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Base editing: Revolutionary therapy clears girl's incurable cancer
- stevespang 4y ago
- pkaye 4y agoHasn't this treatment been use for a while now?
- deleted 4y ago[deleted]
- TaupeRanger 4y agoI'm not sure it counts as "revolutionary" if it has helped only 1 person, and maybe as many as 10-12 per year. It's really the opposite of revolutionary, though I am very happy for this family and their daughter.
- Firmwarrior 4y agoHaha, your comment is like something a venture capitalist would say when he's trying to lowball a startup founder in the show "Silicon Valley"
- quickthrower2 4y agoThere is a time when every revolutionary invention had only helped one person, so far.
- flobosg 4y ago> a revolutionary product, process, or idea is new and exciting and not like anything that has existed or been done before ―https://dictionary.cambridge.org/dictionary/english/revolutionary#cbed-1 https://dictionary.cambridge.org/dictionary/english/revoluti...
- 1123581321 4y agoThe technique is new and will be adapted to other cancers and diseases.
- walnutclosefarm 4y agoActually, it's the other way around. The treatment described is an adaption of CAR-T (Chimeric Antigen Receptor T-cell) therapy, which was approved for use in the United States in 2017, to the patient's specific form of leukemia. It's a challenging adaptation because the cancer cells being targeted are the same type of T-cells that are used in CAR-T therapy, thus requiring the use of donor T-cells, and a number of modifications that are unnecessary when CAR-T is used for other cancers. Base editing makes that easier than earlier forms of CRISPR. But base editing isn't the therapy here, CAR-T is, and while CAR-T is certainly relatively, this patient is not the first to receive, just the first with her particular leukiemia.
- VerminOctopus1 4y agoNo, the parent comment is totally fine. The technique is indeed new and yes will be applied in the treatment of other diseases in the future. Don’t know why you went to open with a contrarian tone.
- walnutclosefarm 4y agoMy point was simply that this is an adaptation of an existing therapeutic tool (CAR-T) to a particular cancer, not something completely novel. It's a leaf on a tree of therapies, not a new tree per se.
- 1123581321 4y agoI don’t see the disagreement! Good info; thanks.
- tsol 4y agoFirst it had to be accomplished, then they can work on getting the price down
- ryangittins 4y agoSure, there is one airplane but that's hardly revolutionary. A couple of guys can fly a few dozen feet. So what?
- selimthegrim 4y agoThis is like if Larry David did an ad for the Wright brothers
- HiroProtagonist 4y agoPretty, pretty, pretty good.
- TulliusCicero 4y agoThis is like the ultimate form of Unimpressed Internet Guy. The article even talks about other trials also underway, so the parent comment doesn't even make any sense: > Dr Robert Chiesa, from the bone-marrow transplant department at Great Ormond Street Hospital, said: "It is extremely exciting. Obviously, this is a new field in medicine and it's fascinating that we can redirect the immune system to fight cancer." > The technology, though, only scratches the surface of what base editing could achieve. > Dr David Liu, one of the inventors of base editing at the Broad Institute, told me it was "a bit surreal" that people were being treated just six years after the technology was invented. > In Alyssa's therapy, each of the base edits involved breaking a section of genetic code so it no longer worked. But there are more nuanced applications where instead of switching an instruction off you can fix a defective one. Sickle-cell anaemia, for example, is caused by just one base change that could be corrected. > So there are already trials of base editing under way in sickle-cell disease, as well as high cholesterol that runs in families and the blood disorder beta-thalassemia.
- deleted 4y ago[deleted]
- tinktank 4y agoIt's a proof-of-concept. That's the hard bit done.
- cactusplant7374 4y agoThis is CRISPR, right? Or is base editing different?
- deleted 4y ago[deleted]
- janalsncm 4y agoHuge news. This will save tons of people as the cost comes down. We are truly living in the future.
- nullish_signal 4y ago
- hughes 4y agoAre you saying Alyssa's rare form of leukemia should not have a cure because she and her friends in oncology might quadruple the planet's population?
- subroutine 4y agoWould you trade (a) total cure for all cancer for (b) the human population to go from 8 to 16 billion? Yes, absolutely. Surely population growth can be dealt with more humanely than killing people off with cancer.
- nullish_signal 4y agoI disagree with the notion of benevolent DOCTORS "Killing people off with cancer". Was the patient body full of DOW Chemical or DDT or Big Gulps or Pharmaceuticals[0]? industrial Society and Old Age are what "kill people by means of cancer" [0] USA being the only country I know of to allow public Advertisement of Controlled medicines
- subroutine 4y agoI'm not sure what you're talking about. Choosing to not cure cancer is killing people off with cancer. The little girl in the article had leukemia. It sounds like you would prefer to let children die of cancer because of your weariness of population growth.
