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Author Topic:   New Antibiotics
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 1 of 17 (511370)
06-09-2009 2:23 PM


This article from ScienceDaily.com talks about a new antibiotic that binds to bacterial DNA and kills bacteria within 2 minutes.
quote:
The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix. It is about the same size as the parts of a protein that recognise and bind with particular sequences of DNA. The high positive charge of the compound enhances its ability to bind to DNA which is negatively charged. When the iron-helicate binds to the major groove of DNA it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes.
quote:
New research at the University of Warwick, led by Dr Adair Richards and Dr Albert Bolhuis, has now found that the [Fe2L3]4+ does indeed have a powerful effect on bacteria. When introduced to two test bacteria Bacillus subtilis and E. coli they found that it quickly bound to the bacteria's DNA and killed virtually every cell within two minutes of being introduced - though the concentration required for this is high.
While I'm sure this could have some amazing short term effects, how is this really any better than the antibiotic drugs we currently use? I concede that it will probably be harder for bacteria to develop resistance to the [Fe2L3]4+ because it does not target any specific sequence, it's not inconceivable that bacteria would. I mean, one way bacteria develop resistance currently is to simply pump the drug out of the cell before it does too much harm. Bacteria already have all sorts of ion pumps, I can't imagine there wouldn't be a way to pump out this one. I think it's also worth pointing out that being so effective at killing bacteria may actually be HARMFUL because it applies a very very high selection coefficient to the bacterial population which will result in much faster evolution.
I don't think we will ever find the magical antibiotic bullet, but the game we're playing now, constantly fighting to stay one step ahead without really considering the evolutionary consequences can't last for long.
I guess my topic for debate is: assuming "they" are able to develop this into an effective therapy, do you think it will succumb to the same fate that most antibiotics have? And, more generally, do you think the pharmaceutical companies will ever get it in their heads that the game they're playing is futile?
Edited by Stagamancer, : No reason given.

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

Replies to this message:
 Message 3 by Phage0070, posted 06-09-2009 4:07 PM Stagamancer has replied
 Message 5 by New Cat's Eye, posted 06-09-2009 5:06 PM Stagamancer has replied
 Message 7 by Perdition, posted 06-09-2009 6:17 PM Stagamancer has replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 4 of 17 (511414)
06-09-2009 4:44 PM
Reply to: Message 3 by Phage0070
06-09-2009 4:07 PM


Healthcare has always been ultimately futile because we will eventually die not matter what. This is no reason to ignore the field completely.
Agreed, and I don't think we should, I just think the method is wrong.
A new and effective antibiotic would save millions, perhaps billions of lives; not forever, but saved nonetheless. I don't see that as "futile".
No, but instead of focusing on developing antibiotics that we know will be useless in 5 to 10 years, why not put more money into antibiotics with low selection factors, i.e. ones that prevent the host from dying without killing 99% of the pathogen. I know there's been some research into this (I can find the link to the one I'm thinking of just now) but I don't think it's enough.

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 3 by Phage0070, posted 06-09-2009 4:07 PM Phage0070 has replied

Replies to this message:
 Message 10 by Phage0070, posted 06-10-2009 9:00 AM Stagamancer has replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 6 of 17 (511427)
06-09-2009 5:53 PM
Reply to: Message 5 by New Cat's Eye
06-09-2009 5:06 PM


What fate have most antibiotics succumbed to?
From my POV they kick ass. I had an infection. I took an antibiotic. The infection went away.
Well yes, obviously antibiotics have done some great things, and they still work for many basic infections. However, MRSA, multi-resistant TB, and other diseases have arisen, and continue to arise. Basically the original antibiotics we used to treat these have become useless.

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 5 by New Cat's Eye, posted 06-09-2009 5:06 PM New Cat's Eye has not replied

Replies to this message:
 Message 9 by Meddle, posted 06-09-2009 8:19 PM Stagamancer has seen this message but not replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 8 of 17 (511443)
06-09-2009 6:48 PM
Reply to: Message 7 by Perdition
06-09-2009 6:17 PM


Re: How does it differentiate?
this could have an adverse effect on the person taking this drug as well as the virus. It seems like the [Fe2L3]4+ just bonds to DNA, not allowing it to do anything from that point.
That's a very good point, and I thought of that too. It was originally developed as an anti-tumor therapy, so obviously, it can get into eukaryotic cells. I would imagine they'd have to develop some sort of delivery system that would only introduce it to bacterial cells (and keep it there), or find some way to make it specific to bacteria DNA, maybe based on either specific sequences or based on protein interactions. I don't really know how they would go about doing that, but it's another interesting idea to discuss.

