h a l f b a k e r yVeni, vidi, teenie weenie yellow polka dot bikini.
add, search, annotate, link, view, overview, recent, by name, random
news, help, about, links, report a problem
browse anonymously,
or get an account
and write.
register,
|
|
|
Removing cancer cells from the tumor environment and implanting them into normal tissue tends to halt their growth [1]. So can doing the reverse help? Can grafting **normal** tissue **into** tumors help reprogram and stop the cancer?
Let's say you have an inoperable tumor - it cannot be completely
removed. Instead of removing the tumor completely, can adjacent normal tissue be grafted into the tumor with the aim of encouraging cancer cells to become normal?
The underlying theory is this: groups of cells are a type of collective intelligence. Cells control and influence each other. They do this by sending messages to all adjacent cells using gap junctions and ion channels, forming a local 'bioelectric network'. Bioelectrical signals are the informational glue that binds multicellular structures together [4][5].
Cancer represents a break in this multicellular contract. Cancer cells tend to disconnect from their neighbours. Their cell membranes become depolarised and they disconnect from local bioelectric signalling [5]. Cancer cells also tend to lose the specialisation of the tissue context they are in. Instead of working as, say, muscle cells or kidney cells, cancer cells become 'de-differentiated'. (Dedifferentiation is the process in which a mature cells returns to its original embryonic, unspecialised state, perhaps to repair an injured body part). Dedifferented cells spend less resources making and operating proteins necessary to lift weight or filter blood. Insted, they focus resources on growth [2]. In this, cancer cells tend to behave somewhat like stem cells - they lose differentiation, they proliferate, and their metabolism tends to switch from the usual 'aerobic respiration' to something called 'aerobic glycolysis' (fermenting glucose using oxygen)[3].
To cure cancer, you may not have to kill cancer cells if you can instead **convince** them to reconnect to the local bioelectric network [4][6]. When that is successful, the cancer cells don't die, but they revert to the normal function of the local tissue. A cocktail of ion channel openers and blockers - so called 'electroceuticals' - may be useful in persuading cancer drugs into normality. For example, in animal experiments, Michael Levin successfully used a hyperpolarising ion channel protein (GlyRF99A-GFP3) to mitigating the effect of oncogenes [6]. Sodium channel blocking drugs taken for epilepsy mitigate the risk of certain cancers [9].
So, can grafting adjacent normal tissue into a tumor reprogram cancer cells toward normality? Can reprogramming be enhanced by 'electroceutical' ion channel drugs [10] before and after surgery? (Maybe even topically applied to the tumor+normal tissue complex during surgery?) For liquid cancers, maybe normal cells can be grafted at at the source of the cancer (e.g. in bone marrow). Preferably, the grafted tissue should not be completely excised from the donor site. It should instead retain substantial physical connectivy to the adjacent donor site, so that it has blood supply and remain ennervated. (The latter is important given the historical note below about Robert Becker and his thoughts about bioelectrical conduction in the nervous system.)
[Historical note]
Using bio-electricity to change the behaviour of cancer cells has a long history. In his 1985 classic 'The Body Electric', orthapedic surgeon Dr. Robert Becker wrote:
"In my group's experiments with human fibrosarcoma cells in vitro, negative and positive currents both speeded up growth by over 300 percent. On the other hand, as mentioned in Chapter 8, we found that we could suspend mitosis in the fibrosarcoma cells with silver ions injected by minute levels of positive current. During one day of exposure, the cells appeared to dedifferentiate completely, and they stopped dividing for a month without additional treatment, even though we changed the nutrient medium regularly"[7].
In his book, Dr. Becker described older research where cancer was induced in salamander limbs. Amputating the limb through the tumor mass led to regeneration of a normal limb and disappearance of the cancer. His investigations into regeneration focussed on the junction between nerve endings and tissue. Dr. Becker hypothesized cancer cells are stuck in a state of incomplete dedifferentiation. He speculated that developing a process to 'dedifferentiate' cancer cells "the rest of the way and then let normal processes in the body turn them into healthy mature cells" would be key to curing cancer. He also thought bio-electric currents were electronic, not ionic, and that their flow occured by means of a concentric, semiconducting sheath formed around nerves by Schwann cells [8].
