Reading articles like this reminds me how little we know. Before we had a theory of germs (viruses and bacteria), we believed that sickness came from phlogiston. This did a decent job of explaining how disease spread, but didn't do a very good job of how explaining how it originated. If you were sick, you were enveloped in a cloud of invisible nastiness, and staying away was a good way to remain healthy. Certain things, like carcasses and stinky puddles, were thought to be carriers of phlogiston.
The thing that I find most interesting about the theory of phlogiston is how close it is. It's almost right, but humanity needed a fundamental shift in the way we thought about disease to actually start to solve the problems of disease. I feel like cancer is the modern form of phlogiston. It's close, but cancer is slippery enough that it's got to be wrong; I want to be clear, though, that the theory may still be useful.
Now, perhaps breaking down cancer into it's distinct forms (breast cancer, skin cancer, etc.) will get us there - this approach may have led us to the discovery af germs as different types of phlogiston. But I can't help but think that our mental model for cancer is wrong.
I don't think it's our model of 'cancer' that is wrong - we can recreate it in lab, we know quite a bit about it, even though it's extraordinarily disingenuous to call it a single thing.
Our model for developing drugs is stuck. Small molecules were unbelievably (literally) useful against invaders of our bodies. They can discriminate and interupt vital processes of one biology without effecting another's biology. This made the development of small molecule drugs in the 20th century against bacteria, fungi, and even some viruses verry effective. Cancer is you. There is no biologically 'other' one can use as a discriminant that doesn't apply equally somewhere else in you. Socially we've built an entire pharmaceutical industry whose talents are focused entirely on a methodology for finding 'interruptors' of foreign disease. And again, that is not cancer.
Look the the new CAR-T therapies for cures to cancer. They disrupt the pharmaceutical industry's methodologies in thier development. There can't be a tox test or a primate study. They are fundamentally customizable, cheap, and curative, but they are the injection of genetically modified immune cells containing invented and designed protein tools - not small molecules. There is literally not yet a vocabulary to distinguish these new therapies from the drugs of the 20th century. They are as distinct from drugs as vaccines - but have literally only been tested on a few hundred people, being approved by the FDA only in the past two months.
The primer is that a CAR is an engineered protein that is inserted into your immune cells with a kind of 'cellular surgery'. Here proteins are the actual machines that accomplish life's tasks within a cell - where small molecules are the fuel, building blocks, and modulators of proteins. From inside the linked reddit post, here's a kind of diagram of the designed CAR from a high-level abstraction layer: https://serotiny.bio/notes/proteins/car19/
These proteins can have additive functions in precisely the way small molecules cannot; they can provide new capabilities to cells - whereas small molecule drugs are almost only capable of disrupting an existing capability.
The reason these engineered proteins are useful now is that we now have not only have arbitrary read access to genomic information, but with recent advances, we also have arbitrary (and economical) write access to DNA that is long enough to encode an entire protein's blueprint (chemical DNA synthesis). And with those capabilities we've rapidly developed the first novel biological tools to deliver that DNA in a biological way (CRISPR). Until recently we could read an entire blueprint, but we could only make copy/paste changes. We can now design them de novo - and to interesting effect. There is a gene for human hemoglobin out there that is v1.1 - it is actually an intelligent improvement upon our existing human 1.0 version of hemoglobin, in that it can not only not aggregate in a way that causes sickle cell disease, but it can disaggregate mal-formed hemoglobin, inhibiting the disease. We can now start to program those new tools into biology in well-designed ways.
Further, with a decade of read-access to life's various genomes, we have started to actually be able to inspect well-written code in other organisms for inspiration.
And combining a few of these technologies, we can now start to think about attacking cancer and the like from first principles rather than simply repurposing our small-molecule hammer... And in their preliminary results they have performed remarkably well.
If I understand this correctly (my biomedical engineering undergrad finally coming to use!):
1. Cancer cells present antigens that are specific to cancer cells and do not occur in healthy cells.
2. CRISPR allows us to genetically engineer someone's existing T cells to target those antigens.
3. When re-introduced, these T-cells target the cancer cells and destroy the tumor.
4. Because they are T-cells, they're effectively distributed through blood to the entire body and are able to affect cancerous cells that may be too small to observe or detect.