- ryanwaggoner 4y agoI believe the world population is expected to peak this century, not because of people dying or starving at higher rates, but because when countries become more developed, their birth rates plummet. I don’t think there’s any reason to think curing all diseases and ensuring no one ever starved again would change that.
- klipt 4y ago> The team at Great Ormond Street used a technology called base editing, which was invented only six years ago. Fun fact: J M Barrie who wrote Peter Pan donated the copyright of both the book and play in perpetuity to Ormond Street children's hospital. It's been a significant source of funding for them over the years.
- monero-xmr 4y ago
- sgc 4y agoYou need to avoid spending the principal + inflation, which is significantly harder to do.
- hilbertseries 4y agoWhy did you make this comment?
- monero-xmr 4y agoRegarding donations - you should donate assets that will produce cash for infinite time. Pure cash donations that are unencumbered are foolish, IMO.
- jacobriis 4y agoAI that filters insane non-sequitur personal anecdotes from HN comments cannot come soon enough.
- sph 4y agoLeave AI out of forums for humans, please. They are not welcome here.
- guiambros 4y agoChatGPT?
- hooloovoo_zoo 4y agoMarvelous! I wonder why she needs a second transplant though.
- t-3 4y agoIt's explained in the article that the second transplant is necessary to replace the white blood cells which should have been fully wiped out by the first transplant of modified cells.
- hooloovoo_zoo 4y agoBut why can’t the modified cells function as regular T cells in addition to the modifications?
- zaroth 4y agoI think they don’t usually last that long. The body won’t keep producing the modified cells. Plus I think the modification made them basically only good for killing the native (cancerous) T cells
- hooloovoo_zoo 4y agoCould be. It would be nice if you could maintain the modification though because then you don't have to worry about some cancerous cells surviving the first wave.
- frontierkodiak 4y agoThe article states “The first base edit disabled the T-cells targeting mechanism so they would not assault Alyssa's body”. Not an expert but I presume the ‘targeting mechanism’ is the T-cell receptor, whose activation is necessary (but not sufficient) to trigger immune response.
- hooloovoo_zoo 4y agoMaybe, but the second transplant also needs to not assault Alyssa.
- fastball 4y agoIn response to the multiple people asking if base editing and CRISPR are the same, the answer is: not quite. Same idea, different enzyme. The enzyme used by CRISPR is Cas9 (which is why you'll often see it referred to as CRISPR-Cas9), which acts like a pair of molecular scissors and cuts strands of DNA at a specific point in the genome. Base editing is a newer technique and utilizes an enzyme called deaminase, which can change the chemical structure of a base pair without doing the "cutting" part. There are specific deaminases based you use depending on which base pair you're trying to modify. To oversimplify a bit: base editing is a more precise version of CRISPR, which is less likely to cause more changes than actually desired, as is a problem with CRISPR. That doesn't make CRISPR obsolete though, because if your goals actually is to remove entire portions of a genome, CRISPR is a more effective technique. Regardless, there is a lot of overlap between the methods: both usually use adenoviruses as the delivery vehicle, you can use both enzymes in tandem, etc.
- nine_k 4y agoThe word more understandable for the software developer crowd would be "patching". That is, changing a base pair in place.
- govg 4y agoI took it to mean doing an in place patch / removal of code (CRISPR) vs doing a more general refactor that results in cleaner code (base pair editing).
- stanford_labrat 4y agoFor clarification, most base editors are a fusion protein with cas9 and the actual editing protein.
- dpatrick86 4y agoSome use cas9, such as dead cas9 (has endonuclease activity removed), and others do not. Great interview where Dr. George Church talks base editing and CRISPR: https://www.foundmyfitness.com/episodes/george-church https://www.foundmyfitness.com/episodes/george-church
- MontagFTB 4y agoIt sounds like this is a continuation of work that was tested as far back as 2015: https://www.businessinsider.com/r-gene-edited-cells-keep-cancer-babies-well-more-than-one-year-on-2017-1?amp https://www.businessinsider.com/r-gene-edited-cells-keep-can...
- hliyan 4y agoGreat to see medical techniques slowly starting to resemble engineering design: 1. Donor T-cells added with receptors to destroy the recipient's cancerous T-cells. 2. Donor T-cells' markers removed to prevent them from attacking each other. 3. Donor T-cells' existing receptors removed to prevent them from attacking the recipient's other cells (since the donor T-cell will see them as 'foreign'). 4. Donor T-cells altered to resist chemotherapy. It seems each of these changes were achieved by editing specific base pairs to break the relevant gene, except perhaps for (1)
- adamredwoods 4y agoTo even have something like this actually respond, in the way they planned it, is a marvel. I know they have worked with T-Cells before, but this is putting it to precise use. Sadly, cancer is vicious. It only takes one rogue cell to keep building, about 2-years for it to surface again. Luckily, this process seems repeatable. I can't imagine the euphoria that family feels right now.