[References]
[1] Page 194, 'Transformer: The Deep Chemistry of Life and Death', Nick Lane
[2] Page 208, 'Transformer: The Deep Chemistry of Life and Death', Nick Lane
[3] Page 203, 'Transformer: The Deep Chemistry of Life and Death', Nick Lane
[4] Page 238, 'We Are Electric', Sally Adee
[5] https://youtu.be/K5VI0u5_12k?t=2193, Bioelectrical signals reveal, induce, and normalize cancer, Michael Levin
[6] https://youtu.be/K5VI0u5_12k?t=2729, Bioelectrical signals reveal, induce, and normalize cancer, Michael Levin
[7] Page 173, 'The Body Electric', Robert O. Becker
[8] https://robertobecker.net, Then /research/wellspring-studies/, Biography of Robert Otto Becker >
Wellspring Studies
[9] Page 234, 'We Are Electric', Sally Adee
[10] https://bio-software-design-platform. appspot.com, Electroceutical Design Environment (EDEn), (Remove space added to URL due to website limit).
Bioelectrical signals reveal, induce, and normalize cancer - Michael Levin
https://youtu.be/K5VI0u5_12k?t=2729
Reference #6 above. From the current leading researching into bioelectricity, Michael Levin [sonam, Dec 30 2023]
Farmer Pain Scale
https://www.youtube...pWtp8c6gS3e&index=3
A perfect test subject for this idea! [Sgt Teacup, Dec 30 2023]
Link to the 'Electroceutical Design Environment' (EDEn)
https://bio-softwar...latform.appspot.com
Michael Levin refer to EDEn in his video at timestamp 2935 seconds (youtu.be/K5VI0u5_12k?t=2935) A creative oncologist could use it to design electroceutical treatment based on 'off label' prescription of existing drugs -- repurposing them to formulate an ion channel cocktail. [sonam, Dec 31 2023]
Clinical trail: Minoxidil (as used in 'Rogaine') for Ovarian Cancer
https://clinicaltri...v/study/NCT05272462
As mentioned in the post, ion channel opening and blocking drugs can persuade cancer cells to electrically reconnect to their neighbouring good cells. ("Take the red pill Neo!"). Turns out lots of existing drugs affect ion channels, so it makes sense to use tools like EDEn to find and repurpose these drugs to target ion channels. One example is minoxidil - the hair loss drug in Rogaine. It acts as a K+ (potassium) ion channel opener, and it 'repolarises' cells. This is it being used in a medical trial for ovarian cancer. [sonam, Jan 01 2024]
In depth review of the cited Transformer book
https://www.goodrea...s,-are%20found%20in
search for the review by Bill Leach, click "show more". I've highlighted the start of the most relevant section. [Loris, Jan 07 2024]
[link]
|
| |
This is one of those times when I miss [MaxwellBuchanan]. He'd start with pithy word-play, then provide education about why and probably how this could(not) be done, and end with a joke. |
|
| |
Best I can do is wonder how the electrodes in the petri dish translate to actual solid tumours in human bodies. Of course, I picture a large scale real-world Operation™ game. |
|
| |
If anybody needs a living body donation to science to explore this, I have a selection of MRI-identified masses which I am currently waiting to have biopsied: 10 months' wait (!) and counting--next appointment if it doesn't get delayed again is mid-Feb 2024. |
|
| |
//This is one of those times when I miss [MaxwellBuchanan]. He'd start with pithy word-play, then provide education about why and probably how this could(not) be done, and end with a joke.// |
|
| |
Yup, Max and 8th, the undisputed stars of this site, Max for the bio stuff, 8th for the engineering stuff. They're why I came to this website over the years, it was like "Wonder what Max and 8th would say about this." Besides being stunningly smart, they were funny as hell and had a great understanding and embracing of the lighthearted fun of this site. |
|
| |
Gotta mention zenxag, we may disagree on absolutely everything but she's one of the 3 pillars of the site from that era that I'll call the golden era of the HB. Gotta give credit where credit is due. And the flame wars between her and 8th were pretty much the best thing on the internet. |
|
| |
//I have a selection of MRI-identified masses which I am currently waiting to have biopsied: 10 months' wait (!) // |
|
| |
Sgt Teacup, I'm so sorry to hear this. Here's a plethora of ideas -- points #1 and #2 are fully baked. |
|
| |
Suggestion:
1. The delay in obtaining a biopsy is bad. From experience with friends (involving liver cancer), delay can mean the difference between being able to operate on a tumor or not. Go to India and have a surgery carried out as medical tourism. I'd suggest Kerala or Tamil Nadu or other Southern Indian states. See wikipedia article: Medical_tourism_in_India |
|
| |
2. Apricot kernels for cancer. It works, as witnessed by a personal friend. See article I wrote about him at enconsed.blogspot.com |
|
| |
3. The TheraBionic P1 'electroceutical' device recently gained US FDA approval for liver cancer. Perhaps you can access it in Europe? |
|
| |
4. This other halfbakery idea on treating liver cancer:
www.halfbakery.com/idea/Cancer |
|
| |
5. Red and infrared light therapy work to make mitochondria more efficient. There are LED boxes you can get on Amazon. I use one by Bestqool. |
|
| |
6. This is a link to the 'Electroceutical Design Environment' (EDEn)
https://bio-software-
design-platform.appspot.com |
|
| |
(Remove space added due to website limit; also added link to main article)
Michael Levin refer to EDEn in his video at timestamp 2935 seconds (youtu.be/K5VI0u5_12k?t=2935)
A creative oncologist could use it to design electroceutical treatment based on 'off label' prescription of existing drugs -- repurposing them to formulate an ion channel cocktail. |
