Promoted from the Ricochet Member Feed by Editors Created with Sketch. Making Pandemic Viruses from Scratch, for Dummies

 
By Photo Credit: James GathanyContent Providers(s): CDC - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #7988.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1314479
Photo Credit: James Gathany, Public Domain. Dr. Terrence Tumpey examines a reconstructed version of the 1918 flu.

With the rapid pace of shiny new discoveries in the biotechnology sector, it’s easy to lose sight of the fact that there are some pretty incredible technologies which have been around for quite some time now but have fallen off the public’s collective radar. One example is something I have done hundreds of times in my career but still seems impossible to those outside of the field: creating a flu virus from scratch. Not mutating an existing virus to make a new strain, but creating an infectious virus from whole cloth using nothing but common, commercially-available laboratory materials. And not just any strain, but the equal ability to make a harmless laboratory strain or reconstitute the 1918 “Spanish” flu.

And this technique is not just limited to the influenza virus: to date, the ability to reconstitute infectious virus from common, innocuous, non-infectious materials – known in the business as “reverse genetics” – exists for dozens of different types of viruses, including (but certainly not limited to) influenza, poliovirus, HIV, hepatitis B and C, SARS, rabies, measles, Ebola, Dengue, West Nile, and on and on. The ability to artificially create a virus is a powerful tool for researchers, as it allows us to create new variants and see what effects a targeted mutation may have, as well as being able to design new strains with more favorable properties for use as vaccines.

However, the ability to construct pandemic viruses whole cloth with no need for any sample of the original virus also poses some powerful threats to public health and safety. So let’s take a look at how this process works and what the implications of this technology are.

Back to Basics: How Is This Even Possible?

The key point to remember about viruses is that they are not only obligate, intracellular parasites, but indeed are not really functioning organisms at all. At the most fundamental level, a virus is just a small amount of genetic material which encodes enough information to a) Hijack a host cell’s synthetic machinery, b) Replicate its own genetic material, and c) Get the host cell to produce a physical package that can bring that genome to a new host cell and insert it into that cell. So while we might conceive of a virus as similar to a bacteria — in the sense of being a small infectious particle that lodges in our body and replicates — viruses are really just genomes that are dependent on everything else they need from the cells they infect.

This crucial fact is what allows us to create a virus from scratch. Genetic material (confusingly, viruses use both DNA, RNA, and DNA/RNA hybrids as their genomes, whereas all other living organisms only use DNA) is inherently easy to create artificially and to manipulate in the lab. With only four bases which assemble into linear chains, DNA is the perfect biochemical building block to work with in a laboratory setting.

Thus, the theoretical steps in creating a virus from scratch are: a) Find the sequence of the virus you want to create, b) Create a synthetic DNA/RNA construct with this sequence, c) Introduce this genetic construct into a cell culture in a Petri dish, and d) you’ve got a virus!

Reconstituting the 1918 Spanish Flu

In a breakthrough which was widely publicized at the time, a group of researchers at the CDC and the Mt. Sinai School of Medicine in New York reconstituted the pandemic 1918 “Spanish” influenza virus in the early-to-mid 2000s. The most technically difficult challenge was actually obtaining the sequence of a virus which had not infected humans in over 80 years. This was overcome by painstakingly isolating segments of viral RNA from several corpses which had been buried in Alaskan permafrost, as well as using several lung biopsies from deceased soldiers which had been preserved in paraffin. Because these specimens were so old, most of the viral RNA had degraded, so the researchers were forced to sequence millions of small fragments – in total, much more than the actual genome length of about 10,000 nucleotides – in order to obtain 100% coverage.

Once this sequence had been confirmed and entered into the database, it was then time to create a new, full-length, intact copy of that genome which could be inserted into a cell culture. This was a fairly straightforward task using machines which automatically synthesize DNA. However, because these machines can only create chains of DNA, but the influenza virus (like many other viruses) actually have genomes consisting of RNA, a few molecular biology tricks are available to convert the synthetic DNA into the RNA form which can then hijack the host cell. This is typically achieved by embedding the DNA version of the genome into a larger DNA backbone which is taken up by cultured cells and contains extra genetic elements which direct cellular enzymes to create an RNA copy of the synthetic DNA which is identical to an actual viral genome. In other words, for our own convenience, we are also tricking the host cell into creating a viral RNA genome out of a piece of artificial DNA – and once the cell creates that viral RNA genome, it immediately sets about hijacking the host cell into producing virus, both by creating new copies of itself and by creating the proteins which will then form the viral particle encapsulating the RNA.

