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Biotech Medicine Science

Doctors Will Test Gene Editing On HIV Patients 263

Soychemist writes "Some people have a mutation that makes them highly resistant to HIV, and scientists think that they can give that immunity to anyone with a new type of gene therapy. The first human trials will start at the University of Pennsylvania this week. Researchers will draw blood from people with drug-resistant HIV, clip the CCR5 gene out of their T-cells with a nuclease enzyme, grow the modified cells in a dish, and then return 10 billion of them to the patient's bloodstream. Those cells will be immune to the virus, and they will keep the patient's T-cell count up even if the rest are destroyed. 'We will see if it is safe and if those cells inhibit HIV replication in vivo,' said the lead researcher. 'We know they do in the test tube.'"
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Doctors Will Test Gene Editing On HIV Patients

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  • by Clover_Kicker ( 20761 ) <clover_kicker@yahoo.com> on Tuesday February 03, 2009 @11:20PM (#26721077)

    What's the worst that could happen, they screw it up and you die?

    • by LaskoVortex ( 1153471 ) on Tuesday February 03, 2009 @11:23PM (#26721091)

      What's the worst that could happen, they screw it up and you die?

      Or they could not treat you and you'd die.

    • by Anonymous Coward on Tuesday February 03, 2009 @11:39PM (#26721167)

      This is what we need. Medicine is far too conservative in so many cases. Death would be a welcome accident in many diseases of terminal illness. Not saying the patient shouldn't decide, but they should certainly have the option to try experimental treatments if they want.

      • by MichaelSmith ( 789609 ) on Wednesday February 04, 2009 @12:17AM (#26721363) Homepage Journal

        This is what we need. Medicine is far too conservative in so many cases.

        I think we need more engineers involved in Medicine, particularly on the implementation side. I wish I could point to this but I remember reading about a scientist who had invented something quite revolutionary who spent the next seven years rebuilding his machine to be small enough for general use. That is the kind of job which should be given to an engineer, but it won't keep the scientist employed.

        • I have heard similar stories about medical devices like the artificial heart but I was under the impression engineers were involved but I could be wrong.

        • by fprintf ( 82740 ) on Wednesday February 04, 2009 @08:05AM (#26723637) Journal

          There are lots of engineers involved. My father ran a small medical startup some years ago and they made a very high tech (for the time) artificial ventilator that used rapid pulses of air rather than the typical high pressure slow pulses. They did lots of experiments on animals and had to jump through all kinds of hoops with the FDA just to be allowed to put the ventilator on a human subject. Essentially the only way, after the animal trials, to get the ventilator on a human patient was for the patient to be unresponsive to conventional treatment, at significant risk of death without intervention, and received signed autorization from the patient or guardian. (get those living wills drawn up and signed if you haven't already!)

          It took years, huge personal and venture capital investment, and eventually the company was bought out and I think the techology disappeared or otherwise got incorporated into standard ventilators. I posted this to illustrate all the work that needs to go into a medical device before it is allowed to be tried on humans... and even then, promising, even successful technology does not always make it in the marketplace. Believe it or not, Doctors are some of the *worst* luddites around and it is incredibly difficult to get enough momentum for a new technology to take hold.

      • Experimental treatments are already available to HIV patients who wish to try them and have been for years now. The FDA loosened the rules on that back in the early to mid 1990s because of the growing epidemic and terminal nature of the illness. Although in recent years the consequences of experimental treatment have to be weighed against the known efficacy of the anti retro viral cocktails that are now available and manage the infection quite well (albiet with some moderate to severe side effects). Should
        • by beav007 ( 746004 ) on Wednesday February 04, 2009 @01:11AM (#26721617) Journal
          Not to be a wet blanket for your argument, but this is being tried on drug-resistant HIV patients.
    • Tyrell: The facts of life. To make an alteration in the evolvment of an organic life system is fatal. A coding sequence cannot be revised once it's been established.

      Roy: Why not?

      Tyrell: Because by the second day of incubation, any cells that have undergone reversion mutations give rise to revertant colonies like rats leaving a sinking ship. Then the ship sinks.

      Roy: What about EMS recombination.

      Tyrell: We've already tried it. Ethyl methane sulfonate as an alkylating agent a potent mutagen It created
    • by jsse ( 254124 ) on Wednesday February 04, 2009 @01:26AM (#26721697) Homepage Journal

      What's the worst that could happen, they screw it up and you die?

