Academy of Achievement Golden Plate award model photoblog Academy of Achievement Golden Plate award model
Wed, Dec 31 19:00 UTC

I first heard about Synbiota at SXSWi this year, when they won an Accelerator Award. According to the announcement, "Synbiota is a virtual collaboration site that connects scientists, researchers, universities and others from around the world to solve complex problems using genetic engineering." That week they announced the world's first Massive Open Online Science (MOOS) event. Called #ScienceHack, hundreds of researchers from around the globe (some as clueless as us!) would use a new "wetware" kit to produce prohibitively expensive medicine at a fraction of the price.

A month later I got this email:

From: Connor Dickie
To: Joi Ito
Cc: Kim de Mora
Date: Apr 17, 2014, at 11:12
Subject: ML alumni wins SXSW prize for SynBio startup & Invitation to #ScienceHack

"I'm writing to invite you to participate in #ScienceHack, our distributed science effort to make real medicine for just a fraction of current costs using Synthetic Biology and the Synbiota platform. O'Reilly Radar recently called #ScienceHack the most ambitious distributed science project, and knowing your interest in biotech, I thought I'd reach out to you with a cool opportunity to learn with us.

Participation is easy - I'll ship you one of our "Violacein Factory" wetware kits, and connect you with Kim de Mora at iGEM HQ (CC'd) who is not only interested to build one of the kits, but also has the required wet lab skills. It will take about an hour and a half for the in-silico design and build of the actual DNA part. Kim would handle the incubation etc. You would then come back to his lab in about 5 days to look at the results.

We recently built a Violacein Factory kit here in Canada, and more recently at Genspace in NYC, and everyone learned a bunch and helped us make significant advances towards our goal of an optimized violacein-producing organism.

I'll be in Boston/Cambridge on the 27th-through-30th as part of a Canadian trade delegation, and will have some time to meet you and chat about the opportunity in person if it interests you.

With regards,

Connor Dickie
http://alumni.media.mit.edu/~connord/

I knew about iGEM. It was the spinout from MIT that brought high school and college students together to hack DNA much in the same way that robot competitions bring together kids interested in robots to hack and learn and compete. What's amazing is that iGEM, now bringing together over two thousand students at their Jamboree, takes the state of the art of synthetic biology and brings it to the masses.

Violacein is a natural purple compound made by Chromobacterium violaceum, a bacteria that is found in the soil in the tropics such as the Amazon. Violacein is created by the bacteria as a natural defense against amoebic creatures that try to eat it and is viewed as a potential anti-parasitic. It also appears to show promise as a treatment for cancer. The problem is that it currently costs $356,000 per gram because of the difficulty of harvesting it in the wild.

An opportunity to learn synthetic biology through doing it (my favorite way to learn) was too good to turn down so I immediately accepted the challenge. I started by taking the required safety courses for playing with recombinant DNA : General Biosafety for Researchers, check. Bloodborne Pathogens: Researchers, check. Hepatitis Information form, check. General Chemical Hygiene (web) and Managing Hazardous Waste (web). Check and check.

Then I started hunting for a place to do the actual work. That turned out to be a bit more of a challenge. Although the kit and process provided by Synbiota were basically safe and non-toxic, work with recombinant DNA and bacteria required a proper wet lab at MIT which are in short supply and used for more important things than the Media Lab director messing around with street bio.

After discussing with the team and looking at what we needed, we decided that my kitchen would be the least disruptive place to do the work.

On July 27, the Synbiota team and Kim from iGEM gathered at my house with a rag tag team of researchers from the Media Lab and elsewhere to work on the Violacein Factory #Sciencehack. We started with a briefing on what we were actually doing.

Our mission was to be one of the hundreds of teams participating in trying to innovate on developing the most effective method of synthesizing Violacein using synthetic biology.

Scientists have determined the metabolic pathway in Chromobacterium violaceum that converts tryptophan, a common amino acid, into violacein. This pathway involves five enzymes and various genetic sequences for their production. These "parts" of genetic code can be positioned differently in the DNA molecule and each combination has different attributes and tradeoffs - the optimal sequence and combination being currently unknown.

The #ScienceHack Violacein Factory Kit co-designed with Genomikon which develops synthetic biology kits, had vials of all of the various genetic "parts" and the other materials needed to assemble these parts into a plasmid. According to Synbiota:

This Kit includes everything you need except:

• pipettes, nitrile gloves, petri dishes, PCR tubes, lab coats (for the full biotech experience, but any ol' trench coat will do!)
• ice buckets and ice
• 42 C water bath with epi tube floaty blanket
• 37 C incubator

All the above can be found around the house, from online suppliers, at your local university lab store, or in a friendly scientist's stash.

Kim from iGEM brought everything from the iGEM lab. He walked us through the kitchen version of the protocol for using all of the equipment safely.

Synbiota, in addition to putting together this amazing #ScienceHack project has developed a suite of online tools to publish and share lab books online (I guess I don't need that fancy paper notebook I bought!), design DNA using a very nice graphical interface and provide researchers with a whole suite of tools to do synthetic biology as a community. Everything was very well designed and worked well.

First, I created an account on the Synbiota website and logged into our notebook. Justin explained the violacein pathway and explained how we can use the online gene editor, GENtle3, (video) to design the gene sequence online.

In GENtle3, we were able to drag and drop any of the genetic parts that came in the kit into our sequence and as long as we followed the basic rules of which parts could be connected to each other. The sequence I designed was Anc-ABEDDDC-Cap, where A, B, C, D, E represent the enzymes that make up the violacein metabolic pathway. (Visit the sequence tab in the Sciencehack project to view this and other designed sequences.)

