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Author Topic: Scientists discover a cure for all RNA viruses.  (Read 2081 times)
Minsc
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November 01, 2011, 12:44:09 AM
 #1

Shows how lousy evolution is.
http://www.digitaltrends.com/cool-tech/mit-researchers-develop-a-technique-to-kill-a-wide-range-of-deadly-viruses/

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November 01, 2011, 01:18:11 AM
 #2

and when it breaks how do we stop it?!

"If we don't hang together, by Heavens we shall hang separately." - Benjamin Franklin

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November 01, 2011, 01:24:36 AM
 #3

Mightily interesting!

All RNA? According to the article it only works for dsRNA. Weird that the lead researcher would hype it up saying that it could cure Ebola considering that all Ebola strains are ssRNA.
From the actual paper:
Quote from: Broad-Spectrum Antiviral Therapeutics, Todd H. Rider, et al, doi: 10.1371/journal.pone.0022572
Our DRACO approach combines two natural cellular processes.
The first process involves dsRNA detection in the interferon
pathway. Most viruses have double- or single-stranded RNA
(ssRNA) genomes and produce long dsRNA helices during transcription
and replication; the remainder of viruses have DNA genomes
and typically produce long dsRNA via symmetrical transcription

So apparently the Ebola strains are ssRNA (taking your word for it), but still produce long dsRNA at some point.

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November 01, 2011, 07:31:17 AM
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How does this show how "lousy" evolution is?
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November 01, 2011, 07:36:02 AM
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There was a thread on SA about this when the story first broke a few months ago.  I'll try to track it down when the forum comes back up in a couple of hours.  It was an interesting discussion in which a few researchers participated.

All I can say is that this is Bitcoin. I don't believe it until I see six confirmations.
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November 01, 2011, 08:01:18 AM
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fascinating, evolution at its best haha
TheBible
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November 01, 2011, 08:08:22 AM
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There was a thread on SA about this when the story first broke a few months ago.  I'll try to track it down when the forum comes back up in a couple of hours.  It was an interesting discussion in which a few researchers participated.

I'm really just curious how this makes evolution somehow look lousy.  It is what it is, it's not like evolution only selects for species, it can and does also select against.
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November 01, 2011, 09:12:01 AM
 #8

We'll see how lousy evolution is when the viruses eventually evolve to become resistant to this technique by not displaying the dsRNA surface antigen on their membranes. It's not a difficult modification, and it happens all the time with viruses.

So far, bacteria and the basic forces of natural selection have managed to outwit most of the advances we have made in the last century. Many bacteria have now developed resistance to the commonly used antibiotics like penicillin, and some are totally impervious to even the most potent ones, like vancomycin. Some of the most dangerous organisms can be found in hospitals, where all the "good" bacteria have been eliminated, leaving only the most dangerous organisms which are resistant to the eradication technique free to thrive. The more (selection) pressure we put on a population, the more rapidly evolution occurs.

If bacteria are able to do this being much more complicated organisms which do not evolve as readily as viruses, just think about the resistance potential viruses have. All they are composed of is a small DNA/RNA fragment floating around in a protein envelope. The potential for successful mutation is huge.

Microbes can't think or plan into the future, yet the more we try to kill them the more dangerous they become - all because of evolution and natural selection. And by killing off all the 'friendly' viruses, what we may end up creating out of this microbiological arms-race is a virus so virulent that it might wipe out the entire human population.

This is the second article I have seen you post, make some uninformed comment about along the lines of 'science is dumb', then scuttle off. And it's the second time I have been baited into a response. Meh, whatever...

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November 01, 2011, 10:47:08 AM
 #9

This is the second article I have seen you post, make some uninformed comment about along the lines of 'science is dumb', then scuttle off. And it's the second time I have been baited into a response. Meh, whatever...
Let's do an intelligent discussion Smiley I agree with most of what you said, there's however this:

If bacteria are able to do this being much more complicated organisms which do not evolve as readily as viruses, just think about the resistance potential viruses have. All they are composed of is a small DNA/RNA fragment floating around in a protein envelope. The potential for successful mutation is huge.
The expression of long strands of RNA are the core of a virus' existence. The long strand of RNA actually represent the virus, they're its genetic material, like DNA is ours. (For most viri anyway, some have actual DNA, but still produce long dsRNA during transcription, according to the paper.)
If the virus itself consists out of long strands of RNA, then a simple mutation will not solve that.

Also, if we have something that can be used against viri right now, and wipes out 90%, then the number of actual mutations happening is also 90% lower, which would at least slow down viri.


