A boy and his atom ...

Today is going to be a very short post, but not much about a new, cutting edge piece of science! More using the incredible technology science has to offer... to create art!

This was a video created by IBM and is officially the worlds smallest stop motion film. It was created to celebrate IBM creating the smallest magnetic memory bit (comprised of only 12 atoms, the current norm is around 1,000,000 atoms, so not bad work!). So to celebrate this, they used the technology in their lab to create a stop motion film .... of individual atoms!

The project was "filmed" using what's called a scanning tunnelling microscope (which was actually invented by IBM researchers who got the Nobel Prize in Physics for it in 1986). Now, your normal everyday microscope won't cut it to see atoms, in fact you can't even use light to see atoms, so the scanning tunnelling microscope works by gently moving a super-fine needle above atoms of the material being "imaged". As the needle moves over a particular atom, a mini-chemical bond is formed between the atom and the needle tip, this can be measured through the needle. The needle tip is moved ("scanned") from left to right, right to left, left to right moving down the material. When something is higher (closer to the needle), then a stronger bond can be detected, but if the atom is far away from the needle then only a weak bond can be detected. As the needle "scans" the material to be imaged, all this data is then compiled into a viewable image!

For this film, the researchers used the bond formed between the tip and the atom to actually move some atoms around, to create a picture! Then they moved them again and took another, and so on to create this amazing stop motion film.

Each small globe is ONE INDIVIDUAL ATOM of carbon monoxide. Think about that for a second!

IBM did a (fairly) easy to follow video on how they made the atoms move, they may do a better job than I did:

And that's it! Hope you enjoyed it, fairly simple concept but done really really well in my opinion!

PS. Apologies to all physicists reading this, hate mail can be addressed to me personally :)

A viral infection of the eye that can cure blindness?

A very controversial area in science is gene therapy with the use of viruses (it really shouldn't be that controversial thou). I realise it sounds quite scary to be injected with an actual virus, but gene therapy using a virus as a tool is a remarkably elegant (and relatively safe) technique which deserves some time to clarify. A search for 'gene therapy' in Pubmed gives back just shy of 40,000 peer-reviewed scientific papers, so it is clearly an exciting, well-researched area of science.

Now, a bit of background. Viruses are sneaky little buggers and have evolved over time to sneak past your normal immune defences and infiltrate your cells, and from there trick the cell into making more of the virus. Normally this is a bad thing such is the case with HIV or the more common virus, the flu. So what happens, if we take away all the parts that allow a virus to make us sick and give it some specific DNA that a patient might be missing. Then the virus will go, sneak into the persons cells and trick the cell into making proteins from that DNA, but the proteins will be good for the patient and replace an otherwise missing protein.

There are many diseases that are caused by a mutation in the DNA which then means the protein isn't made in the patient, so if we could somehow deliver the protein (or at least the blueprints for the protein, DNA) into the cells then we could replace what was missing.

Gene therapy using an AAV virus. (Source: Wikipedia)

Gene therapy has been successfully and safely used to treat many diseases such as chylomicronemia, chronic lymphocytic leukemia, and multiple myeloma and a clever technique has recently been published to advance the use of this technique to treat certain types of blindness.

Inherited forms of retinal diseases afflict 1 in 3000 people worldwide and are primarily the result of mutations encoding proteins in the retina of the eye. Current gene therapy treatment for these diseases involves a needle piercing the eye and penetrating the retina itself to successfully deliver the virus. The diagram below shows just how far back that needle would have to go. The process requires hospitalization, general anaesthetic and runs a real risk of damaging the retina itself. This is because the special viruses usually used in gene therapy (called AAV) cannot get that far back into the eye normally and so need to be injected directly there.

Source: http://encyclopedia.lubopitko-bg.com

A group from Berkeley University has made use of the high rate of evolution in viruses (because they reproduce so quickly) and used directed evolution to "evolve" a virus that has the capabilities to get that far back in the eye. To do this, they took the standard AAV virus and injected it into the gel layer at the outer eye (the vitreous body in the diagram above), they then waited a while (a week) and collected the cells in the retina of the eye to see if any viruses made it that far back. There were some! So they let these few replicate into huge numbers again and repeated the process and repeated it and repeated it, each time only continuing with the viruses that somehow had the ability to reach the back of the eye, therefore selecting the viruses with the desired ability. At the end of all this they found 48 AAV viruses made into the back of the retina and 2 thirds of them were the same virus, they dubbed it 7m8.

