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!