About evolution being lousy: I assume he meant that evolution failed for not creating this defense itself. This is not actually accurate. From the paper:
Quote
Most viruses have double- or single-stranded RNA (ssRNA) genomes and produce long dsRNA helices during transcription and replication; the remainder of viruses have DNA genomes and typically produce long dsRNA via symmetrical transcription. In contrast, uninfected mammalian cells generally do not produce long dsRNA (greater than ∼21–23 base pairs). Natural cellular defenses exploit this difference in order to detect and to attempt to counter viral infections.
So, natural defenses already use this. Basically when it is detected, the "Programmed cell death" (apoptosis) is triggered, and the cell will suicide, preventing the virus in it from using its reproduction tools. But then why are there still viri?
Quote
Many viruses attempt to counter these defenses. A wide variety of viruses target dsRNA-induced signaling proteins, including IPS-1, interferon response factors (IRFs), interferons and interferon receptors, JAK/STAT proteins, and eIF-2α. Some viral products attempt to sequester dsRNA (e.g., poxvirus E3L) or to directly interfere with cellular dsRNA binding domains (e.g., HIV TAR RNA). Virtually all viruses that inhibit apoptosis do so by targeting early steps in the pathway, for example by inhibiting p53, mimicking anti-apoptotic Bcl-2, or interfering with death receptor signaling. Among the few viral proteins that directly inhibit one or more caspases are African swine fever virus A224L (which inhibits caspase 3), poxvirus CrmA (which inhibits caspases 1, 8, and 10 but not others), and baculovirus p35 (which inhibits several caspases but is relatively ineffective against caspase 9).
So why is DRACO effective then?
Quote
The second natural process used by our approach is one of the last steps in the apoptosis pathway
So all viri that prevent apoptosis by blocking one of the signals, get bypassed because DRACO doesn't even go by those signals.

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November 01, 2011, 12:13:46 PM
 #10

The expression of long strands of RNA are the core of a virus' existence. The long strand of RNA actually represent the virus, they're its genetic material, like DNA is ours. (For most viri anyway, some have actual DNA, but still produce long dsRNA during transcription, according to the paper.)
If the virus itself consists out of long strands of RNA, then a simple mutation will not solve that.

Also, if we have something that can be used against viri right now, and wipes out 90%, then the number of actual mutations happening is also 90% lower, which would at least slow down viri.

RNA plays a very complex role in biology, and is relatively poorly understood compared with DNA.

Humans, and indeed all forms of life, rely on RNA for one reason or another. It is not restricted to the virus only. Our genome is encoded in double stranded DNA (dsDNA) in our nuclei, which is wound off it's spindle and read into a single strand of messenger RNA (mRNA). The mRNA is secreted out of the nuclear envelope, travels to the ribsosmes, where it is translated into amino acid sequences (i.e. proteins). So RNA is required for humans to produce proteins - i.e. the structural molecules - that make up our cells. Can the researchers at MIT assure me that their new DRACO will not confuse my RNA with viral RNA?

Also, many viruses have genomes made out of actual DNA, just like we do. RNA viruses are more dominant however, and you are right, a single mutation in an RNA virion might not stop DRACO killing it, but if there was a huge selection pressure put on the RNA virus populations as a whole because of their rapid eradication, then DNA viruses would simply mutate to take up any slack created and thrive due to the lack of host/resource competition, making DRACO irrelevant.

So, natural defenses already use this. Basically when it is detected, the "Programmed cell death" (apoptosis) is triggered, and the cell will suicide, preventing the virus in it from using its reproduction tools. But then why are there still viri?

So why is DRACO effective then?

Quote
The second natural process used by our approach is one of the last steps in the apoptosis pathway

So all viri that prevent apoptosis by blocking one of the signals, get bypassed because DRACO doesn't even go by those signals.

Yes, DRACO is supposedly effective as it induces apoptosis in a way that cannot be prevented by viruses. It really is quite ingenious as a broad-spectrum viral 'antibiotic'. I am in the medical profession myself, and I can see this revolutionizing the treatment of infectious diseases.

But will it be a change for the better? What worries me is the arms-race that we are entering with microbes that are able to evolve at rates MUCH MUCH faster than we can. Because our cells are so much more complex, mutations are usually useless and cause the death of the cell. Mutations in a virus is rarely fatal, because they are so simple.

I visualize the problem with technologies such as DRACO as building a massive antimicrobial 'dam' that is keeping a bubbling river of rapidly-evolving microbes at bay. The river is constantly growing and increasing the pressure, so we have to keep innovating and coming up with technological methods of preventing the cracks in the structure from causing a catastrophic failure. If we drop the ball even once, we are all screwed.

What I try to advocate is a kind of peaceful co-habitation with viruses and bacteria, and very conservative use of antibiotic medications. There is significant evidence to suggest that actually these microbes are VITAL to evolution in general. They assist in the distribution of genetic material, and keep populations in control. It is theorized that a huge chunk of your DNA has actually been injected there by viruses that affected your ancestors.

