Perry Marshall

The effective way the clarinet player does a musical call and response to the singer is just mesmerizing. "Tu vuo' fa' l'americano" by Renato Carosone: cover by Hetty and the Jazzato Band, an Anglo-Italian jazz quintet.

Long post, because apparently many neither understand nor appreciate the intricacies of cancer research and think that pharmaceutical companies and regulators are holding back cures. Your immune system is constantly surveilling your body for both self and non-self recognition. It does this by checking the proteins expressed. If it finds something it doesn't recognize, it ramps up the inflammatory response and attacks. If it is actually non-self, great. If it is actual-self, that is autoimmune disease. Cancer occurs when cells acquire mutations that both 1) alter cell division and 2) cloak those cells from recognition by the immune system. If the second part doesn't occur, then the immune system will recognize that something is wrong and kill the tumor when it's just a few cells. At a high level, many modern cancer therapies are about getting the immune system to recognize the tumor and do all the work on killing it. And yes, it's quite easy to do this. But this is where the "safe and effective" line comes in. If you're treatment just cranks up the immune response in general, you start killing the tumor AND other things. If you give me a decent CAR-T at work, I have tools to boost it in ways that'll eliminate any realistic sized mouse tumor in 24-48 hours. The problem is that it's just a general immune overdrive and the cells start attacking everything. Okay, let's not send the immune system into a frenzy and just use the CAR-T, which is a T cell that has been edited with a protein that we know binds to a protein that the cancer expresses. The hope is, if the cancer cells express X and we edit the T cells to explain anti-X, then they'll go and attack the tumor. But this is where specificity and selectively come in. Your body expresses thousands of different proteins. Sometimes they look very much like each other even if they are different. Say there is a protein called XX expressed in your heart, it shares 99.9% homology (likeness) with X. We inject X-CAR-T cells, they go and kill the tumor, everything looks great. But a few binded to XX in the heart and started inflamming the heart wall. Not good to the point of unacceptability. This step gets especially hard when working in animals because mice and dogs or whatever have different proteins than humans! When we inject human tumors and human CAR-T cells into mice, they are NOT encountering the same proteins (or cytokines, hormones, other immune cells, etc.) that they would in an actual human body. This is just a brief explanation or some of the considerations that go into oncology. Here's another: we monitor experimental mice for max a few months. Even non-experimental mice have a lifespan of ~1.5-2 years. Meanwhile, you want your parent/spouse/child to be in remission for 5, 10, 15+ years! In fact, one of the main outcomes for assessing human cancer treatments is the "5-year survival rate." Mice and elderly dogs don't live for five years!! So yes, scientists and pharmaceutical companies have tools to easily kill tumors. What is hard is developing therapeutics that are BOTH safe AND effective in actual humans **relative** to current standards of care (e.g. a cutting edge treatment isn't "better" if it has a strong response in the first year but a lower 5-year overall survival, etc.) And this is where regulators come in. I expressed multiple times in the comments that I, generally, wish they weren't as risk averse and that I support "Right To Try" laws. But you need to appreciate that regulators **are** in a DIFFICULT position. An analogy: It's proven that nuclear energy is by far the safest form of energy per KwH energy produced. Yet a few high profile accidents, a couple of which didn't even kill anyone, have poisoned a large segment of the population and several nations against nuclear energy. Even though it's safe and a reliable form of carbon-free electricity!!! Now think about that relative to cutting edge medicines.