From the standpoint of the biologist, this is an incredibly simple process. Designing and manipulating the DNA may have been slightly tricky, but once we have that DNA, it’s literally a matter of sprinkling it (in dissolved form) onto a Petri dish full of mammalian-derived cells. Put the cells back into the incubator, wait 24 hours, and the medium on top of the cells is chock full of your virus. Incredible!

Indeed, this procedure is so simple that many research laboratories (including the ones I have worked in) create dozens of new strains of the flu virus on a weekly basis. Find a specific locus you want to study more, introduce a mutation into that locus, create your virus, and run tests with it (in cell cultures, lab animals, etc.) to see what new properties it has.

The Bad News

As you might be guessing (if you’re still reading this far), this process could easily be manipulated for nefarious reasons. So let’s address the obvious question: Could terrorists conceivably recreate the 1918 Spanish flu (or another pandemic virus) on their own?

The answer is a definitive “yes.” As a PhD-level virologist, I wager I could set up a lab using commercial, off-the-shelf technology that would be capable of creating influenza viruses (including the 1918 virus) for between $1-2 million over a time frame of about 1-2 years, given one PhD-trained virologist and a team of three or four capable biological technical assistants. And keep in mind that there are several thousand of us around the world with this experience, and it is very simple for a talented student from a Middle Eastern country to obtain a scholarship for graduate school at a European or American university where he could learn these skills.

What’s more, the techniques are simple enough that nearly any PhD-trained scientist (or laboratory technician with enough experience and resourcefulness) could teach themselves these techniques in about 1-2 years. Thus, it is easily conceivable that a terrorist cell could recruit a Western-trained PhD biologist to lead such a project for a reasonable fee and time span, without necessarily raising any red flags.

The Good News

Before anyone starts building an airtight bubble in their basement, keep in mind how much hype we have heard over the last decade about looming viral pandemics, and how few of them have actually panned out. From SARS, to bird flu, to swine flu, to Ebola, all were sold as the coming apocalypse, yet all were fairly easily manageable (obviously the jury is still out on Zika).

The truth is that we have gotten the worst viruses under pretty good control, be it through vaccination, drugs, or other preventative measures. We have very efficient infrastructure for vaccinating against the flu, polio, measles, or any other virus which could be manufactured in the lab and spread through the air. What’s more, a number of recent studies suggest that we may still be quite immune to the 1918 Spanish Flu, and there is also quite a bit of immunity to polio virus from previous vaccination campaigns.

What about SciFi’s recurring scenario of a rogue syndicate which designs a new “killer” virus in the lab? Here there also seems to be reason not to worry. As mentioned above, research laboratories are constantly creating new variants of many of deadly viruses to observe the effects of those changes. And intriguingly, most of the new variants which are more potent in vitro are duds in actual animal models. Indeed, it’s fiercely difficult to engineer a virus which is more virulent than the strains found in nature while also being resilient enough to get efficiently passed from one person to another.

In other words, there’s a good chance that the viruses we’re exposed to in nature are already the worst that evolution can come up with – that they’ve already reached their optimum. Because of their incredibly small size, every nucleotide of a virus’ genome is multifunctional – and it appears that enhancing a virus’s capability in one aspect leads to a trade-off in some other aspect of its replicative cycle. So, considering how well we’ve managed to neutralize the threat from natural viruses, we probably don’t need to worry much about man made ones, either.

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  1. Misthiocracy got drunk and Member
    Misthiocracy got drunk and Joined in the first year of Ricochet Ricochet Charter Member

    Mendel: Note: this was originally supposed to be published yesterday, 8/15. Apologies for the delay.

    I blame a virus.

    • #1
    • August 16, 2016, at 1:36 PM PDT
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  2. Belt Member

    Very interesting. I think Rainbow Six by Tom Clancy was the first book I read that proposed this scenario. You make an interesting point in that it’s hard to improve on nature, but what do you think of the germs/bacteria/viruses that are evolving out of highly sterile areas like hospitals? I hear a lot of alarm over the ‘superbugs’ that widespread use and overuse of antibiotics (and hand sanitizers!) are producing.

    My biggest concern is that someday some bright researcher in a lab somewhere is going to forget to carry the one or make some other simple error that will lead to something truly catastrophic. I read a book called The Alien Dark some years ago that postulated a virus created to break down plant cellulose for a lumber company that got too good at its role and wound up wiping out all plant life on Earth. The greater danger may come from a simple mistake rather than intent.

