Monday, 16 May 2011

The $1000 genome

My Dad has high blood pressure and my Mum had to receive treated breast cancer but what does this say about my future health? It is possible I have a predisposition to both these conditions but I may also never develop either. The difference comes down to what combination of genes I have inherited and for me to know for sure, my genome would have to be mapped.

The U.S. Department of Energy Human Genome Project Information Web site estimates it would take "about 9.5 years to read out loud (without stopping) the more than three billion pairs of bases in one person's genome sequence"[*]. It therefore unlikely to surprise you that the mapping of your personal genome does not come cheaply. Currently, you're looking at around $50,000 - $100,000 which only seems affordable in light of the fact the first genome to be mapped in 2003 cost $3,000,000,000.

Now, however, a new technique for gene mapping is being developed that could bring the cost down to under $1000. This would allow personal genomics to become available for predictive medicine. As our Origins' colloquium speaker, Professor David Deamer from the University of California Santa Cruz, suggested, you could imagine having your own genome stored on a thumb drive to take with you when you visited your doctor.

Professor Deamer first conceived the idea for the $1000 genome over twenty years ago. He postulated that if it were possible to create a hole in a biological cell that was sufficiently narrow that only a single strand of DNA could pass through it, then the DNA components ("nucleotides") could be analysed and recorded as they were dragged through. Combined, this pattern of DNA components make up your genes[**]. The question was what could be used to create such a tiny channel?

The answer to this did not emerge until ten years later and turned out to be a toxin called alpha-hemolysin. As its description suggests, hemolysin is not normally remotely desirable and is released during staph infections where it burrows into red blood cells and makes them explode (not good). In this case, however, its burrowing ability is exactly what Professor Deamer's team were looking for.

Alpha-hemolysin adheres to a cell's surface and makes a hole through the cell's structure known as a 'nano pore'. When a small voltage is applied, charged particles pass through the cell to create a tiny, but measurable, electric current. When a DNA strand attempts to pass through the hole, it can only just fit. This means it temporarily blocks the channel while it is squeezing through, causing the electric current to drop. The amount the current falls by turns out to be determined by which nucleotide is currently in the way. By measuring the change in current, the genome can be mapped.

The familiar picture of DNA is not of a single strand, but of the double helix. Tied up in this manner, the DNA cannot fit through the nano pore. Instead, it enters the broader, top part of the channel and get struck. From this position, it becomes unzipped until it can finally pass through the hole and out of the cell. The very exact size of the hole is important, since to record the genome accurately, only one nucleotide at a time must exit the cell.

Genome mapping using this technique is not yet available, but Oxford Nanopore Technologies have plans to produce a commercial device using this process. That being the case, there is only really one question left:

Are you ready to know what you really are?

[*] In case anyone is really curious, this figure is calculated by assuming a reading rate of 10 bases per second, equaling 600 bases/minute, 36,000 bases/hour, 864,000 bases/day, 315,360,000 bases/year. So there.

[**] Nucleotides make up DNA strands and stretches of DNA strands make up genes (in case anyone else was confused about the order of the extremely small).

Monday, 2 May 2011

Networks in the brain

So your friend Ben is married to Margaret who is friends with Rachel who shares an office with Rory who worked on a planetarium show with Rob who once received a detention at school for mooning Prince Harry [*]. 

According to the theory of the six degrees of separation, you are no more than half a dozen people away from receiving that front row invite to the Royal Wedding. The idea is that you are connected to every other person on Earth through an average of six people. It is a concept huge social network sites such as Facebook have been testing, but surprisingly it is an arrangement that is reflected in the structure of your brain.

All this I learned at the Royal Canadian Institute (RCI) 2011 Gala. The RCI was formed in 1849 by Sir Sandford Fleming. One of its original roles was to publish a scientific research journal in Canada but now its emphasise is on a weekly public lecture series which covers a wide range of scientific topics. In addition, the RCI helps with grants for students wishing to study science at university and it hosts an annual Gala dinner. The Gala is an opportunity to have a discussion over a great meal with a scientist. One of the twenty five tables at this year's event was hosted by my adviser, Professor Ralph Pudritz, but I shunned his table in favour for one led by a scientist working on the structure of the brain; a topic I knew nothing about. (When I told Ralph I'd rejected his table in favour of another he assured me he 'expected nothing less'. I don't think he meant this to be a reflection of my attention in our research group meetings.)

Our table was led by Professor Mark Daley who worked on models of the brain at the University of Western Ontario. When newly arrived at his institute, Mark explained that he had known very few people.

