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Doctors Will Test Gene Editing On HIV Patients

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.'"

33 of 263 comments (clear)

  1. might as well guinea pig at that point by Clover_Kicker · · Score: 5, Insightful

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

    1. Re:might as well guinea pig at that point by LaskoVortex · · Score: 5, Insightful

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

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

      --
      Just callin' it like I see it.
    2. Re:might as well guinea pig at that point by Anonymous Coward · · Score: 5, Insightful

      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.

    3. Re:might as well guinea pig at that point by RelaxedTension · · Score: 5, Funny

      Or you volunteer, and be the one to get the placebo.

    4. Re:might as well guinea pig at that point by Mauzl · · Score: 5, Informative

      If you RTFA, its people who have drug-resistant HIV who are being experimented on.

    5. Re:might as well guinea pig at that point by dunezone · · Score: 4, Insightful

      Yeah, those modern anti-retroviral are not so perfect though. Most of them are combo drugs which means you take multiple pills at a time. As a result of that the side effects can be extremely painful and dangerous. And I know, its better then death if you don't take them but finding a better alternative is a must. These drugs are expensive and the majority of individuals who have HIV don't have access to these them.

      And just like anti-bioitics. After a certain period of time these drugs become ineffective. Hell, if you start missing doses or cant afford them it could easily be game over.

      The people in these studies are failing current treatment methods. There is nothing left at this point.

    6. Re:might as well guinea pig at that point by linhares · · Score: 4, Funny

      Hope not, that would mean no more Slashdot :(

      You must be old here.

    7. Re:might as well guinea pig at that point by ThrowAwaySociety · · Score: 4, Insightful

      Or you volunteer, and be the one to get the placebo.

      In which case, you are no worse off, and at least get careful observation and conventional treatments for your symptoms.

    8. Re:might as well guinea pig at that point by daveime · · Score: 4, Insightful

      No, the only thing we need to rethink is how the pharma companies can ever justify selling a medication that costs $200 for a single dose.

      You know, Chris Rock summed it up nicely. No one will ever cure AIDS, the money isn't in the cure, it's in keeping you alive and helping you live with it. Just get your "fix" and live for one more day.

    9. Re:might as well guinea pig at that point by beav007 · · Score: 4, Informative

      Not to be a wet blanket for your argument, but this is being tried on drug-resistant HIV patients.

    10. Re:might as well guinea pig at that point by binarylarry · · Score: 4, Funny

      CGI super demons... who cannot be stopped by AIDS alone.

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      Mod me down, my New Earth Global Warmingist friends!
    11. Re:might as well guinea pig at that point by TubeSteak · · Score: 5, Insightful

      These drugs are expensive and the majority of individuals who have HIV don't have access to these them.

      Those drugs are expensive in (mostly Western) countries that kowtow to pharmaceuticals and have not stood up and supported generics.

      India was the first country to start cranking out generics and is probably the sole reason that Big Pharma dropped prices from $10,000~15,000 per year to less than $1,000 on what are now considered second-line drugs.

      Generics were the only thing pulling down insane prices and the USA's response was to setup TRIPS (Trade-Related Aspects of Intellectual Property Rights) which enormously complicated the process of issuing compulsory licenses.

      Off the top of my head: India, Brazil, Thailand and South Africa have all issued compulsory licenses for AIDS drugs.
      AFAIK, Thailand and Brazil are the only two countries to do so post-TRIPS.

      In response to Thailand's compulsory license, the price of one drug dropped by half for many other developing countries. OTOH, a major pharmaceutical said they wouldn't be applying for licenses to sell new drugs in Thailand... and the USA put Thailand on a watch list of countries considered to be committing intellectual property theft. So it was something of a Pyrrhic victory for Thailand.

      Long story short: Big Pharma's bottom line is getting in the way of preventing major health catastrophes in developing countries.

      --
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      o0t!
    12. Re:might as well guinea pig at that point by tjstork · · Score: 4, Insightful

      I'm sure your stance would change if you were someone who was in need of treatment and didn't have the appropriate medical insurance.

