101–110 of 239 posts
CRISPR is an extremely overhyped approach which found a marketing engine via popular science. There is 1 FDA approved CRISPR therapy as compared to 7 for AAV and 7 for Lentivirus. Counting all viral vector therapies that have been approved, we’re sitting at 19 approved therapies versus 1 for CRISPR. I think CRISPR ideas in a lab are just an easy way into the mainstream press, but viral vector delivery is the real fut…
For the state of new cancer-killing drugs and bottlenecks getting them approved, see also the top few posts on https://www.writingruxandrabio.com/archive The post on AI and and cures for cancer is https://www.writingruxandrabio.com/p/a-response-to-dario-amo... .
Cancer treatments are really scary things. There are all sorts of impacts that we have no idea about when using drugs that fundamentally attack pieces of our own body. My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing drugs. Some of the side effects included: * Her heart stopping during a drug infusion. This happe…
Earlier quoted context omitted.
You're correct about CRISPR Cas9. The off-target affects are difficult to manage. The paper describes Cas12a2. This is a different mechanism with discovery origins in - of all things - agriculture. It does not attempt in any way to reprogram cells. It uses a guide protein to locate a specific mutation with exacting precision and, when it activates, unleashes total destruction of the cell. The implications of Cas12a2…
Have you written about your experience anywhere? It would be interesting to see how you approached the research sector as a layperson. Are there any plans to move to in vivo? Best of luck with your research!
I've come to terms with what's happening to my body and that I may not benefit from my efforts.
Background: ~3 years ago I was diagnosed with a very rare MPLW515L-driven blood cancer known as a myeloproliferative neoplasm. My hematopoietic stem cells (HSCs) acquired this mutation and they produce busted downstream products.
Most notably, one of those downstream products are hyper-lobulated megakaryocytes that spew inflammatory cytokines into my bone marrow and destroy the bone marrow niche over time. The destruction happens specifically because the inflammation mobilizes stromal cells and they erroneously produce scar tissue (fibrosis) all along the walls of the good, spongy marrow. There are other sources of damage but this is the one path most aligned to abbreviated survival and transformation into AML.
In effect, my bone marrow is rusting and very slowly failing. The failure could speed up with the acquisition of additional mutations or any other systemic inflammatory condition.
Anyway, 3 years ago my first retail hematologist told me "it's rare, you're fine, take aspirin and go home."
I couldn't accept that - this seemed bad. I decided that if I wanted to know the truth I needed to physically stand in front of the foremost expert in the world on the topic and ask them "what is the state-of-the-art?"
I came to this conclusion after about a year of reading all the most well-cited academic papers about AML, Myelofibrosis, and Essential Thrombocythemia. In particular, anything that mentioned MPL. There are virtually no papers mentioning MPL.
To put that in perspective: 500,000 patients in the US deal with the broad disease category. 5% of those are MPL, and 40% of those are the -K variant. So 10,000 people - which means anything targeting it would be well into orphan drug designation territory. I'd need to find a pretty niche researcher.
So, I laddered up the academic food chain using a little cash (donations), emails, airline tickets, and conference admission. ~2 years after my diagnosis I found myself in a closed-door session called the MPN Roundtable in Chicago with 100 of the foremost experts in the world. No cameras, no transcripts, just some of the greatest minds in the field earnestly debating the path forward to a cure.
I listen carefully to them, ask dumb questions, connect dots across research. I rehomed my care to an academic research hospital specializing in MPN research, and started funding research on the condition it includes my specific MPL mutation. Researchers happily oblige.
Cas12a2 was the keynote topic at this year's meeting and there was _very little_ dissent.
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I'm pretty optimistic. I think it's a threshold question where we need a number of basic technologies to all get over certain bars before the floodgates start to open. Over the past 1-2 decades there has been unbelievable progress at the basic technology level but most people are unimpressed because they haven't translated yet due to not individually being sufficient to cause an explosion of progress. IMO, we're star…
the public experiences biotechnology as decades of nothing, followed by years of everything once bottlenecks align
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I'm pretty optimistic. I think it's a threshold question where we need a number of basic technologies to all get over certain bars before the floodgates start to open. Over the past 1-2 decades there has been unbelievable progress at the basic technology level but most people are unimpressed because they haven't translated yet due to not individually being sufficient to cause an explosion of progress. IMO, we're star…
So we're waiting for the Apple of the medical world to take a bunch of preexisting things to be applied together in a way that makes the whole much more valuable than the pieces. Or we need all of the individual lions to come together to make the Voltron?
For the state of new cancer-killing drugs and bottlenecks getting them approved, see also the top few posts on https://www.writingruxandrabio.com/archive The post on AI and and cures for cancer is https://www.writingruxandrabio.com/p/a-response-to-dario-amo... .
Cancer treatments are really scary things. There are all sorts of impacts that we have no idea about when using drugs that fundamentally attack pieces of our own body. My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing drugs. Some of the side effects included: * Her heart stopping during a drug infusion. This happe…
We relax ‘do no harm’ quite a bit when the alternative is certain death. People like to try stuff in order to hang on to hope. Towards the end I became convinced that she made the wrong choice to do aggressive interventions. Quality of life was very bad.
On the other hand, she gave it her all trying to survive. Hopefully that was satisfying for her.
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CRISPR is foremost a research tool. Calling it "extremely overhyped" without restricting it medical treatment seems disingenuous. The CRISPR-Cas9 gene-editing tool was developed in 2012, so I don't find it surprising that merely 14 years later, there's only one approved treatment. From discovery to approval, drug development often takes 10-15 years, and often much longer for novel techniques. So I'd say it too early…
Why does it take 20 years? Except, of course, that it does not work nowhere near as well as it is being promoted - aka hyped. mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.
> mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.
And yet it took more than 30 years after the first mRNA experiments to develop a successful vaccine. Why it should be so much faster for CRISPR & Co?
What economic / political model would cause the society to prioritize this over adtech? It seems so unsettling that brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.
Then the money will flow.
So how do drugs like this get fast tracked so that people who are in danger of dying can exercise their freedom and opt into experimental treatments very easily
Because of this initial trials consume lots of medical staff to deal with the potential side effects. Normal side effects for cancer treatments include:
* Your gut lining dissolves, your shit leaks into your body cavity, and you get sepsis.
* Your heart stops during the infusion.
* Cumulative poisoning that nobody understands. (E.g. some agents have lifetime limits, and if you go beyond that, then you die. Guess how we found out.)
* Your immune system, and you get things like disseminated fungal infections.
This puts a limit on how many patients you can put into a trial. I'm under the impression that cancer trials are pretty much always full.
Earlier quoted context omitted.
Cancer treatments are really scary things. There are all sorts of impacts that we have no idea about when using drugs that fundamentally attack pieces of our own body. My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing drugs. Some of the side effects included: * Her heart stopping during a drug infusion. This happe…
The point of going slowly is that we make sure something works, even if it has these bad side affects. Do we try experimental drugs with worse effects so that we can find effective ones faster? There are brave souls out there who will participate in clinical trials or experimental exceptions
This makes some sense in terms of compassion and matching new experimental techniques with patients with no hope, but it skews the results highly negative because the patients are already very close to death's door. It does not provide an accurate signal for what the results would be if we gave them to less sick people.
I don't think any of this can be changed without large-scale social acceptance of greater risk in clinical trials and significant support from the government.