"But, I did know Mike." He gestured towards one of the other diners seated with us. "And Mike knew everybody. So if I needed to contact somebody elsewhere in the University, I could go to Mike and the chances were he knew them. This meant although I only knew a few people, I was connected to almost everyone else via only one person."

This, Mark explained, was the premise behind the six degrees of separation. There are a few people who know a huge number of others and these individuals act like hubs. People preferentially attach themselves to hubs (since the hub is likely to meet them through their enormous list of contacts) resulting in them being connected to a great many others through a very small number of steps.

What Mark said about Mike turned out to be entirely true. When chatting to him before dinner he had declared, "Oh, you're at McMaster! Do you know Hugh Couchman and James Wadsley?" I had to confess I did.

Mark continued by explaining that the brain organises its neurons along similar principals. There are hub areas in the brain which have a huge number of neurons connected to them and these link up regions which have sparsely few connections.

This structure can be explored with two major methods. The first is to take thin slices of the brain's grey matter and the second (more desirous for live volunteers) is to watch water flows via an MRI scan.

The consequences of this neural structure have important ramifications both for the effect of brain-damage and in understanding mental illnesses. Damage to one of these hub region, for instance, can result in the head injury being fatal because the brain simply cannot rewire to compensate from such a large loss of connections. Other times, the damage can be severe but limited to one specific area. Mark cited an example of a woman with damage to one hub who was left unable to see.

In most people, the number of hub regions is small and they are found is quite specific areas. One exception to this is in the case of people suffering from schizophrenia, where many smaller hub nodes are seen and in farther flung areas in the brain than for a healthy person. 

A question I asked was whether this was the underlying concept in electric shock treatment for depression? Was the idea to try and forcibly rewire the neurons by destroying their electrical signals and thereby forcing the brain to choose another (hopefully better) structure? Mark said that while this was the correct premise, such treatments were now strongly out of favour. He compared it with chemotherapy, saying you effectively killed a lot of neurons in the hope that you destroyed the bad pathways before you took out all the good. He did describe less invasive treatments which included asking the patient to think of something pleasurable directly after thinking of a traumatic event. Over time, the association can force the brain to rewire and help with post-traumatic stress disorder.

So what is is that governs our thoughts? Is the brain, as Penrose claims in 'The Emperor's New Mind', a system governed by random probabilities via quantum mechanics? Or are we, as Mark assumes in his work, simple Turing machines whose thoughts and actions can be completely predicted based on our experiences? Neither sounded particularly appealing.

"I want another option," I told Mark. He nodded and promised me one after he'd finished his dinner. The problem with being the guest speaker at a meal was the actual food was hard to fit in amidst the barrage of questions.

The third option, he explained as the plates were cleared, was that our mind is like a Bayesian machine which using a mixture of probabilities and input from its surroundings to make decisions. So when faced with the delectable crumble for desert, there was a very high chance that I would take the logical choice and eat it. Then there was the small probability I'd lob it across the table. I love feeling I have choice.

The crumble was rhubarb, in case anyone was wondering.

At the end of the dinner, each table was allowed to pose a question to another group to allow diners the chance to hear about the different areas being discussed that evening. The most important question was posed first and was directed at Professor Jeffrey Rosenthal from the department of statistics at the University of Toronto:

"What is the probability that Kate Middleton will wear a slinky wedding dress?"

"Slinky?" Jeffrey rose to answer the question. "This isn't as close to my area of expertise as you were led to believe!"

[*] Editor's note: any resemblance to real people, in the Physics and Astronomy Department or otherwise, is purely coincidental and Rob has never yet admitted to knowing Prince Harry. Or mooning.

Saturday, 9 April 2011

Black hole menu

It is a depressing fact that over 95% of the Universe can't be bothered to interact with you. By looking at the speed with which our galaxy is rotating, we can infer that the amount of mass present must greatly exceed what we can see in stars and gas. This 'dark matter halo' is the cocoon in which our brightly lit spiral galaxy lives.

One of the puzzling features of these galactic cocoons is their wide range of sizes. It is surprising because the size of a galaxy is proportional to its dark matter halo, yet there are no galaxies found in very small or very large halos. It's a little like looking at the cities in Ontario, and finding everyone lives in Hamilton or London, but there is not a soul to be found in Toronto or Ancaster. Additionally, the large galaxies that do exist tend to have predominantly old stars, with very little cold gas from which new stars could form. So, in our Ontario analogy, Ottawa would be populated only by people over the age of 65.

