Ichi Efu

CATHERINE COSTE
The French Tech Comedy
10 min readOct 8, 2017

This is episode 20 of The French Tech Comedy by DNA cowgirl.

Episode 1: The Science of Sakura

Episode 2: Lost in Telomere Translation

Episode 3: Feel Flee to Donate

Episode 4: Pasteurising Tech With the French Touch

Episode 5: The Newborn Symphony Project

Episode 6: The Unknown 9% of the Human Genome

Episode 7: The Apple Tech Specs Conference

Episode 8: religA.I.on

Episode 9: Hiroshima is Japan’s World Trade Center

Episode 10: Mao’s Robots

Episode 11: Zazen in the Shinkansen

Episode 12: The Last (French) Samurai

Episode 13: To Humanity and Beyond

Episode 14: The Music of Genomic Origami

Episode 15: Direct-to-consumer Ikigami Genetics

Episode 16: Underground Science

Episode 17: Gene Karaoke Groove

Episode 18: The Osaka Forever-Young Army

Episode 19: The Toilet Slippers

“ — There’s a 50% chance of a major nuclear accident happening somewhere in the world.”

“ — Who told you that?”

“ — IBM Watson. Or rather, his made-in-China siamese brother.”

“ — So what? What data did they feed your Chinese Watson? Garbage in, garbage out.”

“ — Actually the US-made ones came up with the same risk or rate ratio.”

“ — China having issues with coal; Japan with nuclear. So what is your new manga about? Some kind of Ichi Efu Millenium?”

“ — More like Millenium with CRISPR, you know, that cool gene editing tool to modify RNA.”

“ — Modifying NRA?!”

“ — RNA. Like DNA, but with an R instead. Biology stuff. What is NRA?”

“ — Gun lobbying in the US. Super powerful. National Rifle Association. As close as it gets to the US government — from all sides. This one, the previous ones, the following ones…”

Kazuto Tatsuta “Au Coeur de Fukushima”, manga

Koba, the manga artist working with Yuki on the French Tech project in Japan, is discussing with Ron, a US native freelance photographer working in Osaka, amateur and connoisseur of local underground culture. They are headed to Farplane — at the top floor of the building, where a burlesque party is taking place. Last time Koba had met with Yuki in the area was a nightmare. She surveyed each and every damn kimono, used or not, in two shops in Nippombashi: Kimonoya and Daifukuya.

“ — How do I get to Shinka submarine bar?”, asked Koba. Ron had been working in Osaka for a couple of years only, but he was quite the insider. He seemed to know everything and everyone in nightlife Osaka.

“ — It’s a great place to have a drink and draw. The place looks like a real-life submarine. What’s your train station? Subway, I mean.”

“ — Shin Fukae, pink line.”

“ — Then the Shinka submarine bar is located at Exit 7 of Tanimachi 6 Chome Station. Tanimachi Line is the purple one. Take the Sennichimae line from Shin Fukae and get off at Tanimachi 9 Chome, change to Tanimachi Line and it’s one stop away.”

Ron was a human GPS; whereas Koba was spending a lot of time at his apartment. In his area, he mainly knew about Don Quijote Namba, cheaper than convenient stores. But every tourist knew this. Japanese people referred to the shop saying “donki” — donkey.

Yuki was panicking. She had just started a new part-time job at Singapore, where she was now living with Nono, the French engineer working with her brother and Facebook Japan, and she was now in charge of re-branding a cosmetic product that was very popular in Japan, making it more upscale. In Daiso Japan, this aloe hand cream was really cheap.