To test if this virus could then be used to treat a disease, they used two mouse models of retinal degeneration caused by malfunctioning proteins in the retina and split each disease model into two groups. In one group they injected the virus, packaged with the DNA required to make the missing/malfunctioning protein, and the other group received the virus by itself without any extra DNA packaged into it. The mice with the 7m8 loaded with DNA had great vision improvements and a protein analysis proved that the retina was in fact producing the previously missing protein.

Immunostaining for RS1 protein (Dalkara et al. 2013)

The above figure is looking for the protein that is normally missing in the one of the diseases (RS1). Panel A shows a picture of the diseased retina and there is no RS1 protein there (you can tell from no greenness), panel C shows what a normal non-diseased retina should look like (lots of green) and in the middle (panel B) we have a diseased retina that had the injection of the virus with the DNA and as you can see it looks just the normal retina in panel C! Magic! Lots of green!

Now you might be thinking? So what? They still need an injection in the eye to get the virus in the first place, and you'd be right! However, injecting into the vitreous gel layer is a simple procedure, done at your local doctors practice, under local anaesthetic and runs very little risk of damaging the retina and this makes it a much more practical solution to those rendered blind from these diseases. Furthermore, this study, as a general concept, paves the way for developing more AAV viruses that are specialised to reach certain tissue or organs.

The study was published on the 12th June in Science Translational Medicine and can be viewed here.

The power of chocolate (and electrostimulation combined with physical therapy)

It will be a fairly short post this week as my PhD has kept me fairly busy with performing brain surgery on mice so spare time has been few and far between.

Building on last weeks post, that looked at the ability to control machinery (such as prosthetics) with the mind only, which has exciting implications for physically disabled people. This weeks paper again has implications for physically disabled people (primarily spinal injuries).

Around half of all spinal injuries result in chronic paralysis in humans and as such there is considerable research into the area to give the patients their movement back. The paralysis results from the injury to the spine actually severing the nerves that connect a particular area of the body with brain, so that they can no longer communicate (hence they loss of movement but also feeling in some cases also). Advances in this area would change many lives.

In a landmark paper published in Science last year (here) a group in Zurich has made a giant step forward in regaining locomotion in spinal injuries. The study was done on rats and used a recovery regime that combined physical therapy, electro-stimulation and injections of a special combination of chemicals... oh, and chocolate.

The rats spines were almost completely severed (a small amount of tissue remained intact but all nerves were severed and they had no control of their hind limbs, seen below). Then the group of rats were split into two groups, one received there aforementioned therapeutic regimen and the other did not (acting as a control).

A video showing the rats inability to walk after the spinal surgery (van den Brand et al. (2012)).

Disclaimer: Now, the for the scientists reading this, the following explanation will butcher the incredibly elegant science involved but it is a necessary evil.

The rats that were receiving the treatment initially were "encouraged" to walk by initiating the reflex walking response. This was done by placing the rats in a specially designed harness (pictured below) and placing them on a treadmill. When a foot begins to drag on the treadmill it stimulates a reflex movement that is akin to taking a step but doesn't require the nerves in the spinal chord be 100% intact. This was the first physical therapy aspect (called "treadmill trained). Another aspect of physical therapy used the same harness and placed the rats on a runway type arrangement (the platform pictured below) and the harness was used to hold them up but provided no directional movement assistance. The second paradigm looked for voluntary movement of the legs rather than the reflexive movements elicited with the treadmill. The second form of physical therapy was called "overground" training.

Source: EPFL (via National Geographic)

The regime also included electric stimulation over the area where the nerves were severed which should act to encourage new nerve growth/connection over the area in question and the same area also received injections of a tailored cocktail of chemicals (for the nerds out there it was serotonin and dopamine agonists, 5-HT1A/7, 5-HT2A/C and D1 respectively) which served to assist in the encouragement of neuronal connections and comunication.

Figure taken from van den Brand et al. (2012)

The above figure essentially shows active nerves in the spine around the area of injury. The key things to look at are first, the marked reduction between intact (no injury) and non-trained (a control), and then look at the huge gains from the overground trained group. Not quite like a normal rat (intact) but a whole lot better than non-trained. You can watch a video of this in the final at the bottom of this post. This graph also shows that treadmill training alone is not enough, the overground training needs to be included to get the full therapeutic effect.

