The Science of Sakura
First episode of The French Tech Comedy
Chinese giant TenBa’s founder Ken Ba, a zillionaire from Shanghai, is sitting at Libro, Tenjin Fukuoka. Cool bookstore. Design: breathtaking. But he’s come here to discuss something even more breathtaking: the spreading of his cancer. Tasting as bitter as Oi Ocha, that Japanese green tea he’s been sipping from all morning. Fukuoka, the city of startups, combined with the country’s expertise on stem cells. In the midst of uncertainty and turmoil, this beauty and, yes, serenity. Beauty heals, they say. But in his case, the professional Geisha who was on his mind, albeit of great beauty, most certainly, was here for a very specific reason that had nothing to do with aesthetics.
Takafumi Nagato, the oncologist who was leading the lab of Bioinformatics for personalised CAR-T-therapies in a Tokyo clinic, said this Geisha Ba has never met with was the perfect match. Instead of koto and haïko and sakura sakura, the usual paraphernalia, Taka had been praising the girl’s T-cells.
« — She’s the perfect match for you. » He carried on:
« — You can’t just inject someone’s cells into another person. The donated immune cells may recognise the body’s cells as foreign and attack them. Normally a T cell is supposed to make a survey inside the body for any intrusion from the outside. We are supposed to remove that T cell receptor, in the hope that the donor cells won’t launch an assault on the recipient’s cells. But there are severe side effects to this. You can die from infection, or it can even trigger your cancer back… »
« — Same as for organ replacement medicine, with anti-rejection drugs, I guess… »
« — More or less, yes ». Taka paused for a second. Few people knew this, but a small majority of those kidney transplant patients who were lucky enough to escape graft or transplant rejection, or infection, ended up dying because of skin cancer, a couple of decades after the transplant, or even sooner in most cases. The immunosuppressive drug has serious side effects. A transplant is not a cure, you are literally sitting on a ticking bomb, trying to buy time… Same story if you remove the damn T cell receptor. Taka’s lab was heavily relying on an A.I. medical program, trying to match patients and donors for CAR-T-therapies. Baidu, Tencent, Alibaba, iCarbonX… China’s technological titans had heavily invested in precision medicine to cure cancer, and they were still pouring in a lot of money.
« — We don’t remove T cell receptors, » explained Taka.
« — Instead, you are trying to match a healthy donor with a cancer patient. »
« — Exactly… Or rather, more or less »
« — … »
« — Actually, we are trying to combine stem-cell derived immune cells, obtained from your own blood and skin, with immune cells from a healthy donor. The Geisha. But instead of having a baby with her, what you’ll get are immune cells just for you, that will be as good as new. The hybrid bioengineered stuff will be made with that cool CRISPR gene editing tool, or more exactly, one of its grand-kids. A sixth-generation DNA and RNA base editor. »
Ba knew the story already.
« — A new program… »
He paused.
« — In this story, I ‘m the lab rat. And also, third cancer recurrence… »
Both men sat silent.
« — Relying on a novel drug and a brand new A.I. program at the same time. Lucky me. »
The donated healthy immune cells had been re-engineered, together with his own skin and blood cells. Ba knew it.
« — I’m small, skinny, and yellowish. The only sure thing in my sex life right now is, or rather are, combined side effects of drug cocktails. So yeah, I guess there are worse things that could happen to me than throwing some Geisha in the mix. »
« — Is that a yes? » asked Taka.
« — I can’t exactly afford saying no to a geisha offering healing with such inventiveness, even if there’s this pimping A.I. thing between the two of us. »
« — Ha! Good to hear I’m not the pimp in your story. »
« — Just curious. Will I get to meet with this geisha? »
« — Is that your way of asking me when we are getting started with the treatment? »
« — That’s a yes. »
« — How about right now? », asked Taka.
« — Wait, you mean right here, at Libro? Aren’t we supposed to do that at your clinic in Tokyo? »
Taka didn’t answer the question, instead, he tried to dodge it. While he was answering his phone, Ba was trying to figure out what kind of donor program was being implemented in the lab of Bioinformatics for personalised CAR-T-therapies, but Taka was very secretive about this. How do they recruit donors, and in the first place, how do they motivate them, screen them, what do they take from them, do they get any money in exchange? Any side effects for them? None of his questions had been answered — and those were rather obvious questions. The basics of this donation program remained a total mystery. Everything seemed to be running through this physician, Taka.
« Japan. What a secretive world, » he thought.
Apparently, Taka was talking with some kind of investor (or journalist) who was investigating about the right dose of off-the-shelf cells for patients, or more exactly, how to figure out the right dose. Ba knew what they had done with his blood and skin cells. They had converted them, or reprogrammed them into embryonic stem cells (induced pluripotent stem cells was the technical expression) having the ability to turn into any type of specialised cell in the body, including, of course, immune cells, or even CAR-T cells that are engineered to fight cancer. Healthy T cells had been grown from one line of stem cells, coming both from him, Ba, and the geisha.
« How do they figure out the right dose for the combination? How do they merge both lines of stem cells, hers and mine, into one? » No answer to these questions so far. The only thing he knew was that this single line of stem cells could be cloned and expanded whenever needed. « Will this be covering risks of relapse? How about those risks? » The questions popped in his head, almost against his will, and made him shiver.
There’s no way Ba was going to start the treatment with none of these queries answered. As soon as Taka was finished with the journalist, investor, whatever, the cancer patient opened his mouth.
« — We are quite not done with our little questions session, I’m afraid, Doc. »
« — Yes. I’m sorry. »
Was Taka sorry about the phone call that had just interrupted them, or about the unanswered questions? Ba was not sure. He wanted to speak again, but his eyes were caught by the background animated image on Taka’s smartphone. A young, stunningly beautiful woman, playing the flute. Probably a total stranger to the world of genetically altered immune cells to fight cancer in a semi-personalised therapy. The initial highly personalised treatment, called CAR-T therapy, used a patient’s own immune cells and took about one month to manufacture, with a $500,000 price tag. The cost and time it took to make each dose put these life-saving treatments out of reach of patients who desperately needed them. The irony was that zillionaire Ba had the money (for him, a drop in the ocean), but time was not on his side…
« — Your girlfriend? Or your wife? », asked Ba, almost by automatism.
« — My sister », answered Taka. He was looking nervous, in an unusual way. That, and the fact that he did not seem too keen to bring his patient to the Tokyo clinic with him…
« — Sorry I asked, » answered Ba, looking intently at Taka’s face.
Both men sat silent for a while. Taka was sweating.
« — Now what are those questions you wanted to ask me? » The oncologist sounded like he was having a hard time trying to keep his voice steady.
« — Actually, I’ve only got one question for you. »
« — Go ahead… »
« — Your sister a geisha? »
Taka stood up and invited Ba to follow him:
« — Now it’s time… Let’s get to this private lounge they’ve prepped for us, shall we?»
« — So that’s a yes, » answered Ba. Together, they walked to the lounge.
For Yuki & Takafumi N.
Fiction inspired by MIT Technology’s article: “Patient Death Won’t Slow Research on Off-the-Shelf Immune Cells to Treat Cancer” by Emily Mullin, Sept. 8, 2017 (link)
Catherine Coste
MITx 7.00x, 7.QBWx, 7.28x1–2 certified
Member of the Walking Gallery of Health Care, founded by US activist Regina Holliday