|
| |
7. Use Rogaine tablets?
I've added a link on usage of minoxidil - the hair loss drug in Rogaine - as a K+ (potassium) ion channel opener that 'repolarises' cancer cells. It is being used in a medical trial for ovarian cancer. I suggest talking to an oncologist about it first. But hey, if it doesn't work, at least you'll have better hair. |
|
| |
Sgt Teacup - I've updated the suggestion list above (added points #2 and 7). I've added a link to the post on a clinical trail on minoxidil for advanced cancer. |
|
| |
Hey Sgt, I just read the part of your cancer challenge. I missed it earlier. |
|
| |
I'm very sorry you're having to deal with this and I'm sure I speak for everybody in that we all hope for a good outcome with this challenge you're facing. |
|
| |
//I have a selection of MRI-identified masses// Positive vibes sent for a good outcome. |
|
| |
[sonam], [doc], [xen], thank you for your good wishes and practical ideas. |
|
| |
The main stumbling block to any medical procedure is lack of access to Doctors, which means a lack of access to tests, scans, and procedures, which is a problem all over Canada. I'm one of the lucky 30% to have a family doc, at least. |
|
| |
I have a large red-LED mat which has done wonders to help with the atypical psoriasis which seems to be part of this journey. Not so much help with the further-inside swollen lymph nodes in my neck and behind my L ear, the 1.6cm mass in my R throat, spot on my R thyroid, R lung. Possible post-Covid sequelae? I got Covid in Jaunary 2019 before anyone around here knew what was happening (ie: no boosters or antivirals available). |
|
| |
I'm a lifelong student of nutraceuticals, herbal medicine, so I've been doing Dr Jekyll-type one substance at-a-time, controlled studies, N=1 :) eg: For almost 100 years, repeated studies have shown TB fully resolved by massive injected doses of Vitamin D3, which also incidentally cleared up outer skin issues, so I'm taking a lot (!) of OTC VitD every other day. Turns out, VitD combined with the anti-inflammatory indometacin (prescribed for my mysteriously appearing Morton's neuroma) is chemotherapy for solid tumours, so bonus! |
|
| |
Funnily enough, one of the Board of Directors for our local hospital just got back from Mexico where he traveled for scans and procedures that have a 2-year wait list here. That says something, the Board of the Hospital leaving Canada for health care; it says 'totally broken system favours the leisure class'. |
|
| |
I'm getting seen relatively quickly for our public system. After the ENT scope and biopsy, I may have to crowd-source medical tourism ideas. Stand by. |
|
| |
$20 from me, let me know where. |
|
| |
Sgt Teacup - good to know you're open to alternate treatments and they benefit you. Praying you get well. Yes Mexico may be a good option. Ask the board member for recommendations! Pity this site doesn't have DMs. Will check this page and your status page in a couple of weeks. |
|
| |
In my opinion, the flame wars were an annoying distraction. The submissions from Lostdog and FarmerJohn as well as UnaBubba's songs were the best things here by far. |
|
| |
We have common ground sir. |
|
| |
Wellness, Sgt Teacup. I've been pounding the drum for indomethacin for years now and more recently after the onset of the COVID pandemic. I'm glad to know you've stumbled upon relief for your inflammation, and pleased to hear there are practitioners available to you who practice complementary therapies. |
|
| |
I do not think that treated cell allographs will work for reprogramming cancer cells, but it's a grand thought experiment. I'll grant you, nonetheless, that electrophoresis coupled with nanoparticles, micelles, or small molecules like mRNAs are already in trials for everything from counterpathology to genetic programming. There are a thousand avenues to access and depreciate cancerous cells, and I hope that it's only a matter of time and finding the right combination of 'magic bullets' and 'tracers' to the point where cancer is as treatable as a vitamin deficiency. |
|
| |