- psychphysic 4y agoIt sounds like they continued chemo. T-cells immune from the chemo targeting cancerous T-cells during the chemo treatment is pretty potent.
- DoreenMichele 4y agoIn layman's terms: She had a particularly vicious form of cancer where the very cells that are supposed to protect your health -- your T-cells -- are the enemy. So they made three edits to donor cells and wiped out her compromised cells. Then gave her a bone marrow transplant afterwards to replenish her immune system with new cells. I'm squeamish about genetic research, but this looks really good to me. I hope she recovers fully and there are no further complications, though I imagine it's too early to guess what her prognosis might be. So there are already trials of base editing under way in sickle-cell disease, as well as high cholesterol that runs in families and the blood disorder beta-thalassemia. That's a big deal for people with those genetic disorders.
- GenerocUsername 4y agoI feel like this type of medicine is more like a research study waiting for a perfect match patient than it is highly personalized treatment... Is this technique broadly applicable? Or limited to very specific cases
- DoreenMichele 4y agoIt looks to me like a somewhat unique opportunity to risk it because without this treatment, she was dead anyway and in fairly short order. So it was a means for them to learn something with very little potential downside. Worst case scenario: The treatment kills her. And she was dying anyway. From the article: In Alyssa's therapy, each of the base edits involved breaking a section of genetic code so it no longer worked. But there are more nuanced applications where instead of switching an instruction off you can fix a defective one. Sickle-cell anaemia, for example, is caused by just one base change that could be corrected. And I already quoted (in my previous comment) the next paragraph that indicates they are already doing trials. This is potentially a big deal and they seem to be pursuing it in a very reasonable and conservative fashion, which is always something that concerns me with this type thing. There's a lot of potential for terrible and horrifying abuse and that is not what I am seeing described here.
- runnerup 4y ago
- ars 4y agoIs there any worry/chance that the modified T-cells will survive and multiply in the body instead of dying out?
- gizmo686 4y agoI'm talking well beyond my competency, but short of one of those T-cells spontaneously becoming cancerous itself, I don't see how. T-cells do not duplicate themselves. Instead, new T-cells are creates in bone marrow. Since they are not editing the genes in the bone marrow, there is no mechanism within the body to create new cells using the modified DNA.
- ggm 4y agoIn heroic medical science history fiction it's a bit of a trope to write "the operation was a success but the patient died" I sincerely hope she survives at least 5 years, and significantly more. If she gets only a single year of treatment -free high quality life outside of respite care, that would be a bitter pill outcome but might still be held a success. Sometimes giving people a year of quality life at end-of-life is a good outcome. The article as written is light on for data and time info. She's had at least 3 post treatment checks one of which was 3 months, the other 2 not stated but 6monthly might not be unusual. Recurrences in blood borne diseases are not unheard of. She had some signs of recurrence at 3 months but it went away. Maybe fragment traces? Non viable remainders flushing out of the marrow? (I don't know if this is even plausible. I'm not in medicine) It's great news, but so was Christian Barnard's first transplant. In modern terms the survival wasn't very long. (200 days in the first 4) A better outcome would be like Steptoe's work on assisted conception and birth. (IVF) and I certainly hope she and future patients have that.
- ausbah 4y agois there any specific reason to think this disease could come "roaring back" aside from general unknowns of a new treatment?
- epgui 4y agoThe fact that she developed cancer in the first place means that she is more likely to continue developing cancer, via a plethora of mechanisms. Cancer is always just a matter of time, for all of us. Subtle mutations accelerate the timeline, and they accumulate over time.
- jordanbeiber 4y agoI’ve started watching star-trek (as it makes me fall asleep immediately) - this stuff sounds like a star-trek episode! Something Dr Crusher would come up with. It makes a distant future where we quickly engineer a fix and inject it seem almost plausible.
- system2 4y agoDr. McCoy would've given green alcohol.
- namaria 4y agoOh man I love getting high and watching the original Star Trek. All the imagined analogue computer technology makes me wonder...
- rmak 4y agoCloser to star gate sg1 episode than star trek, I love that series.
- unsupp0rted 4y agoIt is something Dr. Crusher came up with: > Barclay's Protomorphosis Syndrome > Attempting to cure Lieutenant Reginald Barclay of his Urodelan flu, Dr. Crusher used synthetic T-cells to activate the gene that would fight off the infection. However, an anomaly in Barclay's genetic structure caused the T-cell to mutate and activate all of Barclay's dormant genes, including his introns. The T-cells then became airborne, spreading throughout the ship like a virus and causing the crew to "de-evolve." https://memory-alpha.fandom.com/wiki/Barclay%27s_Protomorphosis_Syndrome https://memory-alpha.fandom.com/wiki/Barclay%27s_Protomorpho...
