A vaccine for pancreatic cancer treatment? | Hacker News Reader

A vaccine for pancreatic cancer treatment?

science.org

178 pointsdcminter144 comments

You need to think of the cost of this kind of treatment at this stage as R&D. If it works thousands of people will benefit, have longer lives and contribute back more than the lifesaving treatment will cost.

we can justify having an option for people’s self preservation instincts without having to make up that fairy tale, more elderly humans will probably be a net negative

Please explain your "fairy tale" descriptor, I don't understand what your are trying to say here.

I think he’s implying that everyone dies, everyone will ultimately live through some life arc, and letting people survive a fatal illness invariably causes the average age of the population to rise and at some point the costs outweigh the benefits. So what’s the point of a longer arc of life?

My personal counterpoint: pancreatic cancers tend to strike anywhere in adulthood, so survival could yet lead to many years of productive life. Also, having grandparents is good, even if they’ve retired. Maybe especially if they’ve retired.

I think you are all in agreement; I interpreted the above comment as implying the exact opposite - don't make economic arguments that people saved will contribute more, because elderly people may not actually do that, but that doesn't mean it's not worth it on other grounds, precisely as you are doing here.

So yieldrcv is not arguing against the treatment, just saying a better argument should be made for it?

yes, jtlienwis is making an economic argument to justify the treatment. yieldcrv is arguing that the economic argument may be invalid (i.e. it's a "fairy tale" to believe the treatment will pay for itself through economic activity, but there are non-economic arguments to justify treatment (i.e. "we can justify having an option for people’s self preservation" - the treatment is an option for self-preservation and self-preservation can be justified on other grounds)

I don't think the top level comment was inherently about money, though. "Contribute back" can mean non-monetarily, or even be implying an indirect monetary gain from them contributing non-monetarily to their families.

Economics is devilishly difficult to really efficiently predict. More reliable lifespans and a larger elderly population can affect the total flow of money in ways nobody can properly imagine, positively or negatively.

From a younger perspective, the effect of eliminating cancers from the equation implies a lot. What is more expensive to the world, years of cancer treatments and palliative care to somebody in their 70s, or somebody living healthily through to 90 years old before dying from heart failure? What about the family cost of caring for a sick elderly relative?

I read yieldrcv as saying that people not dying is good on its own merit, so we don't need an economic argument. The survival instinct is enough justification on its own.

We may not need to contrive some reason why saving lives will actually save us money, and therefore saving lives is good.

If you need an economic reason to save lives, you will have to do incredible gymnastics to justify medical treatment for old people, for instance.

So don't do the acrobatics. We can just say that medicine is good, actually.

correct, I’m not arguing against treatment. fascinating how that stirred people here.

Protip:

Write longer posts in paragraph form that use positive language if you wish to successfully convey complex ideas.

Or don't and people will just think you're a shallow dick.

or as the OP calls it "not reading what he wrote."

Another point to indicate that the elderly do contribute back: if the elderly were a net negative while we evolved (which involved a lot more physical labor than typical work does today), there'd be selection pressures against the genes that confer longevity. And yet we've evolved in a way that the typical person will live long past the age of reproductive viability.

Concretely, humans aren't that much smarter than chimps. We did reach a point, however, where knowledge can be transferred and processed efficiently across individuals ("society"). The elderly play a net positive role in facilitating and maintaining these knowledge transfer networks, particularly to their kin.

An additional personal counterpoint: I know three very productive knowledge workers over the age of 70 who all say they'll stop working when they're dead.

My wife and I can only both work because our elderly parents take on childcare responsibility for us (because paid childcare is very often extremely expensive and very often very overcrowded), and our parents teach and enrich the lives of our children immeasurably.

Take care of the elderly. Build systems and habits of care and compassion that you want to be able to rely upon when you get old.

Not OP, but I think the gist was more about not needing to justify life-saving treatment in terms of cost-effectiveness over someone's life - people just want to live as long as possible, and that's OK in spite of the 'net negative' of increasing the aging population that it can result in.

I think the accuracy of that 'net negative' assumption is definitely not a given and that's what most folks are reacting to.

