppose that you want to count a billion of anything, how long would it take, at one number per second?

Anyone?

It is actually a simple calculation, the kind of calculation that can be done (literally) on a napkin while having a coffee at Sta… I mean, a coffee shop:

Yep, it would take you close to 32 years… that is just 1 billion… more on really big (and small) numbers in future posts!

The Challenge for NASA

Reblogged from THINKING SCIFI:

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Someone recently sent me a link to an interview with Robert Zubrin, where he discusses the financial value of an astronaut’s life. Zubrin points out that NASA is so risk averse it is essentially paralysed, which is a bit harsh and over simplistic, but I understand his point. For what it’s worth, I think NASA’s biggest challenge is the need for projects to transcend politics, as they require decades to come to pass.

Read more… 553 more words

Interesting thoughts!!!!

Autistics: The original Holy People?

I think a lot about autism (actually, I just think a lot, period).  Anyway, about autism, I guess I think a lot about it because it is part of living with a loved one with it. As any parent knows (and this applies to any parent raising a kid with a chronic condition) some days are better than others.  In those days when I can think about autism without being pis.., I mean, upset, sometimes I wonder… From the perspective of a biologist, why do any genes that may contribute to autistic behaviors persist in human populations?

You see, one of the main mechanisms of evolution is Natural Selection, which (very simplified) means that only organisms that survive to the point of reproduction are able to pass on their genes to the next generation. There is much more to say about this, but for this post, it will suffice.

Nobody knows exactly what causes autism. Several genes that are thought to contribute to the condition have been identified, but as with any phenotype, the environment must be involved.

When thinking about how these conditions have persisted in a population, autism is especially difficult to explain because of the evident disadvantages for survival that this condition implies. I can give you the example of my son. My boy, mind you, is very, very smart. Sometimes he susprises us with his insights and whenever we realize that he knows exactly what is going on in certain situations; however, he could walk into traffic without giving it a second thought! I just know that if he did not have us and all of his wonderful, dedicated teachers and aides over the years (well, not all of them, but this is a story for some other time) he would be in danger most of the time!

Now imagine 50,000 years ago or so; any guys like him would be the last ones to react when the proverbial sabertooth tiger showed up, and well, it is pretty easy to predict what happened next.

On the other hand, many individuals with autism display exquisite attention to detail, and are able to notice things that escape us “neurotypicals”. Many of them like to collect things also and can display an impressive (more like obsessive) knowledge of a given topic. In many cases, they will talk endlessly about it.

Could it be possible that autistic individuals were the original “holy men” (and women)? Suppose that a person with autism in those days took an interest on plants. He would know plants that can be beneficial because of some property, like for example pain relief, etc. Maybe she knew a lot about rocks, including the ones that will spark when banged against each other, useful for starting fires. People like this will be revered because of their vast insights and knowledge. As a consequence, they may have been protected and cared for by their tribe, which certainly improved their chances of survival. Also, they may have even been provided with mates to show their respect for them (for humans, it takes two to tango) therefore increasing their chance to reproduce, which ultimately is the name of the game in evolution… And the genes would go on…

These are sheer speculations on my part. I am not aware of any studies that have looked into this. In the meantime, I’ll just keep thinking, just keep thinking…

Why I use planaria in my research

Life has a way of surprising you.  If you had asked me ten years ago what type of research I’d be doing now I would probably have said something like biochemistry, which is what I was doing at the time.

If you have never read my blog (in that case, where have you been?), I use flatworms, specifically planarians in my research. These are very interesting critters. I basically use them as animal models in pharmacology due to multiple advantages, but this is a story for some other time.

I knew very little about planarians, as much as any Bio major that has never worked with them would know. I was aware of their regeneration capacities, but not much else.

