Say youve got a problem. Maybe you cant figure out how to make a gene therapy vector that cant be detected by pre-existing antibodies that everybody already has. Maybe you are trying to figure out how to make an effective HIV-1 vaccine.

You could figure out which portions of AAV or HIV-1 are really important, try to make point mutations here and there, trying to get the virus to do what you want it to do… Or you could just let evolution do all the hard work for you– Letting random mutation and natural selection identify a variant that can perform the tricks youre after.

A lab has already done that with AAV. They started with ‘diversity’ and used evolution to identify gene therapy vectors that could target brains, livers, lungs, etc, and CANT be recognized by pre-existing antibodies.

Now another lab has caught onto this cool idea to help make better HIV-1 vaccines!

Optimization of human immunodeficiency virus type 1 envelope glycoproteins with V1/V2 deleted, using virus evolution.


This lab is starting from a different angle. Instead of starting with diversity and having evolution narrow possibilities down to one/a few variants, this lab is starting with one variant, and letting random mutation and natural selection generate lots of different solutions!

So here is the problem– We cant figure out how to make a vaccine against HIV-1 that generates lots of ‘broadly neutralizing antibodies’, antibodies that can still recognize viruses if they mutate away from what was put into the vaccine.

We can make slightly better vaccines if we chop up env a little bit. If we cut out two really variable regions of env, the Variable 1 loop and the Variable 2 loop, we can make higher affinity antibodies to neutralize viruses, because your immune system can focus on a REALLY important region of env, the Variable 3 loop.

It would also be really cool if we could make envelope trimers that can be excreted by cell lines, so we could just throw them into a vaccine instead of dummy viruses. It would be a LOT easier to make huge quantities of secreted protein, rather than purifying delicate dummy viruses… but if you chop out V1/V2, the secretable Env trimers we have just dont work.

SO! This lab created a whole bunch of potential V1/V2 deletion variants by deleting this region in a few different ways. All of these variants just didnt work as well as a nice wild-type envelope protein. So they took a population of each variant and repeatedly passaged them in T-cells for four and a half months (!!!). Their logic was that even though their V1/V2 deleted viruses were ‘crippled’, the populations would accumulate compensatory secondary mutations to regain their replicative capacity. We know HIV-1 can do this, because thats exactly what happens with HIV-1 drug resistance– Initial mutations to escape antiretrovirals come at a fitness cost, but over time, compensatory mutations lead to a virus that is super fit AND can escape the antiretrovirals. So why not use HIV-1s evolutionary abilities to generate a weapon we can use against it!

At the end of 4 1/2 months, some of the populations konked out. The viruses were crappy at replicating, and eventually went extinct. But some populations got better at replicating, AND more stable… which means they are not only better for making antibodies, they are also better for generating those secreted envelope trimers for vaccines!

Now, this doesnt mean that we will have an HIV-1 vaccine in 2 months.

It doesnt mean that any of the clinical research that comes out of this particular study will eventually end up in a vaccine.

But, its a new tool. Its a new weapon we can at least try against HIV-1.

And we got it by using evilution.

Comments

  1. #1 Brian
    March 11, 2009

    GO SCIENCE!

  2. #2 Strider
    March 11, 2009

    But, but Michael Egnor says evolution is not used in medicine!

  3. #3 Mobius
    March 11, 2009

    Well, Egnorance is as Egnorance does.

  4. #4 Mobius
    March 11, 2009

    Just in case you want to weigh in, I started a thread on Topix/Evolution Debate Forum (aka Darwins Stepchild) on this article.

    “Scientists use evolutionary principles in working toward HIV vaccine”

    http://www.topix.com/forum/news/evolution/TNEBHP10ICIB24RNN

    Maybe I’ll see you there.

  5. #5 Doubting Foo
    March 11, 2009

    Is this something that can be modeled using distributed computer programs like BOINC? http://boinc.berkeley.edu/

    Each BOINC client could represent a distinct population that could “evolve” on its own, perhaps?

  6. #6 Moth Eyes
    March 11, 2009

    There’s also genetic algorithms, in which we use natural selection to find answers to engineering, mathematical and even biology problems (and make a mockery of Dembski’s arguments for ID while at it). I’m doing an honour’s year in it.

    This is a lot more “real” though.

  7. #7 William Wallace
    March 11, 2009

    A similar and possibly better idea.

    Regarding [#6], you’re confused if you think an algorithm you’ve intelligently designed is somehow making a mockery of Dembski.

  8. #8 LanceR, JSG
    March 11, 2009

    A clear misunderstanding by Limp Willy! Combined with a deliberate misinterpretation of science, we’ve got a double play! Hurray for Limp Willy!

    Your namesake would be ashamed of you.

  9. #9 William Wallace
    March 12, 2009

    a deliberate misinterpretation of science

    You mean ERV conflating micro and macro evolution?

  10. #10 eddie
    March 12, 2009

    Are you watching?
    Are you watching?
    Are you watching creo scum?
    Are! you! wat! ching! cre! o! scum!

  11. #11 Tyler DiPietro
    March 12, 2009

    “Regarding [#6], you’re confused if you think an algorithm you’ve intelligently designed is somehow making a mockery of Dembski.”

    Dembski’s mathbabble makes a mockery of itself.

  12. #12 RBH
    March 12, 2009

    WW wrote

    Regarding [#6], you’re confused if you think an algorithm you’ve intelligently designed is somehow making a mockery of Dembski.

