Anyone can mix chemicals in a test tube and claim it’s the cure for something. That’s the easy part. Proving it’s safe and effective, that’s what requires a lot of capital expenditure.
This statement is a drastic characterization, but you could say “half a dozen PhDs can form reasons to believe they may have found a cure for something”, and the paragraph would end the same.
Got my PhD from a lab that works on antibody drugs, they eventually even released one to the market.
I’d argue that our current system is broken. There’s no reliable metric of drug effectiveness in any of our pre-clinical models, and thus we end up going into clinical trials quite blind indeed. And more often than not, what drug gets into trials has more to do with ego and politics than actual scientific merit. And the folks involved in these types of activities are (IMO) the most unoriginal types I’ve ever seen.
There’s a lot we can do to improve our drug development process. It really doesn’t need to cost billions to bring a drug to the market. But the odds are stacked against anyone with a contrarian hypothesis and I just figured I’d save my sweat and leave this field instead.
It doesn’t (have to) cost billions to bring a (successful) drug to market.
And if you pick a single successful example that was discovered in academia, was spun out into a small focussed biotech, and was in a disease area that didn’t require large or multiple studies to make it to market, you’ll have your anecdote to prove your point.
Except… you’d be ignoring the costs of the 90% of drugs that fail in phase 1. You’d be ignoring the huge amount spent on discovery across the industry that never leads to a successful candidate.
Drug discovery and development is difficult because, for all of our clever science, it’s still essentially serendipitous and random. And we’ve not yet figured out how to make a production line out of something that’s random, try as we might. And it’s expensive because of the failures as well as the cost associated with success.
I am perfectly aware that this is the reason they blame for the insane costs - “we have to test so many drugs!”
Yet you seem to have assumed I’m oblivious to the reality when I’ve already pressed I’ve been in the deep end and am aware.
I’ve already given an explanation on why I don’t agree with “its still serendipitous and random” - the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science, even if they’re capable of doing so.
“90% of the drugs fail in phase I” - why are you telling me that when I’ve already given an explanation on why that is so - we don’t have good preclinical models that correlate with drug effectiveness - is it that you didn’t understand what I wrote, or are also neck deep in this cultural quagmire you refuse to acknowledge it?
Right. You can't just choose to run the successful clinical trials anymore than you can choose to only buy stocks that will go up on wall street. you have to run various clinical trials for a drug, and they fail. a lot. that very very expensive with no payoff. the successes have to be so phenomenally profitable that they cover the costs of all the failures. So real change would come from making the costs of those failures go away, without being able to cheat the system. The amount of medicine is believed to work, but is unpatentable, and thus doesn't have the profit motive to be pushed through clinical trials is a huge black badge on the American version of capitalism as being the best way we can organize society for the advancement of science and technology.
All of these things also apply to startups. And creates a VC groupthink of "portfolio theory" that necessitates huge (10,000x) returns, which costs the public a lot of viable small/medium enterprises that are not victims of the perverse incentives.
I wonder if the "optimal" theory is portfolio in this case, or if there is a new generation of VC/pharma investors who want a higher probability at a lower return.
> It doesn’t (have to) cost billions to bring a (successful) drug to market
> you’d be ignoring the costs of the 90% of drugs that fail in phase 1
It depends on what you call "bringing a drug to market".
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* Phase I costs little, around $1M during the trial, and involves only a small group of participants (one or two dozen people), so it's not multi-center and it is manageable by a few people at a biotech. The problem is that most phase I trials fail, but this is not an issue of cost, it's an issue of the way it is decided as explained by ramraj07, another commenter.
Too often it is started on a hunch without solid pre-clinical data, sometimes it is because the drug was tested and failed in another disease and the managers "pivoted" to a new disease because then it costs little to try again, sometimes it's just a "weird IP/financial trick" where you combine an existing drug and an unrelated drug. Then you know you have a relatively efficacious drug, no need for toxicity studies and you can patent it.
On the contrary, many trials could be done on drugs with good pre-clinical data, but that does not happen because it would be hard to patent.
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* A phase III costs around $25M for one or two hundred participants during the trial [0]. It lasts 6 months at most.
Some publications cite much higher numbers (~$1G), but this does not make sense as drugs are often developed by biotechs (startups, in other words) with only a few million in their pockets.
Another cost inflationary cause is subcontracting to CROs, as most biotechs do not have the manpower, knowledge and business connections to conduct the trial.
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* Once a drug receives commercialization authorization, a major company usually buys the rights and then starts the marketing phase. This starts with teaching doctors on how to prescribe and administer the drug. It means publishing articles in the mainstream medical press, inviting doctors to conferences and workshops, and paying medical sales representatives.
It is costly, this is probably where are spend the ~$500M but for me, this is not drug development costs, it's just marketing costs.
The current system is like Churchill's description of democracy: the worst system, except for all the others.
Biology is extremely complex. There's no substitute for actually trying things out on subjects in vivo. For many diseases we don't even know the cause (Alzheimer's for example). Drug companies have all the incentive in the world to improve the system to get better odds; it's not like they want drug discovery to be such a crapshoot.
It’s ironic that you brought Alzheimer’s as an example since it exactly proves your point - drug companies pushed a therapy that targets a highly questionable _symptom_ of the disease, even though every single step of the process gave negative or inconclusive results. It was all about ego and desperate attempts to make profits using iffy drug candidates.