She also needed time to stroll around and discover new places in Singapore, do a lot of people-watching and see the beautiful seaside - and botanic gardens. She had found yoga master classes for a reasonable price (cheaper than in Japan!) and was looking to select one to attend. Also, she needed to update her resume, and seek a place where she would teach yoga and ballet. But Nono had just texted her that Koba would visit them next week-end, staying for a couple of weeks, and he was counting on her to help Koba make the most of his stay in Singapore. She had almost forgotten about Koba and that scifi-ish manga project. But she knew Taka was interested. A manga about biology, T-cells in cancer, and CRISPR-Cas <add a number>…

The number corresponds to a specific cutting activity of the Cas protein. Yuki wasn’t sure. Koba seemed to be more interested in cool sci-fi stuff than in real-life science.

When Koba arrived and soon after he was able to settle down in Nono’s huge apartment in Singapore, Yuki called Taka on Skype, for him to be able to update the manga artist on the science project. Her brother, as it turned out, had cutting-edge (literally) medical news that he wanted to share with the manga artist.

“ — The gene-editing tool CRISPR is based on a natural defense system embedded in bacterial cells that recognizes and destroys invading viral DNA.

What if we could add that same attack mechanism to our own cells? To do it, we need to be repurposing CRISPR to go after a different target: RNA, the messenger molecule involved in transferring and decoding the genetic information stored in DNA.

In diseases like ALS, Huntington’s and some types of muscular dystrophy, RNA builds up and makes aberrant proteins that cause disease. We are particularly interested in these diseases because they have no effective therapies and can be fatal. We want to use CRISPR to destroy toxic RNAs and reverse the devastating effects of disease.

Normally, CRISPR uses a slicing protein called Cas9 that recognizes and chops up the desired DNA, eliminating a mutated gene. We have modified Cas9 to leave DNA alone and instead bind to and cut problematic RNA… We think more than 20 genetic diseases that are caused by toxic RNA repeats could potentially be treated this way.”

“ — Wow. Is it going to work any time soon?”

“ — Good question. The answer is no, though, yes.”

“ — …”

“ — Let me explain the whole thing. Knocking down these RNAs is only temporary. RNA constantly regenerates, so its level in cells eventually rebounds back to normal after a few days to a week. That’s actually a benefit of using CRISPR to target RNA instead of DNA — the effects aren’t lasting. With RNA targeting, there’s no permanent, irreversible damage to the genome.”

“ — But for life-threatening conditions, we’ll need something that will last longer than just a few weeks, right?”

“ — That’s the interesting part for your sci-fi or manga project. You could be designing a virus capsule to carry the CRISPR machinery to the right cells. These viral delivery shuttles would allow the Cas protein to stick around in a person’s cells longer — ideally for years, turning Cas into a mini-arsenal to keep unruly RNA at bay.”

“ — What’s the difference between that CRISPR machinery that will edit DNA and the one that will edit RNA?”

“ — To edit RNA, the approach would probably require repeat treatments over the years. That’s different from using CRISPR for editing DNA, which would be a one-time injection or procedure. Our lab has been working on another cutting protein known as Cas13 that could be used to detect, slice, and track RNA in human cells.”

“ — But what does it have to do with cancer?”, asked Yuki.

“ — We used this protein to reduce RNA levels expressed by three genes associated with cancer.” (1)

“ — Any proof this might work so far?”, asked Koba.

Taka was reluctant to answer this question with all the details, but Yuki knew. Cas13 was the protein that had been designed by Taka’s lab team, including Nono, to cure Ken Ba’s cancer. And Chinese giant TenBa’s founder, a zillionaire from Shanghai, was currently investing loads of money in xenotransplant, aimed at providing humanized organs for transplants, coming from pigs. This potential solution to the crisis of worldwide organ shortage was involving CRISPR, too…

What Yuki didn’t know about, though, was the human cloning experience that was going on in China. Designing a human being that would be more tolerant to highly polluted environments, keeping lung cancer at bay. Another job for this CRISPR tool.