      Probably would. But the way I see it now is, I smoke, I've smoked for 20 years, and I'm starting to get the first reduced lung function and I should quit but probably won't and I'll die from it, dragging myself and the rest of society down for a million bucks in chemo and treatment. What's up with that? Why should I keep 50 kids out of college because I was a dumbass? That's not right. Same thing with HIV. For the most part, you can prevent HIV. You can stay monogamous as much as you can. Don't be a slut, and use a rubber. Don't use needles. Sometimes you have to think about what your impact is on society.

      I think the real problem is the outrageous cost of treatment. Some drugs being manufactured have higher marketing costs then they do for research.

      Maybe the stuff is expensive because it is, well, actually complicated to research, make and produce. Science is a craft and crafts are expensive. I don't doubt that the workflow in a pharma company is probably retarded, and that makes it more expensive, but, at the same time, the problem is really that all the knowledge is completely new, so there's no automation in any of the research. It's not like McCoy can just drop a blood sample into the computer and whip up a batch of cure.

      Anyway, you seem to have a rather callous view on who should or shouldn't get treatment and I think its deplorable.

      That's Democracy. If you want to have private health insurance, have private insurance. Otherwise, accept that, there's going to be people who will make the argument that we should not blow too much medical money on sufferers of illnesses resulting from lifelong self indulgence or excessive risk taking.

      --
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    13. Re:might as well guinea pig at that point by jsse · · Score: 5, Funny

      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...

    14. Re:might as well guinea pig at that point by MoellerPlesset2 · · Score: 4, Insightful

      Chris Rock summed it up nicely. No one will ever cure AIDS, the money isn't in the cure, it's in keeping you alive and helping you live with it. Just get your "fix" and live for one more day.

      Yeah, because Chris Rock has a unique level of insight into the realities of drug development

      It's bullshit. Utter bullshit of the kind that can only come from the cynicism and arrogance that follows total cluelessness.
      Do you think bio-medical researchers are some kind of wizards? Do you think we know so much that we have the luxury of being able to pick and choose between solutions? Bullshit.

      Do we know how the human body works? No, we do not.
      Do we know how diseases work? In most cases, no.
      If we did - Cancer is a good example of an illness known in great detail - does that mean we know what to do about it? It does not.
      If you have an idea of what to do - does that mean it'll work? It doesn't.
      If it works in lab, does that mean it'll work in a live human? It does not. (see the first point)

      Do you know how many drug concepts (that is, ideas) that make it to becoming a finished, FDA-approved drug? It's not even one in ten thousand. With a situation like that, you do not have the luxury of picking and choosing. You go with whatever idea you have, and you take it as far as it'll go. If you're lucky, it might turn into a drug. And it most certainly won't work exactly as imagined from the start.

      Do you know how Viagra, that blockbuster bestseller of 'lifestyle' drugs came about? It was a side effect of a drug originally developed for angina and pulmonary hypertension - a heart drug. The main factor in drug development remains: luck.

      But if you still think there are plenty of good, uninvestigated options for AIDS drug development out there, I suggest you go do it yourself. Maybe then you'll gain some real insight into how complicated reality really is.

    15. Re:might as well guinea pig at that point by CarpetShark · · Score: 5, Insightful

      Like it or not, being a dumbass is part of the human condition. Compassion is recognition of that.

    16. Re:might as well guinea pig at that point by daveime · · Score: 4, Insightful

      Ah you poor blinkered fool. The pharmas spend all their time playing these kind of tricks, and very little time actually developing ANYTHING new.

      ----------

      In Malcolm Gladwell's story in The New Yorker, Gladwell discusses the evolution of Prilosec, a popular heartburn medication that, in one five year stretch alone, earned twenty-six billion dollars. With the patent about to expire in 2001 a good thing was about to come to an end for the drug patent's owner, AstraZenneca. The company set out to create the "new and improved" version of Prilosec, one that would qualify for a new patent and keep the money machine rolling. Ultimately, the company discovered that by making a very subtle change in the chemical engineering of Prilosec, they would have an entirely new drug. But to be issued a patent, they had to prove that the new version was better than the old. They decided that their best opportunity was to focus their testing on something called erosive esophagitis, a condition where stomach acid bubbles up and harms the lining of the esophagus.

