Kabuki Theatre and Desktop Epigenetics
This is episode 3 of The French Tech Comedy, Season 2
Episode 1 of Season 2: Your DNA Will See (and Mutate) Your Credit Card Now
Episode 2 of Season 2: The Bitcoin That Pulled the Double Helix Apart
For Season 1 of The French Tech Comedy (all episodes), see here.
Previously in The French Tech Comedy: In Season 2 of The French Tech Comedy, we follow characters like Japanese oncologist and bioinformatics engineer Takafumi Nagato, who is leading the lab of Bioinformatics for personalised CAR-T-therapies in a Tokyo clinic, and his patient, Chinese giant TenBa’s founder Ken Ba, a zillionaire from Shanghai. Yuki, Taka’s sister, is a French-speaking geisha, meaning “artist” in Japanese, in touch with the French Tech. She just got married to a French engineer who was working in Taka’s lab, Nono, and has secretly donated her healthy T-cells to Taka’s patient who, after his second cancer relapse, decided to try an innovative treatment called “liquid biopsy”. Indeed, Ba is becoming an expert in genomic precision medicine. In his case it is a matter of life or death. Among Yuki’s friends in the French Tech branch is Frederic Mougin, a biologist, founder of the startup Gene-i-us:
“We are developing a patient-centric tool for patients to collect, share & monetize their medical, genomics, lifestyle, IoT data with academics & pharma industry.”
Yuki had promised she would introduce Mougin to people working with Facebook Singapore; among them: Nono. What biz plan can Gene-i-us implement, in order to work with Facebook? Mougin is using a lot of buzz words, but when it turns out Ba’s cancer mutation has entered the stock exchange market, thanks to the efforts of a pharmaceutical company, his oncologist, Taka, fears a Ba Gate. More than ever, the privacy of genetic data is instrumental in the process of developing precision medicine. Singapore is the Chinese Mecca of I.P. and patents. A cryptocurrency, that is seen by financial specialists as a security, is used as a way to reward (healthy and sick) patients in exchange of their DNA data. Yuki is wondering if this kind of money will revolutionise the whole financial and pharmaceutical market as we know it, or will all digital currencies end up behaving like any other tradable financial asset? After all, a security is a tradable financial asset.
— — — — — — — — — — — — — — —
“ — Conventional chemotherapy will destroy fast-growing cells, including cancer cells. Epigenetic therapy will target mutated epigenetic regulator proteins, affecting the cancer cells but leaving the healthy cells intact. There are two possible approaches to reversing the epigenetic changes that take place in cancerous and other abnormal cells. The first is to target the abnormal epigenetic regulators that are ultimately responsible for the changes; the second is to erase and overwrite the modification patterns themselves.
The latter approach is easier and has therefore been better developed, but it has some drawbacks. For example, drugs that remove methyl groups from accidentally silenced parts of the DNA will also indiscriminately remove methyl groups from regions that should stay silent. This lack of specificity can cause drug side effects such as nausea and fatigue. Nevertheless, this non-specific approach does show some promise.”
“ — You mean you have to erase all the highlighting that shouldn’t be there, the trick is not to touch too much of the useful stuff, right?”
“ — Exactly.”
Taka was in the middle of a press meeting, talking to journalists. He had agreed to work with the prestigious Doudna lab in California on a project called “Science and Society”, sponsored by Facebook Japan and their management in Singapore. Many countries were starting to “join the force”, like UK, Spain, Italy, the Nordic Countries, Japan and China, Viet-Nam, Malaysia, etc., but for some reason, France was still reluctant. Yuki was so sorry about this.
“ The principle of precaution has been written in the constitutional law in France,” said Thomas, a famous French blogger and @nthropologist, to Yuki. She had met with him earlier this year, as he was visiting Japan with the rest of the French Tech delegation.
“ — This means that innovative startups like Desktop Epigenetics are banned from working in France. Also, you cannot have your genome (the entirety of your DNA data) sequenced on your own initiative, as this is forbidden by the French Bioethics Laws. You have to follow the doctor’s orders. Most of physicians right now are ignorant about CRISPR, epigenetics, BRCA 1 and 2 testing for women — and even for men, since men can get breast cancer too.”
Thomas was trying to explain why France was so behind in the Genomic Precision Medicine race that was taking place right now. The winners so far: UK, China, and USA. Yuki was listening to Thomas, a frown on her face.
“ — I feel so sorry,” she said.
“ — So do I,” said Thomas. Even if both were sincere, their motivations were worlds apart. Thomas was dreaming of France as an innovative country that had nothing to envy about other places in the world, like Singapore, the Switzerland of Asia, or California, or Shanghai and Shenzhen — Tencent, Baidu and Alibaba in your neighbourhood, clean sky. Yuki’s dream was different. She loved Paris, the old and elegant buildings, she would have wanted to work in France. She was just in love with the language and the culture, whereas having to speak English while living in Singapore with Nono was no fun at all for her. However, the job opportunities for her were in Singapore, not in Paris. She had been creating and extending her own line of cosmetics. A holistic skin beauty solution based on revolutionary water engineering technology, effective and super-moisturising. It was now a famous skin care product in Japan, and had been introduced in all the cosmetic shops on Orchard Road. Its name was “Mizu”, meaning water in Japanese.