5. They become inactive and stowaway in the lymphatic system but if the cancer comes out of remission, an "immunity" type response brings them back.
This is amazing. This feels like science fiction from my childhood and the life changing possibilities unlocked by CRISPR that I was taught in my undergrad classes.
Models can always be improved, but there's a lot of evidence that the current model is on the right path.
I suspect two likely futures for general cancer 'cures'. Both require sequencing the cancer of the patient and then determining which set of growth related mutations it has (thankfully there aren't an infinite amount).
Then you either give them a tailored drug cocktail that either inhibits or activates those specific areas (that you need to take forever like herceptin) or you use something like CRISPR to edit the code directly. Both of these methods require sequencing to be inexpensive and 'precision' medicine. Both methods are also vulnerable to future mutations.
The theory of demonic possession was also not too far off the current germ theory of disease, it just turns out the demons are really little and there are lots of them.
Phlogiston theory was about fire and how it works. It was disproved with the discovery of oxygen and its role in fire. I don't know of any connection between this and theories of disease. I heard the old suspected cause of diseases like plague was so called "bad air" among other things.
Its not so much that we know little, but that we keep making assumptions based on limited data. Assumptions that end up hampering our efforts in the long run.
You may also be interested in Dr. Bruce Ame’s “Triage Theory of Nutrtion” - basically, chronic deficiencies of nutrients makes your body prioritize short term survival over long term, and these trade offs bear consequences in the long run:
Ames had become well aware that many micronutrient (vitamins and minerals) deficiencies are associated with chromosome breaks and cancer in humans, such deficiencies having caused DNA damage in rodents or human cells in culture. It had also been established that chromosomal breaks cause early aging. As a result Professor Ames proposed that DNA damage and late onset disease are consequences of a ‘triage allocation mechanism’ developed during evolution to cope with periods of micronutrient shortage.
Do I understand it correctly? If you can block the nerves then the tumour losses one of its ways to interact with the host's organism. It does intuitively make sense.
That's my understanding too. I'm shocked it never occured to me that the nervous system had its role in tumors even though we see nerves around and these are still .. well cells.
The thing that I find most interesting about the theory of phlogiston is how close it is. It's almost right, but humanity needed a fundamental shift in the way we thought about disease to actually start to solve the problems of disease. I feel like cancer is the modern form of phlogiston. It's close, but cancer is slippery enough that it's got to be wrong; I want to be clear, though, that the theory may still be useful.
Now, perhaps breaking down cancer into it's distinct forms (breast cancer, skin cancer, etc.) will get us there - this approach may have led us to the discovery af germs as different types of phlogiston. But I can't help but think that our mental model for cancer is wrong.
Our model for developing drugs is stuck. Small molecules were unbelievably (literally) useful against invaders of our bodies. They can discriminate and interupt vital processes of one biology without effecting another's biology. This made the development of small molecule drugs in the 20th century against bacteria, fungi, and even some viruses verry effective. Cancer is you. There is no biologically 'other' one can use as a discriminant that doesn't apply equally somewhere else in you. Socially we've built an entire pharmaceutical industry whose talents are focused entirely on a methodology for finding 'interruptors' of foreign disease. And again, that is not cancer.
Look the the new CAR-T therapies for cures to cancer. They disrupt the pharmaceutical industry's methodologies in thier development. There can't be a tox test or a primate study. They are fundamentally customizable, cheap, and curative, but they are the injection of genetically modified immune cells containing invented and designed protein tools - not small molecules. There is literally not yet a vocabulary to distinguish these new therapies from the drugs of the 20th century. They are as distinct from drugs as vaccines - but have literally only been tested on a few hundred people, being approved by the FDA only in the past two months.