Kazuto Tatsuta “Au Coeur de Fukushima”, manga
Kazuto Tatsuta “Au Coeur de Fukushima”, manga

CRISPR was also used to engineer biofuels, or bioengineered algae, to get energy in a more sustainable way. Bacteria helping produce biofuels. But all this was more or less sci-fi stuff: right now, coal, nuclear and oil seemed to be here to stay… Pollution in China and India would not evaporate tomorrow morning…

“ — Unless we can re-design ourselves with CRISPR,” said Koba:

“ — Cloning. But beware the Ichi Efu cloning: they tried to clone god in the US, they got gun instead. Also three letters, also starting with a g, but something happened on the way to heaven…”

“ — If you want to write about what’s happening right now, in precision medicine, in the US,” said Taka to the manga artist:

“ — Strata Oncology said today that it has partnered with the University of California, San Francisco to launch a new initiative called StratifyProstate, which aims to expand access to precision medicine for men with metastatic prostate cancer by accelerating clinical trial enrollment.

Under the initiative, eligible metastatic prostate cancer patients anywhere in the United States can now receive no-cost New Generation Sequencing (NGS) testing via enrollment in the Strata Trial, an observational study sponsored by Strata to study the impact of sequencing on clinical trial enrollment.

The larger 100,000-patient Strata Trial is currently available to advanced cancer patients with a variety of solid tumors and lymphomas, and was launched in February 2017 at select clinical research sites.” (source)

Yuki was already asleep when Nono, back from work, invited Koba for a late dinner. It was already close to 1:00 am, but this was Singapore… They discussed the consequences of the CRISPR tsunami. And how they should outline the storyboard for the French Tech manga. Nono as well as the rest of the team were great fans of French movie maker Luc Besson. Koba would turn Yuki’s personality into Millenium’s character Lisbeth Salander, the female hacker — Nono found this very funny. Wasn’t the Japanese geisha always complaining about the hollow conversations she could hear around her most of the time? Nono had been working in a gaming company where they could spend 3 hours in meetings discussing the color of the superhero’s panty. Meanwhile, shopping at Aeon supermarkets in Tokyo or Fukuoka, Yuki could see very old ladies, alone, who were trying to get some food. They were literally broken in two by rheumatism. Each time she saw that, her heat was broken. She thought about her grandma, very old now, but still fit. For how long? Preventing the pandemia of aging was what mattered most. In Japan, the population was declining, losing 300,000 people each year. And this wasn’t due to the Ikigami.

“ — So this is how I see it,” said Nono to Koba:

“ — The clone, or the original, wanting to leave the clone alone, without standing in his way, ends up transferring his soul in a cybernetic body, filled to the brim with A.I. innovative tech. Leaving the Earth in a probe, he is headed to some kind of stars. This is how Opus 1 of The French Tech manga project ends. For Opus 2, the action takes place 1,000 years after that, on Earth and in deep space. Opus 3 sees the come-back of the android on Earth… In 500 years, the evil will return, and so will we. At least, this is what Luc Besson says.”

On the next day, Yuki, after a short discussion with Koba who seemed to be hard at work, sent a text to her brother Taka. Yesterday’s Skype session was helpful for the manga artist! She wrote:

“ — Speaking of cloning. That innovative science communication project of yours has legs…”

Besson’s Valerian and the City of a Thousand Planets (link)

“This motley trio — who vaguely resemble older, de-feathered cousins of Marvel‘s space fowl, Howard the Duck — periodically appear throughout the film to offer important information to intergalactic agents Valerian and Laureline (Dane DeHaan and Cara Delevingne)…for a price. I love them because they are very cynical, very polite, and make deals all the time, Besson tells Yahoo Movies. They’re also useful because they speak over 500 languages, so you can use them whenever you need to.” (source)

Link
  1. Source: Arming Bodies with CRISPR to Fight Huntington’s Disease and ALS, by Emily Mullin, MIT Tech Review, October 5, 2017

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

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CATHERINE COSTE
The French Tech Comedy

MITx EdX 7.00x, 7.28.1x, 7.28.2x, 7.QBWx certified. Early adopter of scientific MOOCs & teacher. Editor of The French Tech Comedy.