My drug vs. Pablo Escobar

I find it difficult to write science. My first drafts always include far too much detail. I get carried away. I can’t explain the drug without mentioning PD-1. I can’t mention PD without naming it directly. I can’t name it without explaining apoptosis. But then the drug has little to do with apoptosis and I just end up confusing myself. So, for the sake of simplicity, I shall not define PD-1. For those interested there is always Wikipedia.

Blood is composed of different cells. I have spoken of neutrophils, which fight bacteria, but I haven’t really mentioned lymphocytes, which is odd because I have a lymphocytic cancer. You’ll have to excuse me; I am bound to get out of my knowledge depth rather quickly. This may be why I haven’t mentioned lymphocytes before, a small knowledge gap there. Lymphocytes are the backbone of the immune system. There are two types of lymphocytes. B-cells, which find and remember pathogens, and T-cells, which do the killing. Within the T-cells there are many sub-types, but only two I wish to talk about today: regulators and effectors. The regulators ensure that your immune system does not fight itself. They deter the effectors, who want kill things. Usually the regulators are the good guys, maintaining a calm within the body. Sometimes they are complacent, leading to autoimmune diseases, and sometimes they are corrupt. You see, PD-1, perched on the outside of a cell, is much like Pablo Escobar paying off the cops. They even call it an immune checkpoint. Pablo uses his henchmen, ligands PD-L1 and PD-L2, to encourage more regulators, and assassinate effectors. Those effectors who survive turn up to the crime scene where they are swamped by regulators: “Move along, nothing to see here.” And so the cell survives when really it ought to die. My super-secret (or not so-secret) drug is a PD-1 inhibitor. It is an antibody (human IgG) that binds to PD-1 and prevents corruption. I don’t know Colombian history well enough to expand my Escobar metaphor. Perhaps I should have thought of that before I began.

It turns out that my subtype of Hodgkin’s lymphoma, along with a couple of other notable cancers, has an increased cellular PD-1 expression. I believe this is due to 9p24.1 over-amplification. This chromosomal mutation also leads to an upregulation of the JAK2 pathway (possibly my favourite pathway) which feeds back on itself to promote cell proliferation (i.e. cancer), produce more henchmen (PD-L1 and PD-L2), in turn recruiting more regulators. I guess the 9p24.1 mutation could be deemed cocaine. It would be great if my drug could destroy the cocaine, but it is limited in its abilities. All it can do is eliminate Pablo.

One half of chromosome 9 and its faulty ways

The catch, there is always a catch, is that PD-1 expression in small quantities is perfectly normal. In fact it is necessary. Unfortunately, my drug cannot distinguish between normal and abnormal levels. It binds not only to Escobar, but to every other Pablo in the body. This could lead to some overzealous effectors exterminating some rather essential cells. The key word there is could. It may not. We shall see.

A couple of months ago, my super-secret drug was approved by Medsafe. It is now officially safe to use in New Zealand. But not for my disease. For other cancers, cancers that have decent data sets. I rocked up to Wellington for my first treatment since my release to Nelson. It was going to be great; a quick scenic flight over the Marlborough Sounds, bloods taken, treatment initiated, a cheeky bone marrow, and an evening flight home. How naïve! Nothing ever runs according to plan. Surely I ought to have learned that by now. The drug hadn’t arrived. It should have, but it hadn’t, and nobody knew why. Maybe it will arrive tomorrow. Mike and I wait. I entertain my sister’s cat for a bit. Then her neighbour’s cat. Then a stray, who really is making a right nuisance of himself, but I am restless so I will tolerate his disobedience for a while. I know, I know I am reinforcing negative behaviour patterns. What are you gonna do? I sat on the couch, read, lay, rolled over, read, sat up, stood, oh a piece of candy, lay, rolled, sat, lay, stood, sat, paced, candy, paced. Where the bloody hell was this drug? Huh? There are only so many chin scratches one can give in a day. Wellington had quickly lost its charm. The drug did not arrive tomorrow. Perhaps the next tomorrow. No? Had they chosen kayak as a transportation method again? They hadn’t. It was a document issue. The drug had previously been imported as an experimental, unapproved drug. Since its approval status had changed, the import documents had also changed. I believe the drug was having a lovely little vacation in a customs lock-up somewhere in Auckland airport. I disputed the need for different paperwork; the drug is still unapproved for Hodgkin’s, it shouldn’t need the new paperwork. Apparently bureaucracy doesn’t work like that. The drug did arrive, it was just a week late. 

All that you have read so far was typed over a month ago. The 31^st of May, so Word helpfully informed me. It seems like you have missed all of June. I would love to be able to declare myself extremely busy; moving on with life, running about town, running even. Alas, this is not quite true. Sometime in early June, Mike and I moved into our own place. We are living by ourselves for the first time in nearly a year. I am now struggling with life's everyday exhaustions. One load of laundry and a batch of dishes is enough to send me crawling back to bed with my tail between my legs. A 4pm fever leaves little energy for dinner preparation, which is usually left to Mike along with any other domestic duties I have missed. Suddenly it is eight-thirty, and I haul my sorry ass upstairs, for eight-thirty is now my bedtime. And repeat. The world is pretty much coming to an end if the vacuuming needs doing. As it does now. I have developed an attractive wheeze, a wheeze that turns into an emphysema like cough, enhancing my beauty. Oh winter and your cursed temperatures. To be fair, fevers are far more tolerable in winter than summer.

Ok, now that vile self-pity paragraph is done with. I guess I thought by complaining about it maybe everything would miraculously clear up, this searing back pain would cease, and I could start to enjoy things, anything, again. But it is like so many situations faced by so many people. Everything will be better when we move back to Nelson. Everything will be better when we get our own place. Everything will be better when…. No. There is no magic fix. There may never be a fix. It sure is hard work.

Right let’s pick this up a bit. Positives. Oh, my Hickman line has been removed. No more looking like something from a Kilgore Trout story. Also, I believe it has been over three months since my last blood transfusion. I got quite excited about that. Yus, my crossmatch sample is active for seven days now. The transfusionists out there get me. That is probably the end of the positives for now, we don’t want to overdo the excitement now do we? It might start me wheezing.