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First U.S. use of CRISPR to directly target cancer seeks approval (statnews.com)
206 points by ChefboyOG on June 13, 2019 | hide | past | favorite | 46 comments

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.

There's a LOT of effort going into cancer research. It's just cancer is not one thing. It's not like HIV. There are many many different types of cancers, and they are currently treated and diagnosed differently. They are expressed differently. Many cancers are extremely treatable now thanks to research (testicular cancer >98% survival rate), while others are not at all (<1% for pancreatic).

main problem with pancreatic cancer is lack of detection. Virtually no symptoms or markers until very late stage.

That's true, though the five year survival rate is still pretty dismal (34%) if they find the pancreatic cancer early, when it is still localized.


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.

I used to work in Cancer research. Saying “I want to cure cancer” is analogous to saying “I want to cure viruses,” not “I want to cure HIV”.

Having said that, progress has been made for certain types of cancer, just not as fast as anyone would like.

I agree 100% about prioritizing prevention. At the very least, governments could stop subsidizing/mandating the production and use of carcinogens!

For example, California used to mandate extremely high levels of known-carcinogenic flame retardants for furniture, and the result was new forms of cancer that only occur in California. (This was fixed a few years ago, but used furniture, or anything upholstered is crazy-risky.)

It took years for the state senate to act, despite strong scientific evidence. The flame retardant industry had the strongest lobby, but everyone else, from Ikea (and, separately, their factory workers), to fire fighters, to environmental groups were for lifting the mandate.

Hundreds, if not thousands, of analogous stories are playing out today.

Just yesterday, I read that general mills (and also nature valley) use roundup as a pre-harvest desiccant to kill and dry out oats before harvest, leading to ridiculously high levels of glyphosate in kids cereal (like Cheerios) and “healthy” granola bars.

Best practice for non-organic farming is to apply herbicides well before harvest so they can break down / wash off the final product. Spraying during harvest should be criminalized!

Desiccation is terrifying. Glyphosate is fat soluble so it has a chance of getting into seeds that will be the basis for vegetable oils.

Organic canola oil is probably a good idea now that the practice is widespread. Non fatty items are less problematic.

There has been a TON of research into cancer. Pretty much every big Pharma company spends a lot of money on it and if you look where VC money is going for start-ups, over half is in the oncology space.

If anything, some question if that should be dialed back and spent in other disease areas.

> The sheer amount of unregulated, harmful practices that has come to define our current lifestyle is abominable.

As someone who is tired of hectic urban life, I certainly concur with the above statement. It is an extremely disturbing trend. I know I don’t want to turn a blind eye to what is happening, but at the same time I don’t know what else I can do except being stoic.

>I know I don’t want to turn a blind eye to what is happening, but at the same time I don’t know what else I can do except being stoic.

I've been thinking about that for a long time, and still do. I reckon the best option is having a mindful and critical attitude while doing our best to come up with alternatives. Persevering in having a constructive mindset always goes a long way.

> I'm really frustrated with how little effort has been devoted to cancer research in such a long period of time

It may seem slow but for a while now most of research budgets and acquisitions are for oncology. And still now most pharma companies are engaging a majority of their r and d spending into oncology.

I may sound cynical, but I wonder if pharma companies would ever be interested in search for a cure for a malignancy or other deadly disease. Wouldn’t it be harming their own interests?

Why would a profit-driven company turn away curing the second leading cause of death? It's a market whose yearly demand is going to be in the tens to hundreds of thousands in the US alone, even if you're only going to be on the drug for a short amount of time.

Hep-C is now curable. Wasn't 10 years ago.

You're wrong.

An insulin company will not cure diabetes - but a startup looking to disrupt them will. Circle of life/business, in pharma like elsewhere.

If that were true no pharma company would ever develop vaccines. Yet it is not the case.

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.

Mostly with you, but... birth-control pills?

Can't speak for parent, but birth control pills artificially boost estrogen levels.

My wife just emerged from a multiyear battle with aggressive HER2/ER/PR positive breast cancer after taking decades of birth control pills.

Correlation is not causation, but NHS are extremely strict about chemically induced menopause via Tamoxifen now, to suppress her natural estrogen production.

With the exception of cancers where checkpoint inhibitor and engineered T cells work (i.e. 60% of melanomas) I agree that others, like solid tumor which are hard to reach and slow to detect, haven’t had the same attention.

checkpoint inhibitors were pioneered in solid tumors.

Checkpoint inhibitors (PD-1 hunters like keytruda) and CAR-T therapies are brand new, extremely exciting, they work, and they’re shockingly new.

I'd be curious to know what percent of cancer-related grant proposals to nih or nsf are being rejected due to bugetary restrictions.

A lot.

The National Cancer Institute funds about 11% of new R01s, which is the mechanism that funds most academic labs. Their payline is among the lowest of the NIH’s Institutes, though to some extent this might be because they are one of the largest institutes and people chase the money: you could probably find a home for any proposal at two or three institutes. More data here: https://report.nih.gov/success_rates/Success_ByIC.cfm

With a few exceptions, the NSF doesn’t fund things that directly address diseases, so it’s hard to find a number for cancer specifically. Nevertheless, the overall payline is pretty similar.

That said, I’d argue that the solution is not (just) more money, but massive changes in how we fund and organize research too.

Do you have concrete ideas about what other strategy we should use to fund and organize research?

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.

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.

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).

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.


> 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?"

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.

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.

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.

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/2018/02/21/5853365...

This is such a great idea. Much more direct than trying to train the immune system with a vaccine.

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.


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.

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

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).

Messing with transcription factors? Sounds a bit like shotgun debugging

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.

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.

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.

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.

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.

That makes sense! Thanks for the insight!

Isn't cancer mainly 'just' uncontrolled cell growth? From your description I was thinking of viruses.

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