    • #2
    • August 16, 2016, at 4:13 PM PDT
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  3. DocJay Inactive

    I’m still not convinced the filoviruses , or is that filoviridae, aren’t quite yet done with us. Ebola is some nasty stuff man.

    • #3
    • August 16, 2016, at 4:45 PM PDT
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  4. Belt Member

    Of course now my brain is trying to catalog all the books and movies where pandemics are a plot point. Also how dumb they can be.

    One thing about a successful virus is that it can’t be too successful. It needs to be just successful enough that the host doesn’t actually die, just gets annoyed. In that sense, Ebola can be too successful because an outbreak can wind up killing off the hosts before it can spread too far.

    • #4
    • August 16, 2016, at 5:12 PM PDT
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  5. Belt Member

    By the way, let us know how your interrogation with the NSA goes.

    • #5
    • August 16, 2016, at 5:15 PM PDT
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  6. J. D. Fitzpatrick Member
    J. D. Fitzpatrick Joined in the first year of Ricochet Ricochet Charter Member

    Great read!

    • #6
    • August 16, 2016, at 5:39 PM PDT
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  7. John Walker Contributor

    For DIY Bond villains, here is where you can download the RNA sequences for many variants of the influenza virus.

    • #7
    • August 16, 2016, at 6:13 PM PDT
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  8. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    Belt: what do you think of the germs/bacteria/viruses that are evolving out of highly sterile areas like hospitals? I hear a lot of alarm over the ‘superbugs’ that widespread use and overuse of antibiotics (and hand sanitizers!) are producing.

    Resistant bacteria are a completely different story. The genome of a simple bacteria such as E. coli is about 500x larger than that of the flu virus, so there’s a lot more room to play with, genetically speaking.

    In the case of most “superbugs”, they’re not developing the resistance to antibiotics themselves, but they’re receiving resistance-encoding genes from other bacteria who already have copies of the resistance gene.

    RNA viruses are typically (but not always) too small to develop or accept “new” functionalities, so this is much less of a concern. However, viruses certainly can and do develop resistance to drugs, but in a much different manner. One current strategy is to develop antivirals which will cripple the virus if it tries to mutate toward resistance.

    • #8
    • August 16, 2016, at 6:46 PM PDT
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  9. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    DocJay: I’m still not convinced the filoviruses , or is that filoviridae, aren’t quite yet done with us. Ebola is some nasty stuff man.

    I’m not particularly concerned.

    The human filoviruses discovered to date all appear to cause hemorrhagic fevers. The good news is that hemorrhagic fevers tend to be difficult to spread by aerosol – and without that delivery route, they’re always going to be very slow spreaders and easy to stop. And for them to mutate into respiratory viruses would probably require them to lose most of their virulence.

    • #9
    • August 16, 2016, at 6:47 PM PDT
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  10. DocJay Inactive

    Mendel:

    DocJay: I’m still not convinced the filoviruses , or is that filoviridae, aren’t quite yet done with us. Ebola is some nasty stuff man.

    I’m not particularly concerned.

    The human filoviruses discovered to date all appear to cause hemorrhagic fevers. The good news is that hemorrhagic fevers tend to be difficult to spread by aerosol – and without that delivery route, they’re always going to be very slow spreaders and easy to stop. And for them to mutate into respiratory viruses would probably require them to lose most of their virulence.

    I know those things of course but they are still nasty. My worry is a designed one that is spread by the respiratory pathway. Of course the designers would likely die from it too then.

    • #10
    • August 16, 2016, at 7:11 PM PDT
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  11. Grosseteste Member

    Thank you for your horrifying contribution! I did not know we could do this yet.

    • #11
    • August 16, 2016, at 8:41 PM PDT
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  12. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    Grosseteste: I did not know we could do this yet.

    I figured there would be a number of members here who didn’t know this ability existed.

    In actuality, the first “artificial” virus (poliovirus) was created over 30 years ago, the first “artificial” influenza virus over 25 years ago. So this is definitely a mature technology.

    On the other hand, new challenges are still arising. A few years ago, an influenza strain was isolated from bats for the first time, but bat flu proved incompatible with the typical reverse genetics strategies, so researchers were left with one tool less to study this new, unusual virus. I’m proud to say my former lab (where I did my PhD) was able to crack this nut last year, and figure out how to reconstitute the bat flu in cell culture.