      You'll lose all your body hair; become a human-biting-albino that're very sensitive to sunlight; start biting humans and then turn them into your kind; you'll keep your biting until the T-virus in your body because air-bourne infecting disease, when you'd find no human alive for you to bite.

      I didn't mean it'd happen, but since you asked for the worse...

    • by giafly ( 926567 )
      The worst outcome is these "doctors" help HIV evolve to defeat this mutation and the donors die too.
      It sounds like the equivalent of giving low doses of antibiotics to people or animals with conventional diseases.
      Antibiotic resistance [wikipedia.org]
      • Uhh how would the donors die? Their aids virus molecules don't suddenly evolve when the patients' do. Life is prototype based, like javascript, not class based, like java.

  • by Caboosian ( 1096069 ) on Tuesday February 03, 2009 @11:39PM (#26721165)
    You don't say.
  • Price Tag? (Score:4, Interesting)

    by Anonymous Coward on Tuesday February 03, 2009 @11:40PM (#26721177)

    Hopefully the researchers are successful in their endeavours but you've got to wonder about the costs associated with such a procedure. With something like a 33 million estimated people infected with HIV world-wide I wonder what percentage would actually be able to afford treatment :/

  • 'We will see if it is safe and if those cells inhibit HIV replication in vivo,'

    Alas, poor Vivo. I knew him, Horatio.

  • bravo (Score:5, Insightful)

    by Ritz_Just_Ritz ( 883997 ) on Tuesday February 03, 2009 @11:47PM (#26721225)

    While strides have been made in HIV treatment, it's still a death sentence. Doctors can keep the patient alive longer, but they can't prevent the inevitable.

    With so many people in the developing world suffering from HIV, it would be nice to see something like this fast tracked. I am sure that some of those folks, now intimately familiar with their own mortality, would be eager to participate knowing that they could potentially help other people.

    • Re:bravo (Score:5, Insightful)

      by BlueParrot ( 965239 ) on Tuesday February 03, 2009 @11:55PM (#26721251)

      While strides have been made in HIV treatment, it's still a death sentence. Doctors can keep the patient alive longer, but they can't prevent the inevitable.

      Life itself is a death sentence. We all die sooner or latter, it's merely a matter of how long it takes and many HIV positive patients die from unrelated causes ( such as car accidents ). If you catch HIV when you're 70 there's a good chance you will die from some completely unrelated condition, such as stroke, heart failure, or lung cancer from a lifetime of tobacco abuse. Not saying an HIV infection is to be taken lightly, but believe it or not, it is far from the worst diagnosis you can get.

      • Life itself is a death sentence.

        Possibly not if we get the ability to directly edit our genes.

        • by TheLink ( 130905 )
          Looking at all the people here who can't spell, giving them the ability to directly edit their genes will certainly result in death sentences.

          Heck they might not even get past the first word. :)
      • Yes indeed my observant friend, death is in fact also a disease. I say death to death!!!

      • Comment removed based on user account deletion
        • by TheLink ( 130905 )
          No. You're not trying hard enough.

          The doctor could say, "Hey don't tell anyone I said this, but there's this place in Switzerland where you can go get yourself euthanized before it gets really bad".

          Or imagine a diagnosis where the doctor runs away from you screaming, "Stay away from me!".

          And that's just a start.
    • Re: (Score:3, Interesting)

      With so many people in the developing world suffering from HIV, it would be nice to see something like this fast tracked.

      I doubt they view this as a 'cure'. It's research, in both gene therapy and HIV.
      If it works, I'd assume the next step would be to try to develop a procedure where they did this to bone marrow cells - the cells that produce T-cells - and thus let the body create its own HIV-resistant T-cells. That might work well enough to be a 'cure' - an HIV patient with leukemia was given an HIV-re

    • Re:bravo (Score:5, Informative)

      by Anonymous Coward on Wednesday February 04, 2009 @12:28AM (#26721421)

      Actually, this is far from the truth. I am an HIV-positive individual and based on the fact that my HIV was detected early and also that I started on HIV medications within the first year of contracting it my lifespan has been extended to the point where I will most likely live a full life. Before contracting HIV I thought it was a terrible thing to have and that I would kill myself if I ever got it. I have news for you: it is a terrible thing, but just like everything else in the world you get over it and with HIV medications having nearly NO side effects and once-to-twice daily dosing it makes life worth living.