In 2001 I started my PhD work with Prof. George P. Hess, Cornell University, with a project on the biochemical pharmacology of neurotransmitter transporters. I was in an interesting situation, as I was the “resident biologist” in the research group of a hard-core physical chemist/biochemist! You see, physical chemists and biochemists (God bless them) usually do not tend to think very highly of biology. Too many moving parts, I guess…(:-)…

I was running a reference search circa 2003-2004 and I found a paper from 2001 published in the European Journal of Pharmacology (EJP). This paper described some aspects of behavioral pharmacology using planarians. I thought that it was pretty cool! I went to George very excited and told him that we should try to use planarians to test some of the compounds that we were working on from a biochemical point of view. Well, George was standing up. At about 6’4″ he easily towered over me. He said something like: “Well, when you have your own laboratory, you can play with them”. Guess what? That is exactly what I did! Incidentally, I try to remind him of this story every chance I get (I know, I’m a meanie). In all fairness, he was right, of course. At that time, if I’d started a project from scratch it would have finished my degree much later. Also, because of it, I was able to take the project with me as a new Assistant Professor. Since then, I have published several papers on planarian pharmacology, my latest one as a coauthor with the researcher who published the 2001 EJP paper!

I feel blessed (or very lucky, depending on your philosophical stance) that I had an advisor who did a great job. Moreover, he did it with my best interests in mind. I’d like to think that I am following his example when I train one of my own research students. Thank you, George.

From light to light

I am always thinking about something. I have this constant sense of urgency that keeps telling me that every moment that I am not thinking, I am wasting time. That’s just who I am.

The other day I was driving to the supermarket. As I turned on the signal light at a corner, I thought about how the light in the car’s dashboard got there. That blinking light got me into thinking about the story of that small amount of energy, in the form of a few photons, that were detected by my retina, processed in my brain’s visual cortex and perceived as light by my consciousness (what is consciousness anyway?).

The beginning of the story of this tiny amount of light could go all the way to the Big Bang itself, simply because the story of our Universe started right there. Before the Big Bang, we have very little idea of what was going on. In fact, there are many good reasons to think that it makes no sense to talk about a time “before” the Big Bang, since time itself seems to have been created at the very same moment when our universe was born, 14 billions years ago, give or take a couple of million years.

Anyway, to speed things up I will start this story with two hydrogen atoms within our sun, say, about 300-400 millions of years ago.

Stars generate their energy through a process called nuclear fusion. In younger stars, the main players are hydrogen atoms, which are the most abundant type of atoms in our universe. The physical environment at the center of stars is brutal to say the least. The temperatures and pressures there provide the conditions that make atoms collide with each other with a lot of energy, oftentimes with such force that it allows them to overcome the natural repulsive forces that keep them separate.

When this happens between two hydrogen atoms, they fuse with each other, initiating a series of events that end up forming a different kind of atom, helium. This is when things start to get interesting. In these series of steps initiated by fusing two hydrogens, the intermediate physical entities leading to the final product, helium, possess slightly less mass than the sum of the masses of their precursors.

The main reason why is this small amount of remaining mass is so important is because in our physical universe, matter is a form of energy; you may have heard this stated in another way, E=mc2. This fact was firstly realized and formulated by no other than arguably the best-known scientist ever, Albert Einstein. Based on this relationship, even a small amount of mass (m), when multiplied by the (squared) speed of light in a vacuum (c) which is 300,000 km/second, results in a big amount of energy (E).

There is order in this universe of ours, as we can describe it with generalizations (we call them laws) that explain its fundamental properties. The first of these laws states that energy cannot be created nor destroyed. This is the so-called First Law of Thermodynamics. By the way, the Second Law of Thermodynamics basically states that it is way more difficult to build something up than to destroy it (in my mind, this law applies to everything, from molecule formation to personal relationships, but I digress…).

Now, think about the example that we talked about when a helium atom is formed through the series of steps initiated by fusing two hydrogen atoms. What happens with the small amount of matter that remains during these steps? It is released as energy! This happens many, many times within stars; this is why so much energy is generated there. And it does not stop with helium. All the heavier atoms found in nature are also formed in a similar way, yes even carbon. Quite literally, we are stardust.

Let’s follow that energy that is released in our original example from a long time ago, with that little remaining mass left from hydrogen fusion.