And “biology is complex” is the type of truism I hinted at. You can always say that whenever you fail. Biology is complex and Alzheimer’s is the most complex of them all, to be sure, but I hope you’re aware of the. Alzheimer’s cabal allegations that the entire field was mutilated by a bunch of people into believing and pursuing the wrong hypotheses for decades.
A utility-maximizing drug discovery system would, I think, devote some effort to biological experimentation on healthy humans, giving them chemical probes to see how that affected their biology. As is, ethics requires we get this information accidentally, for example from that famous recreational drug chemist who gave himself Parkinson's Disease with a botched synthesis that made a highly neurotoxic chemical. And some of the information comes from drug trials. A useful drug is not the only value obtained from a drug trial -- each trial is also a test of a hypothesis about the mechanisms of a disease.
One of the books of the "Colossus" trilogy (about a computer that takes over the world) had the computer doing this sort of medical experimentation on randomly selected drafted subjects, with the idea of maximizing overall utility. It shows the problem with utility maximization as a goal, similar to the requirement that people give up a healthy kidney if someone else needs a transplant.
I'd agree with a lot of that in terms of both many drugs being 'discovered' in clinical trials as oppose to earlier ( a lot of it it about choosing the right patients and dose ), and the differences in mindsets between researchers and those often involved in the clinical trial side.
One of the things you've missed is the strong restrictions put on pharma in terms of promoting use of existing drugs beyond the existing approval ( which makes sense ), and the almost complete freedom Doctors have to do what they want - they can just decide to prescribe something off-label if they think it might help.
It can take a very long time for new ideas to become new products - and a lot of that is inertia ( nobody else is doing it ).
I think the restrictions on pharma, while doctors have more freedom is quite helpful. There are some problems here as well where this freedom has been abused, but overall that isn't a problem in my opinion.
Clinical trials are long and expensive, the medical advisory board wants compensation as well. But even startups can theoretically fund new therapies if they and their medial advisory boards get subsidies. It is a lot of risk though because for most drugs or medical devices, the real effectiveness can only be determined later in the trial itself.
Many thanks for saying what I suspected when looking at the research publications and clinical trials on neurodegenerative diseases. I was starting to think I was an unproductive perpetual malcontent.
For example, memantine has been tested 5 times in ALS. There even no pre-clinical studies that show any positive effect of memantine in animal models. This seems so bizarre to me.
Well to be fair, big pharma doesn't release preclinical results the same way that academia does. There might be no published work to support the hypothesis, but that doesn't mean they haven't done preclinical work.
I am not an expert (I am a retired R&D telecom engineer) but here is my take:
* As for cancer, there are several (many?) ALS variants. The first gene to be associated with ALS was SOD1 G93A allele in 1993. It stayed the only ALS gene known until 2006. That was a curse for research as ALS with SOD1 origin is less than 2% of total cases, and even for SOD1 there are dozens of mutations associated with ALS, some with 6 months of life expectancy, others with 20 years.
* Most commercial animal models are SOD1 G93A mice [0]. The G93A mutation represents roughly only 0.4-1.4% of all ALS cases worldwide, yet it is the most used animal model!
SOD1 G93A ALS models are also the less costly animal models.
* I think another important thing is that ALS starts often in hands (split hand phenomena) and targets skeletal muscles. But humans' nervous system for hands is very special, only shared with other upper primates. Other mammals like mice have an interneuron between the upper and lower motor neuron for hands. We do not, there is a direct connection between upper and lower motor neurons, reflecting the importance of manipulation for humans. Therefore for me, we can't prove with mice at pre-clinical stage, that a drug is efficacious or not (many drugs have some efficacy in animal models, but none in humans).
* Some publications pretend they can use individual cells, fishes, or nematodes as animal models. That's laughable, it's ignoring the importance of anatomy and physiology. We are complex animals, our hormones, our immune system, and our metabolism are important to understanding ALS. The proof of that is that ALS patients who have the best life expectancy have a BMI of 27.
* Other publications pretend to make their own animal models with some chemical, like BMAA, a neurotoxin found in certain cyanobacteria. Those publications smell bad behavior for me.
Is this a market that can be disrupted? It sounds if you know how to save a few billion and introduce more science based drugs, it’s ripe for an overtake.
Pointing the finger at regulation is misleading IMO. The regulations for bringing a drug to market are essentially quite simple: prove that it’s better than what currently exists.
What makes it difficult is the word “prove”
It turns out it’s obscenely hard to make a drug that’s good, and even harder to prove that it’s good.
> prove that it’s better than what currently exists.
So how do you do that ethically? How do you justify taking off something that you know works to some extent and try something completely new or worse placebo? ie don't you have to construct the trial in the context of existing treatments etc?
These are the kind of challenges that makes drug development slow - in the end you don't do one trial, but a series of trials, slowly building confidence and making the case.
Often that's what takes the time during the clinical phase.
Of course it would be much faster to go straight to a big trial that would show how well your treatment works in conditions optimal to it - however that kind of 'move-fast break-things' approach involves potentially breaking things which happen to be people.
Regulation just reflects the cautious 'first do no harm' philosophy.
Now let's be honest - big pharma will simultaneous complain about regulation and the cost of development, and at the same time know it creates barriers to entry - there is always some frustration about the slowest of regulatory authorities to adopt new methods - however you wouldn't want your regulatory to be gungho.