The absence of small galaxies in small halos is explainable by the violent deaths of stars. As a star such as our sun reaches the end of its life, it will throw a large fraction of its substance into the surrounding area in an explosion called a supernova. In a small galaxy, this can blow so much gas out of the halo cocoon that it destroys the galaxy, leaving behind a star-less dark matter halo.

The absence of very large galaxies in the biggest halos however, is more of a mystery. The amount of mass in these galaxies would be so large that any gas that is ejected away from the disc by supernovae will be dragged back down by the gravitational pull of the remaining matter. In the last Origins talk of the semester, Professor Tim Heckmen from John Hopkins University in Baltimore proposed that the answer lies with super-massive black holes.

The most sinister objects in the Universe, a black hole is where so much mass has been squeezed into such a tiny volume that the speed needed to escape its gravitational pull is greater than the speed of light (and that's the fastest speed there is!). For the Earth to become a black hole, it would have to be compressed down to the size of a grape. Super-massive black holes containing the mass of billions of suns, reside at the centre of galaxies. How they have formed is hotly debated but what is known is that the larger the galaxy, the larger its super-massive black hole. Of course, something that destroys everything that enters it does not have the best PR, so going to these objects for answers feels like asking a kraken to attack a single ship; the probability of having any vessels left at the end of its foraging seems rather low.

Professor Heckman's theory is that gas close to the black hole is pulled towards it like water swirling down a drain. As it approaches the edge of the hole, the energy the gas is loosing (by dropping down the black hole-drain) is converted into heat at a rate that is much more efficient than nuclear fusion. The resulting radiation is the most intense source in the Universe. If enough gas falls in, the black hole can go through a 'feeding frenzy' and produce jets that evacuate huge holes in the galaxy. These jets fill the halo with hot gas, removing all the cold star-forming gas from the disc. If the jets are strong enough, the galaxy could be destroyed completely. If it isn't, then the resulting cavity around the black hole removes its food supply and the jets turn off. Yet, as the ejected gas cools, it falls back down to the galaxy, serving up another black hole dinner.

Why though, would this mechanism not occur in our own Milky Way, destroying us and smaller galaxies along with the bigger ones, kraken style? The answer, Professor Heckman explains, is that the super-massive black hole needs feeding with a lot of gas to produce the powerful jets. One possible source of this food is from supernovae as they blow away their outer layers. This gas might initially go into the halo, but as it returns to the galaxy, it could be drawn into the black hole which would then start to feed and produce jets. Larger galaxies will have more stars and therefore more supernovae, increasing the food supply to a point where jets can be formed. This means that the lifecycle and star production of a galaxy is intimately linked to its super-massive black hole. To understand one, Professor Heckman said, you need to understand the other.

At the end of the talk, there was one important question on the audience's mind:

Which came first; the black hole or the galaxy?

Monday, 28 March 2011

A picture is worth a 1000 words

While at a conference in Italy in 2009, I attended a talk on new observations of a nearby spiral galaxy. The speaker presented several interesting results but had to confess she did not have an image of the galaxy, since they were still waiting for data from the Hubble Space Telescope. From across the room of eminent astronomers came a collective sigh of disappointment.

It was hard not to laugh. In fact, I don't think I succeeded. The idea that professionals in the field would bemoan the lack of a pretty picture was deeply amusing; surely we should all be above requiring such frivolities? 

The truth, however, is that visualisation is an intricate part of successful science. Presenting your data in such a way that the main results stand out makes for better communication, without which scientific ideas cannot be shared, tested or accepted. This was the concept behind the "Science Illustrated" conference in Toronto that Masters student, Mikhail Klassen, attended last month and was badgered into talking about at the department's weekly journal club.

Mikhail explained that the conference discussed how the way you present your results can both help and hinder the viewer. Consider, for instance, the block of letters in the image at the top of the page. If you were asked to count the number of occurrences of the letter 'v', it would take you at least a few minutes to carefully examine each line. If instead each 'v' was coloured red, the task becomes a matter of seconds. A more extreme example is that of Anscombe's Quartet which is shown in the bottom half of the image. These four data sets have statistically identical properties, including exactly the same average and spread. If these were actual scientific measurements, a glance down the columns might cause you to think that they were showing the same result. However, if you plot them on a graph, you can see at once that they show completely different trends.

On the other hand, you can also choose to visualise data in a way that confuses the viewer. A famous example of this was a power point slide showing the current situation in Afghanistan. So crowded with interlinked lines was this plot, that General Stanley McChrystal, the US and NATO force commander, remarked dryly:

"When we understand that slide, we’ll have won the war."

