7 ms·

First U.S. use of CRISPR to directly target cancer seeks approval

206 points by ChefboyOG 7y ago

ebg13 7y ago
It's a safe first step. These patients are guaranteed to die very soon without a miracle, so the risk of causing a new cancer doesn't matter.
- cannonedhamster 7y ago
  Statistically likely, not guaranteed. I'm already statistically likely to be dead and resistant to chemo but so far so good. The patients know the risk though and decades is dramatically longer a time frame than they likely have. Hopefully this works wonders and can be pushed to other types of cancers.
  - achievingApathy 7y ago
    Wouldn't accepting only those that had such advanced cancers though skew any results? I'm very much in favor of these individuals getting any and all help they can as soon as possible but I want to remain optimistic about the validity of the results. (I can't tell if you meant to imply that you are in remission or going through chemo now).
- Symmetry 7y ago
  I'm sort of glad we've changed our approach. Back in the early days of gene therapy in the 90s in one of the first attempts at curing OTC[1] the medical ethics board decided that the trial could only be conducted on people with a non-lethal version of the disease. It was thought that people whose only alternative to the treatment was death wouldn't be able to say no and thus couldn't give the required consent. [1]https://en.wikipedia.org/wiki/Ornithine_transcarbamylase_deficiency https://en.wikipedia.org/wiki/Ornithine_transcarbamylase_def...
  - ebg13 7y ago
    > thus couldn't give the required consent While they weren't technically wrong, holy throwing the baby out with the bathwater, batman. This is the problem with single-issue voting. I wonder if they have logicians on these panels. "So you want to take a person who will live...and maybe make them die...because you don't want to test on someone who will die?"
    - Symmetry 7y ago
      Well, yeah, I think that was a very bad call. But from the hospital's perspective nobody was going to blame them if some children died of a currently incurable disease. But people might very well blame them if there was a problem with the treatment. And there was a problem with the treatment, so maybe it was selfishly good for them that they had this procedure.
thatoneuser 7y ago
This will be very interesting to see. Would this be the first big use case of crispr?
- inciampati 7y ago
  All throughout biology people are using CRISPR/Cas for endonuclease and binding activity. A lot of engineered plants for instance are based on this system. It is not simple to apply to adults, unless it's by engineering a cell culture (like T cells).
ddon 7y ago
China is experimenting with CRISPR on people from 2016, NPR have an article about this [1]. It involves using cells from his own immune system, known as T cells, after they have been taken out of his body and genetically altered in a lab. * [1] https://www.npr.org/sections/health-shots/2018/02/21/585336506/doctors-in-china-lead-race-to-treat-cancer-by-editing-genes https://www.npr.org/sections/health-shots/2018/02/21/5853365...
- AlexCoventry 7y ago
  This is such a great idea. Much more direct than trying to train the immune system with a vaccine.
  - AllegedAlec 7y ago
    We tried something similar with children with SCID [edited] a while back. Many of them were accidentally given leukemia. Not saying we shouldn't try this, but genetics are capricious, and we should be very careful when trying things like this on humans. Plants and test animals are one thing, but when we're doing trials on humans, there's a lot more at stake. https://www.sciencedaily.com/releases/2008/08/080807175438.htm https://www.sciencedaily.com/releases/2008/08/080807175438.h...
yread 7y ago
Messing with transcription factors? Sounds a bit like shotgun debugging
teh_infallible 7y ago
That’s ironic- I was under the impression that CRISPR actually caused cancer, as targeting a single gene has the effect of altering hundreds of other genes.
- ztratar 7y ago
  Not really sure where to start, but 1) CRISPR's altering doesn't necessarily only alter one gene, and 2) altering one gene doesn't necessarily alter "hundreds of other genes" either.
  - AllegedAlec 7y ago
    CRISPR isn't as specific as the (popular) scientific literature makes it out to be. It's way better than most other methods, but there's always a chance that other genes (or transcription factor binding sites, or any of myriad other constructs in the genome) are also hit accidentally.
    - hobofan 7y ago
      Is that a big risk though? I imagine that for a patient (and with that a specific genome with specific editing errors) you could extract some cells, grow an in vitro culture, and test the CRISPR on that? You could then sequence the altered genome and see how much genes were "collateraly edited" and only if the result is non-risky apply the medication to the patient.
      - AllegedAlec 7y ago