Just to be clear, most drug trials for anything where we have an effective treatment are not “new drug vs placebo”, but instead “new drug vs standard of care”. Thus the goal being to prove it’s better than what already exists.
Sure - it rather depends on how good the 'standard of care' is or how much consensus there is on what that should actually be.
If the standard of care is already good and you don't need a placebo - then you have another problem - you probably are going to have to do quite a big trial to get the stats to show a significant difference, and you are going to find it harder to persuade people to participate with an experimental treatment if there already is a fairly good treatment.
The whole point about the challenges with clinical trials is that it's not an intellectual exercise in designing the perfect experiment and 'just doing it'.
It's about persuading yourself, the regulators, the doctors and ultimately the patients that it's something you should try - and before you've done your first trial you don't have any human data to show it's safe and effective - all a bit chicken and egg - the solution is often to move slowly in stages.
This is particularly difficult for drugs that affect the brain, like MDMA for PTSD in veterans. What do you use as the control group for that, when patients and clinicians can tell that who got the real thing and who did not. I call this the bridge problem. In order to do science, you have to have a control group, but if I built a bridge across a ravine, we don't have to have cars drive off a cliff and fall into the ravine in order to scientifically prove that the bridge works and exists. We engineered a bridge and put it there and obviously if there was no bridge cars would just fall into the ravine so we don't need to test that the bridge exists. We design the bridge, we rate it up to a certain capacity, we don't test it until it fails, we simply prohibit really heavy trucks from driving on smaller bridges that can't take their weight.
We can't do any of that for drugs that affect emotions and consciousness because we're barely in the stone age of our understanding of the brain and the technology we have to affect it.
Purdue Pharma, fentanyl and doctors abrogating responsibility for patient safety is an example of 'go wild'.
On your second point - I'd agree that a lot of animal experiments are not that informative - but lets be clear 'clinical trials' are simply experiments on people.
I'm not sure I'd want to give Musk, Zuckerberg or Bezos free reign to experiment on desperate people in the medical space.
Depends on whether you treat people as just grist to your money making mill - or perhaps you think the ends justify the means?
Uber disrupted taxis because taxis were a sleazy experience, with dirty old cars, “broken” meters and rude drivers that tried to get you to pay extortionate prices if they knew you were in a pinch.
Stop trying to venerate the taxi industry, they’re horrible.
There's no hoping you can push through. The US Government has complete top-down control over the sale of prescription drugs in the US, from clinicals to approval to distribution & sale.
The sole reason Uber pulled off what they did, is there's no national authority governing taxi style services for all states and cities, it's a state and local effort. So Uber counted on navigating around zillions of slow local governments long enough to get big, and it worked very well. You can't do that in prescription drugs, the feds have a big hammer and can (and will) use it anytime they like.
Absolutely, and if you recall, even YC tried to get in on this idea.
Except they did the same mistake anyone who comes up with this disruption plan commits (including Google with Calico, or Zuck with CZI) - they recruit existing academics to do the disruption. Unfortunately this just fails miserably because they’re culturally corrupted to think of standard dogmas (like there can never be a single cure for cancer). I remember a time when other such dogmas existed (remember how it was considered impossible to de-differentiate somatic cells?).
The other mistake tech bros make in biology is they think they can make any cool idea work if they are smart enough. Because this is actually true in tech. But biology is restricted by laws of nature. If a drug doesn’t work, it can’t be made to work. There’s no room for wishful thinking.
Third mistake I see often is individual bias towards fields that they come from. Someone who has an RNA background will only try to use RNA to solve everything, likewise with antibodies, or imaging, etc. The current research funding system incentivizes such thinking and it becomes entrenched in anyone already in this field. There’s never a thought of “which is the exact technology and approach I should use to solve this problem independent of what I’m an expert at?” So a lot of projects are doomed from the start.
As long as you’re cognizant of these three facts, I think it’s very possible to disrupt this field.
Perhaps immune-based therapies like CAR-T are based on the premise that there are many cancerous cells in your body all the time, but your immune system deals with them, and it’s only when it fails to do so that you end up in the pathological state. So the “single cure” is the normally-functioning immune system?
That might be part of it. And yet sometimes people with normally-functioning immune systems also get cancer. So while that might be an effective treatment for some patients it's not going to be a universal cure.
There is no free lunch in biology. Augmenting the immune system to better attack cancer is going to cause other problems. It's so naive to think there is some simple solution that will improve on a billion years of evolution. I mean it's not impossible but realistically what are the odds?
There won't be any magic for cancer. It's just going to be slow grind to solve one hard problem after another.
There is no free lunch outside biology either. The problems that come with stronger immune systems may be more tractable or at least less unpleasant than cancer.
Also, you seem to be very pessimistic. Many interventions in the history of medicine, like washing hands or the first vaccine against smallpox, were almost "magical" in their efficiency: they addressed a lot of problems through a relatively trivial intervention.
It is likely that a lot of this low-hanging fruit has been picked up, but you insinuate that there isn't any low-hanging fruit to begin with, only an endless slog of attacking hard problems. That is way too negative.
Some mammal species like bats, whales and naked mole rats seem to be extremely unlikely to get cancer. Which may be an indication that a very efficient immune system can keep cancer in check indefinitely.