The first-level Google results are all PR-heavy so I'm hoping you can share something more granular and explanatory.
https://www.reddit.com/r/medicine/comments/6x6q6v/fda_approv...
https://www.reddit.com/r/Futurology/comments/6wqtc8/mass_gen...
The primer is that a CAR is an engineered protein that is inserted into your immune cells with a kind of 'cellular surgery'. Here proteins are the actual machines that accomplish life's tasks within a cell - where small molecules are the fuel, building blocks, and modulators of proteins. From inside the linked reddit post, here's a kind of diagram of the designed CAR from a high-level abstraction layer: https://serotiny.bio/notes/proteins/car19/
These proteins can have additive functions in precisely the way small molecules cannot; they can provide new capabilities to cells - whereas small molecule drugs are almost only capable of disrupting an existing capability.
The reason these engineered proteins are useful now is that we now have not only have arbitrary read access to genomic information, but with recent advances, we also have arbitrary (and economical) write access to DNA that is long enough to encode an entire protein's blueprint (chemical DNA synthesis). And with those capabilities we've rapidly developed the first novel biological tools to deliver that DNA in a biological way (CRISPR). Until recently we could read an entire blueprint, but we could only make copy/paste changes. We can now design them de novo - and to interesting effect. There is a gene for human hemoglobin out there that is v1.1 - it is actually an intelligent improvement upon our existing human 1.0 version of hemoglobin, in that it can not only not aggregate in a way that causes sickle cell disease, but it can disaggregate mal-formed hemoglobin, inhibiting the disease. We can now start to program those new tools into biology in well-designed ways.
Further, with a decade of read-access to life's various genomes, we have started to actually be able to inspect well-written code in other organisms for inspiration.
And combining a few of these technologies, we can now start to think about attacking cancer and the like from first principles rather than simply repurposing our small-molecule hammer... And in their preliminary results they have performed remarkably well.
Some more discussion:
http://www.onclive.com/web-exclusives/expert-discusses-appro...
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/u...
If I understand this correctly (my biomedical engineering undergrad finally coming to use!):
1. Cancer cells present antigens that are specific to cancer cells and do not occur in healthy cells.
2. CRISPR allows us to genetically engineer someone's existing T cells to target those antigens.
3. When re-introduced, these T-cells target the cancer cells and destroy the tumor.
4. Because they are T-cells, they're effectively distributed through blood to the entire body and are able to affect cancerous cells that may be too small to observe or detect.
5. They become inactive and stowaway in the lymphatic system but if the cancer comes out of remission, an "immunity" type response brings them back.
This is amazing. This feels like science fiction from my childhood and the life changing possibilities unlocked by CRISPR that I was taught in my undergrad classes.
His other book (The Gene) is also great.
The current model allows drugs like Herceptin to be found that target the actual mechanism of action of a specific cancer (rather than just targeting the growth more generally)(https://www.amazon.com/Her-2-Making-Herceptin-Revolutionary-...).
Models can always be improved, but there's a lot of evidence that the current model is on the right path.
I suspect two likely futures for general cancer 'cures'. Both require sequencing the cancer of the patient and then determining which set of growth related mutations it has (thankfully there aren't an infinite amount).
Then you either give them a tailored drug cocktail that either inhibits or activates those specific areas (that you need to take forever like herceptin) or you use something like CRISPR to edit the code directly. Both of these methods require sequencing to be inexpensive and 'precision' medicine. Both methods are also vulnerable to future mutations.
(Also Phlogiston was attempting to explain fire, not sickness: https://en.wikipedia.org/wiki/Phlogiston_theory)
This is not far away from backing up the link between long term stress and cancer.
Ames had become well aware that many micronutrient (vitamins and minerals) deficiencies are associated with chromosome breaks and cancer in humans, such deficiencies having caused DNA damage in rodents or human cells in culture. It had also been established that chromosomal breaks cause early aging. As a result Professor Ames proposed that DNA damage and late onset disease are consequences of a ‘triage allocation mechanism’ developed during evolution to cope with periods of micronutrient shortage.
Thus some forms are more related to lifestyle, while others more related to genetic inheritance.