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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.'"
What's the worst that could happen, they screw it up and you die?
You don't say.
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 :/
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.
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.
You *know* there's going to be an Emacs mode for gene editing.
The test subjects have drug resistant HIV.
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.
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.
Quattuor res in hoc mundo sanctae sunt: libri, liberi, libertas et liberalitas.
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 as to say that if HIV mutates into not requiring CCR5, then this new strain could spread and theoretically be worse than the current HIV strain in the wild.
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.
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.
HIV is a bastard because it's relatively benign and very hard to transmit. A normal deadly virus like Ebola kills you quickly, HIV keeps you healthy and able to infect others for years. It's mainly transferred by sex, which is a big bummer for all of us who like to sleep around which includes lots of gay men.
But once you have it, you won't get rid of it. Nothing special either, because most people live with the chicken pox virus for most of their lives. That usually doesn't kill you, though...
X.
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 think of my accidental select-all, delete-key combos:
"Oh shit... undo, undo!"
æeee!
Cancer's one possibility.
Right now HIV can't attack cells that are missing that gene, and people with that mutation are rare enough that it isn't advantageous/necessary for HIV to develop another mechanism. However if you inject cells with this mutation into someone that doesn't normally have it, and they don't manage to clean out all the HIV from the person's system, then the combination of both of those cells in proximity is about as good as possible an environment for HIV to develop a mutation that can provide a new method of attack.
Reservoir of HIV-infected cells - check.
Depleted immune system that is subject to other viral infections that could cross contaminate with HIV - check.
Small group of immune resistant T-Cells that might be incapable of wiping out well-settled-in, drug resistant HIV - check
These guys theoretically could wind up spurring the evolution of a new strain of HIV that attacks the few people that are currently resistant. The bright side to this is that the T-Cells should die off naturally with no replacement. So if it doesn't work and they don't try to prolong the experiment with extended and repeated treatments, the window of risk is relatively short.
Laissez lire, et laissez danser; ces deux amusements ne feront jamais de mal au monde. - Voltaire
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.
I like my beverages with warning labels!
"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."
"The agriculture ministry is not in charge of Gundam" - Japanese ministry official.
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:
Because it's a faulty/mutated gene, and not an alien organism, I imagine. I could (very easily) be wrong, but presumably the immune system doesn't deal with differences on that scale, unless they cause abnormalities further up the scale in the cell or something.
I wouldn't put any money on that scenario.
HIV resistant people are carriers of the virus yet it's not a terminal disease for them. As such, it's a win-win situation for both man and virus. If the virus mutates to a more agressive variant that circumvents the resistance and kills the patient then that strain of HIV is dead and gone(maybe stored in a fridge somewhere).
Is it likely such a mutation would happen in all resistant carriers? No way. And considering that todays model of HIV is actually less agressive than the original i'd say that if anything the virus will mutate to a more tame variant. After all from an evolutionary standpoint the fittest virus does no direct noticeable harm to it's host.
the problem with that of course is it the basis for many a scifi movie; direct genetic manipulation resulting in a number of box office scenarios: - mass death (pick one...) - zombies (Resident Evil - the t-cell accident; was supposed to be a cure) - intentional mutation (Xmen 2 - the guy that made wolverine) - super soldiers (Super Soldier - the movies part 1 and 2, captain america) - Battlestar galactica (skin jobs and pro-creation attempts) - mutegenics wars - lots of super soldiers (Star Trek - not to be confused with Khan who is a eugenic offspring) - replicants (Blade Runner - note the replicants learned how to do this themselves...) - serenity (reavers were gene mutated - with the best of intentions of course) - I am Legend (someone else mentioned it already) I am sure the list goes on.