It seems like you're the negative one here. There is nothing inherently negative about living longer - just potential to have learned far more than others from experience. Any biological issues with existing for longer can have solutions, for which may be tackled better with more good minds put forth to the task.

nah, people just choose not to read what I wrote

but it is illuminating to see a passionate audience’s reading comprehension ability

it says treatments and extending life is desirable and doesn't need a reason and the reason presented would be a waste of energy to debate and quantify while doing so isnt even necessary, read it again until it makes sense that way

That, or what you said was being a jerk and you got called out on it.

and of the accuracy of the statement?

I downvoted you for this part, fwiw:

> more elderly humans will probably be a net negative

You haven't thought this through and need more life experience to understand why this is important. When the experience comes you will not enjoy it. You will be lesser for it but you will understand.

How do we get to the point where this therapy doesn’t require a team of scientists to manufacture? Is there a future where every cancer center has a DNA sequencer and mRNA synthesizer?

By doing research like this. Universities prove it's viable, then companys productionize it, sometimes with incentives from the government

Also, how do we get there without effectively creating bioweapons lab capable of immense damage in the wrong hands?

Googling the cost of DNA sequencing suggests that "human genome sequencing cost decreased from $1 million in 2007, to $1000 in 2014". That's pretty amazing.

It’s been 9.5 years since 2014. Wonder how far down it’s come since then.

The $1,000 'cost' was the actual lab cost previously, we're now at a point where consumers can buy WGS for under $400, so the equivalent supplies/materials cost must be well below that;

https://sequencing.com/products/purchase-kit

With the Novaseq X the cost is approximately $200 a genome. One the current challenges is storing the hundreds of gigabytes of data per genome.

1TB SD cards are a thing for 150USD now? Maybe two for physical redundancy and some Reed-Solomon stuff on each card?

I wonder if that would be cheaper in the long term than the typical NFS plus off site tape backups and/or cloud backup used by the places I have worked. I suspect it would become a logistical nightmare to store and keep track of thousands of SD cards.

I mean we still give DVDs for MRI results here...

Edit: I'd prefer my biostuff data to stay mine and not be saved in multitude cloud piñatas...

It'd be pretty amazing to have something like the optical storage jukeboxes but for SD cards. Expensive, but amazing.

I found the issue about storage quite interesting, went digging and I found this article: https://medium.com/precision-medicine/how-big-is-the-human-g...

Although the article does not mention it anywhere, I thought such repetitive byte sequences could be compressed quite well with simple file compression. Went digging again. I was wrong, compression of FASTQ genome sequence files IS a thing: https://en.wikipedia.org/wiki/FASTQ_format#Compression

It goes far beyond that.

By the time any real analysis is done on these data, they're extremely compressed via other file formats that extract the important signal. Alignment data is stored in BAM/CRAM [1], [2] formats, and variant data in VCF [3]

[1] https://en.wikipedia.org/wiki/Binary_Alignment_Map [2] https://en.wikipedia.org/wiki/CRAM_(file_format) [3] https://en.wikipedia.org/wiki/Variant_Call_Format

Is there a service that burns your results after giving them to you?

I don't need an AI eugenic death squad coming after me in 20 years.

What about an AI-dispatched procreation team coming to milk you for everything you’ve got?

https://nebula.org/whole-genome-sequencing-dna-test/

Depending on options like depth and quality, a hundred to 500 hundred dollars.

Don't forget "Your Insurance Will Totes Pay for It" CEOs like the Epi-pen guy.

500 hundred (50,000) may still be low.

Got mine done at 100x coverage (BGI genomics short read) for about 1000$ a couple years ago.

(The 1000$ figure you're citing is probably benchmarking against 30x coverage, so 1k for 100x is a pretty good price.)

Part of my research involves designing these cancer vaccines. There are different delivery mechanisms, but the need to synthesize medical-grade peptides or mRNA vaccines is one of the major drivers of cost. The sequencing costs are pretty minimal at this point, but analysis of that data by a team of experts is part of that cost as well. This is still largely bespoke stuff that can't quite be standardized because we're still figuring out the best approaches, but there are quite a lot of people working on it!