        T-Cells are remarkable tricky to grow in-vitro. Most of them only grow after presented the particular antigen (for the non-biologists: the part of the virus/bacteria which they recognise) which they are keyed to. I haven't looked at the actual proposals, but I figure they'll take T-Cells, use CRISPR on those directly, clean them off (so you don't accidentally CRISPRize other cells in the body) and re-inject them directly so they won't die off. You could sequence part of them before insertion, if you manage not to kill the rest of the T-Cells with the wildly differing in vitro environment, but by that point you're playing a numbers game. The non-specific CRISPR action (called off-target mutagenesis in the literature) is a low probability event, but if you sequence part of the T-Cells, you could easily miss one with a bad (read: non-lethal) off-target mutation.
leshokunin 7y ago
Love this. I really hope they get to try properly. Similarly to giving people the right to die, I wish people could get full clarity on these trials and make up their own mind. I hope it works out for them. We really need cancer to end.
Funes- 7y ago
As someone who lives with and takes care of a cancer patient, I'm really frustrated with how little effort has been devoted to cancer research in such a long period of time, taking into account that it's been several decades of misery now for millions of people--and a lot more to come; that's for sure. Besides governments allocating less funding to research, prevention and treatment--for cancer as well as other grave ailments--than they could, what especially irks me is this: negligent practices carried out by big corporations to which authorities have always turned a blind eye. The sheer amount of unregulated, harmful practices that has come to define our current lifestyle is abominable. Radiation, pollution, carcinogenic and generally unsafe food, hygiene products, food and liquid containers... All factors whose pervasiveness correlates with cancer cases skyrocketing. We should all be willing to reflect upon what we're doing to our personal and collective health, and if our lifestyles are actually sustainable or do require to be reformed.
- gravelc 7y ago
  Really sorry to hear what you're going through. Cancer is a terrible terrible thing for the sufferer and their carers alike. I do however disagree with some points made; as a researcher who doesn't work in cancer, I often see it as a very well funded area of science relative to almost all others (in Australia at least, and I suspect the rest of the Western world). Obviously there are differences in funding for various cancer types, which is caused by a range of factors. Research funding across most areas could be improved IMO. I'd add that on average, the biggest risk factor for cancer is age - we live longer than in the past, thus we're more likely to get cancer. There are other risk factors of course, but apart from things like smoking, being irradiated or infected with certain viruses, they likely pale in comparison to simply growing old and collecting a long list of mutations in various cells over time, with awful consequences for the unlucky.
- mellowdream 7y ago
  Blame it on boomers in both business and government, running both in true live fast die young fashion. Plastics pollution, BPA in our receipt paper, drugs and hormones being pissed out into our toilets into the common water supply - large parts of the global economy have been allowed to thrive due to neglect of appropriately pricing in negative externalities, if they are considered at all. What is the TRUE cost of using plastic in everyday product? What is the TRUE cost of the advertising and adoption of birth control pills, or OTC drugs? Some people benefit from short-term profits now, but in the end everyone loses.
magicalhippo 7y ago
Just wanted to mention... if you (or one you know) get cancer, once the type of cancer has been established, ask where it typically spreads to. Monitor changes in those areas. A relative got cancer in a lymph node, and got it successfully operated out. A couple of years later got shortness of breath and back pain. Doctors gave asthma medication for the breath and physio for the back pain. After a year of no real progress, an unrelated shoulder x-ray showed spots in the lung tissue. X-ray technician noticed this and escalated it, and only when they verified it did we learn that the original cancer typically spreads to the lungs and bones... Now in this case, finding the cancer had spread to the lungs and spine a year earlier probably wouldn't have done much to delay the inevitable, but it would have allowed them to start pain medication much sooner, making that year less painful.
- edwhitesell 7y ago
  This is definitely good advice. Also, from my own experience with cancer that spread: get a second opinion from another oncologist (get a third if you feel the need). It's your body, it's your life, do your homework. After all of that, do your follow-ups. Oddly enough, I'm two years out of my initial diagnosis, sitting in the oncologist's waiting room for results of my latest scans as I write this.