My belief in what might happen sooner, rather than later, is that synthetic and fully compatible organs will be developed. Mini-kidneys, for example. We could all use a third one of those, yes? For cancer, perhaps a Mini-Thymus ... I mean, fix that low T problem or make sure there's plenty of excess capacity for synthesized hematopoietic stem cells that will further differentiate into working immunity. Maybe that 'last yard' approach to allograph-derived immunity will solve some illnesses and avoid the Jesse Gelsinger problem, i.e., we can't fully control viral infections with current technology. |
|
| |
Anyway, best wishes for continued good health! |
|
| |
P.S. Perhaps I was a bit too quick to dismiss allographs as a cell reprogramming route. I offered no support for my belief, and that can be viewed as dismissive. Here's why I doubt that healthy cells have sway over cancerous cells. |
|
| |
Each of our trillions of cells has an exact copy of our DNA. The DNA functions as a template for the tens of thousands of proteins that function in its host cell to act as enzymes or as building blocks for larger inclusions of cells, such as the nanopores or markers on cells surfaces. Obviously, not all cells are equal! There's a difference in form and function between cells in different tissues. Yes, the nerve cell's connected to the muscle, etc; but, we have only one DNA. |
|
| |
That, to my point, is an oversimplification. One predominant theory of cancer is that cancerous cells arise due to mutations in DNA. This leads to another common oversimplification: Cancer is alien, foreign to our natural constitution. It really could not be more like us than could any cell from our neighbor. That is, in a nutshell, why I doubt the effectiveness of allography or grafting 'normal' (non-mutated) cells within or proximal to a tumor will undo a DNA mutation. Were it to work, then stem cell injections would be a cure-all, and ... come on. |
|
| |
//This is one of those times when I miss [MaxwellBuchanan]. He'd start with pithy word-play,// |
|
| |
In his absence, you're stuck with a relative neo(plasia)phyte like me... hmm, needs work. |
|
| |
Anyhow, looks like we need a cancer biologist, or, considering their last few decades of performance, maybe not. |
|
| |
//Removing cancer cells from the tumor environment and implanting them into normal tissue tends to halt their growth [1].// |
|
| |
No, it doesn't. A completely standard experimental protocol in cancer biology is to take a cancer-derived cell line, say HepG2 as a proxy for a hepatocarcinoma, and implant it under the skin of a nude (immunocompromised) mouse. There it will grow in an unlimited fashion. This works for huge numbers of different cancer-derived cell types. |
|
| |
However, the environment a tumor creates within and around itself is important to it's self-preservation, relative acidification and anoxia are features that inhibit immune surveillance for example. |
|
| |
//can adjacent normal tissue be grafted into the tumor with the aim of encouraging cancer cells to become normal?// |
|
| |
The adjacent normal tissue is perfused, innervated, connected etc. Chopping it out and putting it into a disconnected tumor microenvironment will lead to either apoptosis/necrosis of the majority of the cells and maybe a few normal fibroblasts etc. crawl out alive. |
|
| |
//groups of cells are a type of collective intelligence.// |
|
| |
//sending messages to all adjacent cells using gap junctions and ion channels, forming a local 'bioelectric network'.// |
|
| |
Yes, wait until they discover all the other signaling, hormones, metabolites, oxygen. Wait until they discover these special long-distance electrical cells that can influence things meters away! |
|
| |
//Their cell membranes become depolarised and they disconnect from local bioelectric signalling [5].// |
|
| |
Broadly, yes, but why is this happening? |
|
| |
//may not have to kill cancer cells if you can instead **convince** them to reconnect to the local bioelectric network [4][6]. When that is successful,// |
|
| |
You're negotiating with terrorists at this point. Also "When" is doing an awful lot of work in that paragraph! |
|
| |
//Can reprogramming be enhanced by 'electroceutical' ion channel drugs// |
|
| |