Pancreatic cancer terrifies me and keeps me up at night. It has virtually no symptoms until it’s too late. My friends dad was diagnosed with pancreatic cancer and died 6 weeks later.

Every time a celebrity dies of cancer I always hope that it’s not pancreatic but the numbers keep increasing. Patrick Swayze, Steve Jobs, Alex Trebek, Aretha Franklin, now Jerry Springer.

As someone with type 2 diabetes it’s something I worry about very often.

There are lots of other tumours that are just as deadly as pancreatic adenocarcinoma.

Steve Jobs died of a pancreatic neuroendocrine Tumour. It should not be grouped with pancreatic adenocarcinoma. The former is approximately 7-8% of all pancreatic tumors and has a much better prognosis of almost 90% at 5 years if it's caught early. In Jobs case it was. Pancreatic adenocarcinoma has a dismal prognosis of <10% at 5 years.

Edit. My Pancreatic cancer knowledge is a bit outdated but I recall type 2 diabetes being a risk factor for pancreatic cancer. I believe in some cases pancreatic cancer can cause diabetes because of the damage it does to the pancreas.

Yep. Ex-wife has neuroendocrine carcinoid tumors in her liver and pancreas, with the main tumor removed from her lung aroun 18-19 years of age.

Unless your tumors are functional(i.e. they are neuroendocrine tissue and can secrete hormones) or rapidly growing, it's not a very severe disease and there are treatments available. After 6 years of monitoring by a leading oncologist, she was told she would live a long life and die of something else.

That doesn't stop me from needing to pay her huge amounts of money for alimony, but it is what it is. Steve Jobs died because he was an idiot who tried quack therapies.

it's still very rare especially for young people. as someone with a degree of health anxiety, I sympathize, though.

Yeah, I'm right up there with you. My uncle died of pancreatic cancer about 15 years ago, and like you said, by the time he knew about it, it was way too late.

I wish there were easier ways to check for it early.

I lost my dad to PC just 2 months ago.

Same story: about 6 weeks from diagnosis to death. He was in otherwise good health for a 76 year old.

Fuck PC.

You can help here: https://pancan.org/

Sorry to hear that. It must have been terrible for him. My dad died because of PC about 8 years ago. It was just a bit over a month from the first scan to death. Makes me cry just remembering how awful those days were (for him, and for our family).

Alan Rickman was diagnosed in 2005 with prostate cancer. He died in 2016 from pancreatic cancer.

Matt Bencke, co-founder, CEO of Mighty AI, had pancreatic cancer. see https://finance.yahoo.com/news/change-day-170633700.html

and [TRIGGER WARNING - sad] https://www.wired.com/story/the-day-i-found-out-my-life-was-...

I love that this is advancing treatment; I was somewhat disappointed that apparently, you must HAVE cancer first in order to create the vaccine.

If there was a vaccine that prevented this before it happened, I would be in line.

They focus the immune system on the tumor by teaching it to identify some "neoantigens" in the tumor. Turns out that tumors express various strange proteins in their cell wall, I suppose because of the inherent genetic instability.

Anyone know why this can't be a silver bullet for most tumors? Like, a way to target an intrinsic characteristic of cancers that in theory could be very effective on most of them.. sounds too good to be true. So, what's the catch?

It's true that the whole problem of cancer therapy is "how do I target these cells over here, while avoiding the rest of your healthy cells, when they look mostly the same" And you're right that this is a really exciting and promising approach!

A partial list of the "catches" at present are

1) tumors are really good at down-regulating the immune system. If they weren't, they would have been cleared already

2) we're still fairly bad at knowing which of the many mutations in a tumor are going to be good neoantigens - that is, which ones the immune system will be good at recognizing and ramping up against

3) It's expensive to design personalized therapies for every patient, but may be necessary (see some of my other comments below)

4) Tumors aren't single cells, they're collections of them that can have different characteristics. Just like with other therapies, sometimes immunotherapies kill 99% of the tumor, but leave that 1% to come roaring back. (same idea as antibiotic resistance)

So yeah, lots of hurdles to overcome, but overall, I'm genuinely excited about the rapid progress we're making in the area of immunotherapies. It's impossible to overstate the effect that sustained research funding has had on the rate of advances in this field.