After about 100 to 200 thousand years after this fusion event (yes, that long; look it up, it is a fascinating story in its own right) that energy, which originated near the center of the sun, reached the surface and was emitted as radiant energy (light). After about 8 minutes after being emitted, the light that happened to travel in the direction of the earth, arrived here. At that time, life had already invented the process of photosynthesis. Some of that energy was captured by specialized structures within cells, called chloroplasts, which in turn contain molecules capable of capturing light and convert it into chemical energy, ready to be used by life in various ways, including the synthesis of macromolecules such as proteins, nucleic acids, etc.

Did you notice that we started with matter, which was converted to energy and now that energy was converted to matter again?

Over time, the plant that captured the energy and used it to generate nourishing chemicals was eaten by an animal that, upon dying, went through the process which forms what we call today “fossil fuels”, the main source of energy that we use in our society. Some of that fossil fuel was used to make gasoline, which I put in my car. When I drive the car, a part of that gas burns in a controlled way; a very small part of that matter is converted to kinetic energy (movement), and yet a smaller part of that kinetic energy is used to partially charge the car’s battery, which in turn feeds the electrical system of the car. So, when I turned the signal light on, the photons that left the sun all those millions of years ago, were converted into photons again, which I perceived as the blinking light in my dashboard, going full circle.

So, you see, I am always thinking about something; it is fascinating how a simple observation can initiate a train of though that can lead to so many interesting concepts! It works for me; it may work for you too. You will never know where you may end. Read, think and be merry!

A wonderful “thank you” card

Over the years, several students have surprised me with thoughtful “Thank you” notes, sometimes just to show appreciation for a semester of study or because I wrote a recommendation letter on their behalf when they are applying to grad school, medical school, etc. These kind thoughts always leave me with a warm feeling inside…

Today, I got the most imaginative card. It came from one of my pharmacology students, and used the course topics (and my research) as a theme.

Things like these make my day. It is wonderful to feel appreciated!

Here it is!

Brain Awareness Week at Philadelphia

Last Thursday I volunteered at a very interesting national event, the Brain Awareness Week (BAW). The BAW is “…an inspirational global campaign that unites those who share an interest in elevating public awareness about the progress and benefits of brain and nervous system research…” (From the Society for Neuroscience BAW website).

The BAW was launched in 1996, as a joint enterprise of the Society for Neuroscience and the Dana Alliance for Brain Initiatives. This is a worldwide effort that includes more than 2,000 universities, schools and related institutions.

The BAW event in my “neighborhood” was held at the Franklin Institute, Philadelphia, PA, USA.

Since 2006 the two-day long Brain Awareness event at the Franklin Institute has been coordinated by graduate students, postdoctoral fellows, and researchers in the Philly Society for neuroscience chapter, including Dr. Maria Waselus, Dr. Jill Yersak, Dr. Russell Buono and Dr. Sara Jane Ward, with contributions of graduate students Ann Mae Di Leonardi and Jordan Trecki. I want to thank Dr. Ward for providing the Philadelphia’s BAW historical background.

Ongoing sponsors and supporters include the Farber Institute for Neuroscience at Jefferson, The Society for Neuroscience, AllSwim swim cap company, and Just Born candy company. Each year, 75 – 100 local scientists from over fifteen different institutions to volunteer at the Philadelphia BAW, who interact with over 1000 students, teachers, chaperones, and families visiting the museum. Some of the visitors’ favorite activities include drawing the parts of their brain on a wearable swim cap, being part of a Pavlovian learning experiments, protecting “egg” heads from damage from a fall, and viewing and handling real human brain material, including pathological specimens.

It was a lot of fun! We were in a big room with stations answering questions from the public, including many schoolchildren. Some of the topics explored in the stations were:

Guess which station was I at?

(:-)…

The planaria table for this year’s BAW was the idea of a friend and collaborator, Dr. Robert Raffa from Temple University. Dr. Raffa is actually the reason why I work on planarian pharmacology. I will tell you the story some other time…

In the meantime, here are some pictures!

Baldscientist, Dr. R.B. Raffa and a model of an invertebrate friend.

Baldscientist and Ben Franklin himself! He looked taller in the history books…

Talk to you soon!