Oh god. This happens in science, self-promoting scientists repackage something and give it a jazzy name and present it to the relatively uneducated in exchange for attention and funding. We're calling drugs that interact with ion transport "electroceuticals" now are we? Well, they've been around for centuries. You can try just throwing ion transport manipulation at the problem, it will be easy to get something to work in a dish. At the scale of a person, those drugs will have the normal targets which will be sensitive, otherwise the drug wouldn't be a drug. The tumour will sit protected in it's poorly perfused microenvironment constantly proliferating and evolving around the problem. |
|
| |
Ultimately, as Max pointed out, cancer is a genomic disease. All the downstream stuff is interesting, but ultimately just symptoms of the mutations. We can't just recapitulate a non-tumor environment and expect the cells to start behaving like normal tissue. Remember, the original cell WAS in that environment, completely outnumbered and surrounded by all the right cytokines, hormones, metabolites etc. It proliferated anyway. This is completely replicable, see my 1st paragraph. |
|
| |
//10 months' wait (!) and counting--next appointment if it doesn't get delayed again is mid-Feb 2024.// I'm not an expert, but detection speed is everything in cancer. I'd investigate if private fine needle aspiration (FNA) biopsy is possible/financially feasible. The histology is relatively routine and cheap. I'd also investigate getting a lawyer to send a letter outlining the obvious mismanagement and subsequent patient mental distress, for which compensation will be sought as a matter of course. Also, see attached bill for private biopsy. If US education depts. are a reasonably proxy for other large Govt. bodies, then the mere whiff of legal action makes them panic and they capitulate every single time. |
|
| |
I'm with bs0u0155 in doubting this would work. |
|
| |
[bs0u0155] - Thanks for the detailed reply. This is your key objection, so let me address it with some more context: |
|
| |
>> Removing cancer cells from the tumor environment and implanting them into normal tissue tends to halt their growth [1]. |
|
| |
// No, it doesn't. A completely standard experimental protocol [...] cancer-derived cell line [...] and implant it [...] it will grow in an unlimited fashion// |
|
| |
Both statements are correct. Your statement not rebut mine because you speak of some *cell lines* derived from cancer tissue, while I speak of in-vivo cancer. Cell lines continue to mutate (and diverge) as they are propagated in the lab (see article PMC6262811 on nih.gov) |
|
| |
Here's additional context from reference # 1. It's from page 194 of the book 'Transformer' by biochemist Nick Cave, published in 2022. Here, speaking against oncogenetic mutations being the sole cause of cancer, the author made the claim about cancer cell growth being halted when implated in a 'normal' environment. |
|
| |
"Plainly they do not always cause cancerous growth. On the contrary, taking cancer cells from a tumour microenvironment and implementing them in a normal cellular environment **tends to halt their growth**, and often promotes programmed cell death.
It's quite encouraging that cancer cells can be rewired in this way: the same generic mutations are not invariably associated with the same cell fate. This view is consistent with older work which shows that transplanting the nucleus from one cell type to another does not alter the phenotype of the recipient. The cytoplasm determines the cells state, not the genes in the nucleus. In other words, genes are switched on or off by signals from inside (or outside) the cell. Mutations are not necessary to cause cancer - merely a cytoplasm that sends the wrong signals." |
|
| |
sonam, you're relying a lot on a couple of popular science books (one of which incidentally doesn't seem to be visible to me on e.g. amazon). |
|
| |
It's maybe not a bad place to start your journey, but let me advise you that these books are not guaranteed to be completely reliable. Some are good, some are bad... there are some hilariously awful ones. |
|
| |
These sources are probably not going to persuade people who know a little about biology.
The thing is, it's not even that individual quotes you've used here are untrue, necessarily. It's well known that some cancers can be modified by external factors. In fact, medical science does this already - my Dad it literally undergoing a course of hormone adjustment in preparation for further treatment right now [1].