There are various strategies that cancer cells can use to evade the immune system. They can simply stop expressing the neoantigen. Also tumor cells can express proteins that suppress immune cells.

The genetic instability works both ways, the weird neoantigens sometimes get expressed but theres so much heterogeneity in some tumors that the immune resistant cells can get selected for very quickly.

Clumsy headline. It's a vaccine that inoculates against pancreatic cancer. It wouldn't inoculate against the treatment for pancreatic cancer, because why would anyone want to develop a vaccine that prevents a cancer treatment from working? Headline vaguely reminds me of Brain Candy, 1996.[1]

[1] https://www.youtube.com/watch?v=xAn-mdS-otE&t=0m15s

> after years of work, BioNTech says that they can get it down to less than $100,000/dose. I'm sure it can be driven down further, but this is highly unlikely to ever be cheap. They also got an anti-PD-L1 antibody and a four-component chemotherapy cocktail (those last two have already been tried in PDAC therapy without the vaccine dose, to unimpressive effect). The vaccine was administered across nine doses

Wow, $1mm to save a life. (This math works in the rich world.)

If it's your life, it might be worth it.

> it might be worth it

It’s absolutely worth it if you can afford it, which the rich world can. But personalised medicine forces us to face, in stark and dollarised terms, the inequity of healthcare access across the world.

Not to worry, it’ll be 1000x cheaper in 10 years.

> it’ll be 1000x cheaper in 10 years

Personalised medicine has high cost floors. The factors which would enable a triple order-of-magnitude reduction in its cost would sooner realise massive savings elsewhere, which means it’s unlikely a niche cancer treatment would be prioritised.

Then give it 50 years, have to start somewhere

My plan is to get it via a hospital which accepts public funds. This requires them (by law) to offer a payment plan that works for my income level.

I'm fine with """paying $1M dollars""" via a monthly bill of $50 or whatever until I die and the rest of the debt evaporates.

> requires them (by law) to offer a payment plan that works for my income level

Which is a rich-world perk. (That, to be clear, we absolutely should offer our people.)

Side note: do you have a link to more on this law? Currently dealing with an uninsured friend for whom we’re pooling resources for a medical treatment.

Certainly - here's the CFPB's page on it:

https://www.consumerfinance.gov/data-research/research-repor...

Note that this is for lower-income households

Is your friend in the US? If their income is low enough they would qualify for expanded Medicaid or ACA subsidy.

I always wonder if they take assets into account with this?

I wouldn't want to burden my family with the debt.

Especially if it might not ultimately work.

That said, I appreciate that costs will go down over time--even if only somewhat, if the author is correct.

If it doesn’t work you get your money back.

The worst case scenario is it works but you die in a car crash anyway.

Stand and deliver, your money or your life.

i happen to know that this is the lupin express!

Yeah, best to just not have developed it, or to wait until a more equitable country like Norway develops it. Then it will be fair.

Norway and Germany aren't that different I'd say.

Damn haven't thought of Adam Ant in years. Nice

It's cheaper than cancer, the loss of work and the tens if not hundreds of thousands of dollars spent on treatment, $100K is totally reasonalble.

personalized medicine of this form is one case where at least for now the cost makes obvious sense. You’re paying like 8 FTE PhDs to hand-build you a therapy from your own body. It’s not even close to automated.

but: if it doesn’t work, sometimes you get your money back! (novartis has never had to pay out)

https://www.fastcompany.com/40461214/how-novartis-is-defendi...

Maybe there's a possible job in helping them automate this?

safe bet people are working real hard on it; it’s just like, cell cultures are fussy and biology doesn’t care about you, so it’s very much an uphill fight.

one dream job of mine would possibly be working on the data side of this though

That won't lower costs, only increase profits

That's bullshit, because it can do both. Increasing the amount that can be made by 10x could both reduce unit costs by 8.5x and increase unit profit by 1.5x. Get outta here with your pessimistic external-locus-of-control communism

Automation has a tendency to do both increase profits and lower costs. This is because as the price decreases the market increases. There's 500,000 new cases of pancreatic cancer a year in the world. How many of them do you think will have access to a One Million Dollar treatment?