      For the first month of the study, the new drug's impact on this problem was identical to Prilosec's. Bad news for the drug company. But in the second month, tests showed that there was a 90% heal rate with the new drug versus 87% with Prilosec, a difference of only 3% for one month but good enough to qualify for patent protection. Thanks to this small and insignificant improvement, AstraZenneca gained FDA approval, was awarded a new patent and put the drug on the market under the name Nexium. The cost for a month's supply of Nexium is about $120. The cost for the now generic version of Prilosec? About $20 for a month's worth of pills.

    17. Re:might as well guinea pig at that point by GlassWhale · · Score: 5, Insightful

      I don't know what you'd achieve by telling HIV-infected children that many adults contract HIV through their own carelessness. Likewise I can't see the point of telling them there's no Santa Claus. Doesn't make it less true though.

    18. Re:might as well guinea pig at that point by fprintf · · Score: 4, Informative

      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.

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    19. Re:might as well guinea pig at that point by stranger_to_himself · · Score: 4, Informative

      You could be worse off, as the study may require that you go off the regular HIV cocktail you are taking to suppress it.

      They would find it hard if not impossible to get ethical approval for that kind of study. If an effective treatment exists, controlled trials are controlled against that, and not against a placebo.

  2. Price Tag? by Anonymous Coward · · Score: 4, Interesting

    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 :/

  3. Re:Sounds expensive... by dunezone · · Score: 5, Informative

    Every time someone posts about HIV we get a jackass like you. There are people who have HIV and didnt contract it through sex or drugs.

    There are people who were born HIV+ because their mother was a carrier, there are people who have been raped and now carry the virus, there are people in the medical field that contract it because some drug addict freaks out while they tend to them. Hell, even though we test blood now many people contracted it through blood transfusions before they tested it.

    Oh and by the way. Condoms don't give 100% protection against HIV its about 80-85%.

    HIV is a bastard of a virus. Our immune systems can usually handle most viruses without intervention. You cant win on your own against HIV. It will destroy the immune system eventually.

    If this treatment is successful at this level. At least we can give life to those who didn't have the choice.

  4. bravo by Ritz_Just_Ritz · · Score: 4, Insightful

    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.

    1. Re:bravo by BlueParrot · · Score: 5, Insightful

      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.

    2. Re:bravo by Anonymous Coward · · Score: 5, Informative

      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. :)

    3. Re:bravo by The+FNP · · Score: 4, Insightful

      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.

  5. M-x genotype-mode by Anonymous Coward · · Score: 5, Funny

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

  6. Mod parent down - didn't RTFA by LonghornXtreme · · Score: 4, Informative

    The test subjects have drug resistant HIV.

  7. Potential Failure RIsks: by LonghornXtreme · · Score: 5, Informative

    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.

  8. Re:Unanswered questions by MoellerPlesset2 · · Score: 4, Informative
    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, 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.

  9. Re:CANCER by Wain13001 · · Score: 5, Informative

    For the most part, T-cells die off naturally.
    People infected with HIV do not have to deal with a problem of too many t-cells, so in this case it's not much of a concern.

    Most importantly though, T-cells do not replicate to create more T-cells. They come from a type of lymphocyte starter cell (a stem cell essentially), which reproduces in the bone marrow.

    Taking t-cells from your body, and then reintroducing them to your body will not give you leukemia (literally meaning "White Blood", refers to various cancers of white blood cells).

    More than likely this is just a test, not *the cure*. The point being to see if the modified t-cells survive long enough to keep the count from dropping (as it would via a normal HIV infection). If it does work, then we can start developing methods to modify bone-marrow in order to make the new t-cells your body creates have the altered gene.

    Of course, I'm not an expert, and the article is unfortunately slim on details, so this is basic speculation.

  10. Not to dampen hopes, but... by wickerprints · · Score: 5, Insightful

    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

  11. Re:Sounds expensive... by rrkap · · Score: 4, Insightful

    I should add that this isn't a reason not to pursue research for cures for HIV. It's a very interesting problem and this technique may have broad application if it works. Also in some parts of the world HIV is very common and hard to avoid.

    Just as we would treat a heart attack in a 400 lb man, so we should also treat someone with HIV as best we can.

    --
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