      While some may speculate on whether or not I really know what I'm talking about, I do. I am a healthcare professional. For those of you who are wondering why I didn't post this under my account, I would rather not taint Google's results with gossip for my next employer. :)

      • Re:bravo (Score:4, Insightful)

        by The FNP ( 1177715 ) on Wednesday February 04, 2009 @02:06AM (#26721975)

        Actually, I figure this is exactly why /. has ACs. We put up with nearly every other AC troll post so that occasionally we can read 'Confessions of a HIV+ Slashdotter'. I don't need to know your identity to read your anecdote. Also, I respect your right to privacy and AC posting more in this case than if you were merely stating a preference for Windows over Linux.

    • Doctors can keep the patient alive longer, but they can't prevent the inevitable.

      Technically that's true, with or without HIV

  • by Anonymous Coward on Tuesday February 03, 2009 @11:48PM (#26721231)

    You *know* there's going to be an Emacs mode for gene editing.

  • Gene editing? (Score:2, Redundant)

    by TFer_Atvar ( 857303 )
    I'm (pretty) sure it's not like it sounds, but the idea of gene editing immediately conjures up something like a gene Wikipedia in 50 years or something, and that's terrifying and hilarious at the same time.
  • by LonghornXtreme ( 954562 ) on Wednesday February 04, 2009 @12:13AM (#26721341)

    There are 3 big risks / problems I see with this approach:

    #1: The modified T-Cells attack the host after they are reintroduced. Think of it like auto-immune disease or transplanted-organ rejection. This could cause effects ranging from a mild food allergy to death. Anyone know how much damage 10 billion rogue T-cells could do? I sure don't; however, I do know that they aren't a straight 1 T-Cell used up for each 1 antigen.

    #2: Unmodified T-cells attack the modified T-Cells because the surface of the modified T-Cells (i.e. the CCR5 protein) could possibly trigger an immune response. This would render the modified T-Cells kind of pointless. Seems like this would have better chance of working on patients with full blown AIDS rather than merely HIV+.

    3: Modified T-Cells survive and are unaffected by HIV; however, these surviving modified T-Cells are just clones of the one original T-Cell that the lab modified. So in essence, you have injected the test subject with 10 billion of the same T-Cell. Unless the doctors have a way of massaging the genes on a representative sample of T-Cells, then this is kind of useless to the patient. What good are 10 billion T-Cells if they are each only good for tagging one antigen? Meaning, that the 10 billion T cells could only respond to a single stimulus, i.e. they could all only fight one strain of the common cold, but not anything else.

    Disclaimer: I have a BA in bio from a public ivy; however, my GPA wasn't that great, and I didn't pursue a career in the field. I very well could be overlooking something substantial in immunology etc.

    • Re: (Score:2, Informative)

      It sounds like what they're thinking of doing is more like: (1) draw up 10 billion T-Cells, (2) use an enzyme to cleave off the CCR5 proteins, (3) filter out the enzyme+proteins, and (4) reinject the T-Cells. Ie, I don't think issue 3 would crop up (or, at least, it'd be much more limited in scope). The real issue, as I see it, is that those 10 billion T-Cells will eventually die. Not knowing enough about how proteins on the cell membrane are created/carried over during mitosis, it'd seem the biggest iss

      • by sokoban ( 142301 )

        It sounds like what they're thinking of doing is more like: (1) draw up 10 billion T-Cells, (2) use an enzyme to cleave off the CCR5 proteins, (3) filter out the enzyme+proteins, and (4) reinject the T-Cells.

        Proteins aren't cleaved, a zinc finger nuclease is used to mutate the CCR5 gene so that it is the HIV resistant type. These are then cloned.

      • Re: (Score:3, Informative)

        by Muad'Dave ( 255648 )
        The article said that this first test was to see if the new T-cells would live and if there would be any effect on the HIV load. This isn't the cure, only a step in that direction.
    • Re: (Score:3, Informative)

      by sokoban ( 142301 )

      I don't think 1 will be a problem. All T Cells have a CCR5 membrane protein, but the HIV resistant ones have a mutant type CCR5 protein. CCR5 is the way in which T cells get infected by HIV, and people with mutant type CCR5 genes survive quite well.