This is not to mention how much of this tech could be shared with other treatments for other diseases.

That might be a thousand times more expensive. It’s not software, it’s biological processes that are hard to automate.

There are lots of folks working on problems surrounding automation and reproducibility to enable science in this space. One such effort that I contribute to is [pVACtools](https://pvactools.readthedocs.io/en/latest/), (there are others as well). We do have a small team of developers who work in concert with scientists and clinicians to build these tools.

How would I apply for a job like that? I’ve always had a strong interest in bio and computers (and physics, and psychology, and…)

I don’t know if 8 PhDs is entirely accurate, biotech teams are a thing and usually there are a good mix of non-PhD technicians who support an individual project.

I image it like ML teams in tech - the PhDs are building the models and the non-PhD are exposing the model, jockeying the data, etc.

You're right that there are a variety of folks working on these things, both in academia and industry, but it's more complicated than "PhDs do this, others do that". It comes down to knowledge, ability, and experience, and the best research groups grab onto that wherever they can and slot people into the roles that are right for them.

Seems more like politics where I'm at. My company won't let you work on the models without a PhD. Literally all I would do as an "ML Developer" would be cleaning and moving data plus APIs to provide input/output.

I’m glad there are options in development! Let’s hope there are parts of this that can be reduced in cost with scale

> $100,000/dose

I really wish I could see a transparent breakdown of that number. How much of that is the amortized cost of R&D, marketing costs, salaries for the executives and management, etc? How much of it is actual production costs, and what do those look like (raw materials, equipment, labor)? How much of it is profit? What else could be baked into that price?

Does anybody here know of any publicly available reports that detail cost breakdowns for pharmaceuticals like this?

I think you are probably right that this is some sort of Hollywood style accounting.

That's not far off from the rates for producing custom order medical-grade peptides and/or mRNA vaccines, coupled with the expertise needed to design, administer, and monitor them. It's certainly not a case where they produce it for 100 dollars and sell it for 100k. The market for this stuff is beginning to develop, and I hope that we'll see new innovative companies begin to produce them more cheaply.

This is absolutely not surprising. When I was doing my MSc, I'd often use up about 5000$ just in single-use plastic consumables in a day. There were zero profit incentives related to my project, it was pure fundamental research. Wet labs are insanely expensive to run.

Do you think it will be that price forever?

For as long as the biotech company can keep it there

I'm as critical of pharma pricing as the next guy, but this really is a case where you're getting a custom vaccine design just for you, and the profit margins probably aren't very high. I certainly do think it'll come down eventually, but there are lots of factors slowing that down.

Presumably even less in countries with socialized medicine where the government buys in bulk.

In this case it looks like probably not, at least in the short term, because it's all extremely personalized.

Perhaps at some point, a 'generic' neoantigen profile vaccine can be produced that is somewhat effective. How much variance can there be amongst 500,000 cancer patients?

There is a lot of great work going on thinking about this very problem. One common theory goes like this:

There are lots of tumor "driver mutations" that are causative and occur in lots and lots of patients. These would make great targets for a vaccine like this, in theory.

But - Tumors have to evade the immune system in order to gain a foothold. (We have all had many cancerous cells that were cleared away without anyone ever knowing!). If a mutation is particularly good at activating the immune system, it's unlikely to survive long enough to cause cancer. So one of the features that a mutation has to have in order to become a driver is that it's bad at being recognized by the immune system! That means the most common mutations that we'd like to target with cheap, mass-produced vaccines may not work very well.

There's some evidence on both sides at this point, with lots more data being collected, but it's certainly something that us folks researching the problem are keenly following!

The Hep-B vaccine used to cost $100K and now it's about $4000 (in the US where we get screwed). Honestly a $20K vaccine that would protect me from the big killer cancers would be a check I'd write in a second and I'm not a rich man.

Isn't hep-b integrated in the penta/hexa-valent doses for kids? (expensive compared to the old boring individual or tetravalent ones, but subsidized in France at least, so I guess French social security has more negociation power than little me? right?).