206 points by ChefboyOG 7y ago

It's a safe first step. These patients are guaranteed to die very soon without a miracle, so the risk of causing a new cancer doesn't matter.

cannonedhamster 7y ago
Statistically likely, not guaranteed. I'm already statistically likely to be dead and resistant to chemo but so far so good. The patients know the risk though and decades is dramatically longer a time frame than they likely have. Hopefully this works wonders and can be pushed to other types of cancers.
- achievingApathy 7y ago
  Wouldn't accepting only those that had such advanced cancers though skew any results? I'm very much in favor of these individuals getting any and all help they can as soon as possible but I want to remain optimistic about the validity of the results. (I can't tell if you meant to imply that you are in remission or going through chemo now).
Symmetry 7y ago
I'm sort of glad we've changed our approach. Back in the early days of gene therapy in the 90s in one of the first attempts at curing OTC[1] the medical ethics board decided that the trial could only be conducted on people with a non-lethal version of the disease. It was thought that people whose only alternative to the treatment was death wouldn't be able to say no and thus couldn't give the required consent. [1]https://en.wikipedia.org/wiki/Ornithine_transcarbamylase_deficiency https://en.wikipedia.org/wiki/Ornithine_transcarbamylase_def...
- ebg13 7y ago
  > thus couldn't give the required consent While they weren't technically wrong, holy throwing the baby out with the bathwater, batman. This is the problem with single-issue voting. I wonder if they have logicians on these panels. "So you want to take a person who will live...and maybe make them die...because you don't want to test on someone who will die?"
  - Symmetry 7y ago
    Well, yeah, I think that was a very bad call. But from the hospital's perspective nobody was going to blame them if some children died of a currently incurable disease. But people might very well blame them if there was a problem with the treatment. And there was a problem with the treatment, so maybe it was selfishly good for them that they had this procedure.

thatoneuser 7y ago

This will be very interesting to see. Would this be the first big use case of crispr?

inciampati 7y ago
All throughout biology people are using CRISPR/Cas for endonuclease and binding activity. A lot of engineered plants for instance are based on this system. It is not simple to apply to adults, unless it's by engineering a cell culture (like T cells).

ddon 7y ago

China is experimenting with CRISPR on people from 2016, NPR have an article about this [1]. It involves using cells from his own immune system, known as T cells, after they have been taken out of his body and genetically altered in a lab. * [1] https://www.npr.org/sections/health-shots/2018/02/21/585336506/doctors-in-china-lead-race-to-treat-cancer-by-editing-genes https://www.npr.org/sections/health-shots/2018/02/21/5853365...

AlexCoventry 7y ago
This is such a great idea. Much more direct than trying to train the immune system with a vaccine.
- AllegedAlec 7y ago
  We tried something similar with children with SCID [edited] a while back. Many of them were accidentally given leukemia. Not saying we shouldn't try this, but genetics are capricious, and we should be very careful when trying things like this on humans. Plants and test animals are one thing, but when we're doing trials on humans, there's a lot more at stake. https://www.sciencedaily.com/releases/2008/08/080807175438.htm https://www.sciencedaily.com/releases/2008/08/080807175438.h...

yread 7y ago

Messing with transcription factors? Sounds a bit like shotgun debugging

teh_infallible 7y ago

That’s ironic- I was under the impression that CRISPR actually caused cancer, as targeting a single gene has the effect of altering hundreds of other genes.