A common error, if slightly less extreme than the above example, is to pick a bad colour scheme. Using colours that are similar to one another can obscure the trends you are trying to illustrate. Our brains also have a 'perception priority' when dealing with visual input, placing relative position above colour. This means that if an important result is, for example, the maximum density in your galaxy, it could be that plotting this on a line graph is more effective that colouring an image of the galaxy by density.

Mikhail went on to point out that there is also an ethical side to data presentation. By plotting two quantities against one another to demonstrate a relationship, you are excluding any information about other, possibly important, factors. A non-astrophysical example of this is a reconstruction of the Air France flight 358 that crashed in Toronto in 2005. From a reconstruction of the plane landing, it appears to be a pilot mistake; the plane drifts, touches down too late on the runway and over-shoots to crash into the creek (no fatalities). However, there is no weather information in the movie and eye witnesses report strong rain and winds with terrible visibility. As scientists, it is our duty to state clearly what is and isn't shown in our plots to ensure we do not mislead our audience.

Mikhail's final point from the conference was to remind us that communication of results depends on our audience. If we are presenting our findings to the public, we will be competing with Lady Gaga for their attention! This might lead us to choose difference visualisation techniques than if we were presenting to other astrophysicists. Although, if my experiences in Italy were anything to go by, that isn't necessarily the case.

[Thanks to Mikhail for sharing his (very clear!) slides from his presentation. The bottom right image showing plots from Anscombe's Quartet was taken from wikipedia.]

Monday, 21 March 2011

Sneaky little hobbitses

Despite what you may have claimed over coffee this morning, 18 million years of evolution separates your landlord from a gibbon. If it's any consolation, he's only about 5 million years from a chimpanzee. After that time, our own branch of the tree-of-life evolves through a series of distinct 'hominids' before producing grad students.

But who were our ancestors and what did they look like? Is it possible to distinguish them from other branches of the ape family tree?

This was the topic of today's Origins Seminar, given by Dr Dean Falk from the School for Advanced Research in Sante Fe, New Mexico. Dr Falk is what is referred to as a 'paleoneurologist', a peculiar sounding term for someone who studies fossilized brains. Ancient remains of mammals can have a cast of their brain (known as an 'endocast') preserved via sand and other debris filling the cavity between skull and tissue. This hard coating is protected from weathering by the fossilised skull which slowly wears away, leaving the natural endocast in its wake.

The process of analysing an endocast is not an easy one since it is only an imprint of the brain's surface, so no internal information regarding the neurons or chemical structure is preserved. However, by comparing endocasts from humans and apes with those from ancient remains, much can be learnt about our own evolution.

Of course, it does help if the ancient remains you are studying are not fake. A famous example of this situation is the "Piltdown Man". Discovered in the UK in 1912 in Piltdown, East Sussex, these fossilised remains were exposed as a forgery in 1953. Rather than being the missing link between humans and chimpanzees, this skeleton was created from a human skull attached to an orangutan's jaw. The teeth had been filed down and the bones stained to look like a single specimen. In part, its success as a hoax was due to it fitting in with the preconceived idea that a measure of evolution was the brain-case size; the prevailing belief was that brains became bigger first and the rest of the body, including the jaw, changed afterwards. The discovery was also pleasing to local scientists who embraced the idea that the first human was an Englishman!

In reality, however, the first hominids were found in Africa. Ten years after the 'discovery' of Piltdown Man, Raymond Arthur Dart discovered the remains of the 'Taung Child' in South Africa; a fossil dating back 2-3 million years. With its small ape-sized brain and location far from England, the Taung Child contradicted everything seen in the Piltdown Man, making it a controversial discovery. Dart examined the brain endocast and concluded that, while the brain was relatively small, it was advanced due to its structure. In particular, he identified two groves whose positions matched those found in humans but not in apes.

Ultimately, Dart's analysis was proved to only be partially right, but the technique of examining the position of the brain's major groves (sulcal patterns) is the main way of differentiating hominid brains from our ape cousins. These differences come about as regions of the brain that were previously separated become more interconnected in humans.

Interestingly, our own ancestors were not the only bipedal species walking around Africa 300 million years ago. Paranthropus are thought to be an extinct hominid species, unrelated to us. Their brains were characterised by a prominent central ridge from which strong jaw muscles would have been attached. Our relatives were the Australopithecus africanus, of which the Taung Child is an example. The migration and spread of A. africanus is thought to be north out of Africa and then into Europe and Asia. This has been called into question recently, however, by the discovery of a hobbit.

