• 1 Post
  • 20 Comments
Joined 1 year ago
cake
Cake day: July 5th, 2023

help-circle


  • Me too, but there is one UK retailer (Co-operative) that makes it hard for you. They will have, say, a punnet of strawberries with 200g strawberries in it for £3.50 and another one with 300g for £4.50. The labels will say “unit price: £3.50/unit” or “£4.50/unit”. (No, really?) So you have to do your own maths. Luckily other markets are sensible enough to actually provide price per weight. And in Tesco, when a given product is cheaper for clubcard holders, it will even give price per weight twice, for both normal price and clubcard price.

    Btw. I don’t work for Tesco. I just needed to vent about Co-op being dicks; Tesco just serves as a good counter example of how this should be done, in case any Co-op executive is reading this.











  • This is probably going to be an unpopular comment, but I wanted to present the view in favour of what I call WFW (working from work). I’m sure it’s always going to be different for specific cases, but I do see benefits of WFW. We have an open plan office and a lot of casual conversations between us turn into serious conversations about projects and sometimes they have important outputs. Sometimes you overhear a conversation that you realise you know something about and you make a valuable contribution to it. None of this happens when people are WingFH. I’m lucky enough that my only line report is a hard working person, so I let them WFH probably a bit more than other managers let their reports, but I still like when they are WFW because of the contributions that they make to those conversations I mentioned above.

    I’m an introvert, so I totally get the argument of being able to focus better when you’re not surrounded by people and their conversations, but at the same time I honestly noticed that my productivity decreases when I WFH. I’m sufficiently honest with myself to notice that and feel bad about it and this is actually the main reason why I do commute for an hour every day just to WFW, even though our company policy says that we can WFH 3 days a week and my job is 95% desk based.

    I think it’s often has to considered for individual cases because as I said, my report does 110% whether they WFH or WFW, but I know from other managers that some of their reports really stuttered and stumbled when they were asked “so you WedFH yesterday, what did you do exactly?”

    I’m not trying to say “everyone should stop WFH”, but it seems to me that most of the comments in this post are aligning with “just let your employees WFH!” and I wanted to present the other point of view, from the perspective of a non-senior manager who also has some non managerial responsibilities himself.


  • Of course it needs to be controlled and regulated. Like any other drugs. One of the reasons drugs are expensive is because there is so many regulatory hurdles that drug makes have to deal with before they can touch a patient.

    I get your hypothetical, but it has two shortcomings. Firstly, training the immune system against cancer mutations is fairly easy, because the mutations are not present during the process of T and B cell maturation, so in the population of circulating naive T and B cells in a patient, there are likely to exist ones that are going to recognise the cancer antigen. Whatever proteins drive the dark pigmentation of skin or green eye colour will be used to drive the negative selection of T and B cells in the person with dark skin or brown eyes. And so, even if you administer a “vaccine” encoding these proteins, their immune systems will not be able to mount a response against them.

    Secondly, what about the practicalities. Say you made the anti-green eye vaccine - how do you administer it to people? I’m assuming we’re not talking about some dystopian future where forcing people to receive injections that contain biologicals killing them is legal. It’s not the kind of “vaccine” that you could just spread in the air or add to drinking water for it to take effect.


  • I think the first point to make is that this is not really the patient’s own genetic information, but that of their cancer, something they desperately want to get rid of. And the second point is that to my knowledge, there is no county on earth, where taking part in a clinical trial would not require the patient’s consent, which is to say, all people in the study were informed that the genetic sequences of their cancers will be analysed and used to generate a vaccine.

    As for the potential to become a weapon, you would have to elaborate, because I really don’t see how the Moderna vaccine strategy could be weaponised.


  • In general, mutations can happen anywhere on any gene, so every patient’s cancer will have its unique signature of mutations. However, like in the evolution of organisms by natural selection, most random mutations will have a detrimental effect and the cells carrying it will die. Some of the mutations will be neutral and despite the change in the amino acid, the cells harbouring it won’t survive better or worse than cells that don’t have it. But a few mutations will make the cancer cells proliferate faster or evade the immune system better, which will lead to these cells surviving and ultimately overtaking the population of the cancer cells. The latter mutations often happen in the same places on the same genes, and in melanoma for example, in as many as 41% of cases the 600th amino acid in a protein called BRAF mutates from valine to alanine (so the code for that mutation is “BRAF V600E”), and BRAF is only one example of such genes that commonly mutate in the same position.

    So to answer your question - I don’t know Moderna’s exact protocol, but my guess is that the tailored vaccine will contain a mixture of these commonly occurring mutations and some mutations that are unique to the patient.



  • The target antigens are from human cells, but they are human cells that mutated and hence became cancerous. What Moderna does, is it takes DNA from these cells, sequences it and finds where exactly the mutations occurred. A mutation means that there is a different sequence of amino acids in a protein, which in effect makes it a new and distinct antigen. This way, they select antigens that are present in the melanoma cells, but not in normal cells of the body. Then they take these mutated sites and use them to generate mRNA that will encode them all, be used to synthesise these mutated antigens, and train the immune system to react to them as alien antigens. The treatment described in this article is a combination of the mRNA vaccine with Keytruda, which is a cancer therapy based on an antibody. The antibody targets a protein from the PD-1 / PD-L1 axis. This axis is used by normal cells to tell the immune system not to attack those cells, because they are body’s own cells. Cancer cells often mutate like crazy, but then exploit this PD-1 / PD-L1 axis basically to say to the immune system “nothing to see here”.

    As for Rabies, I think we already have pretty well working vaccines, so we’re not really in a dire need for new ones.

    As for prions, it would be tricky. The reason prions do what they do is not that they are mutated proteins, but misfolded proteins. This is to say they assume the wrong shape, even though the sequence of amino acids in them is the same as in the healthy version of the protein. And this in turn means that they were synthesised based on a healthy, unmutated version of mRNA. And this in turn means that there is no mutation that the Moderna vaccine strategy could employ to train the immune system to recognise that prion protein.