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 7 by Perdition, posted 06-09-2009 6:17 PM Perdition has not replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 11 of 17 (511571)
06-10-2009 1:26 PM
Reply to: Message 10 by Phage0070
06-10-2009 9:00 AM


Needless to say this technology makes it easy to spot and kill those wolves, but what of the remaining 10% that can still hide? Eventually all wolves will end up being the non-pink kind but will this prevent their eventual extinction? What if we come up with a second windfall that kills 90% of those remaining wolves, and we get this windfall within 2 months of the first?
But here's the problem. When I mentioned antibiotics that kill 99% of the pathogen, that's only in the person who's been given the antibiotic, you're never going to kill 99% of the world population of a pathogen with antibiotics alone. Also, bacteria reproduce way faster (and evolve much faster) than wolves. Bacteria can develop resistance to drugs in a matter of days, and medical research just can't progress that fast.
20% of bacteria might be resistant to Med A.
20% of bacteria might be resistant to Med B.
How many are resistant to both Med A and Med B? Much fewer.. maybe 5% overall.
But those 5% are given a wide open playing field by the destruction of the rest of the population by those meds. Like I said, bacteria reproduce and spread pretty damn fast. Look at malaria, which is caused by a protist (multicellular) pathogen. Even so, there are multiple strains with various resistances to the drugs used to combat them.
How about Med D, nearly useless on the original population since it only takes out 1% overall? On the other hand it completely obliterates every last strain that was resistant to A, B, and C.
So far, we've never found a drug that can kill absolutely everything.
Look, I'm not saying that pharmaceutical research is completely in the shitter. I know antibiotics have done and currently do all sorts of good; I'm glad I had them when I got strep throat. I know not all of them are useless. But the idea that "evolution is slow" does not hold for bacteria and many other pathogens. Basically what I want to see is an application of evolutionary theory to medical and pharmaceutical research, but it is not happnening.

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 10 by Phage0070, posted 06-10-2009 9:00 AM Phage0070 has replied

Replies to this message:
 Message 12 by Phage0070, posted 06-10-2009 2:49 PM Stagamancer has replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 13 of 17 (511611)
06-10-2009 4:34 PM
Reply to: Message 12 by Phage0070
06-10-2009 2:49 PM


Surely you are not suggesting that we should eliminate that open field by allowing it to be packed with competition?! "Good lord, this man is being ravaged by malaria! Don't worry though, we can limit its damage by simultaneously infecting him with some bubonic plague and various types of flu!" If we can treat 95% of the ailment we SHOULD! We are guaranteed for that treatment to be better than doing nothing, and the worst case scenario of an infection immune to everything we have would still be functionally equivalent to your original proposal.
This is obviously ridiculous. My ACTUAL argument is that we should focus on reducing virulence, not killing everything we can. Who cares if you've got bacteria living in your that only give you the sniffles, or better yet, do nothing at all. Let's use that intellect we have to direct evolution in a beneficial way. That's a win for everybody. For example, Dr. Read, a researcher at Penn St., is looking into using a fungus as a pesticide for mosquitoes in malarial areas. The fungus tends to infect and kill mostly older mosquitoes, which, as it happens, also tend to be the ones that act as vectors for malaria. So, by attacking the older mosquitoes (that have already reproduced) you're not putting heavy evolutionary pressure on the mosquitoes to evolve resistance to the pesticide, but you're still cutting the incidence of malarial infection way down. That's using evolutionary theory applied to public health and medicine. This is more of what I want to see.
Dr. Read also is doing research into how drug resistant and vaccine-escape (epitope) mutants erode the effectiveness of chemotherapy and vaccination. His research mostly deals with vaccines, but many of the arguments can also apply to antibiotics.