    • #12
    • August 16, 2016, at 9:46 PM PDT
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  13. Caryn Thatcher
    Caryn Joined in the first year of Ricochet Ricochet Charter Member

    Mendel:

    Belt: what do you think of the germs/bacteria/viruses that are evolving out of highly sterile areas like hospitals? I hear a lot of alarm over the ‘superbugs’ that widespread use and overuse of antibiotics (and hand sanitizers!) are producing.

    <edit>

    In the case of most “superbugs”, they’re not developing the resistance to antibiotics themselves, but they’re receiving resistance-encoding genes from other bacteria who already have copies of the resistance gene.

    <edit>

    This is not entirely true. Plasmid sharing happens among some bacterial species, but not all. Much resistance is developed through mutation, by the bacteria themselves and then selected by antibiotic pressure–either by under or over use thereof. Once selected, there is expansion and then transmission. Voila, outbreak. That’s the sort of stuff I work on. I can go into more detail on any step if anyone is interested. I don’t want to hijack Mendel’s very interesting and well written topic.

    • #13
    • August 17, 2016, at 8:14 AM PDT
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  14. Misthiocracy got drunk and Member
    Misthiocracy got drunk and Joined in the first year of Ricochet Ricochet Charter Member

    John Walker:For DIY Bond villains, here is where you can download the RNA sequences for many variants of the influenza virus.

    Could one print it on a t-shirt?

    I like the idea of printing “dangerous” formulae on t-shirts, like encryption keys, chemical formulae for explosives, etc.

    • #14
    • August 17, 2016, at 8:37 AM PDT
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  15. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    Caryn: This is not entirely true. Plasmid sharing happens among some bacterial species, but not all. Much resistance is developed, through mutation, by the bacteria themselves and then selected by antibiotic pressure–either by under or over use thereof. Once selected, there is expansion and then transmission. Voila, outbreak. That’s the sort of stuff I work on. I can go into more detail on any step if anyone is interested.

    Caryn, could you give an example of this? This is certainly how the resistance process works in viruses, but in bacteria almost all of the examples I learned about in grad school were extra resistance genes (usually enzymes which cleave antibiotics or pumps which pump them out of the cell), not intrinsic resistance at the active site of the antibiotic.

    • #15
    • August 17, 2016, at 9:16 AM PDT
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  16. Misthiocracy got drunk and Member
    Misthiocracy got drunk and Joined in the first year of Ricochet Ricochet Charter Member

    Belt: My biggest concern is that someday some bright researcher in a lab somewhere is going to forget to carry the one or make some other simple error that will lead to something truly catastrophic. I read a book called The Alien Dark some years ago that postulated a virus created to break down plant cellulose for a lumber company that got too good at its role and wound up wiping out all plant life on Earth. The greater danger may come from a simple mistake rather than intent.

    Frankenstein was first published in 1818. How many electrically-powered cadaver monsters are there running around so far?

    Fiction ≠ Fact.

    • #16
    • August 17, 2016, at 9:25 AM PDT
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  17. civil westman Inactive

    DocJay:

    Mendel:

    DocJay: I’m still not convinced the filoviruses , or is that filoviridae, aren’t quite yet done with us. Ebola is some nasty stuff man.

    I’m not particularly concerned.

    The human filoviruses discovered to date all appear to cause hemorrhagic fevers. The good news is that hemorrhagic fevers tend to be difficult to spread by aerosol – and without that delivery route, they’re always going to be very slow spreaders and easy to stop. And for them to mutate into respiratory viruses would probably require them to lose most of their virulence.

    I know those things of course but they are still nasty. My worry is a designed one that is spread by the respiratory pathway. Of course the designers would likely die from it too then.

    Have you just invented “suicide sneezers?”

    • #17
    • August 17, 2016, at 9:40 AM PDT
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  18. The Reticulator Member

    Mendel: almost all of the examples I learned about in grad school were extra resistance genes

    I did not know it worked that way. Thx.

    • #18
    • August 17, 2016, at 10:43 AM PDT
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  19. Underground Conservative Coolidge
    Underground Conservative Joined in the first year of Ricochet Ricochet Charter Member

    What was unique about the 1918 flu virus? Was it constructed in some particularly virulent way or did it just have the right circumstances to spread? I know nothing about these things and don’t even know if I’m asking the question correctly.

    • #19
    • August 17, 2016, at 11:03 AM PDT
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  20. Caryn Thatcher
    Caryn Joined in the first year of Ricochet Ricochet Charter Member

    Mendel:

    Caryn: This is not entirely true. Plasmid sharing happens among some bacterial species, but not all. Much resistance is developed, through mutation, by the bacteria themselves and then selected by antibiotic pressure–either by under or over use thereof. Once selected, there is expansion and then transmission. Voila, outbreak. That’s the sort of stuff I work on. I can go into more detail on any step if anyone is interested.

