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Femtosecond Laser Shatters Viruses
wattrlz writes "In a development reminiscent of nineteenth century pseudo-science, the father-son team of Kong Thon and Shaw Wei Tsen recently demonstrated that the tobacco mosaic virus can be destroyed in vitro by nano-scale mechanical resonant vibrations induced by repeated ultra-short pulses from a laser. The total energy required is reportedly far below the threshold for human tissue damage and the technique should generalize to human pathogens. Cleaning stored blood is one obvious application."
Do not look into the femtosecond laser with your remaining Capsid.
(and you thought I was gonna say eye...)
liqbase
Considering that viruses are essentially bundles of proteins, and this laser trashes the virus, how would the laser not trash proteins in cells potentially containing the viruses?
Assuming the technique also leaves shark tissue undamaged, I got the perfect delivery mechanism in mind.
Kong Thon? There's a man waiting for a video game event to be named after him.
Kwisatz Haderach
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DNA, for example, would be closer to the size of a virus. You could end up with an intact cell wall containing nothing but debris.
Can this be tuned --or perhaps tuned with the assistance of another chemical marker-- to act as a "hunter killer" for auto-immune activated diseases such as multiple sclerosis, lupus, etc. where the resonant pulses would only kill the erroneously activated white blood cells and not the non-reactive white blood cells?
Because if so this becomes in effect a computerized vaccine against a wide variety of ailments that have no other good medicinal choices. And because computing power is still rising exponentially faster than just about any other form of tech, this could be a whole lot quicker to market.
...Open Source isn't the only answer -- but it's almost always a better value than the alternatives...
What? I don't think even the heaviest chain-smoker gets infected with tobacco mosaic virus. I'm sorry, I just don't see the "obviousness" of this application.
More music, fewer hits
Shattered
Destroyer
The Safety Dance
She Blinded Me With Science
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Patrick Doyle
I mod down every jackass who puts his moderation policy in his sig. Oh, wait a sec....
First, This will only work if the resonance breaks the bonds inside the proteins that create the subunits that self-assemble into the viral capsids. If the resonance only separates the weakly-bound subunits, then the resulting fragments will tend to re-self-assemble into whole viruses again. To use a bricks and mortar analogy -- if the device only breaks the mortar, the bricks can reused. The trick is to break the bricks.
Second, this solution requires a specific pulse frequency for each virus. It's not a broad-spectrum disinfectant. That suggests that viruses can easily evolve to defeat the device. Mutants that add a few non-functional amino acids to their capsid protein chains or that decorate the capsid surface with different biochemical groups would change the resonant frequency and allow mutants to escape and breed. One can even imagine evolution selecting for viruses that have inherent damping so that no resonant frequency can build enough energy to disrupt the shell. For example, a virus might become effectively heterozygous so that its shell is randomly constructed of two slightly different subunit sequences. A capsid that is not perfectly crystalline would lack a strong resonant frequency and escape disruption.
Overall, this looks like a very promising weapon in the on-going arms race against viruses.
Two wrongs don't make a right, but three lefts do.
This is (more or less) just some people who do a lot of Raman scattering deciding to try their technique to analyze virus particles and then noticing that some of them were damaged in the process. All of the other stuff (in particular the HIV) is largely BS - a few physicists who know almost nothing about biology going after NIH money by putting the magic "HIV" buzzword into their grant applications.
The slightly cool thing about it is that you can target particles below a certain size (like viruses) without causing much damage to larger particles (like host cells).
In terms of actually engineering this into a system for filtering blood (one of the main applications they envision), there are enough problems that it has no hope of succeeding in practice. Even if you could actually overcome all of those and build a system that could use this technique to destroy all of the virus particles in blood on a practical scale, many viruses that could contaminate whole blood (including HIV) will have uncoated and set up shop in the white cells, which would go on to release new virus after the treatment so this would offer no protection at all.
For the same reason, you couldn't use this as a treatment even if you could somehow expose every cell in a patient to these pulses (which would be impossible unless you cut them into paper-thin slices).
If the Tsens are actually unaware of this, then that alone should raise a huge red flag because anyone with the slightest bit of background in virology would know this.
About the only thing this *might* be good for (other than generating press and bilking naive investors out of their money) is as a laboratory technique for killing all of the free virus in a very small sample without harming the cells.
As a scientist, this kind of thing makes me sick, and it illustrates some of the harm caused by profit-motivated research in university settings (in particular, things Arizona State University's Biodesign Institute).
It's great when science and discovery naturally leads to practical (and profitable) products, but this kind of thing is what happens when people put the goal of making money ahead of actually doing real science.
Blood cell's don't have nuclei, so no DNA.
There is no replacement for displacement.
Being as they are using the resonant frequency to destroy the virus, I imagine the differences in the mechanical structures between viruses and other surrounding material would isolate the applied force to the virus. Disclaimer: This is no where near my field of study.
The list begins and ends with "Safety Dance". Why would you need any other music?! (sings)"Everybody pull up your pants..."