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 12 by Phage0070, posted 06-10-2009 2:49 PM Phage0070 has replied

Replies to this message:
 Message 14 by Phage0070, posted 06-10-2009 5:48 PM Stagamancer has replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 15 of 17 (511637)
06-10-2009 6:46 PM
Reply to: Message 14 by Phage0070
06-10-2009 5:48 PM


This seems like it would actually place evolutionary pressure on increasing virulence since the window of infection becomes smaller.
Except, it could only increase virulence at the vector stage, and in order to get transmitted, a disease needs to not kill off its vector. I would actually predict there wouldn't be an increase in virulence then, because it would only serve to kill off it's own vector. It could even, perhaps force a host or vector switch that would make it all the easier to manage.
All he has managed to do is reduce the number of vectors without needing to produce a new pesticide.
Um, reducing vectors is a good thing. Vector-transmitted diseases tend to be more virulent than non-vector-transmitted ones. Eradication of the disease is pretty much not going to happen, so let's focus on decreasing virulence and transmission.
Instead if we wanted to actually reduce their virulence we should place an evolutionary advantage on infecting something other than humans. We could do this by, say, destroying every human malaria case that we can find thus making human-infecting malaria strains less fit as they are less likely to reproduce.
By saying "destroying every human malaria case" do you mean killing people with malaria? If so, I assume you're trying to be satirical, and I don't really get why you're so against evolution based approaches to fighting disease. If that's not what you mean, then what exactly are you getting at?

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 14 by Phage0070, posted 06-10-2009 5:48 PM Phage0070 has replied

Replies to this message:
 Message 16 by Phage0070, posted 06-10-2009 8:44 PM Stagamancer has replied

  
Stagamancer
Member (Idle past 4915 days)
Posts: 174
From: Oregon
Joined: 12-28-2008


Message 17 of 17 (511641)
06-10-2009 9:19 PM
Reply to: Message 16 by Phage0070
06-10-2009 8:44 PM


I don't recall anything about malaria being detrimental to the life cycle of mosquitoes so any of those would have no particular impact on the vector.
quote:
This study makes it clear that genetics play a part, too, and that mosquitoes are not just passive squirt guns for malaria parasites.
Plasmodium parasites do hurt mosquitoes, Dr. Vernick and Dr. Wirth said. They damage salivary tissue, make the mosquitoes fly less vigorously and lay fewer eggs and, to gain a toehold in the insect, may depress its immune system.
"The mosquito doesn't want to be infected, so it has responded with this very powerful mechanism," Dr. Vernick said, referring to what he called the "resistance island" on the mosquito genome.
-Mosquito Isn't a Happy Host for Malaria, Tests Indicate
Anyway, I'm not interested in picking apart this example; I was using it as just that: an example of the direction I'd like to see more research go in. I'm not saying this specific approach is perfect.
We have eradicated diseases before so there is no reason to think it cannot happen again.
True, but the there are very very few diseases we have eradicated, and they are definitely not the norm. There is no reason to think we'll be able to eradicate all diseases.
quote:
The vaccine success stories involve acute childhood infections. A striking feature of the natural history of these diseases is that first infections invoke immunity that is sterilizing, strain-transcending, and usually lifelong. Such acute infections either kill their host or are rapidly cleared. The pathogens persist by exploiting susceptible individuals, typically non-immune children. Why natural selection failed to find these organisms a way to penetrate previously exposed hosts is unclear, but it is evident that it did not. There must have been intense selection on all of them to break though natural immunity in the pre-vaccine era. An evolutionary solution would have been no easier in the vaccine era. Acute childhood diseases were easy targets for vaccination: natural immunity was already evolution-proof; all that was needed was for vaccines to induce something similar.
The diseases that are the focus of much of today’s vaccine development differ notably from acute childhood infections. The populations of pathogens causing diseases like flu, malaria, and pneumococcal disease frequently consist of a rich diversity of strains able to successfully infect previously infected individuals.
-"Pathogen evolution in a vaccinated world" (emphasis mine)
If we can consistently cure a large majority of human cases before they manage to reproduce and spread then that is strong evolutionary pressure for being unfit for the environment.
Or, instead of host switching, they could just evolve more resistance. There are more ways to neutralize a threat than just destroying your enemy. (BTW this is not me advocating disease rights or something, I just think it's too much effort, when there are probably easier ways)

We have many intuitions in our life and the point is that many of these intuitions are wrong. The question is, are we going to test those intuitions?
-Dan Ariely

This message is a reply to:
 Message 16 by Phage0070, posted 06-10-2009 8:44 PM Phage0070 has not replied

  
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