I certainly don't think that eliminating bacteria and viruses en-masse, with these broad-spectrum sledge hammers such as DRACO, is a good idea. It would be catastrophic for the ecosystem, and it would make our immune system's irrelevant - and when things are irrelevant in biology, natural selection is quick to get rid of them for efficiency reasons. An example of this is the insects and animals living in pitch dark caves who have vestigial eyes (i.e. eyes that were gotten rid of by evolution) as they no longer needed them once they moved into the cave and out of the sunlight.

I would much prefer to see some kind of antiviral technology that can be tailored to individual patients and individual viral genomes, so that all the 'good' viruses and 'good' bacteria will be left alone. This could be achieved by immunotherapy, i.e. modulation of the human immune system itself. It's a long way off, but I think it will be possible within the next 50 years.

I'm just calling for caution with things that we don't fully understand yet...

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November 01, 2011, 01:22:42 PM
 #11

RNA plays a very complex role in biology, and is relatively poorly understood compared with DNA.

Humans, and indeed all forms of life, rely on RNA for one reason or another. It is not restricted to the virus only. Our genome is encoded in double stranded DNA (dsDNA) in our nuclei, which is wound off it's spindle and read into a single strand of messenger RNA (mRNA). The mRNA is secreted out of the nuclear envelope, travels to the ribsosmes, where it is translated into amino acid sequences (i.e. proteins). So RNA is required for humans to produce proteins - i.e. the structural molecules - that make up our cells. Can the researchers at MIT assure me that their new DRACO will not confuse my RNA with viral RNA?
That's what testing is for, of course. If you take a look at for example figure 6B in the paper (link), you can see that the cells clearly suffer no problems due to the DRACO. It has already been tested in mice, actually, as shown in figure 9 and in the text, so in vivo applications seem to work well.

Also, many viruses have genomes made out of actual DNA, just like we do. RNA viruses are more dominant however, and you are right, a single mutation in an RNA virion would not stop DRACO killing it, but if there was a huge selection pressure put on the RNA virus populations as a whole because of their rapid eradication, then DNA viruses would simply mutate to take up any slack created and thrive due to the lack of host/resource competition, making DRACO irrelevant.
Are you sure there is a lot of host/resource competition in viri? I think their main opponent would be the immunesystem, which means resource competition doesn't come into play. I may be wrong about this though.

But will it be a change for the better? What worries me is the arms-race that we are entering with microbes that are able to evolve at rates MUCH MUCH faster than we can. Because our cells are so much more complex, mutations are usually useless and cause the death of the cell. Mutations in a virus is rarely fatal, because they are so simple.

I visualize the problem with technologies such as DRACO as building a massive antimicrobial 'dam' that is keeping a bubbling river of rapidly-evolving microbes at bay. The river is constantly growing and increasing the pressure, so we have to keep innovating and coming up with technological methods of preventing the cracks in the structure from causing a catastrophic failure. If we drop the ball even once, we are all screwed.
I don't believe your dam analogy is accurate. This would be more accurate: We build a dam against most current viri, by preventing long dsRNA to be present. Then, because of mutation, there might come a virus with a method of replication that doesn't use long dsRNA, which can be represented by water not blocked by the dam. A spill-over, if you like. This doesn't mean however, that the dam is cracking; i.e., it doesn't mean that suddenly all viri have this dsRNA-less reproduction.
Of course, the new viri can still be countered the normal way; by specific binding to virus types.

I certainly don't think that eliminating bacteria and viruses en-masse, with these broad-spectrum sledge hammers such as DRACO, is a good idea. It would be catastrophic for the ecosystem, and it would make our immune system's irrelevant
At the very least it creates a unique solutions for "difficult diseases". Things like ebola, but also strains of influenza we don't have any anti-virals against. Using it en-masse, is an interesting option, which should be considered very carefully, if it is possible.

What I try to advocate is a kind of peaceful co-habitation with viruses and bacteria, and very conservative use of antibiotic medications. There is significant evidence to suggest that actually these microbes are VITAL to evolution in general. They assist in the distribution of genetic material, and keep populations in control. It is theorized that a huge chunk of your DNA has actually been injected there by viruses that affected your ancestors.



when things are irrelevant in biology, natural selection is quick to get rid of them for efficiency reasons. An example of this is the insects and animals living in pitch dark caves who have vestigial eyes (i.e. eyes that were gotten rid of by evolution) as they no longer needed them once they moved into the cave and out of the sunlight.