Some drugs not being able to make it into phase 1 clinical trials sounds like a functioning regulatory system to me. The bar isn't astronomically high for a phase 1. Like sure, you can't just do it in your garage like a web startup, but there are reasons for that. If anything, there are way too many drugs floating around in LDT right now, hence why those are being faded out.
There are companies trying to address this right? Have you seen biorce and other new ventures? Hopefully it can bring some innovation and reform to old processes.
That being said, we're talking about human lives either way so it needs to be thought through and avoid unintended disasters through lack of care.
This article is about a phase III RCT that the hospital managed to do without major industry capital injection. This truly was a major achievement (I have been involved in a phase III RCT myself). It was published in the New England recently: https://www.nejm.org/doi/full/10.1056/NEJMoa2402604
This trial is using an existing drug in a potentially novel way (before surgery as opposed to after surgery). I dont think it really lives up the original article title.
Argh, I'm so sorry, I linked to the wrong New England paper in my post above. (That is a different major achievement from the same institution, but the above was industry funded as others correctly pointed out).
The correct New England paper about this treatment is here:
This one is TIL therapy, where you basically take tumor-infiltrating lymphocyte from the patient, stimulate them ex vivo, and put them back.
The reason this is so impressive -- and highlighted by this article -- is that large phase III trials like this have now become so complicated due to various technical, financial, logistic, ethical, and above all regulatory challenges, that they are now mostly done by companies, or at least as joint ventures with companies (and often in jurisdictions with less of these issues, certainly not in the EU like this one). It is very, very impressive to pull off something like this as an academic institution (at least in Europe). What's more, the funding came from KWF (the Dutch cancer foundation), which is actually a public charity that mainly relies on donations.
I work in this field. Doing phase 3 clinical trials costs between $5,000 to $20,000 per patient per year.
This particular drug did a phase 3 with 423 patients for 2 years, so you're looking at a cost of $4M to $16M just for this one trial alone. Then add on top all the CMC (manufacturing) research that needs to happen, the regulatory filing work, etc, etc.
Unless someone has a few hundreds of millions sitting around, you aren't bringing a novel drug to market without external funding.
When hospitals are contracted to do work in a clinical trial setting they take their costs and multiply it by 10 (at least). This was done in house with in house resources. This hospital has its own pharmacy that can synthesize drugs and give it to the patients. The pharmacy probably charged just the material costs internally and not for the time.
All of those examples are at best pharmacies with compounding capabilities and/or sterile fill capability.
They aren't manufacturing any medicines in those pharmacies. They are buying final product and then preparing it for administration.
GLP and GMP certified don't mean they are manufacturing. GLP are lab best practices and GMP is manufacturing, but it covers a lot of ground, so a basic pharmacy can be GMP and all they do is prepare sterile product.
From the article translation it sounds like they have phase 3 data and submitted or are about to submit an application to the European Medicines Agency.
That means they have gone all the way to prove it’s safe and effective, and now have to convince the regulators.
Drug development faces a forecasting problem, not a measurement problem. In the same way that temperature, pressure, and humidity readings have been collected for centuries, it wasn’t until we developed models and computational power that accurate weather forecasting became possible.
Similarly, in drug development, we’ve long had access to extensive pre-clinical data and measurement tools. However, without predictive models to interpret this data, we will continue to struggle to forecast a drug’s safety and effectiveness in humans.
Interesting coincidence that for the last several decades, the rate of success of a drug advancing from a phase 1 clinical trial to approval is about 10%, which was just about how good we were at forecasting tomorrow’s weather between 1900-1950.
Does it? There is a billion people on this planet without adequate medical system - whose health is not considered worth investing into. If they get auto-diagnosed by app (zero-cost), they could volunteer for a free chemical trial (delivery of package), a application of said package (local nurse - not free) and a series of follow up scans + analysis.
The office behemoths involved are optional. Whats missing is tools to scan the body locally for cheap. The rest can be automated or distributed to people with an interest in success (high-level-analysis by the cure developers).
PS: Yes, its a deeply broken system- and its also on the point where the well-off blue blooded caste starts to blame the lower-classes for the misery inflicted upon them again- aka, if you are of low blood, you are obviously lazy because you spend so much time in bed being sick. Ideology can be a very effective tool to deactivate compassion.
Yeah, not doing human testing on poor folks without a choice is really "angelic" and "perfect". Very high bar to set, how could we possibly achieve such high standards of morality?
Step 1: Create economic conditions in which vast numbers of people can’t afford medical care
Step 2: Offer them the “choice” of possibly receiving care by being medical guinea pigs for those who created the situation that deprived them of medical care in the first place.
A non-help, because waiting for the idealized version of help - is still less worth than a "could-help" but under coercing economic conditions. A feel-good ideological purity is less preferable outcome then a tainted Samaritan.
Since these are cancer trials I'm assuming no test subjects get paid, and university PhDs research for free, like in every other field, so what necessarily has to be expensive about it?
If you have to pay 200 homeless to take your 0.0001% better than placebo antidepressants in the context of a huge corporation, and maybe redo the trial a few times, I can see how that gets expensive, but I don't see why it's a de facto rule.
But even the big trials it's weird how expensive people say they are. Most other products require a lot of high paid labor to produce, think of a video game studio for example, also without any guarantee it won't flop, and it certainly takes longer to develop than to do a clinical trial.