The other thing is that normal, noncancerous tissue is... kind of fragile. As bs0u0155 points out, many tissues are very reliant on a complicated support system. Grafting tissue is kind of awkward at the best of times. |
|
| |
The problem with cancer is rarely about dealing with the bulk of it. That's generally the easiest thing to deal with. |
|
| |
[1] Prognosis seems good, don't worry. |
|
| |
[reensure] - Good points. I guess this is the crux of your objection below, so let's address it with more context from the source of my information: |
|
| |
// "One predominant theory of cancer is that cancerous cells arise due to mutations in DNA [...] That is, in a nutshell, why I doubt the effectiveness of allography or grafting 'normal' (non-mutated) cells within or proximal to a tumor will undo a DNA mutation. "// |
|
| |
Here's additional context from reference # 1. It's from page 194 of the book 'Transformer' by biochemist Nick Cave, published in 2022. Here, he's speaking about the idea of DNA mutations causing cancer. |
|
| |
"Yet the evidence against this dismal genetic determinism is startling. If a cancer is a clone deriving from one rogue cell, then the mutations that caused it to go awry should be written into all its descendants: all the cells in the tumour. That's not always the case. Different mutations are found in different parts of many tumours, often with little if any overlap. The implies that the mutations accumulated during the growth of the tumour, rather than triggering its inception. In fact, later accumulation is quite plausible, as cancer cells are well know to develop genetic instability, meaning they accrue new mutations faster than normal cells. These may well exacerbate disease progression, but such heterogenticy is inconsistent with ongogenic mutations *causing* cancer in the first place" |
|
| |
Please see also my annotation addressed to bs0u0155 -- there, I've quoted the same author making the claim about cancer cell growth being halted when implanted in a 'normal' environment. |
|
| |
One correction: I'm proposing a hypothetical procedure that resembles autografts (transplants from one's own tissue), not allografts (tissue transplanted from another person). The idea is the 'grafted' tissue be as vascularized and enervated as possible from the get-go, by retaining connection to the donor site. So it's unlike a traditional autograft. |
|
| |
[Loris] - Blessings for your dad. :-) |
|
| |
// These sources are probably not going to persuade people who know a little about biology.// |
|
| |
While this is Half-bakery, I do hope people here believe my sources. The author of the 'Transformer' book is a Professor of Biochemistry at University College London. You can find the book on Amazon if you search for its full name: 'Transformer: The Deep Chemistry of Life and Death'. Or search for ISBN 978-1788160551.
(I'll also update reference #1 in my main post - just "Transformer" is too generic a name) |
|
| |
Ah, Nick /Lane/.
I did wonder why Nick Cave was branching out from music into pop-sci writing at this point in his career. |
|
| |
Regardless of his qualifications, I would advise against putting too much emphasis on bullish statements from his book. For example, from the quote you gave: |
|
| |
::If a cancer is a clone deriving from one rouge[sic] cell, then the mutations that causedf it to go awry should be written into all its descendants: all the cells in the tumour. That's not always the case. Different mutations are found in different parts of many tumours, often with little if any overlap. The implies that the mutations accumulated during the growth of the tumour, rather than triggering its inception. In fact, later accumulation is quite plausible, as cancer cells are well know to develop genetic instability, meaning they accrue new mutations faster than normal cells. These may well exacerbate disease progression, but such heterogenticy is inconsistent with ongogenic mutations *causing* cancer in the first place:: |
|
| |
All the earlier individual statements may be true[1], but the last line looks pretty weak to me, even if it's written dogmatically. |
|
| |
[1] I have my doubts about the 'if any' in "...often with little if any overlap." |
|
| |
[Loris] Thanks - I fixed some transcription typos (I'm not the best touch typist). |
|
| |
I remain convinced by the book. The next statement after my excerpt ended is literally, "I could go on"; the author then makes a couple more arguments. It's one thing to appeal to authority saying he's better qualified to make these assertions. More importantly, his statements make sense and agree with much research over the years by other scientists questioning whether the theory of ongogenic causation is both necessary and sufficient to explain cancer (for example, see article PMC3941741 on nih.gov about "Cancer as a metabolic disease"). |
|
| |
The author is not simplistic or bullish, but appears pretty balanced. From page 195: |
|
| |
"None of this is to say that mutations don't occur in cancer; obviously they do. Nor am I suggesting that they cannot play a decisive role in its development; they can certainly lock cells into a pattern of growth making it harder to revert (although we've noted that changing the microenvironment can switch off growth). The question is, are genetic mutations the primary cause of cancer? And if not, what is?" |
|
| |
To be clear, I'm not saying that he's totally wrong. I found a long review of 'Transformer: The Deep Chemistry of Life and Death', and it looks decent.
It's certainly not one of those awful pop-sci books where you can't trust a word. |
|
| |
But, the thing is, it's basically human nature to big up your ideas, both in overstating the evidence and exaggerating their novelty.