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From listening to Dr. Tsen, it really does seem to work for free virions floating in solution - but once they unpackage themselves and infect a cell, it does nothing.
From the article: Tsen says the technology could provide immediate benefits for clearing viruses in blood stored in blood banks. So they're not going after viruses that have already infected cells.Patrick Doyle
I mod down every jackass who puts his moderation policy in his sig. Oh, wait a sec....
A nice idea. I must be one of the rather few people who have worked with ultrashort pulsed lasers, Raman scattering, and viruses; and I really appreciate the interest of the concept. But I doubt very much that it will ever be a practical tool. Destroying M13 virus in pure water is a far cry from a real application.
If I understand it correctly, the technique exploits the fact that ultrashort laser pulses are not monochromatic but have a significant band width, to excite a vibrational frequency of the virus through resonant Raman excitation. Or, the vibrational mode of the viral capsid is about 8 cm^-1, and the excitation laser contains both 23,529 cm^-1 (i.e. 425 nm) and 23,521 cm^-1 (the Stokes-shifted matching frequency). If you excite the vibrations of the capsid hard enough it will break, as in the old trick of the singer breaking a glass.
But actually, a 100 fs laser pulse has a rather broad spectrum, and therefore is going to excite much more than just that single vibrational mode. Effect on viruses is claimed at a peak power of 50 MW/cm2 -- that is megawatt per square centimeter -- which is rather respectable, even if the average power is low. So I fear that this technique is not going to be very selective. I suppose that in theory you could also excite the virus with two longer-pulse (i.e. picosecond) lasers tuned to have a specific frequency difference, but then the average power required to get a threshold peak power of 50MW/cm2 is likely to be a problem.
Of course, if you are going to use this on a virus like HIV, you will need to target the immature form (which has a shell of gag protein under the envelope) and the mature form (in which gag has been processed into matrix and capsid). You also need to cope with the irregular structure of the virus, which does not have the icosahedral symmetry of many other viruses, its considerable genetic variability, and its variable morphology. HIV capsids occurs in at least two forms, cone-shaped (most of them) and tubular (less frequent). So its Raman frequency spectrum is likely to be complex and a broadband killer may be what you want -- may be.
The reported excitation is a frequency-doubled pulsed beam at 425 nm, which is violet. Blood strongly absorbs light at such wavelengths; hemoglobin even has an absorption peak there. You would have to tune to the red to do anything useful in blood without killing the blood cells, but a standard frequency-doubled titanium-sapphire laser will really struggle to generate red light -- a yellow-tinged green at 550 nm is about the limit. A different laser technology or a much more complex system (with a parametric oscillator) would be required to get there. And even a red laser might be absorbed enough to make blood boil in the focus of the beam.
Last but not least, even if your could destroy all viral particles in a blood sample, that would by no means make that blood safe! The raison d'etre of viruses is inserting their genome into cells to be replicated there. Destroy all viral particles, and there might still be viral genomes in the cells, as RNA or DNA, ready to replicate in the host; even viral proteins ready for assembly into new viruses. It would still be unacceptably dangerous to use that blood.
Frankly, I think this is a misuse of the technology. If it has any applications at all that will be in the study and detection of viruses, not in decontamination. It might be developed into a simpler, cheaper alternative to CARS microscopy.
"This technique will be very useful to disinfect all the viruses, known or unknown," Tsen said. "This will make blood transfusion very safe."
Do you see the BS? They say here: UNKNOWN. Lets suppose, you can calibrate the laser against a known virus without harming human cells/tissue/whatever. How do you calibrate this magic laser to several unknown viruses at the same time?
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There seems to be a lot of people here confused on how this laser can destroy the virus without harming the host cells. Please allow me to explain the natural wonder that is "Natural Harmonic Frequencies".
First, imagine pushing someone on a swing. If you want to make the swing go higher, you have to push it just as it starts to swing forward. That way, the swing's energy is increased by the amount of your push, while still getting the full benefit of it's stored potential energy, and Hey, Presto - the swing goes higher. Because of the way swings (and wave energy functions of most sorts) work, the time between each optimal push remains the same. This is the key.
Imagine a sine wave. If you view the wave at the right frequency - every PI units - you'll see the same value. If you were somehow pushing on the wave at those points, you would be changing the amplitude of the function by the same amount every time. If, however, you view the wave at the wrong frequency - say, every 1 unit - you'll get a different section of the wave each time. Over time your pushes will cancel each other out in this case.
Now, if you push enough kinetic energy into pretty much anything, you create a short-lived wave within it as the energy which has not yet been absorbed or lost in some manner reflects back and forth within the structure. Imagine water sloshing in a tub or a building swaying in an earthquake. The speed at which this wave moves back and forth across the structure is the structure's natural resonant (or harmonic) frequency. This is what is being taken advantage of by this pulsed laser.