    WW, you’re a fool. Dembski persistently misrepresents GAs in order to avoid the fact that they generate “CSI” in exactly the same sense WAD uses the term in No Free Lunch. WW is in essence saying that if an intelligently designed experiment that uses solely Darwinian evolutionary mechanisms in an intelligently designed Petri dish produces, say, a novel metabolic process, that process was intelligently designed. Hell, on WW’s bizarre view, that one can design an algorithm to model hurricane dynamics means that hurricanes are intelligently designed.

  13. #13 Jonathan
    March 12, 2009

    Why don’t you just isolate the proteins HIV binds to when entering a cell, find the genes that code for the protein(s) or reverse engineer a gene from the protein, implant the gene into e. coli and let the bacteria replicate the protein, then use that protein to trigger a “premature ejaculation” of the viruses before they can infect cells? Or I just missing some crucial information as to why that’s impossible/ineffective?

  14. #14 BAllanJ
    March 12, 2009

    Maybe WW just thinks the whole earth is just a big computer designed to complete a giant algorithm… to answer the great question… and maybe it’s controlled by lab mice?

  15. #15 Stephen Wells
    March 12, 2009

    So now wally has inadvertently claimed that evolution by natural selection is an intelligently designed algorithm… not a very clear thinker, is he?

  16. #16 ERV
    March 12, 2009

    WW still rabidly jealous of Rho– You mean ERV conflating micro and macro evolution?

    How, exactly, is fragmenting the genome of eight species of virus to recombine them to make numerous brand new species of virus not macroevolution, even using the Creationist definition of the word?

    Because its all ‘still a virus,’ and Creationists are too dumb/arrogant to understand the magnitude of diversity of ‘viruses’?

  17. #17 LanceR, JSG
    March 12, 2009

    Limp Willy blathered:

    You mean ERV conflating micro and macro evolution?

    Right. Because pennies never add up to dollars. Small incremental changes over time can never add up to large differences.

    The whole “micro/macro” issue is a red herring. Whenever creobots get pressed into a corner with specific examples of evolution they whip out their micro/macro whine. It’s bull$hit, and you know it.

  18. #18 ERV
    March 12, 2009

    Lance, even using Creationists IDiotic definition of ‘macroevolution’, these studies most certainly DO result in macroevolution. The AAV study would be comparable to smashing the genome of Balaenoptera acutorostrata, bonaerensis, borealis, brydei, edeni, omurai, musculus, and physalus and getting a brand new species of whale, Balaenoptera brandnewicus.

    But Creationists dont understand this with ‘viruses’ because to them, a virus is a virus is a virus.

  19. #19 Rev. BigDumbChimp
    March 12, 2009

    You mean ERV conflating micro and macro evolution?

    You mean you still think that one exists but the other doesn’t despite all evidence to the contrary?

  20. #20 Rev. BigDumbChimp
    March 12, 2009

    But Creationists dont understand this with ‘viruses’ because to them, a virus is a virus is a virus.

    I wonder what “kind” a virus is?

  21. #21 Paul
    March 12, 2009

    I wonder what “kind” a virus is?

    Demon.

    That is what causes disease, right?

  22. #22 Escuerd
    March 13, 2009

    But ERV, it’s microevolution because viruses are microscopic. They’re still tiny, and therefore still the same thing.

    Show me a virus giving birth to a rabbit, or your THEORY is wrong.

  23. #23 William Wallace
    March 13, 2009

    How, exactly, is fragmenting the genome of eight species of virus to recombine them to make numerous brand new species of virus not macroevolution

    As a layman, and you can correct me if I am wrong, but first, it sounds like the splicing is a form of intelligent design.

    Second, in the context of the tree of life, even assuming for the sake of argument that you’re correct in characterizing genetically distinct populations of viruses as “species” (and I am certainly not qualified to argue otherwise), in the context of the big picture–the diversity of life, e.g., using the tree of life, are you forming new trunks, or relatively infinitesimal branches?

  24. #24 MartinB
    March 13, 2009

    WW: “You can’t have macroevolution with new species”
    ERV: “This *is* a new species.”
    WW: “But you can’t have macroevolution with new genera…”
    Never let creationists enter a football field – they would move the goalposts faster than you can shoot at them…

  25. #25 Eric Saveau
    March 13, 2009

    Wally farted-

    I am certainly not qualified to argue

    Wow. A truthful statement from Wally! Mark your calendars everyone; this is a day to remember!

  26. #26 don
    March 14, 2009

    Yay! I always thought evolutionary startegies such as these would be too slow to do anything useful… But that’s just because I didn’t count on the awesome evolutionary speed of viruses. Viruses rule.

  27. #27 Quarkey
    March 31, 2009

    Why don’t you just isolate the proteins HIV binds to when entering a cell, find the genes that code for the protein(s) or reverse engineer a gene from the protein, implant the gene into e. coli and let the bacteria replicate the protein, then use that protein to trigger a “premature ejaculation” of the viruses before they can infect cells?

    Well the problem is that there’s a lot of sugars on that envelop protein. E coli can’t really make sugars on proteins so it really messes up the protein and doesn’t look like the real thing any more. So you have to vaccinate with the protein produced by mammalian cells. And then still you have the problem that most of the antibodies will be directed against the V1 and V2. Therefore this group is trying to take them out.

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