Has Carl June Found a Key to Fighting Cancer?
phillymag.com
phillymag.com
For those who don't want to read through the lengthy human interest story wrapping the news here, from a quick read I gathered they're basically modifying T-Cells:
> In their natural state, T cells usually aren’t able to kill tumor cells, partly because they can’t latch on strongly enough. But June was fascinated by scientific papers showing it was possible to change this. A few researchers—first an Israeli named Zelig Eshhar in the ’80s, then other investigators around the world—had discovered that you could force a T cell to stick to a tumor cell and kill it. To pull this off, you built an “engineered T cell”—a T cell never before seen in nature. You altered the T cell’s genetic blueprint by injecting a new gene into the cell. The new gene would tell it to build a new molecular limb. The limb, called a “chimeric antigen receptor,” would sit partly inside the cell and partly outside, and it could send signals either in or out. One signal it could send was: kill. Another was: replicate.
> June loved this approach. So elegant. Put the immune system on steroids. What if you could train the body to fight cancer on its own? What if, instead of replacing a patient’s immune system (as in a bone-marrow transplant) or pumping him full of poison (chemo), you could just borrow some cells, tweak them, and infuse them back into the patient? In theory, the engineered cells would stay alive in the blood, replenishing themselves, killing any tumors that recurred. It occurred to June that one infusion could last a lifetime.
It seems this research has been going on for 10+ years. How many people have died because of the glacial regulatory pace of cancer research?
It seems this research has been going on for 10+ years. How many people have died because of the glacial regulatory pace of cancer research?
One of these statements explains the other - verifying research is safe with trials takes time, it's not something that should be rushed.
We have the regulations we do because we caused harm in the past. They didn't spring fully formed from the minds of regulators, they happened because researchers killed and maimed people by not doing the necessary verification before human trials began.
I'll start believing this once you show that a "reputation system" (don't these already exist?) actually does anything to stop quacks from peddling diluted water as a cure-all.
If you relied on reputation alone to regulate the medical market, feel-good snake oil treatments would prosper at the expense of legitimate medical advancement.
The same "reputation systems" that saved us from the million miracle-cures sold on late night tv, from "green coffee diet" to "Oxygenated water"?
Do you honestly believe that people with a fatal illness, dealing with people offering a "cure" for that fatal illness, are free to make a rational choice?
Do nothing. Make your time. You are going to die pretty soon. Try to make yourself and your family comfortable.
Take what treatment your insurer allows. You die more slowly, with a small chance of remission, but also with a small chance that the treatment will kill you sooner. Maybe your won't consume your family's assets.
Take what treatment you can afford. Die even more slowly (probably), with a small (but probably better) chance of remission, but also with a small chance that the treatment will kill you sooner. You may consume all your assets, and or incur huge debt/bankrupt your family.
Get yourself into an experimental trial. There is some chance that you will be in the control group (if one is used) in which case, you will die. There is some chance to suffer some adverse reaction in which case, you may be removed from the trial, back to step 1. There is some chance to suffer some catastrophic adverse reaction, in which case you will die, and if you are unlucky the death will be worse than death by cancer/chemo. There is some remote chance the treatment will work as good or marginally better than existing treatments, you win, congratulations. There is some very extremely remote chance the treatment will work amazingly (as in fairy-tale amazing) well, epic win. It may cost little or nothing, but who cares what it cost, you're alive and you just helped save the lives of many others.
People whine about how slow the pace of research is, but that's not because clinical trials are so slow - it's because most drugs fail. The vast majority of drugs that work in animal models get bounced in Phase 1 (when they show unacceptable toxicity in humans so great it can't be dosed) or Phase 2 (where it just shows no effectiveness in humans at all - not even some level of effectiveness that fails in cost/benefit analysis). this is the problem with people complaining "But every delay kills people!"
No. You don't know going in whether it's going to work - that's why you're doing a trial. And from a naive position, the probability is pretty clear that it's very unlikely it's going to work. There's absolutely no reason to think any particular drug is worthwhile, and every to worry about its side-effects. With a sample size of 12, this one may yet became a last-ditch drug with toxicities worse than chem/rad. We don't know yet. Using this is an example of over-cautiousness is ridiculous.