I would much prefer to see some kind of antiviral technology that can be tailored to individual patients and individual viral genomes, so that all the 'good' viruses and 'good' bacteria will be left alone. This could be achieved by immunotherapy, i.e. modulation of the human immune system itself. It's a long way off, but I think it will be possible within the next 50 years.
Viri have indeed be very important in human evolution. But human evolution is long-scale. As you mention yourself, we are at the brink of a large change in biological evolution: at the much shorter scale of ~50 years, we will start actively modifying our own immune system, or rather, our own DNA. This will change things a lot.

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November 01, 2011, 04:22:28 PM
 #12

That's what testing is for, of course. If you take a look at for example figure 6B in the paper (link), you can see that the cells clearly suffer no problems due to the DRACO. It has already been tested in mice, actually, as shown in figure 9 and in the text, so in vivo applications seem to work well.

I read the paper, but it seems they have only tested it on 11 mammalian cell types. There are about 210 distinct types of cell in the human body alone, and they have only carried out in-vitro human tests that do not replicate the normal cellular environment. It is a promising study, and I know these things take time, but they have a lot more testing to do in order to convince me of the safety and viability of this treatment.

Especially considering that the vast majority of viral illnesses are self-limiting, completely resolving over a number of days with non-antiviral care alone. So weighing the risks and the benefits, unless this treatment is definitively proven 100% safe (unlikely), it could not be recommended over non-treatment no matter how high the efficacy.

Are you sure there is a lot of host/resource competition in viri? I think their main opponent would be the immunesystem, which means resource competition doesn't come into play. I may be wrong about this though.

Evolution itself can only occur in the face of a resource-struggle. This is a universal principle, and is a pre-requisite for natural selection. So any form of life on the planet competes for resources in some shape or form, or else it would not exist. A virus would find it difficult to infect a host, for example, if the host's immune system is already at 100% due to the presence of a pre-existing infectious disease.

I don't believe your dam analogy is accurate. This would be more accurate: We build a dam against most current viri, by preventing long dsRNA to be present. Then, because of mutation, there might come a virus with a method of replication that doesn't use long dsRNA, which can be represented by water not blocked by the dam. A spill-over, if you like. This doesn't mean however, that the dam is cracking; i.e., it doesn't mean that suddenly all viri have this dsRNA-less reproduction.
Of course, the new viri can still be countered the normal way; by specific binding to virus types.

This is not correct. If there is a massive selection pressure put on the virus population, such as DRACO, any mutations that are advantageous can be transmitted very rapidly by horizontal gene transfer. I.e. transmission of genes from an organism without being a direct offspring of the organism itself. This can rarely occur in more complex organisms, but it a typical trait of viruses. Also, because of natural selection, any virus that doesn't have the mutation will (by definition) be killed by the selection pressure, leaving only the mutated successful viruses alive. All of this can result in periods of hyper-evolution following a significant stressor.

However, this is not really what I meant with the analogy. Consider the damn to be an antibiotic, and the water to be a particular microbe. If the antibiotic suddenly becomes ineffective at treating the infection, then the damn has been effectively breeched as there is no effective treatment other than that single antibiotic. I know we have multiple antibiotics available, but this essentially translates to a crack in the damn being patched over, which will eventually fail in the same way until the entire structure can no longer cope. Unless we start to use our antibiotics more carefully, I can guarantee you that we could all be suddenly (i.e over the space of a few years) drowned in microbes that we have no effective treatments for.

The analogy though is admittedly not perfect, but I just wanted to illustrate my point about the anti-microbial arms race, and how microbes are much more effective at evolving than we are at innovating. It may not seem like it, but when you have a patient who has a methicillin-resistent Staphylococcus Aureus infection and you have no working antibiotics to treat them with, the reality of the damn-bursting becomes much more striking.

At the very least it creates a unique solutions for "difficult diseases". Things like ebola, but also strains of influenza we don't have any anti-virals against. Using it en-masse, is an interesting option, which should be considered very carefully, if it is possible.

I do see the potential of a therapy like DRACO, it might even be able to cure HIV! But If we use it over-judiciously I would be extremely worried about the kind of viruses that might emerge after the inevitable occurs and they eventually evolve a defense for DRACO. It could leave them completely impervious to our own host-defences (as they work essentially the same way), leaving our immune systems totally useless without technological assistance and further innovation in the future.

The more we try to kill viruses and bacteria, the more dangerous and virulent they become. This is a fact, and we have no hope of eradicating them completely. And even if we managed to do that, we would be signing the death certificate of every other organism on the planet, because future evolution and horizontal gene transfer would no longer be able to occur.

Instead of coming up with new methods of destroying viruses, we need to accept them as something that is necessary and natural, and only treat infectious diseases which would likely kill the patient if left untreated. Very few viruses fall in this category.

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November 02, 2011, 05:55:50 AM
 #13

What's the approximate price? Wink I need it right now cough-cough...
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November 02, 2011, 06:30:54 AM
 #14

Will this cure zombie bites?

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