There's kind of a history of this in biology - for example, Stephen J Gould had a long career writing popular books on palaeontology - and loads of them talked about his concept of "punctuated equilibrium" in evolution. (That is, the idea that evolution tends to proceed in 'fits and starts' - periods of rapid change, followed by long periods of stasis.) To read one of his books, you had the impression that this was a paradigm shift; everyone up to that point was just totally wrong on this.
However, I think the general consensus among evolutionary biologists at the time was that it was certainly an interesting and valid point, but it wasn't /that/ big a deal - no-one in the field would have claimed that evolutionary change had to occur at a constant rate, because that would be idiotic. He was just showing how variable the rate actually was in practice. |
|
| |
So when I see:
"Different mutations are found in different parts of many tumours, often with little if any overlap."
I'm like - well, obvs. Full-on cancer cells mutate like crazy. But if there's /one/ mutation in common, does that count? If yes, then in the sense that actually matters the claim is in essence invalid, if no, well, what evidence is there for that? (If you are aware how modern sequencing works, you know it won't be as simple as ~we sequenced two separated samples from the same cancerous lump to get two complete genomes and found zero mutations in common~) |
|
| |
And the next sentence:
"This implies that the mutations accumulated during the growth of the tumour, rather than triggering its inception."
What does he actually mean by this? It's widely recognised that cells which are predisposed to growing a bit more quickly are on the first steps of the path towards cancer. If he's merely pointing out that this may be due to a change in metabolic state (differentiation) rather than mutation, then it's pretty banal, to be honest. If there are /some/ tumour types where there's a stack of de-differentiation, and it's already growing like crazy before any mutations necessarily happen, well, that's interesting... but what fraction of cancers is that, a) by type, and b) by medical case? |
|
| |
And more pertinent to the grafting proposal - If you find such a tumour at that early stage, is it really easier or more reliable to graft more tissue inside than to treat it with hormones and/or chop the whole thing out?
(I would lay good money on the answer being 'no'.) |
|
| |
//On the contrary, taking cancer cells from a tumour microenvironment and implementing them in a normal cellular environment **tends to halt their growth**, and often promotes programmed cell death.// |
|
| |
Sure, I have no problem with that. Cells get mutations all the time and there are many mechanisms to catch this and the cell dutifully becomes senescent or kills itself. If that doesn't happen, then the immune system picks it off. Cells early in the process will be fragile and dependent like their progenitor cells. It's the process of tumor growth, genetic instability, selection and evolution that ultimately results in a lethal disease. Give it time, however, and the transplanted tumor will possibly just die, or it may mostly die back and then re-grow adapted to its new environment. It takes regular tumors a long time to generate cells that leave the tumor and survive in the circulation, then, those cells have to lodge in a new organ and adapt to that and grow new metastases... this can be years, decades even. |
|
| |
//If a cancer is a clone deriving from one rouge[sic] cell, then the mutations that caused it to go awry should be written into all its descendants:// |
|
| |
No. There are many stages between origin and end stage. Along the way the cells acquire the ability to divide endlessly by turning off contact inhibition, gaining the ability to grow telomeres etc. Part of that involves multiplying various chromosomes, moving whole sections of chromosomes around and damaging DNA repair programs. It's perfectly possible that all cells in a tumor are types D-G for example. The original mutant cell, "A" begat "B" then "C". A may then be totally maladapted to the environment created by cell types D-G and go into apoptosis. |
|
| |
//This implies that the mutations accumulated during the growth of the tumour, rather than triggering its inception// |
|
| |
Lots of mutations, the vast, vast majority, are accumulated after the proximal mutation(s), that's not controversial. The proximal mutation(s) may not even have to be recognized oncogenic mutations, they just have to produce an environment that ultimately leads to them. |
|
| |
To counter the argument that DNA mutations are the proximal cause, you have to refute an awful lot of evidence. For example any way of mutating DNA, chemical, radiation, time etc. Will cause cancer. You can simplify that down, take cells that behave normally, mutate their DNA and you end up with cells that behave like cancerous cells. WITH NO CHANGE in environment, just DNA mutagenesis. |
|
| |
Obviously this is then refined, certain mutations that turn off some proteins and turn others on are very powerful oncogenes. Then other mechanisms, like oncoviruses, viruses that mutate DNA and cause cancers. I think this author is likely a standard grifter. |
|
| |