- yread 4y agowow it goes from ok to completely nuts within one sentence. Activated introns hahaha
- beaned 4y agoDo people with base-edited DNA pass their modified genes on to their offspring?
- elektrontamer 4y agoGerm cells need to be edited for that. The edited T cells can't get inherited.
- gizmo686 4y agoNo. The only DNA that gets passed to offspring is what is in the sperm/eggs. Collectively these are referred to as the "germline". Research into germline editing is illegal in the US, and frowned upon internationally. The most famous case is from 2018, when Chinese researcher He Jiankui created the first genome-edited babies. Using CRISPR to give the babies resistance to HIV-1. [0]. This change will propagate to the decedents of the subjects [1]. The Chinese Academy of Science, along with the global medical community, denounced this experiment; and He Jiankui was arrested. [0] The necessary mutation, while rare in humans, is naturally occurring, and generally thought to confer HIV-1 resistance. [1] Subject to normal genetics that arrises from sexual reproduction, where a given parent is responsible for only half of a child's genes.
- NaturalPhallacy 4y ago>Research into germline editing is illegal in the US, and frowned upon internationally. I would bet money someone's doing it anyway.
- mr_toad 4y agoThere seems to be more money in not doing it. Why sell something permanent, when you can sell the treatment again and again to each generation? So if we want to start getting cynical we could suppose that there are shadowy forces trying to prevent the development of this technology.
- Doorstep2077 4y agoThis looks pretty great, hopefully a huge step forward for the medical industry and finding cures for cancer. Unfortunately don't know too much about it; wish there was something that allowed me to learn about medical problems easily, without needing to understand the jargon
- uwagar 4y ago
- thdespou 4y agoNoone is forcing you to accept anything. If else the girl and parents had to make that decision and accept the risks. They would probably had to sign a legal document as well. Maybe you need to chill out of the conspiracy mindset.
- uwagar 4y agolol. said the same thing about covid vaccine and then brought in the mandates.
- once_inc 4y agoWhen is the head of the department going to do a televised interview? > https://youtu.be/B3xY6Ffy_wE?t=68 https://youtu.be/B3xY6Ffy_wE?t=68
- namaria 4y agoWe are at the "assembly" stage of genetic tinkering. Manually changing over the 'machine code' of the cell, the linear sequence of physically bound instructions. I wonder what the future might bring in terms of higher level programming of cells.
- ricardobeat 4y agoVery similar report by the same author from 2015: https://www.bbc.com/news/health-34731498 https://www.bbc.com/news/health-34731498 It doesn’t explain what “designer immune cells” were, so it’s hard to tell what’s different in this more recent treatment.
- Duller-Finite 4y agothat study used TALENs; this one used CRISPR base editors
- chrisweekly 4y agoIMHO this is a good reminder that the word "incurable" means "as-yet unsolved", it's not an absolute.
- smeej 4y agoTangential, but I wonder how long it'll be before we start combining these recent advances in AI with a dataset like Medikanren and identifying really custom treatments.
- lebuffon 4y agoThis is a wonderful outcome and amazing science and all involved are to be commended for saving this girl's life. However would it not make more sense to try and prevent the disease in society, since there is a viral component to it? It is a retro-virus and was first discovered in 1977. Is there even research on a vaccine? We have one for cervical cancer. (Hit's a nerve since I have a child with Lymphoma) https://www.who.int/news-room/fact-sheets/detail/human-t-lymphotropic-virus-type-1 https://www.who.int/news-room/fact-sheets/detail/human-t-lym...
- daniloalmeida 4y agoI just read the title to get hopeful. Now I'm in the comments to be realistically disappointed.
- thewatcher23 4y ago
- deleted 4y ago[deleted]
- dossy 4y agoFinally, debugging human software - this is the inevitable future we've been waiting for.
- avetisk 4y agoAm I the only one who feels like a “directly editing on production server” déjà vu?
- noisy_boy 4y agoI guess they could/may have done UAT on a lab animal before the prod deployment?
- dfawcus 4y agoHow did they remove / destroy the T-cell killing T-cells before the the 2nd marrow transplant? Otherwise, it would seem they (the engineered T-cells) would hang around, and destroy the T-cells created by the marrow transplant.
- StockHuman 4y agoFor clarity’s sake, > “Base editing allows scientists to zoom to a precise part of the genetic code and then alter the molecular structure of just one base, converting it into another and changing the genetic instructions.” can be reduced to “gene editing.”