This is the most misinformed unknowing take in all of the comments.
You can’t just recruit “200 homeless” and have it pass research standards. The homeless population is the most difficult of all to track, maintain accurate records, and even recruit for that matter. You think the homeless just line up for novel drug trials and report back for updates on a strict schedule?
You need good candidates for the trial. You need them to follow up. You need admins to properly track them and ensure it’s at least mostly accurate. Even the best trial candidates won’t follow the protocol correctly.
I (not homeless!) was recently in a vaccine trial (Moderna's mRNA vaccine for RSV). The trial paid me $100 per office visit, just to show up. There were periodic phone checkups ($50) and a weekly status check through an app ($10). I did follow the protocol pretty damn well. There was an incentive to come in and get checked when symptoms occurred, including when I came down with COVID at one point after a trip to Europe.
If you genuinely think the medical and pharma industry don't exploit homeless and other marginalized populations out the wazoo as lab rats. They also only stopped doing it to prisioners when it was made illegal, because that's what they did before. Of course using them has a lot of practical problems, as you outline, other than the much bigger ethical issue.
You managed to miss the whole point of the comment though.
Which is, how is it possible that a multibillion dollar industry, exploiting both the test subjects AS WELL as the researchers in the form of practically free PhD candidates can still claim it's one of the most dificult / expensive endeavours? Where does the money go? When you look, it goes to the bureocrats and to the "bio-investors".
> Most other products require a lot of high paid labor to produce, think of a video game studio for example, also without any guarantee it won't flop, and it certainly takes longer to develop than to do a clinical trial.
You have to try really hard to make a video game no-one wants[0]. You might not recoup all your investment, but you won't sell zero copies. A drug can have all that money poured in, and nothing come of it.
I guess it's easier to casually mention you might not recoup your investment when it's not your $200mil but my point it's just that there's a lot of speculative technical research or cultural output that is very hard to predict outcome, some of these things also requiring high paid labor, and we don't have a huge thing around "omg if they don't all become billionnaires selling drugs nobody will make drugs because it's so hard and expensive", meanwhile people are going to space and so on.
More people are developing drugs than going to space. And going to space is valuable and makes billionaires, because it's a super high risk, high reward industry. If you want to make it into only a high risk industry, no one is going to space.
Of course it's valuable, I just gave you another example of a difficult industry with highly paid labor that doesn't need all the bullshit pharma needs like extra crazy patenting systems, protection from side effects and then still cry that without them there would be no drugs because the process is so expensive. You've misinterpreted every comment in this chain.
PhD candidates are paid salary in the Netherlands. Less of course than the senior trial researchers at pharma. I also would not assume there is no compensation for subjects as thats part of the medical-ethical process and not just ‘it helps the subject so no money’.
The €30k to €35k per year they make in this context approximates to free. Any normal company has to pay much more than that for less. A non-phd software engineer will get paid much more to change button colors for example. So that can't be the reason they are expensive and a PhD candidate is doing many other things than just helping to run trials.
> Any normal company has to pay much more than that for less
In most EU countries, the employee receives much less than what they cost the employer. In France, if an employee gets 30K euros, the employer has to provision ~45K Euros.
What's your point? I've lived in 3 different european countries, I'm familiar with fully loaded costs, I don't see how social security changes anything. By paying more for less I mean PhDs candidates are very cheap labor for what they bring to the table.
>Drawing up such a dossier is a profession in itself. An important detail: the EMA is asking for around €350,000 to assess the book.
This is a massive understatement of the regulatory hurdles at play. I have worked on dossiers that took 200 man-years at 400k per person. This is the development part of pharma R&D. The dossier might be a thousand pages submitted, but that can easily be 100,000+ pages on the backend.
There's a reason that even billion dollar companies crumble and fail under the documentation complexity.
My wife (MD) tells me that vaccine refers to anything that induces an immune response against a pathogen or disease. In this case the vaccine causes anti-EGFR antibody production
> In this case the vaccine causes anti-EGFR antibody production
English is not my native tongue so I have some problem to parse your sentence. I prefer the writing in the publication cited above [0] even if it's probably the same meaning:
"CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF"
It parses fine to me, but then I'm a native English speaker (and I don't claim to know whether its content is actually true). Strictly speaking, there should be a comma after "case", which may have helped you but is unusual unless you're writing something really formal.
Here's the sentence restructured:
... vaccine refers to anything that induces an immune response against a pathogen or disease. Here is how that definition applies in this case: the vaccine causes the immune system to produce anti-EGFR antibodies.
> Neither of the vaccines prevents cancer; rather, they are a kind of immunotherapy that prompts the body’s immune system to battle the disease in patients with non-small cell lung cancer.
Not 100% sure, because I've only heard about vaccines in preventative contexts before, but based on this description my guess would be that "anything that tells your immune system to Do Stuff" counts as a vaccine. Versus something like Herceptin, which also treats cancer, just with ready-made antibodies that were grown in a lab.
There are also immune modulators that aren't vaccines. Interferon, for example, or more recently the famous checkpoint inhibitors that take the brakes off immune attack of cancer cells.
If federal funds are used to develop a medication or vaccine, it must not be patentable, otherwise it is a corporate welfare giveaway trading lives and poverty for money.
AI will change everything. Especially disrupting pharma, Hollywood, law and lawyers, and medicine. Only question right now is who will win the race and be authoritative?
