How to biohack your cells to fight cancer – Greg Foot


Ok,
so you, are a 4 billion year old
meat robot. Yeah, you heard me right. In fact, as you’re made of
30-ish trillion cells, and each of those have their own task, you’re a robot made of trillions
of mini robots- you are a mega-meat-bot! And your mission, for the past 4 billion
years or so- and for as long as you keep
playing this game of life- is to safeguard the code. To duplicate it.
To pass it on. The thing is, you’re rubbish at
copying your own code. Every time it’s copied, errors crop up. Not good when an error makes
a robot worse at surviving, but sometimes a mistake
helps them survive… and they pass that glitch in the code on- that’s evolution in a nutshell, right? Which means you’re not the result
of some fancy design, I’m afraid. You’re a result of billions of
years of bad copies. Go you. Another reason you’re not totally awesome is because that megabot of yours
often breaks down. Fortunately, cardiologists, immunologists,
microbiologists- all the “ists”- have spent centuries figuring out
our sensors and wiring so if something does go wrong,
they can usually fix it. Where they struggle, though, is when
the machinery turns on itself- when a copying error leads a cell
to start dividing uncontrollably, to grow and multiply into a tumor. That’s cancer. And sadly, even with the might
of our modern medicine, some cancers evade treatment. But this is where a new band of
biologists step into the story: The “Synthetic Biologists.” These biohackers are mashing up science,
medicine and engineering to rewrite the code and fix
the un-fixable. Biohackers are going into a
patient’s genetic code and reprogramming their own immune system to recognize cancer cells
and destroy them. It’s called CAR T-cell therapy,
and it’s awesome. See, you’re constantly under
attack by pathogens- single-celled bacteria, viruses and fungi. Despite deciding, back in the day, to stay solo and not ‘avengers assemble’
like you did, those pathogens see you, in all
your mega-meat-bot glory, as a fortress ripe for the plundering. Thankfully, you’ve got a security team
in place to battle these invaders- your immune system- and some of it’s top guards are
your white blood cells. They trawl the darkness
that is your inner space, checking the IDs of any cells they pass… although they’re not name badges, but rather protein fragments on
the cell’s surface called antigens. There are two types of these guards:
T-cells and B-cells. T-cells check those antigen IDs
using special claws- receptors that lock with a
particular antigen. If they find a match, they attach and
they release toxic chemicals that burst open the
invading cell’s membrane. Their B-cell workmates create antibodies- loads of small proteins, little claws that latch perfectly onto
a particular antigen, marking them for destruction. These two comrades have got your back and your immune system is brilliant at
spotting and fighting pathogens that invade from outside. However, they’re not so good at spotting your
own cells that have gone rogue. The antigens on cancerous cells
don’t look weird, they look a lot like your own cells, and the T’s and B’s aren’t
programmed to attack them. The usual way to deal with cancer is
to try to cut the tumor out, or turn to radiotherapy and
then chemotherapy to destroy or block the
growth of cancer cells, but if it’s a blood cancer, if it’s
floating around your whole body, you can’t do that. And if the blood cancer actually starts in
your white blood cells- those key guards in your immune system- you’ll really struggle to spot it. That’s the case with acute
lymphoblastic leukemia, and that’s where CAR T-cell therapy
is kicking butt. The biohackers are reprogramming a
patient’s own immune system to recognize particular antigens- those
particular protein fragments- on the cancer cells. To do it, you first need millions
of a patient’s T-cells Then, to get a T-cell to do
something different, you need to replace its normal
code with something new, something you’ve designed. What synthetic biologists can now do
with DNA is super cool- they use a computer to put together
their own sequences of bases- the chemical letters that spell
out the DNA- then they model what that new genetic
code will do on a computer and then make those sequences
on a DNA printer- yeah, that’s a thing!- printing not with ink, or with a plastic
polymer like in a 3D printer, but with those fundamental
building blocks of life, with those A’s and C’s and T’s and G’s. The new code they designed for a
T-cell has 3 key instructions: 1. It tells it how to recognize
and kill a cancer cell. More specifically, how to modify an antibody- what the B-cells make to latch
onto a target antigen. The antibody is modified to
make a new receptor that can detect the particular antigens
on the specific cancer. 2. It tells it to make copies of itself
when it finds that cancer cell and 3. It tells it to survive
in the patient’s body. To get this new code into
the patient’s T-cells, you use a vector- it’s something that will easily
infect the T-cell and carry that bespoke DNA in with it. And voila!
One CAR T-cell. The name comes from a fire-breathing
monster from Ancient Greece, that had a lion’s head, a goat’s
body and a serpent’s tail. It was called “Chimera”-
a name that has now come to be used for something that contains two or
more different types of tissues or cells. As this newly engineered cell’s genetic
code is part T-cell, part antibody, it’s a “C”himera and it goes in search
of the cancer’s “A”ntigen using its new “R”eceptor. Before you put the multiplied up
T-cells back into the patient, you give them a mild dose of chemotherapy
to wipe their existing T-cells. Then you simply reinsert the
now modified T-cells- the CAR T-cells- and they follow their normal DNA
programming to move and search. However, thanks to their new
butt-kicking code, they’ve changed what they’re looking for: they’re now on a mission to find the
cancerous cells and destroy them. Unlike conventional chemical-based drugs that get used up or excreted from
the body pretty quickly, CAR T-cells are living drugs that stay in
the patient’s bloodstream for years. That’s a huge pro. The flip side is that they’re expensive- each CAR T-cell treatment is
bespoke to the patient- and it’s more difficult to get them to
work with common cancers like breast or lung, because you need a
specific antigen on the cancer cells for the CAR T-cell to target- and it’s much easier to find
that in blood cancers. It’s still early days, though, and there’s an exciting
future for CAR T-cell therapy. Researchers like Dr. Martin Pule
and his team at UCL, are working on improving the leukemia
and lymphoma treatments even further, and there’s recently been some
promising work on solid cancers. Thanks to CAR T-cell therapy, the survival rate for B acute
lymphoblastic leukemia has improved hugely -nearly all patients go into remission- which means that leukemia cannot
be detected anymore- and most patients stay in remission. Biohacking is here, and it can reprogram your own
genetic code to enable your mega-meat-bot to do things it’s never been
able to do before!

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