      2 may be a problem, and I think will be the biggest hurdle here.

      3 Shouldn't be a problem. Zinc Finger nucleases are able to delete the genes from a bunch of different cells at once. The idea is that you get a whole lot of T-Cells, Remove the 32 base pair segm

  • Unanswered questions (Score:3, Informative)

    by Michael Woodhams ( 112247 ) on Wednesday February 04, 2009 @12:26AM (#26721407) Journal

    Alas, I have enough biology to have questions not answered in the short article, but not enough to extract the answers from the referenced paper. (I did notice that the news article was slightly incorrect on one point. They are not actually 'clipping out' the CCR5 gene. They cause a break in the gene which gets imperfectly repaired, so that the gene becomes nonfunctional.)

    Are these T cells capable of 'reproducing' and having an unlimited number of descendants? This is not the case for many types of cells - it is part of what makes stem cells special. The paper refers to T4 cell lines, which suggests that they can indefinitely reproduce.

    If the treatment works, how long will it last? (If the answer to the previous question is 'no', the answer to this one will likely be be 'about as long as the lifetime of a T cell.' If the answer to the previous question is 'yes', the answer might be 'for a lifetime.'

    Do the modified T cells have to come from the patient? If not, the treatment will be much cheaper: Do the extraction and genetic modification once, breed up a big batch, treat dozens of patients. If not, you need to do the genetic modification once for each patient.

    Once you have a bunch of immune T cells, will they be able to eliminate HIV from the body? (I suspect not: I understand that as a retrovirus, HIV is very good at hiding dormant for a long while.)

    The answers to these questions are the difference between this being a laboratory curiosity and this being the elimination of HIV in developed countries within 5 years.

    • by MoellerPlesset2 ( 1419023 ) on Wednesday February 04, 2009 @12:41AM (#26721491)
      Not that I'm an immunologist, but:

      Are these T cells capable of 'reproducing' and having an unlimited number of descendants?

      T cells are produced by the bone marrow. They don't reproduce on their own.

      If the treatment works, how long will it last?

      The lifespan of an average T cell is on the order of 10-20 weeks. I believe. Shorter in HIV patients.

      Do the modified T cells have to come from the patient?

      Who knows? But not necessarily. After all, you get plenty of foreign T-cells with a blood transfusion. But I don't think anyone is necessarily viewing this treatment as a 'cure' in itself.

      Once you have a bunch of immune T cells, will they be able to eliminate HIV from the body?

      That's not known. But they've done it [telegraph.co.uk], with positive effects. Note how 'cure' is put in quotes, as it should be.

      The answers to these questions are the difference between this being a laboratory curiosity and this being the elimination of HIV in developed countries within 5 years.

      That is ridiculous. It's neither.

    • CCR5 **delta 32** (Score:3, Informative)

      by CarpetShark ( 865376 )

      They are not actually 'clipping out' the CCR5 gene. They cause a break in the gene which gets imperfectly repaired, so that the gene becomes nonfunctional.

      Indeed. They seem to be trying to modify CCR5 to be CCR5 delta 32, which is the variant which is less prone to HIV (but not immune). The nonfunctional aspect is very important, as you wouldn't want to simply engineer a foetus to have this gene instead of normal CCR5 genes. From wikipedia:

      The [CCR5 delta 32] allele has a negative effect upon T cell fu

  • Mutations (Score:2, Insightful)

    by Spooon69 ( 758526 )
    The HIV virus has a high rate of mutation, one of the reasons it sticks around in your body and your immune system has to keep attacking it, it's pretty much a "new" virus every time. What's to keep the virus from mutating and avoiding the CCR5 requirement it currently has? CCR5 doesn't seem to be a requirement for a normal human immune system (one of the many types of backups the immune system has), thus some percentage of the population being perfectly healthy without that receptor. I'd even go as far
    • Re: (Score:3, Informative)

      >What's to keep the virus from mutating and avoiding the CCR5 requirement it currently has?