Yuki means snow in Japanese. So she had started a blog a couple of years ago, with a pseudo: Mademoiselle Neige.
“ — Is it true that you just co-founded Desktop Epigenetics, a new startup in Fukuoka?”
“ — Yes, that’s correct. Ken Ba, the founder of TenBa, agreed to cover our needs, our first financial round was successfully completed the day before yesterday. We have raised funds for the upcoming couple of years, according to my estimations, but CRISPR ain’t cheap. By the way, most of the people working in this startup are already working in my lab. We have already secured 32 patents.”
“ — Is it true that you are also working on a cryptocurrency, and that the project is addressing the issue of protecting the privacy of genetic data?”
“ — I am afraid I am not at liberty to discuss this with you today, sorry.”
“ — You recently stated: after significant efforts to enhance the efficiency of this process, we are left with the conclusion that this gene repair strategy is still some way away from clinical application. Is it still the case?”
“ — No, thank you for asking this question. We are making quick progress. Patients who experience a relapse of their cancer need our innovative treatment, we are trying to speed things up as much as we can.”
“ — Can you tell us a bit more about the drugs called histone deacetylase (HDAC) inhibitors?”
“ — Yes. Those drugs prevent the removal of acetyl groups from histone tails. They can thus restore the transcription of silenced genes, including tumour suppressors, and have already been approved for use against some cancers. Their benefit might be limited to cancers with very specific types of epigenetic abnormalities, but they are also being tested as treatments for other diseases, including Kabuki syndrome.”
“ — What is Kabuki syndrome?”
“ — It is a genetic disorder caused by a mutation in an epigenetic regulator. It causes distinctive atypical facial and skeletal features, among other symptoms. It owes its name to a traditional form of Japanese theatre, kabuki, the stage makeup of which was thought to resemble the facial characteristics of those with the disorder. About three quarters of cases are caused by inherited mutations in the MLL2 gene. The MLL2 highlighter protein usually adds transcription-activating methyl groups to histone tails; mutation of the protein, as occurs in those with Kabuki syndrome, eliminates this function.
Other cases of Kabuki syndrome involve mutations in the KDM6A gene, which normally codes for an eraser protein that removes repressive methyl groups from histones. The effects of KDM6A and MLL2 mutations are essentially the same, both involving the inappropriate repression of gene transcription.” (1)
“ — Is it true Desktop Epigenetics is also working on that cancer mutation that is now traded on the stock exchange market? Are you competitors to the pharmaceutical company that successfully listed this genetic data on the stock exchange?”
“ — Every startup can be described as a competitor to big pharma, until it gets bought by a pharmaceutical company,” said Taka with a smile.
“ — You once said that startups are the new R&D in the pharmaceutical industry, since those conglomerates are not investing in R&D anymore?”
“ — Did I actually say this? I cannot remember, but maybe there is some truth in this statement, who knows?”
“ — As you may be aware, hackers working for the government in Beijing were able to identify the owner of the cancer mutation data. Authorities in Beijing are hiding the identity of the owner, leading us to guess that it must be a rich Chinese citizen. Any idea who might that be?”
“ — …”
Taka was starting to sweat.
“ — Did you know that so far, 13 journalists got arrested in China for trying to write on this subject, some of them, according to certain sources, might even have been executed? The patient must be big in China, which leaves us with a couple of alternatives to chose from: either he is a communist party executive, or a tech zillionaire. As a journalist, I pray for the second alternative to come true. No doubt it will spice things up for us, American life science journalists, living in the Twittler era.”
Taka suddenly wished he never got involved in the damn science and society thing. Worldwide famous scientist Doudna, when kicking off the project, talked about CRISPR and its use to cure diseases. The blurring of the frontier between curing and enhancing, and so on and so forth. She never said scientists would have to deal with a gene editing tool, CRISPR, that also happened to be a geopolitical editing tool. How ironic. The medicine that one day would enable us to erase genetic diseases already had a side effect: geopolitics.
“ — To wrap things up, let me just remind us that the future is already here — it’s just not very evenly distributed. William Gibson. That’ll be all for today, thank you everybody.”
The windows of the meeting room overlooked the famous Ghibli clock of Tokyo. The Ghibli glockenspiel was coming to life, it was 6:00 pm. Taka drank from his bottle of fresh water and left the press conference room, trying to take deep and slow breaths.
(1) Epigenetics, a graphic guide, by Cath Ennis and Oliver Pugh, pages 128, 143, 144, 145. I bought this great book a few days ago at Kinokuniya bookstore Singapore.
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