The announcement of the three feet tall hominid remains found in Indonesia came in 2004. The attractively named, "Lb1" was female with very short legs and therefore seemingly disproportionate long arms. Her feet were genuinely long, stretching a length equal to the distance between her knee and ankle. The remains were found with primative tools, similar to those found in Africa, and she would have lived alongside giant Komodo dragons, which is a slightly unnerving prospect for someone only three foot high.

At 417 cubic centimetres, Lb1's brain was chimp sized but the endocast revealed advanced features reminiscent of a human over an ape. Her discovery opens many questions, with schools of thought differing over whether Lb1 can be a new human species from our ancestry when her brain is small and she was found so far from the picture of migration out of Africa.

One thing that appears to be clear from the endocast discoveries is that brain evolution can occur in many different ways. It is possible to rewire and reorganise our grey matter without it becoming larger. This leads to different combinations throughout the fossil history; a difficult challenge to place in logical order. So in short, size does matter, but it's not just about how much you've got. It's what you're doing with it that counts.

Wednesday, 9 March 2011

Can you build a transmitter?

"You claim that there are many Earth-like planets while finding none!"

"But we have found many Jupiter-sized planets and they should be rarer than Earth-sized so the trend is pointing towards a large number!"

I was sitting in the audience of "The Great Extraterrestrial Debate", an event hosted by the Centre for Inquiry in Toronto. It was part of the organisation's "Extraordinary Claims" campaign which is designed to put some of today's most controversial allegations through a critical examination. This evening's topic surrounded the likelihood of alien life interacting with us on Earth.

The debate comprised of a panel of three individuals whose profession gave them a stake in this field. The first was Astrophysics Professor, Ray Jayawardhana, from the University of Toronto, whose research focusses on planetary formation outside our Solar System. The second was science fiction author, Robert J. Sawyer, and the third was Seth Shostak, a senior astronomer at S.E.T.I. (Search for Extraterrestrial Intelligence) Institute.

Despite being labelled a 'debate', it was stated upfront that all three panellists were in agreement; to this date, there has been no strong evidence for life outside of Earth. That said, the three unique view points being brought to the table did lead to passionate discussion. The above snippet was between Ray Jayawardhana and Robert J. Sawyer and was wrapped-up by Seth Shostak who pointed out:

"Ray and Rob arguing shows how hard it is to find stupid life. If they can built a basic radio transmitter (and you should all ask yourself now if you can do that) then their biology doesn't matter!"

Apart from the thinly veiled implication that S.E.T.I. would not count most of the audience as 'intelligent life', Dr Shostak's point highlighted a fundamental difference between his work and that of many astrobiologists; S.E.T.I. is only interested in life-forms that can talk to us. This bypasses all the problems with defining what life is and how we should go about detecting it when it is likely to be nothing like our own (a problem previously touched on in this post).

But is it really likely that we will make contact with aliens who can communicate with us?

Seth Shostak and Ray Jayawardhana both discussed the recently launched Kepler mission which is uncovering a flood of planets, with 1235 possible candidates identified in the first year of operation alone. This is in comparison to the 500 planets that have previously been discovered in the last 15 years. This huge influx of data in such a short time indicates the vast number of planets there must be in our galaxy which suggests that it would be a miracle if we were the only life to have been created on any of them. Dr Shostak also added that S.E.T.I.'s current failure to find life should not be interpreted as an absence of extraterrestrial intelligence. Currently, S.E.T.I. has only searched a tiny patch of the sky and declaring the Universe baron of life based on such a survey would be the equivalent of searching a square kilometre of Africa and concluding there were no elephants on the continent.

On the other hand, even if life did evolve on another world, we might have a problem with timing. Robert J. Sawyer made the argument that while the human race has existed for a few thousand years, there is a much narrower window between the invention of radio (needed for communication with S.E.T.I.) and the creation of the atomic bomb. It could be that almost as soon as a life-form can communicate, it self-destructs. Dr Shostak counted this by stating that the invention of rockets would take place in the same time-frame to launch the bombs, which gave the possibility of members of the species leaving the destroyed planet behind them to colonise somewhere else. He suggested that, like cockroaches, a life-form such as humans would be impossible to fully wipe out.

So ... if you're not able to build a transmitter, S.E.T.I. consider you too stupid to be interesting. If you ARE able to build a transmitter, you are analogous to a cockroach. Everyone feeling good? Then I'll continue...