By firing this laser at the same frequency that the virus happens to vibrate at, a wave is set up in the virus. Since the laser's pulse comes again at the optimal "pushing" time, the amplitude of the vibration increases. Other cells are being vibrated by the laser as well, but because their natural harmonics are different, the pulses cancel themselves out in those cells and they're fine. The targeted virus however, vibrates harder and harder until it literally shakes itself apart.
In recent years, determining the natural harmonic frequencies of large structures has become an important part of engineering. More than one large structure has been destroyed by seemingly insignificant forces which just happened to be coming at the right frequency!
See this for more mathematical details
Any plan which depends on a fundamental change in human behavior is doomed from the start.
Having read TFA, I still worry.
1. All proteins in your body, and all proteins your body can possibly assemble for a virus capsid (and it must, because that's how virii multiply) are made of the same 20 aminoacids. The result, however, can range from relatively simple enzymes to gigantic mollecules, and they're folded in lots of funny ways too, to work like they're supposed to.
I.e., I wouldn't be _too_ surprised if for _some_ particular frequencies (i.e., some very narrowly defined types of virii), something else in your cells had a resonance on the same frequency. Even if the total power isn't enough to vapourize a cell, it could still be pretty deadly.
2. A capsid isn't a monolythic thing, it's made of several proteins which assemble themselves in that shape. That's how your body produces more capsids for the viruses an infected cell manufactures. It produces the capsid pieces, and those then assemble themselves around the pieces of viral DNA or RNA that were copied too.
So I'm curious exactly in what way are the capsids "shattered" by that resonance. If it shatters the proteins themselves into aminoacids, yeah, that's the end of it. But then, see point 1, I'd worry which other proteins it can destroy like that. If it just shatters the (relatively) weaker bonds between the individual proteins that make the capsid, I would imagine that at least some of them will simply reassemble. Remember they're proteins which are pretty much built to do just that: connect to each other and form a capsid.
3. Their claim that it can shatter HIV virii, while leaving the T cells intact, seems somewhat missing the point. It's the kind of solution that a physicist would imagine, if he doesn't know much about how a virus works.
So let's get a bit into (a very over-simplified summary of) how a cell works, and a virus multiplies. (Warning: it's still a long read.)
Your cells are basically a chemical computer whose function include building more building blocks for itself, or for more copies of itself. Your proteins, for example, are encoded by your DNA, as triplets of nucleotides. One such triplet is a "codon", and it identifies one aminoacid. (With some redundancy. You use 20 aminoacids, but since there are 4 possible nucleotides and there are 3 of them, there are 64 possible combinations. So it's quite usual that 2 or 3 different combinations mean the same aminoacid.)
When a cell needs more of a certain protein, it first copies a segment of DNA to RNA and lets it loose. Each Then a ribosome reads that just like a piece of tape, one codon (group of 3 nucleotids) at a time, and assembles a chain of aminoacids matching that sequence. For each codon, it adds the matching aminoacid to the chain, and moves one position further. One codon means STOP, and when it reached that, it lets go of the newly built protein and stops.
A virus works much the same. It builds more capsids, for example, by just letting loose a chain of RNA in your cell, which contains the information on how to build a capsid piece. (If it's a DNA based virus, it will first have to transcribe it to RNA, same as your cell does.) When enough of those capsid pieces have been built, they assemble themselves in a capsid around such a RNA chain.
At the same time, of course, the virus will also have to get your cell to transcribe the RNA piece. That, however, is just a sub-case of the previous paragraph. One of the proteins encoded by the virus, is the "RNA replicase". It's an enzyme which copies RNA strands. So the virus will let one piece of tape with that information loose inside your cell, the cell transcribes it to RNA replicase, which in turn starts copying RNA strands non-stop. Some will be surrounded by the capsid pieces to form new virii, but some will just keep getting interpreted by your ribosomes, so the cell keeps producing more capsid pieces and more RNA transcriptase.
To sum it up, an infected cell is, essentially, reprogrammed to keep producing viruses until it bursts. It's those pieces of gene
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How do you calibrate this magic laser to several unknown viruses at the same time?
:D
With funding of course!
Even if there is no way to use this method to destroy viruses without damaging other cells couldn't this be used as a way to sterilize objects?
But I'm not good enough at immunology to know if once killed, the MS causing cells would be gone or if the bone marrow would simply repopulate the count again later.
...Open Source isn't the only answer -- but it's almost always a better value than the alternatives...
Since all the blood cells are removed from the donated plasma, it'd be much easier to make sure there was zero effect on what is left (normal blood proteins), and there wouldn't be any cells to make new virus.
One virus. Two viruses.
The urge to say virii, is hypercorrection. Which is to say... wrong.
But don't take my word for it:
http://en.wikipedia.org/wiki/Hypercorrection
http://en.wikipedia.org/wiki/Plural_of_virus
http://linuxmafia.com/~rick/faq/plural-of-virus.html
http://homepages.tesco.net/J.deBoynePollard/FGA/plural-of-virus.html
So unless you are trying to be cute, the plural of virus is viruses.
And know you know!
This is when a stupid person, feeling personally hurt by learning, will whine about language changing over time.
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