Additionally, the slowest part here wasn't the clinical science - it was the basic science. Gene therapy has been a failure for decades, and we've been repeatedly going at it to try and get it to work. It's not as though this is the first clinical trial for a gene therapy: it's just one of the first to be worth anything.
Glybera is a gene therapy which has been approved for medical use.
Yes, it has been approved, but only very recently, in late 2012. It is also the first such drug that has been approved (and to date, the only one), and this happened under 'exceptional circumstances'. The usual standard of supporting evidence was forgone because the disease it treats is so rare. The company is explicitly required to supply further supporting evidence, and the rules for its use are very strict.[1]
eg:
A new prostate cancer drug trial has been so successful doctors have decided to stop it early. Medics at London's Royal Marsden Hospital were testing a powerful alpha radiation drug on 461 people while another group of the same number were being treated with a dummy drug. Patients taking the new drug experienced less pain, side effects and lived longer. Researchers were so astounded with the results they decided to stop the trial and started treating all 922 patients taking part in the study because they said it would be unethical not to.
http://www.dailymail.co.uk/health/article-2041301/Prostate-c...
You have to be extremely careful about this, otherwise you can end up with much worse significance than simple analysis would suggest (and then that kills people).
In this case, it's not even the regulatory environment. As the article mentions, the treatment is as fantastically expensive as it is fantastic. A lot of the skepticism isn't that it can't work, but that it might be too expensive to be viable.
The kind of trade offs re: safety vs "getting things done" comes up quite a bit. The key optimism I pulled out of it was that cancer research is progressing exponentially, but this is harder to see because the general public only sees through the lens of "cured/not cured". But I think most cancer researchers would say "progress is being made, and faster than ever before with increasing velocity". Then again, the cure was around the corner in the 70s.
But yeah, cancer is bad news and a disease many of us will be forced to face in our lifetimes...
Most areas of research are simply not mature enough to move forward at the exponential pace that computer technology leaped forward into our society. What is required? More hard work!
The title is: "Has Carl June Found a Key to Fighting Cancer?"
Fighting cancer and curing it are hugely different. Yes, this is a human interest story that outlines the success of a particular patient using a particular method, it's great, but it seems disingenuous to use the title that is here.
> The title is: "Has Carl June Found a Key to Fighting Cancer?"
And here we see the other side of not being able to change (editorialize) titles. I can see both sides of the argument, but I think this example forms a good reason to disallow giving articles different titles.
Does it actually matter? It's not like you can clean your body completely of pathogenic viruses and bacteria either.
So in the long run, rather than sitting around waiting for the tumors to weigh 7 pounds because every other current treatment failed as per the article examples, this might be an early treatment option. Certainly "processing" 7 pounds of dead tumor is going to be hard on your biochemistry. But years or months earlier in the progress of the disease, a couple grams of dead tissue, maybe even less, eh, no big deal.
Gangrene of a leg, today, well that's gonna be a tough one. Minor infection of a toenail six months earlier, eh, no problemo.
The interesting part of the human interest puff piece is they ran several trials and of course only the successes get any commentary. Curious what happened with the failures, ranging from no effect to maybe the treatment killed them. Although the journalist thinks what happened to the most successful patient will define the future of this treatment, in the real world, what happened to those folks where it didn't work is likely to define the future. Compared to the amount of ink spilled about baseball, not much was mentioned, which sounds like good news...
The other idea I have is MDs are not overly dumb, so if its possible for natural or artificial kidneys to filter the bad stuff to the outside while keeping the good stuff inside, they would probably just absolutely flood the patient with IV fluid. The original article was very detailed about the experience; this didn't make the article, so I don't think they were doing it.
Please do not use the word "cure" when talking about cancer. The article's submitter invented this headline -- the article doesn't support it in any way. In fact, it says this: "Scientists don’t talk about “curing” cancer. A cure is the hope so great, so seemingly out of reach, that it must never be invoked. They’ve built a wall around the word."
And well they might.
If I get cancer I want a cure. If anybody in my family gets cancer I want them cured.
This wariness of using the word cure is just because of the idiots in this world. People who can't understand percentages and possibilities. People who believe that anecdotes prove a point.
HN doesn't have to conform to that silliness.
Not using the word cure is the rational response to the fact that there is no cure for cancer -- there is only remission.
> If I get cancer I want a cure. If anybody in my family gets cancer I want them cured.