Then there is the problem that if aliens were to appear, how would we react? Contrary to popular movies, it was deemed unlikely that such a discovery would cause rioting in the streets. For one, the signal would be coming from so far away that it isn't going to affect your ability to buy your morning coffee from Tim Hortons any time soon. Secondly, 1/3 - 1/5 of the population believe aliens are here already doing (and I quote Seth Shostak) "experiments your mother would not approve of", so a significant fraction of the world would not even be surprised.

Robert J. Sawyer suggested that it might be unhealthy for our own future to discover a more advanced life-form. If it could be shown that most life did survive their 'technological adolescence', then the human race might not strive as hard to solve its own problems, being content to let time take its course. Dr Shostak took this idea to a more personal level by saying that tenured professors might find it depressing to know all their scientific research had been solved a million years ago by this advanced alien race. Professor Jayawardhana, however, seemed to think this would save on having to publish more papers!

Finally, Robert J. Sawyer pointed out that S.E.T.I. did make one very big assumption:

That life, if it's out there, would be remotely interested in us.

Monday, 28 February 2011

Moving through a living cell: a mystery

It was a suspicious case.

To all appearances, the motion within the living cell looked thermal; a movement of particles caused by heat. Yet the temperatures needed to produce that degree of motion exceeded 30,000 K. That would equal one very very dead cell.

So what was going on?

A question about living cells was a surprising one for a Physics colloquium. The visiting speaker was biophysicist Professor David Weitz from Havard University, and he assured us that he was constantly reminded by his biologist colleagues that he still thought very much like a physicist. Evidently, this had not been meant as a compliment, but it was a relief to his current audience who looked slightly fretful when cells were mentioned in the talk title.

He started off by reminding us of the random walk that particles will perform if they are suspended in a liquid. The famous experiment in which this was first observed was performed by Robert Brown in 1827 who was examining pollen grains in water. There is a rather nice demonstration of what he saw here. This effect became known as 'Brownian motion'. The cause of Brownian motion is the water molecules that are buffeting the larger pollen particles as they move around. The temperature of the water dictates how much energy the water molecules have and therefore how much they will bump around the pollen particles. Since this motion is entirely dictated by heat, it is an example of thermal motion.

There is one thing, however, that must be true for Brownian motion: the liquid must be in equilibrium and not undergoing any overall changes such as heating or cooling.

And if there is one thing known about living cells it is that they are not in equilibrium.

So how was it that when tiny beads are placed into a cell, they move in the same way as pollen grains on water?

It was strange and a closer inspection of the situation proceeded to reveal two more mysteries: Firstly, between steps in their random walk through the cell, the beads would appear trapped. They would vibrate slightly as if caught on a spring before freeing themselves to move to their next location. This small-scale movement was not seen in normal Brownian motion, so did it have a different cause or was the same force responsible on both scales?

The second oddity was that if the temperature of the cell was fixed, but all chemical activity ceased, the motion stopped. Brownian motion, being thermal, is entirely dictated by temperature. If the temperature remains constant, all Brownian-type movement should continue. Here in the cell, though, the lack of chemical activity was a clearly a key factor.

It was looking more and more as if this motion only looked thermal, but was driven by something else entirely.

Professor Weitz's group then studied the motion of the cell's microtubules. These are the most rigid structures within a cell and their movements, like that of the beads, can be measured. By creating a controlled cell-like environment in the lab, conditions within the cell could be changed to monitor their effect on the microtubules.

Really, it was a lot like simulations where I turned on physical processes such as star formation one by one to see their effects on an evolving galaxy. Galaxies ... living cells ... clearly they were all the same!

The results from these experiments pointed to the presence of a driving force that was shaking up the cell's internal network. In addition to the microtubules, the cell has a support structure of smaller filaments and it was these thinner components that were being moved about. The shaker was molecular motors; large molecules found in all living organisms. These can change their shape when they come into contact with ATP --an energy transmitting chemical-- causing material around them to deform. This motion of the smaller filaments pulls in different directions around the microtubules causing them to undergo the small-scale trapped vibrations that were seen in the beads. As the microtubules grow, they bend under this jiggling surrounding movement causing them to distort or perform a random walk, just like the pollen grains in the water.

So the cause for the microtubules or beads movement was not so different from Brownian motion in that it was the motion of the small-scale surrounding material that was having an effect. However, the reason for the background motion was not heat, but the driving force from the molecular motors.

Case closed.