That's interesting. I was just reading about how high dose IV vitamin c can induce cell death in a wide variety of cancers, but somehow, despite this being known for decades, nobody has done rigorous research on it.
From what I can tell there are several things like this - that have promising anti cancer effects, that just don't really get that much attention because there's not a patent possible.
Really makes me think much less of medical science. Even if you couldn't patent any thing you'd think you could get fame and fortune by devising a useful therapy.
When my wife was alive, some people in her group tried it. There's not much evidence.
>> that have promising anti cancer effects
I don't know why people gravitate towards the "simple" remedies for cancer, or pose that money making is a barrier for these remedies. Remember, research costs money! DO the funding yourself if you think there's a miracle cure here. (hint: there's not.)
> That's interesting. I was just reading about how high dose IV vitamin c can induce cell death in a wide variety of cancers, but somehow, despite this being known for decades, nobody has done rigorous research on it.
Sigh. Vitamin C quackery again.
Vitamin C at high doses is cytotoxic, so it works against rapidly dividing cells. Cancer cells also preferentially concentrate vitamin C because they are under oxidative stress.
However, just like with most of other generally cytotoxic treatments, cancer cells quickly evolve resistance to it. And the overall toxicity of vitamin C makes it uninteresting as a treatment.
That's actually pretty interesting. Pancreatic cancer is one of the most aggressive cancers, and without many therapeutic options. Vitamin C is basically another drug to complement the existing standard-of-care drugs. Not a silver bullet, but definitely helpful.
Thanks for providing a plausible explanation. Do you know of any links (ideally peer- reviewed research) supporting the quick evolution of resistance to vitamin C? If not I'll google around.
That's a generic cancer resistance mechanism. That's why most of cancer treatments fail eventually, the cancer cells evolve to tolerate the levels of chemotherapy agents that are lethal to regular cells.
In the articles linked in this thread, large-dose vitamin C prolonged survival, but didn't clear the cancer. It's exactly what you'd expect from a chemo treatment.
Vitamin C in large doses becomes a pro-oxidant because it reduces metal ions, and they in turn then become catalysts for oxidative reactions or even directly oxidize stuff.
> Doctors want the best outcomes for themselves. If they’ve found an effective treatment that others are overlooking then they’ll seek to publish
However often the work required to prove something is effective is beyond a capacity of a single Doctor. Also in terms of wanting the best outcome for themselves - sometimes that involves not putting their career at risk by trying unproven treatments on patients ( you are focussing on the outcome when it works, not the more likely outcome and consequence of it not working ).
So sure 'miracle' cures are unlikely to lay undiscovered - but most improvements in medicine are incremental, rather than miraculous.
I don’t disagree with anything you’re saying. But it sounds like the parent said there’s a miracle treatment that the medical community is ignoring for lack of a financial incentive (and they then go on to mention a financial incentive?)
That's a ridiculous reading of my comment. Vitamin C induces cell death in a variety of cancers. That's what I wrote and it's not controversial, it's documented in dozens of studies. I went on to link an article by medical doctors and cancer experts (on cancer.gov) who explain how this works and also explicitly state that it's not being researched due to lack of financial incentive.
I can't stop you from refusing to read sources - but you should know that you're totally wrong here. I can, and have in this thread, cited multiple high quality sources.
Not read the Vitamin C literature but there is an obvious contradiction in what you say.
ie how can you have sometime which is both obviously beneficial - backed up by dozens of studies and yet complain about lack of research - if it's so clear then why do we need more research?
I also suspect doctors don't require FDA etc approval if they wanted to prescribe vitamen C - so what's stopping them? Lack of research? But I thought you knew?
Having said all that it is beyond all doubt true that commercial organisations can't afford to spend money on researching drugs with no prospect of return - however I wouldn't characterise that as evil big pharma blocking something - it's simply just that's it's not their role.
That role belongs to organisations either funded directly by the public ( charities ) or indirectly ( taxes ) for the greater good.
I’m not saying all doctors are perfect or even good, but surely there would be at least some occasions where a patient tries this supposedly very effective treatment, gets better, and the doctor is left curious.
No, not your personal experience, but the experiences of the others. For example look up Linus Pauling's writings on the subject, and the writings of his detractors. Spend atleast 50 hours on it.
> - Doctors want the best outcomes for their patients. They’ll use whatever treatment is most effective.
They will often do what make them the most money. Also remember that is doctor is subject to rules and regulations. He risks loosing his license if he does not toe the line. Your average medical student is about half a million dollars in debt when he/she graduates.
> - Doctors want the best outcomes for themselves. If they’ve found an effective treatment that others are overlooking then they’ll seek to publish.
Doctors do want the best outcomes for themselves, but if you manged to become a doctor, it means that you have never learned to question authority. Many doctors believe that what they are taught is Gospel. A doctor or a medical student who questions authority, will either not make it through medical college, or will have a license revoked.
>- Patients want the best outcomes for themselves. If there is an overlooked treatment then they’ll communicate it to their doctor.
A patient is generally ridiculed, or ignored by the doctor if he suggests something that he thinks is better.
It goes without saying that there are exceptions both among doctors and patients.