ztratar 7y ago
Not really sure where to start, but 1) CRISPR's altering doesn't necessarily only alter one gene, and 2) altering one gene doesn't necessarily alter "hundreds of other genes" either.
- AllegedAlec 7y ago
  CRISPR isn't as specific as the (popular) scientific literature makes it out to be. It's way better than most other methods, but there's always a chance that other genes (or transcription factor binding sites, or any of myriad other constructs in the genome) are also hit accidentally.
  - hobofan 7y ago
    Is that a big risk though? I imagine that for a patient (and with that a specific genome with specific editing errors) you could extract some cells, grow an in vitro culture, and test the CRISPR on that? You could then sequence the altered genome and see how much genes were "collateraly edited" and only if the result is non-risky apply the medication to the patient.
    - AllegedAlec 7y ago
      T-Cells are remarkable tricky to grow in-vitro. Most of them only grow after presented the particular antigen (for the non-biologists: the part of the virus/bacteria which they recognise) which they are keyed to. I haven't looked at the actual proposals, but I figure they'll take T-Cells, use CRISPR on those directly, clean them off (so you don't accidentally CRISPRize other cells in the body) and re-inject them directly so they won't die off. You could sequence part of them before insertion, if you manage not to kill the rest of the T-Cells with the wildly differing in vitro environment, but by that point you're playing a numbers game. The non-specific CRISPR action (called off-target mutagenesis in the literature) is a low probability event, but if you sequence part of the T-Cells, you could easily miss one with a bad (read: non-lethal) off-target mutation.

leshokunin 7y ago

Love this. I really hope they get to try properly. Similarly to giving people the right to die, I wish people could get full clarity on these trials and make up their own mind. I hope it works out for them. We really need cancer to end.

Funes- 7y ago

As someone who lives with and takes care of a cancer patient, I'm really frustrated with how little effort has been devoted to cancer research in such a long period of time, taking into account that it's been several decades of misery now for millions of people--and a lot more to come; that's for sure. Besides governments allocating less funding to research, prevention and treatment--for cancer as well as other grave ailments--than they could, what especially irks me is this: negligent practices carried out by big corporations to which authorities have always turned a blind eye. The sheer amount of unregulated, harmful practices that has come to define our current lifestyle is abominable. Radiation, pollution, carcinogenic and generally unsafe food, hygiene products, food and liquid containers... All factors whose pervasiveness correlates with cancer cases skyrocketing. We should all be willing to reflect upon what we're doing to our personal and collective health, and if our lifestyles are actually sustainable or do require to be reformed.

gravelc 7y ago
Really sorry to hear what you're going through. Cancer is a terrible terrible thing for the sufferer and their carers alike. I do however disagree with some points made; as a researcher who doesn't work in cancer, I often see it as a very well funded area of science relative to almost all others (in Australia at least, and I suspect the rest of the Western world). Obviously there are differences in funding for various cancer types, which is caused by a range of factors. Research funding across most areas could be improved IMO. I'd add that on average, the biggest risk factor for cancer is age - we live longer than in the past, thus we're more likely to get cancer. There are other risk factors of course, but apart from things like smoking, being irradiated or infected with certain viruses, they likely pale in comparison to simply growing old and collecting a long list of mutations in various cells over time, with awful consequences for the unlucky.
mellowdream 7y ago
Blame it on boomers in both business and government, running both in true live fast die young fashion. Plastics pollution, BPA in our receipt paper, drugs and hormones being pissed out into our toilets into the common water supply - large parts of the global economy have been allowed to thrive due to neglect of appropriately pricing in negative externalities, if they are considered at all. What is the TRUE cost of using plastic in everyday product? What is the TRUE cost of the advertising and adoption of birth control pills, or OTC drugs? Some people benefit from short-term profits now, but in the end everyone loses.

magicalhippo 7y ago

Just wanted to mention... if you (or one you know) get cancer, once the type of cancer has been established, ask where it typically spreads to. Monitor changes in those areas. A relative got cancer in a lymph node, and got it successfully operated out. A couple of years later got shortness of breath and back pain. Doctors gave asthma medication for the breath and physio for the back pain. After a year of no real progress, an unrelated shoulder x-ray showed spots in the lung tissue. X-ray technician noticed this and escalated it, and only when they verified it did we learn that the original cancer typically spreads to the lungs and bones... Now in this case, finding the cancer had spread to the lungs and spine a year earlier probably wouldn't have done much to delay the inevitable, but it would have allowed them to start pain medication much sooner, making that year less painful.

edwhitesell 7y ago
This is definitely good advice. Also, from my own experience with cancer that spread: get a second opinion from another oncologist (get a third if you feel the need). It's your body, it's your life, do your homework. After all of that, do your follow-ups. Oddly enough, I'm two years out of my initial diagnosis, sitting in the oncologist's waiting room for results of my latest scans as I write this.