You just changed the subject. Wanting a cure, and having a cure, are obviously different topics.
> This wariness of using the word cure is just because of the idiots in this world.
So scientists, and medical ethicists, are idiots. Good for you -- I prefer it when a person reveals his ignorance without beating around the bush.
> People who believe that anecdotes prove a point.
It is you who are relying on anecdotes. Scientists evaluate evidence, and the evidence says there is no cure. Anyone who claims otherwise is deluding himself.
I was responding to the fact that people seem scared to hope. There is no cure yet (probably). But to not hope that somebody has just found a cure is just silly.
But unlike a lot of diseases where we can usually pretty much guarantee that we wiped it out, we can usually do no such thing with cancer.
A cure has a vastly stronger expectation.
The day remission is something that happens in so few cases it's a rounding error, we can start talking about it being a cure.
No, it merely has to be about as reliable as a "cure for pneumonia". It doesn't have to exceed that limit and approach a "cure for a laceration" or a "cure for appendicitis" both of which basically don't spontaneously reappear (assuming surgical removal of appendix)
You're overlooking something very important -- we know what causes pneumonia, but we don't know what causes cancer. When we treat pneumonia, we're treating a cause. When we treat cancer, we're treating a symptom.
The reason for "remission not cure" is because we don't have any way to definitively say there won't be a recurrence, and this will remain true until we fully understand cancer.
This will happen. It may take the tools provided by molecular nanotechnology, and a generation of oncological research, but it will. To accept that cancer is special is irrational deathism.
You clearly haven't decided what position you're taking. A cure is not remission in 95% of cases. A cure is a cure, with no chance of a recurrence if there is no further exposure to the responsible pathogen. Take malaria, for example -- do you think malaria victims experience spontaneous recurrences, far from the anopheles mosquito and its hitchhiker, plasmodium falciparum?
> To accept that cancer is special is irrational deathism.
In modern scientific medicine, anything we don't understand is special and deserves our attention. We don't understand cancer and it's deadly. Therefore it's special for perfectly scientific reasons.
To call cancer just another disease is simply irrational -- and dangerous thinking.
So it goes with even the most advanced, futuristic cancer treatments. There will always be cases where the treatment kills the patient, or fails to affect the disease in any way. It will be the job of medical research to make those rare cases rarer.
And by the way, if cancer is not a disease, then what the heck is it?
Both false and unrelated to the present topic.
> Does the flu shot provide benefit 100% of the time? No: in some cases it's killed people.
And cure still means cure.
> So it goes with even the most advanced, futuristic cancer treatments.
And none of them offers a cure.
> And by the way, if cancer is not a disease, then what the heck is it?
You must first locate where I claimed that cancer is not a disease.
I see where you're coming from, but the differences between pneumonia and cancer aren't as great as you think.
If you have pneumonia, they give you an antibiotic. They can test for the presence of the pathogen, but they can't ever say you are "cured". Take c. difficile infections. They treat the symptoms, but you can "relapse".
In cancer you can test for the presence of the mutated cells (minimum residual disease). Often what they'll do is count the mutated cells from a biopsy, and with this current treatment, the number of remaining cells is less than the lower limit of detection.
Of course, this is only true in the liquid cancers. Solid tumor cancers don't work the same way.
That is an effect, not a cause. Your claim is like saying that auto accidents are caused by cars getting too close together. That's only a symptom of an underlying cause.
> I see where you're coming from, but the differences between pneumonia and cancer aren't as great as you think.
We know what causes pneumonia. Because of this, we can suggest behaviors that will prevent it before the fact, we can identify it unambiguously, and we can cure it after the fact. This isn't true about cancer -- we don't know what causes it, therefore we cannot proactively prevent it, we can't identify it very efficiently (there are always false negatives and positives) and we cannot cure it. There's no comparison.
> They can test for the presence of the pathogen, but they can't ever say you are "cured".
Of course they can. In infectious disease, they can test for the presence of the causative pathogen -- no pathogen, no disease. In cancer, to do this, we would first need to identify the cause. But we don't know the cause, we only know the effect.
> In cancer you can test for the presence of the mutated cells (minimum residual disease).
This is like saying we can test for the presence of a car crash by measuring bent bumpers and inflated airbags. That measures effects, not causes.