Either you are not from the USA, are trolling, or don't really know the U.S. medical system. Yes, maybe a few private practice doctors are greedy, but generally, doctors "in the system" don't personally generate more funds by doing things different, prescribing more drugs, etc. They are on salary. As far as other types of doctors (eg. chiropractors), they DEFINITELY drive home more money by prescribing more, requiring return visits, etc. But I call them doctors only by the loosest of definitions.
I am baffled by your second paragraph. It is just plainly illogical.
The third paragraph tells me that you ARE possibly from outside the USA, or that you have only seen a few doctors and they were proud or rude. We (personally) have seen private doctors, hospital doctors, country doctors, etc. over 50 years (at least 50-60 different ones). And the preponderance of our evidence shows you are either misinformed, or you are a patient who wants to self prescribe treatments that are medically unsound or 'fringe'. And, yes, those WILL be ignored by any average doctor. But then you could always fly to Mexico and get those useless treatments for low cost...
All I will say is this: We have different assessments of the situation. And yes I do live in US.
Some of what you point out is correct: Most doctors are on salary, but they are often (implicitly) required to bring in more business by the organization they work for. If they don't, they risk loosing their license/job on some pretext. In totality what I said overall hold true. These are statements from the renegade doctors themselves. Of course you are going to dismiss them as fringe, quacks etc.
Labeling someone is a fringe and easy way to dismiss them, it does not involve any work. What time have you spend listening to these fringe MDs? What time have you spent examining their patient outcomes/reports? Any yes, it goes without saying one has to be discerning even among the fringe MDs.
One must wonder if the therapy works if it's as trivial and simple as you say.
Rarely are these things straightforward and clear cut.
That being said, I recently broke my ankle, and found that the protocols still often include 6 weeks off it, despite modern evidence largely showing zero downsides (and some benefits, especially in terms of early recovery) to weight bearing immediately - Probably costing possibly billions of dollars in lost productivity and unnecessary PT every year.
I probably shouldn't get too high on my horse about random unexplored therapies - plenty of things in medicine that are just done some way because that's how it's always been done.
Medical trials to prove its safety in human subjects -- pretty essential -- is a lengthy, multi-stage process that is extremely expensive to carry out.
IIRC medical research is really expensive, hence money-seeking is to fund it within capitalism.
Also IIRC the rewards are oversized compared to the costs, but that doesn't change that the costs are also huge. Does mean I'm generally in favour of getting every government to quadruple public spending on this though. Whatever the current spend is, we can do more.
I don't see how something like high dose vitamin C IV is very expensive. I would assume a handful of oncologists could do the whole thing themselves. We get X patients a year, we randomly suggest the vitamin C IV to half, the half with vitamin C did better or worse by these metrics. Vitamin C is not expensive and they have to collect the outcome data for everyone involved anyway - so where is the expense coming from?
If it has benefits then more doctors will start to do it and more data will become available. If not, onto the next thing.
I'm not a physician and not in the medical field, but I would hazard a guess that a lot of the expense comes from just doing the work. What specific doctor will administer the vitamin C and monitor the patients? How do you isolate that the vitamin C dosage increase is effective? Who is going to create the vitamin C in the proper dosages? Who is going to write about it to make sure that it's legally approved? The human body is very sophisticated. The trials have to be done in a scientific way, following the established procedures of ethical medical treatment, peer reviewed, etc. And let's say you start giving vitamin C to some of these patients and they start having bad reactions and it makes their disease worse? Who covers the hospital stay? Who pays for their care?
Just looking at a few things there I'm guessing that's a few million dollars at the very least.. and even so you have to look at opportunity cost. Is this the best and most promising path of research for the physicians and researchers? Are there more promising compounds? Etc.
Deeply disappointed by the comments replying to this. I would reply to each individually, but feel like I'd get throttled by hackernews, so I'll just reply to everyone here.
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shepherdjerred writes that this is unlikely because doctors want what is best for their patients and would notice a cure were it available.
This is kind of true. Some doctors do know about and prescribe vitamin c with typical therapy. Here is an umbrella review of hundreds of such cases documenting positive results from using vitamin C.
The issue is not whether doctors will prescribe it - I expect anyone could ask their doctor for it. Vitamin C is safe, well tolerated, and shown to mitigate symptoms of chemotherapy. Doctors can and do prescribe it.
The issue is why an apparently promising therapy isn't getting better testing to establish whether or not it is effective despite it being known for decades.
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adamredwoods writes that while his wife was still alive people in her group tried it.
I'd love to know more - especially type of cancer and whether the vitamin c was administered orally (no effect expected) or by IV (depending on type of cancer possible effect expected) and at what dosage.
Here's a randomized controlled trial showing substantial benefits of high dose IV vitamin C for patients with advanced pancreatic cancer - they live longer, the cancer progresses slower, and their quality of life is generally better.
Adam goes on to suggest I should do the funding myself if I think there is a miracle cure here.
There are a couple ideas here. If I or a loved one ever develop cancer - then of course (depending on type of cancer) I would take high dose IV vitamin C, along with similar therapies that are well established as safe and potentially useful.
As far as "Doing the research myself" - honestly, I might. My path would be to construct a website compiling the research, explaining why people with cancer should try this, explaining how you can get your doctor to prescribe it to you (or, since you don't need a prescription to take vitamin c, how you can DIY), and have functionality to support people registering that they are a cancer patient who has decided to take vitamin c (or not) and give updates.
The hope with the website would be that it could compile enough raw data to become compelling to medical professionals.