This isn't a preventative vaccine like that. It's something that has to be developed after you have cancer to target your tumor's specific mutational profile. So mass production (just churning out the same thing in bulk) isn't really an option! Costs will probably come down eventually, but it's going to take research, technology development, and hard work to make that happen.

Is it possible that there is only a relative handful of these profiles and we can have these vaccines already on hand for each of them?

Huh.

I had Twinrix (Hep A+B combo vaccine) at least twice because I'd forgotten I'd had it, and only found out later when I put my medical notes into a spreadsheet.

Just had to ask and the NHS did it for free.

Maybe they meant the Hep-C treatment?

Perhaps, but (as an outsider) I can easily believe the USA charges $4k for stuff the NHS will hand out free without asking if you've already had it.

Napkin math: the typical estimate for the statistical economic value of a human life (in the US) is $1M-$10M. So if each vaccine course can be targeted such that it saves a life with 25% likelihood, it's likely a net positive. Future iterations and new technologies based on it would hopefully drive the cost down further.

In the US it was on the order of 10M$, not adjusted for inflation, a decade or two ago (source: publicly available DOT documents).

To be more precise, the rich world can afford to spend money on developing such treatments.

It is entirely possible that 30 years from now, the same therapy will cost 1000 USD per dose, with most of the expensive stuff automated away.

Yeah, every normal US people is paying 10x for the basic medical treatment compared to other developed countries in order to fund this treatment for the super rich.

BioNTech is German, not US.

"Eschew flamebait. Avoid generic tangents."

https://news.ycombinator.com/newsguidelines.html

Vaccine seems like the wrong term as I think of it as preventative. Perhaps there is no precise term for a treatment that uses the immune system to fight an existing disease in the body

There are two types of vaccines: prophylactic (to prevent or ameliorate the effects of a future infection by a pathogen) and therapeutic (to fight a disease that has already occurred, such as cancer).

Rabies vaccine is also given after infection.

Tetanus can be too

That is post-exposure antibodies which kill the virus, plus the vaccine.

Perhaps there is no precise term for a treatment that uses the immune system to fight an existing disease in the body

Immunotherapy?

Regardless, vaccine is indeed the word used in the field. You should just update your definition.

So the Covid MRNA vaccine requires many boosters and doesn’t provide protection for long.

What are the odds this will be the same?

In this specific case boosters are likely unnecessary because pancreatic cancer isn’t contagious and if it works all the persons current cancer cells are dead.

As to the need for boosters, it’s more a question what benefit a booster provides vs its risks and costs. Frequent measles boosters aren’t recommended in the US in large part because the disease is already rare here. COVID is however still very common which changes the exposure risks part of the equation.

This is also why vaccine boosters for measles are recommended when you travel to specific countries. https://wwwnc.cdc.gov/travel/page/travel-vaccines

Covid MRNA vaccines short lived effect was more to do with the characteristics of the virus and the way our immune systems generally function, IMO.

I'd be fine with spending €100 per year on each of ten vaccines that each need annual boosting, if that reduced by merely 10% my risks from each of the top ten likely causes of death and QALY reduction at whatever my age is in any given year of my life.

This isn't that cheap, not yet at least, but I think "what's the cost?" is a much more important question than "does it need boosters?"

I am not entirely sure why you are getting downvoted. It says right in the study

> Vaccine-expanded T cells were durable, persisting up to 2 years despite post-vaccination mFOLFIRINOX treatment

So yes, that seems to suggest you may have to keep going back every couple years for more boosters.

Call me crazy but I am of a firm belief that the cause of almost all cancers is viral in nature. It is a combination of a viral infection and a failure of the innate immune response to stop the virus. I believe we are stopping these viruses all the time in our daily life and it is only when our immune system is under duress (ex: age, smoking, chemical, etc.) that it fails to stop these viruses.

I'm not a virologist, or a medical practitioner, just someone who's interested casually in the subject of cancer and viruses.

This is not true. Some cancers are caused by viruses. Many oncogenes were initially discovered in viruses. But the majority of tumors are definitely not caused by viruses.

This was a hypothesis in the field for a number of years, and has been disproven. If you want a good overview of the history of cancer, I recommend “The Emperor of All Maladies” by Siddhartha Mukherjee.