> Often what they'll do is count the mutated cells from a biopsy, and with this current treatment, the number of remaining cells is less than the lower limit of detection.
Counting abnormal cells only reveals how little we know. We detect cancer by detecting abnormal cell growth. We measure progress in symptomatic treatment by counting abnormal cells. We declare a remission by making that count approach zero using agents that kill abnormal cells. There are any number of cases where the count of cancerous cells was below the limit of detection, but still caused a recurrence.
In 1979, smallpox was declared to have been globally eradicated. How? By identifying the responsible pathogen, then systematically destroying it everywhere it appeared. This was only possible because we know what caused smallpox, and we could treat the cause, not the symptoms. Because of what we knew, we were able to call smallpox permanently cured.
We cannot do this with cancer, because we don't know enough about how it works. All we can do is tell people to avoid risky behaviors, behaviors that, for often-unclear reasons, increase one's chance to contract this disease. Then, once the disease's symptoms appear, we have crude methods to deal with it, like trying to kill the cell masses that represent the disease's primary symptom.
Based on a comparison with other diseases, cancer treatment is unbelievably primitive -- it would be like treating a finger infection by cutting off a person's hand. And guess what? Before germ theory and before antibiotics, that was the treatment -- cut off the infected limb before the infection spread through the body.
The reason we don't tell people they're cured of cancer is because of science. In science, there are no fairy tales -- everything depends on evidence. And we don't have the evidence science requires to declare cancer cured.
Its OK to have a near religious belief in unusual definitions; its just useless when trying to talk to the general public, especially if they operate under the logical opposite of your personal definition. I believe this is a "Startup Lesson". Redefine words for yourself and folks in your affinity group all you want, but trying it with the general public is likely not to work very well.
For example of what the general public defines as a cure, examine the 1850-whatever cholera outbreak in London. The prevailing theory of "bad air" was pretty much blown away when statistical analysis pointed to one particular water well, which had its handle removed. That outbreak of cholera was successfully cured, without understanding much other than it had nothing to do with air and apparently revolved around the use of one particular water well.
It's not at all unconventional -- in fact, it is the most common definition, and cancer doesn't meet it, which is why medical ethicists insist on "remission".
The point is that, given the public's common understanding of the word "cure", i.e. that after treatment a particular disease has been eradicated, cancer cannot be cured, only placed in remission.
> That outbreak of cholera was successfully cured ...
Now you're desperately trying to inject this word into sentences where it has no place. The cholera outbreak was stopped, but the problem of identifying the cause remained, just as with cancer. Therefore, no cure -- it's the wrong word.
Another example would be to respond to a Plague outbreak by moving to the country, as Newton did. Is that a cure? Of course not -- it's a survival strategy, but it has no depth or insight.
Remember that Semmelweiss was unable to get doctors to wash their hands, even though he had excellent statistical support for his suggestion, because he couldn't explain why his suggestion worked.
> Its OK to have a near religious belief in unusual definitions; its just useless when trying to talk to the general public, especially if they operate under the logical opposite of your personal definition.
Thank you for making the exact point I have been trying to make, to wit: in fairness we must pay attention to the public's understanding of this quotidian term. Most diseases that have treatments in modern medicine, also have cures. Cancer doesn't. To claim otherwise is to violate medical ethics.
Pneumonia is not cured by testing for the presence of the pathogen. You are given antibiotics (chemotherapy) and when you get better, you are cured. In fact, many people who never get pneumonia with test positive for the pathogen. Why don't they get sick? We don't know.
My take away at the end of the book was that for all of the "war on cancer" hyperbole going back to the 50s, up until the mid-90s, we just didn't know enough about cancer to really be fighting it. I feel a lot more optimistic about the next 50 years of cancer research than the previous 50.
http://www.amazon.com/Emperor-All-Maladies-Biography-Cancer/... (non-affliate link)
Did a quarter of the patients just die?
I got bored with it so I went and found this, from Carl June himself:
http://www.youtube.com/watch?feature=player_detailpage&v=1sA...
The added benefit here is that the antibodies can be produced en masse and delivered as a drug rather than reprogramming the person's T-cells.
edit: for an example rather than a hypothetical, see polio
edit2: also, if this works, an enormous chunk of doctors, medical researchers, and scientists are going to drop whatever they're doing and frantically attempt to apply this technique to every cancer one can think of