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Panzer04 asks "if the therapy works if it's as trivial and simple as you say" - why isn't it being done?
Vitamin C is sometimes used. That's why we have hundreds of case studies and, in some cases, randomized controlled trials and other experiments documenting its use and efficacy.
My comments here aren't based on what I say or think - my original source was an article explaining the research on cancer.gov. Vitamin C (again: high dose and IV administered) is known to have potential benefits for cancer patients.
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cyberax says "Sigh. Vitamin C quackery again" and then offers a partial explanation of the mechanism for how vitamin C causes cell death in cancer cells - which is better explained in the link I originally provided.
cyberax then claims, without evidence, that cancer cells quickly evolve resistance to it. I don't believe there is any such evidence, having read several papers on this and never seeing it mentioned - nor, by my understanding, is it plausible that cancer cells could fundamentally change how they work to get immunity to this. Perhaps I'm wrong though and cyberax could supply some evidence.
I notice in the replies to cyberax pfdietz says "There is evidence that high doses of antioxidants can make cancer worse" - and then links 2 papers exploring the use of vitamin E as a cancer treatment. Vitamin E, despite sharing quite a few letters with Vitamin C, is a different thing.
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dennis_jeeves2 writes that "Linus Pauling (of the Nobel Laureate fame) working along with some physicians did do 'rigorous' research on it".
This is not correct and explained in the first few paragraphs of my original link. Linus Pauling used orally administered vitamin C which results in weaker blood concentrations and therefore less impact on cancer. The modern method uses IV administered high dose Vitamin C (which I was careful to write in my comment).
While Pauling's method shows little effect in randomized controlled trials, high dose IV Vitamin C does show benefits.
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insane_dreamer writes that "Medical trials to prove its safety in human subjects -- pretty essential -- is a lengthy, multi-stage process that is extremely expensive to carry out."
Pretty meaningless comment. The safety of vitamin C is already well established.
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pjc50 also cites Linus Pauling - which, again, is explained in the first couple paragraphs of the link I originally posted. High dose orally administered vitamin C doesn't work - there are limits on how much you can increase blood concentration through oral administration, so most of the high dose is lost.
That's why, as explained in my original comment/link, the modern protocol uses IV administered vitamin C.
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alphan0n quotes an XKCD strip saying "Bullets can induce cell death in a wide variety of cancers as well."
A bad comment because the tests I've been linked to have been in vivo, and my original link explains why this kills cancer cells and not healthy cells.
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That's my review of the comments. I would characterize them as exceptionally uninformed - which is odd. Why would people feel the need to comment on a subject they don't know about and simultaneously refuse to read the outline I originally linked which answers all the questions and criticisms posted here?
This is what I call a cogent, measured and robust rebuttal to several opposing viewpoints. I don't have much to add as a response of my own on the specifics but just want to mention that what your comment tacitly points out repeatedly is very common in the comments on this site, for many subjects and especially those that seem to provoke a certain popular hive-mind response:
People writing completely half-baked, often deeply ignorant opinions on complex, nuanced subjects out of mostly emotional disdain, but phrasing their responses in such a way as to easily fool someone who doesn't know said subject well that they at all know what they're talking about and are thus arguing rationally.
You may be interested in the VITALITY study out of China from 2022. 400+ people given FOLFOX + Avastin (standard of care, first line for colorectal cancer) vs FOLFOX + Avastin + high dose Vit C.
Thanks for sharing. This is an interesting, though somewhat disappointing, paper.
One thing I didn't get while reading it was the specific blood concentration achieved. I noticed they mentioned 12 rounds with 3 infusion days and 1.5g/kg. I'm assuming they injected that amount daily.
I noticed they injected over a period of 3 hours. To my knowledge the half life of vitamin c in blood is only 2 hours. I wonder if the concentration of vitamin c ever got sufficiently high to induce apoptosis.
At IV clinics near me they offer 75g bags of vitamin c on the website that are administered over an hour. I bet you could go back to back and get a higher concentration. In the same trip I wonder if you could get something fun - an IV clinic near me offers a nootropic, methylene blue, might charge you up for a day of studying cancer treatments.
One final idea I've had, not sure how useful it is to you, is that you can an at home ultrasound for a few thousand dollars. You should be able to use it to see your intestines and the tumors growing inside. You could use this to monitor your own treatment - i.e. take daily pictures and examine before and after vitamin c therapy, to see if it does anything.
Best of luck to you. If you want to bounce ideas for DIY cancer treatments off of anyone let me know and we can exchange emails.
>That's interesting. I was just reading about how high dose IV vitamin c can induce cell death in a wide variety of cancers, but somehow, despite this being known for decades, nobody has done rigorous research on it
Linus Pauling (of the Nobel Laureate fame) working along with some physicians did do 'rigorous' research on it, and I think had published a book on it. You should be able to check the Linus Pauling Institute and find literature on it. I probably did it over a decade back. Predictably he was ridiculed (IMO wrongfully) for it by people who did a very shoddy job of looking into the nuances.
The last I checked in the US the Riordan clinic offers Vit C for Cancer. There are probably several other practitioners who will not publicize that they treat patients for cancer (and several other chronic conditions) for obvious reasons.
This statement is a drastic characterization, but you could say “half a dozen PhDs can form reasons to believe they may have found a cure for something”, and the paragraph would end the same.
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