    Caryn, could you give an example of this? This is certainly how the resistance process works in viruses, but in bacteria almost all of the examples I learned about in grad school were extra resistance genes (usually enzymes which cleave antibiotics or pumps which pump them out of the cell), not intrinsic resistance at the active site of the antibiotic.

    All of those things are factors in antibiotic resistance. The efflux pumps, etc, can be intrinsic to the bacterial species, making them inherently resistant to particular antibiotic classes. On the simplest level, eg., drug classes designed selectively for gram-negative and -positive species attack different parts of the bacterial cell wall/membrane, exploiting those differences. These, nonetheless, are considered part of “wild type” resistance.

    Acquired resistance comes about either through mutation–which goes on constantly–or transfer of resistance from one species to another via plasmids or transposons. Once acquired, antibiotic pressure selects for resistant strains (by killing the susceptibles). Those remaining are predominantly resistant, increase in prevalence, and then cause relapse or are transmitted to other hosts.

    • #20
    • August 17, 2016, at 11:10 AM PDT
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  21. Caryn Thatcher
    Caryn Joined in the first year of Ricochet Ricochet Charter Member

    Underground Conservative:What was unique about the 1918 flu virus? Was it constructed in some particularly virulent way or did it just have the right circumstances to spread? I know nothing about these things and don’t even know if I’m asking the question correctly.

    Short answer, from an epidemiological standpoint, is: both. Mendel can tell you the viral level answers better than I can, I’m sure. I suspect he can also cover the epidemic stuff (World War I had some to do with it). If not, let me know.

    • #21
    • August 17, 2016, at 11:15 AM PDT
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  22. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    Underground Conservative:What was unique about the 1918 flu virus? Was it constructed in some particularly virulent way or did it just have the right circumstances to spread? I know nothing about these things and don’t even know if I’m asking the question correctly.

    A great question, and there still isn’t complete scientific consensus.

    There are three broad hypothetical possibilities: 1) the virus is simply more potent, 2) there were huge populations which were much more susceptible to infectious diseases in general because of WWI, and 3) the 1918 strain was an antigenically new strain and there was no underlying immunity in the global population.

    And so far, the answer seems to be “all of the above”. If you infect mice or ferrets with the 1918 flu and compare them with animals infected with more “normal” strains, those infected with 1918 die much more rapidly.

    However, that can’t be the entire story. If you look at the age distribution of people who die from a normal flu epidemic, it’s primarily infants and the elderly. For 1918, the distribution skews much more toward young and middle-aged adults – who theoretically should always be the healthiest.

    Part of this phenomenon likely reflects soldiers living in camps under poor hygienic conditions with little access to medical care. But there is also a valid hypothesis regarding immunity: the 1918 flu virus was antigenically different from the other flu viruses which had been circulating for several generations. The last time a virus which was similar to 1918 had been in the human population was about 40 years previously, so nobody under the age of 45 or so had antibodies to a virus similar to 1918, while many people older than that presumably did.

    • #22
    • August 17, 2016, at 11:30 AM PDT
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  23. Mendel Member
    Mendel Joined in the first year of Ricochet Ricochet Charter Member

    Caryn: Acquired resistance comes about either through mutation–which goes on constantly–or transfer of resistance from one species to another via plasmids or transposons. Once acquired, antibiotic pressure selects for resistant strains (by killing the susceptibles).

    My understanding was that the spontaneous appearance of resistance through point mutations is an exceedingly rare phenomenon (since multiple mutations are typically required), and therefore that the vast majority of resistant bacteria in clinical settings acquired their resistance through horizontal transfer (or descend from progenitors which acquired it through horizontal transfer).

    Obviously the original resistance must have been developed through iterative spontaneous point mutations (or perhaps translocations within genes). But from a clinical perspective there’s a huge difference whether spontaneous appearance of resistance within a facility is likely or not – for the flu virus or HIV, it is a very likely phenomenon. However, my understanding was that for bacteria, it is exceedingly rare for resistance to occur spontaneously within a facility but is nearly always brought in from the outside. This difference would have strong implications for clinical practice.