The end result? The rats regained control of their legs! In the final phase of the study the researchers placed chocolate at the end of the stair-case (in the overgound training) and noted that the rats were near on SPRINTING to get the chocolate (albeit still in their harness). After this complex course of therapy the rats regained full voluntary movement of their hind limbs but struggled to walk on fours completely unaided indicating there is more work to be done.

The researchers did a video explaining some of the concepts which I have included below.

Once again ... Science is rad! Till next week

- Si

Telekinesis and Telepathy .... Pseudoscience or science?

Today's piece of science is actually pieces of science, related to the same phenomena. One I have been wanting to write about for a long time and had planned on writing about it this week and the other paper coincidentally came out last week on the same sort of thing so I will combine them together. They are on the subject of telekinesis and telepathy (cue mandatory eye-roll). These are terms we associate with the sci-fi thrillers of yesteryear but they may be closer to reality than we think.

Both the studies I am writing about rely on the core principle that in it's most basic form all of our brains are wired in an extremely similar fashion and so brain activity in particular areas isn't entirely random and that readings of brain activity through technology such as EEG and fMRI scans may one day be able to extract useful data from someone's brain.

The first study was published in the journal of neural engineering on June 4th and can be read here. A group from the University of Minnesota have developed a new BCI (brain-computer interface). The group used the non-invasive EEG technique and used a high number of electrodes planted on the head (in order to get a more accurate reading) and from here they asked the participants to think of directional thoughts (I'll explain this in a few moments) and they recorded the brain activity. They then took several of these "thought-patterns" and told the computer that when a certain thought pattern was registered that a small remote control helicopter should do different movements and so created the first thought controlled helicopter.

Where other groups have failed in the past has been the encoding of the directional thoughts, for example, a participant may have been told to think of something vague such as "move left" in order to generate the command for the helicopter to move left. This group made it very specific and told the participant to think of forming a tight fist with their left hand - This encoded the helicopter moving left. This specific thought generated a much stronger and much more reliable thought pattern for the EEG to read and so made the movement of the helicopter more accurate.

The participants were then asked to complete a small obstacle course (two suspended rings) and to guide the helicopter through them. One of the videos can be viewed here:

The various participants performed with varying degrees of skill and the other videos can be viewed here.

This group from Minnesota has created a protocol by which an individual can control a drone with nothing but their mind (and some pre-encoding stages). The group is looking to progress this technology in to the area of prosthetics which may have huge implications for those with artificial limbs or wheelchairs.

The other paper I want to talk about takes this concept a step further and invokes a whole new level of creepiness. Taking someone's thought patterns and making them encode something, while amazing, isn't that fascinating biologically. A group from Duke University in collaboration with a group from Edmond and Lily Safra International Institute for Neuroscience in Brazil have developed a protocol (see diagram below) whereby tiny electrodes were planted into specific areas of one rats brain and then they put similar electrodes in exactly the same places in another rat. From here, they got the first rat (we'll call him the controller) to perform several tasks that included making decisions based on visual stimuli and physical stimuli. With the electrodes in the controllers brain they recorded the brain activity during the decision making process, encoded it to a computer and then transmitted the signal to the other rat so that the electrodes would generate the same thought pattern in the second rat (we'll call him the player). What happened was, when the controller was making a decision, his thoughts were then transmitted straight into the players brain and like magic that player began doing the same things and making the same decisions a remarkable percentage of the time.

Protocol for transmitting signal. Source: Pais-Vieira et al. (2013)

Source: Pais-Vieira et al. (2013)

Figure A on the right shows the percentage of the time the rats made the correct choices when the signal was transmitted into their brain. Here the encoder is our controller rat and the decoder is our player rat and the last one is a rat with no stimulation. Figure B showed that the response was fairly consistent between trials and that figure A wasn't a fluke. Figure C looks at the optimum number of electrical pulses given to the 'player' rat and there seems to be a threshold that lies somewhere between 26-40 pulses.

This study is for me (a neuroscientist) very intriguing as it shows the same electrical signal can generate the same behaviour in two distinct animals which lends evidence to the idea that the brain (at it's most basic level) has a common wiring diagram for all of us.

The groups work was published in the journal Nature (the creme-de-la-creme of science journals) earlier this year and the (open-source) paper can be viewed here for those of you who want the gory mathematics and physics behind the experiments.

So there you have it! Telekinesis and telepathy isn't all that far away after-all!  And the potential implications for humanity ... Well that's just scary!

Until next week! - This will be a Friday thing so while you are killing time at work on Friday waiting for the weekend, this can provide a little entertainment! Don't forget to share this around if you enjoy it :)