Thanks, I'll check that out. Bought it on Kindle and will give it a read.

where we agree:

* not all cancers are caused by viruses.

* only some cancers are caused by viruses.

where we disagree:

* that science has proven the majority of tumors are definitely not caused by viruses.

could you kindly share a few of the studies disproving the majority case? in particular, i'm interested in the sample size and diversity powering these refutations.

to clarify, i'm not saying you're wrong. simply seeking to learn more.

my research has uncovered misleading conclusions based on studies with flawed methodology/logic. for example, this study [0] states, "epstein-barr virus plays no role in the tumorigenesis of small-cell carcinoma of the lung." based on a sample size of 23.

[0] https://pubmed.ncbi.nlm.nih.gov/14752524

You're going to want to start with the PCAWG consortium, who looked very closely at viral involvement across a host of cancers. Their numbers:

Cohort: 2,658 cancers across 38 tumor types Findings: Overall, 23 virus genera were detected across 356 patients with cancer (13%)

You can read all of the details here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076016/

I'm not saying that there aren't other mechanisms (sustained inflammation, etc) that might contribute to the aetiology of some other cancers, even without clear viral integrations, but we can state pretty strongly that many cancers are not directly caused by cancer.

thank you for sharing, will dig into this.

Sure, a 2020 study from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, looking for viral evidence in thousands of tumor genomes and transcriptomes[0]. Part of a massive, cross-institutional effort.

"Searching large pan-cancer genome and whole-transcriptome datasets enabled the identification of a high percentage of virus-associated cases (16%)".

Far from majority.

[0] https://www.nature.com/articles/s41588-019-0558-9

thanks for sharing. will dig into the methods.

based on ebv studies i have read (happy to share if you want), some papers use flawed methodologies for viral detection (e.g., checking for limited set of viral proteins).

to reiterate, we mostly agree, except i adopt a more restrained stance: the conclusion supported by science is that viral causation is provable in some cancers -- but not a majority.

which is a subtle, but crucial difference, from concluding that viruses do not cause a majority of cancers (much higher bar IMO).

for instance, past studies may have used flawed detection methods or extrapolated from unrepresentative samples like the lung cancer study shared earlier.

Sure, absence of evidence is not evidence of absence. But these PCAWG results have been discussed to death since they were published, and its pretty sound science.

You could also take the bottom-up approach of asking what DOES cause certain cancers. That's a whole other discussion.

Considering all this, if you still have doubts that "viruses do not cause the majority of cancers", I think you will likely be skeptical about pretty much all of biology.

i do think flawed studies are more common than people realize (e.g., lung cancer one linked above, ebv ones referenced).

i wouldn’t say i’m skeptical.

more willing to say “unsure” until the underlying methods and logic have been validated.

based on personal anecdotes only, scientists seem too rushed and overworked, forced by our broken system to cite without verifying logic or methods first.

to be honest, part of me hopes you are right and all the virus science is sound. it would save me a lot of time and money.

thanks for sharing your thoughts and providing resources to check out.

This is not really controversial. The majority of cancers in humans are not caused by viruses.

Second that, its a great book.

I'm a biochemist with a biomedical background. Everything that follows is a simplification, but it's truthy.

We understand pretty well what causes cancer in "otherwise healthy individuals" (eg.: assuming there aren't particularly bad genes involved... which is a whole thing on its own), it's not a big mystery. We know with total certainty that "cancer in general" is not usually caused by viruses, although some viruses are notorious for causing cancer.

What causes cancer is whatever causes tissue injury and inflammation, with some probability. This is why smoking causes cancer, why drinking alcohol causes cancer, why sunburns cause cancer, why ionizing radiation causes cancer... The more chronic or frequent the injury/inflammation, the more the odds stack up against you. Viruses that cause chronic inflammation cause cancer.

(There are also a bunch of things that directly cause mutations including some of the above, and those cause cancer too, with some probability, if they overwhelm error-correction mechanisms.)

Is it specifically inflammation or rapid cell regeneration which inflammation can cause?

In short, both, via a variety of mechanisms.

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