    • #23
    • August 17, 2016, at 11:33 AM PDT
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  24. Pilli Inactive

    <snip> And this technique is not just limited to the influenza virus: to date, the ability to reconstitute infectious virus from common, innocuous, non-infectious materials – known in the business as “reverse genetics” – exists for dozens of different types of viruses <snip>

    OK. You can create new and dangerous viruses from non-infectious materials. It would seem that the real trick would be to beat the sword into a plowshare and find a way to convert a dangerous viral infection into something harmless–while in the human body. For example, a cure that would convert a Hepatitis infection into something harmless the body can get rid of. Kind of an anti-virus virus.

    • #24
    • August 17, 2016, at 11:53 AM PDT
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  25. Underground Conservative Coolidge
    Underground Conservative Joined in the first year of Ricochet Ricochet Charter Member

    Thanks for the answers. Additionally, it’s also interesting how the 1918 flu was almost forgotten despite its carnage.

    • #25
    • August 17, 2016, at 11:56 AM PDT
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  26. DocJay Inactive

    Mendel:

    Caryn: Acquired resistance comes about either through mutation–which goes on constantly–or transfer of resistance from one species to another via plasmids or transposons. Once acquired, antibiotic pressure selects for resistant strains (by killing the susceptibles).

    My understanding was that the spontaneous appearance of resistance through point mutations is an exceedingly rare phenomenon (since multiple mutations are typically required), and therefore that the vast majority of resistant bacteria in clinical settings acquired their resistance through horizontal transfer (or descend from progenitors which acquired it through horizontal transfer).

    Obviously the original resistance must have been developed through iterative spontaneous point mutations (or perhaps translocations within genes). But from a clinical perspective there’s a huge difference whether spontaneous appearance of resistance within a facility is likely or not – for the flu virus or HIV, it is a very likely phenomenon. However, my understanding was that for bacteria, it is exceedingly rare for resistance to occur spontaneously within a facility but is nearly always brought in from the outside. This difference would have strong implications for clinical practice.

    The resistance rates of urinary infections are becoming extremely tedious to handle. This is a huge change from 20 years ago when I started.

    • #26
    • August 17, 2016, at 12:00 PM PDT
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  27. DocJay Inactive

    Underground Conservative:Thanks for the answers. Additionally, it’s also interesting how the 1918 flu was almost forgotten despite its carnage.

    We will have another pleasant one at some point although the few contenders have fizzled. The stronger the immune system the worse the disease in 1918 so instead of the usual old folks and kids it was healthy adults ( unless my memory is crap today).

    • #27
    • August 17, 2016, at 12:02 PM PDT
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  28. The Reticulator Member

    DocJay:

    . However, my understanding was that for bacteria, it is exceedingly rare for resistance to occur spontaneously within a facility but is nearly always brought in from the outside. This difference would have strong implications for clinical practice.

    The resistance rates of urinary infections are becoming extremely tedious to handle. This is a huge change from 20 years ago when I started.

    So maybe the Obama policy of centralizing and consolidating medical clinics is, in effect, turning them into death panels.

    • #28
    • August 17, 2016, at 12:02 PM PDT
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  29. Caryn Thatcher
    Caryn Joined in the first year of Ricochet Ricochet Charter Member

    Mendel,

    I keep running into issues with the word limit. This article talks about naturally occurring and acquired antibiotic resistance in Mycobacterium tuberculosis, my dissertation bug. It’s the one about which I know the most and a great example of drug resistance being driven by antibiotic selection. There are brief sections on the molecular mechanisms, the genetic basis of resistance, mutation, and adaptation.

    In short, there are naturally occurring drug-resistant mutants and known rates of their prevalence in a given wild-type population. For example, there might be 1:10E9 rate of resistance to a particular drug. If the infection involves 10E8 bacteria, then 10 will be inherently drug resistant and remain after treatment. Usually this isn’t a problem, as the immune system will easily mop up those 10. But that assumes full treatment that wipes out all of the susceptibles. If treatment is incomplete and, for example 1000 bacteria are left, the rate of resistant mutants is now 10/1000 or 1%. Give the disease a chance to reach the previous population of 10E8 and you’ve got a million drug resistant bugs there–more than the antibiotic can handle. That’s the antibiotic pressure/selection problem.

    As far as outbreaks within facilities, resistance can develop as above or come from outside. Community- and hospital-acquired pneumonia were thought to differ greatly, but we’re finding more similarities. It’s not as simple as we thought and the bugs don’t always read the books!

    • #29
    • August 17, 2016, at 12:08 PM PDT
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  30. Caryn Thatcher
    Caryn Joined in the first year of Ricochet Ricochet Charter Member