      The virus uses the CCR5 receptor as its binding and entry point into the cell [wikipedia.org]. There are other receptors it might/may use, but CCR5 is the predominant one, especially early in the infection. As such, it's the gateway: if you can block it, that massively reduces the viral effectiveness.
      The process of developing a treatment for a disease is finding something the disease absolutely needs and targeting that. This is

  • by wickerprints ( 1094741 ) on Wednesday February 04, 2009 @01:38AM (#26721771)

    Instead of just making the typical /. armchair commentary about the zillion ways in which this proposal would be foolish or at best useless, I'm going to give a different angle on this.

    First, on a global scale, the most sophisticated HIV treatments are administered to the relatively wealthy. Only when such a treatment is deemed effective does it start to spread down to the poor, due to economics. The old anti-retrovirals of yesterday are today's low-cost options for the millions of HIV+ individuals in developing nations. That's just the reality of the technological development of disease treatment. However, this "trickle-down" mechanism, combined with natural geographic and genetic variations, has led to the evolutionary branching of HIV into significantly distinct strains, with characteristically different disease modalities.

    Second, we have as yet no drug that is able to eliminate HIV in the body. The currently available treatments are at best able to turn HIV into a chronic, managed condition. This has some very interesting (some would say alarming) socioeconomic implications. What we are finding is that over time, HAART therapy has evolved from a multiple-dose-per-day regimen that was difficult to maintain, to a more easily managed schedule, leading to better therapy adherence in patients. However, some of these drugs are poorly tolerated in many individuals, and over time, HIV is known to develop multiple resistances due to poor adherence or tolerance. The more disturbing situation, however, is that in many gay communities, the practice of "pre-exposure prophylaxis" has become alarmingly common. What is happening is that some HIV- gay men are obtaining anti-HIV drugs and taking them prior to knowingly exposing themselves to potentially HIV+ individuals through unprotected sex.

    From a scientific standpoint, it is fascinating that this development is as successful as it has been. But from the standpoint of a gay man who takes every precaution to educate myself and follow safer sex practices and does everything in my power to serve as a role model for responsible behavior, I find it totally abhorrent that there are guys who expose themselves willingly to HIV in such an unethical manner, in light of all the AIDS deaths that have come before us and all the tireless work of our most brilliant scientists, medical care providers, and public health advocates. They have even given this "PrEP" cute names and euphemisms to disguise the utter insanity of what they are really doing (like they have done with the term "barebacking" to refer to unprotected anal intercourse). If there is anyone on the face of this earth that deserves to die of this terrible disease, it is them. And I don't say that lightly. Some of you might say that these people would have had unprotected sex with or without the drugs, but you have to realize that it is partly through the action of these individuals that drug-resistant HIV is spread. It is for this reason I dare stand in judgment against them.

    So this brings me to my third point. The CCR5 discovery is notable in that it confers strong resistance against HIV-1. Two copies of the gene are required for this resistance. However, the transmission of other strains of HIV may not be blocked by the presence of this gene. Even if this therapy were to work, I doubt it would be effective on a large scale. Some of these patients, if you cure them, will simply go out and have more unprotected sex. If you don't believe me, reread the previous paragraph.

    The only way human civilization will ever rid itself of the scourge of HIV is if we discover a vaccine or outright cure for all its strains. No chronic management or piecemeal therapy will be sufficient, because there are always people who will do things that will enable the virus to mutate and survive. Ever since the discovery and announcement of the virus in the 80s, this simple fact was apparent to me. But the untold billions of dollars in revenue that HIV research and managemen

  • I don't mean to be a pessimist, but it seems that this will, if approved, be a lengthy and costly procedure.

    I'm unaware of the types of legal wrangling for a doctor and a hospital before a procedure is taken. I'm also unaware if there are any ethics reviews done prior to risky operations/treatments (brian, heart, gene therapy). Given at least the legal risks, unless there's a 99.999% success rate, I'm not sure doctors or hospitals will want the procedure in-use (even if the person is likely to die of HIV/AI

  • by blind biker ( 1066130 ) on Wednesday February 04, 2009 @03:58AM (#26722507) Journal

    "I'd like darker skin and, uh... healthy eyes? The latter is kinda more important, so if I can have only one, then that should be it.

    On the other hand, if you give discounts for multiple edits, then why not. Throw in a large-penis-gene, too. I hear that's all the rage, these days."

  • I guess after this they can get to work on the *important* things. Like giving us wings, tails, claws, snake-slit eyes and other mostly cosmetic features...
    I feel kinda sorry for the HIV Patients they are using as Guinea pigs though.

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