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 31st 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.
