Readit NewsAnyone can pat themselves on the back for pointing to the worlds problems and saying "this could be better!"
There are always exceptions to everything in biology, but the general mechanism of most chemotherapy drugs is that they preferentially kill or stall rapidly growing cells. That's why hair often falls out and you get skin issues. My point is that a successful immune response often involves rapid division of immune cell populations as well, which is dampened by chemo. You are also ineligible for many clinical trials if your blood cell counts get below a certain level.
Yes DNA-damaging chemotherapy drugs can induce p53, but many cancers inhibit p53 anyway. I'm not sure you would want to trade a general induction in p53 for losing a huge portion of your overall T-cell count right before injecting yourself with an oncolytic virus (depending on the tumor type).
You raise a number of good points, and there are a lot of subtleties including regulatory T-cells, which you mentioned. However, if you have the expertise and the means to design a custom treatment/regimen for yourself, I think that you can potentially do a lot better than just going through the meat-grinder of clinical oncology where the first line treatments are years behind cutting edge academic work. This paper supports this idea. I am not recommending that everyone who has cancer forgoes chemotherapy in favor of trying something risky, but as you said every individual case is different and it should be your decision whether you want to try a high-risk high-reward strategy or whether you want to go through multiple rounds of non-curative treatments which only slow down the inevitable and gradually sap away your strength and immune function. Especially if you have enough expertise in a relevant subject matter.
For example, my mother was diagnosed with stage 4 of a rare HPV+ squamous cell cancer. She was an expert on co-stimulation and immune tolerance, since she that is what she studied in the lab (https://tts.org/74-ixa/889-ixa-in-memoriam-agnes-marie-azimz... ). At times she was educating her doctor on co-stimulatory mechanisms, since he barely knew enough answer her questions and he would say the same types of things that you are saying: "it's complicated" "it might help clear cancer cells" etc..
There are a lot of customized treatments that she envisioned trying using her extensive expertise, and probably could have done so with the reagents in the lab or with her colleagues' help. Ultimately, she decided to trust the medical system but she did not respond to any chemotherapy. The one session which led to a reduction of tumor growth also led to a reduction in her blood cell counts (it was FOLFIRI), so the chemo had to be stopped. After that, she enrolled in an experimental cell therapy but it didn't work. Of course, the chances of it working are a lot less when her strength, general health, and immune function were already diminished.
It's one thing to talk about the complexities and the ethical risks of trying an experimental therapy, but when it happens to you or a loved one, the cost of failure is a lot higher and you might rethink your risk appetite. I am talking specifically about rare versions of tumors where the prognosis is poor.
In general, I don't even understand the point of making doctors go through all of the training they do, if they are forced to just follow the cookie cutter guidelines, which are influenced by the established drug companies.
There are risks, but having cancer is a risky business right from the get go.
> You're in the awkward position of arguing that an expert in a field doesn't understand what she is doing while citing evidence to support yourself that you (by construction) don't have.
No. I'm in the non-awkward position of arguing that non-experts should be careful about interpreting a single case study without context. Especially in a way that implies miracle cancer cures are sitting around in labs with no one paying any attention to them.
I don't think the average HN reader understands just how many wildly different treatments, drugs and therapies are being thrown at different cancers and how quickly medical oncology moves as a field. Cancers are an extremely complex family of diseases. Early results and case studies are correspondingly extremely difficult to interpret due to the variation in individual responses and disease course.
The existence of a "miracle" cancer treatment is almost ruled out from first principles. But if such a miracle treatment is sitting around in a lab, it would be non-trivial to tell it apart from the thousands of other promising candidate therapies that go on to pan out to nothing.
There's no shortage of cancer patients at end-of-life stage undergoing aggressive treatments and/or experimental therapies in clinical trials for minimal to no survival benefit. For almost all of these patients, the best option for them and their loved ones will end up having been a palliative or best supportive care model.
You say that, but the article suggests otherwise. This virologist did believe that her colleagues were sitting around not rolling out something that would cure her. It is pretty easy to see how a lot of cures would be stuck in the research world, unable to get to patients; there is no reason to believe they are moving quickly to bring cures to market. You can see people arguing up and down the thread how they have higher priorities than testing stuff to see if it might work.
And because her outcome was so unexpected and unusual it got published as a case study. What you don't see are all the cases where the experimental miracle cure treatment did not work. What you also won't see in headlines are all the trials where putative miracle cures and other promising treatments failed to demonstrate survival benefits in larger cohorts than 1.
One of the counterintuitive things about cancer is how badly individual cases and responses to treatment generalize to the broader patient population. If you didn't know any better, you could easily read a story like this and think "wow, this breast cancer cure was just stuck in a lab somewhere!" But to put a story like this into context, you need to understand just how many individual miracle remission stories there are, and how varied individual cancers and responses to treatment are.
There are potential miracle cures almost everywhere, and a large number of them are being aggressively researched, tested on cancer patients at any given time - often as part of combination therapies. Some of these promising technologies do become breakthrough cancer treatments that create durable remissions, such as checkpoint inhibitors. The rest fizzle out.
But she was only able to do so because of having the skill and access needed to self-administer the cure. How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?
This isn't a case study about a breast cancer cure. This is a story about a single individual's cancer's response to an experimental treatment. For comparison, there are case studies of spontaneous remission in refractory cancers triggered by seasonal flu.
Virologists aren't sitting around waiting to develop cancer before they decide to roll out the miracle cancer cures. Oncolytic viruses have been researched, studied and tested on cancer patients for almost a century now.
Really smart to use the viral therapy before chemotherapy, since chemotherapy dampens the immune system, and the immune system probably promotes further tumor clearance once the tumors soften and are full of viruses.
1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system.
2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness.
3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway.
4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors.
5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival.
This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.
It's more of a "not even wrong" statement. It's the kind of useless and reductive analysis poor leaders trot out from a position of personal frustration after failing to surmount the challenges involved in steering a complex, messy, human institution towards success.
It's incredible how consistently this maladaptive "everyone just work harder!!" mentality crops up among failed leadership in institutions of all kinds and sizes. In this respect, Schmidt is no different to the average frustrated restaurant owner, blaming his business failures on his staff's work ethic, "no one wants to work hard these days" and other copes.
Let's say we go ahead and assume that long grinds and 100% in-office attendance is the only way a successful and highly engaged team can look. Getting to that point would still require leadership to perform the actual hard work of creating the right conditions and incentives for that successful, engaged work to emerge. Shaking your fists at the air and saying "work harder people! we need to win!" doesn't cut it.
If Schmidt allowed himself to look more closely and reflect more deeply, he would realize that Google is and was full of extremely hard workers. But their "hard work" more likely took the form of navigating Google's political structures and chasing up internal promotions and prestige.
you document what you can now in hope someone down the line uses it like the German guy and nightingale
If you observe people in their daily work, you will see there are many reasons why people do not document things. Time constraints, incentive structures, liability, general trade-offs and ambiguities. This is true not just in software/engineering but in any line of professional work.
There's plenty of grandstanding about the importance of documentation, but not much interest in understanding why people don't document in the first place.