The sequence had to start with the Anchor--Origin-X' part because that was the part that was attached to the magnetic bead. One of the keys to being able to do all of this amazing work in a kitchen had to do with this innovation.

In the kit were tiny sub-micron magnetic beads with the anchor part - a strand of DNA attached to it. What this meant is that we could use a small but very strong external magnet held to the side of the container - the epi tube - to pull all of the genetic material we were working with to the side of the epi tube allowing us to insert and extract liquids from the container using pipettes while leaving our working material secured to the container.

What we needed to do after designing our sequence was to assemble it. We did this putting the beads in a epi tube, adding a "wash", removing the wash, adding a genetic part from a color coded tube that corresponded with the next link in our design, adding the T4 DNA ligase, the "genetic glue" to attach that new part to the strand on the bead, removing the excess material, washing again, and then repeating until we had added each part in order to the bead. Theoretically, we should now have a long strands of DNA attached to each bead representing our version of the DNA sequence (plasmid) that we designed.

The last step was to use a buffer to remove the bead from the strands and we had a little drop of genetic material that when inserted into a living bacteria should create all of the enzymes necessary to produce violacein from tryptophan.

The next step was what was called "transformation" which is the process that takes our plasmid and inserts it into a bacteria, in our caseE. coli. The "competent" E. coli designed for easier transfection were created at iGEM. The process we used for transformation was called "heat shock" which involved adding our genetic material to a salt solution with the E. coli and then rapidly heating it which caused the genetic material to be absorbed into the E. coli. The device used for heating, I noticed, had a sticker from the "MIT Property Equipment Office" on it. Definitely a bit punk rock. After the "shock" we added liquid material with nutrients and minerals that "rebooted" the E. coli, waking it up and preparing it to be incubated for execution of the DNA code we just inserted.

The E. coli were then spread onto petri dishes with Jello-like "food" as well as an antibiotic, chloramphenicol. The chloramphenicol would kill all other bacteria on the dish except our own because we had cleverly included a chloramphenicol resistance building genetic part in our sequence.

We then sent the petri dishes back to iGEM for incubation. The results were not perfect, but none-the-less, it looks like violacein and other molecules from the pathway were created (some other got different colours). The images of my petri dish show a kind of blackish zig-zag smear which are billions of bacteria producing metabolites because the executed DNA I designed and created. At this point I don't know for sure whether violacein was created - I need to do more verification and experimentation, but for a first go at building a complex metabolic pathway, not too shabby. Something else that is cool, is that my intended DNA design was very long, 12,000 base pairs, the next #ScienceHack step is to verify that the entire code I designed was actually assembled properly. We shared our designs, protocols and procedures with the rest of the teams. The next step was to look at the work of the other teams and try to find out what we could improve and try again.

In two half days of work, we were able to do in our kitchen what would have been Nobel Prize winning work a decade ago. We designed a sequence of genes, actually assembled the genes and then injected them into a bacteria and rebooted the bacteria.

Also, unlike traditional labs where one team would do the work and publish a paper and then other teams would try to replicate the work, we worked as one large team of parallel labs sharing our work as we went along, iterating, innovating and discussing.

I think that there is a good chance that one of the hundreds of teams will discover an efficient way of synthesizing, extracting, and purifying violacein and that soon we will have something that will probably initially look something like a homebrew beer brewing contraption producing the extremely rare compound for researchers with instructions on how anyone can build one of these violacein factories.

--

Disclosure : After this experience, I was so excited that I donated to iGEM and decided to invest in Synbiota.

Last year, a group of Media Lab students visited Shenzhen with, bunnie, an old friend and my hardware guru. He's probably best known for hacking the Xbox, the chumby, an open source networked hardware appliance, and for helping so many people with their hardware, firmware and software designs. bunnie is "our man in Shenzhen" and understands the ecosystem of suppliers and factories in China better than anyone I know.

With his help, my students saw and experienced a ecosystem that we all benefit from, but mostly don't see or even realize exists. I have been living vicariously through the stories and reports of my students until last week, when I finally got my own tour of Shenzhen with bunnie.

bunnie insisted that we keep the group size very small because we would be going to places that couldn't fit many people and we wanted to be nimble. As chance would have it, Reid Hoffman, my old friend and founder of LinkedIn and the provost of MIT, Marty Schmidt, both were interested and available so this formed our odd little tour group.

The first stop on the tour was of a small factory run by AQS -- a manufacturer with operations in Fremont, California as well as Shenzhen. They mostly focus on putting chips on circuit boards. The factory was full of Surface-Mount Technology (SMT) machines which use computer programmed pneumatics to pick and place chips and other components onto circuit boards. In addition to the rows of SMT machines, there were lots of factory workers setting up the lines, programming the equipment, testing the results using x-rays, computers and eye balls and doing parts of the process that made more sense economically or technically to do by hand. AQS is the factory that is manufacturing thecircuit stickers designed by Media Lab student Jie Qi and Media Lab grad, Ayah Bdeir's, littleBits. What's great about AQS is that, with the help of bunnie, they have started working closely with startups and other projects that previously would have had a very hard time finding a partner in China because of the small volume, high risk and usually unconventional requests that go hand-in-hand with working with entrepreneurs and our creative students.

What was more impressive to me even than the technology were the people that bunnie introduced us to, such as the factory boss, John, and the project managers and engineers. They were clearly hard-working, very experienced, trustworthy and excited about working with bunnie and our friends. They were willing and able to design and try all kinds of new processes to produce things that have never been manufactured before. Their work ethic and their energy reminded me very much of what I imagined many of the founding entrepreneurs and engineers in Japan must have been like who built the Japanese manufacturing industry after the war.

In all of the small factories that we visited, including AQS, the factory workers lived in dorms surrounding the factory and ate together and lived together. All of their living expenses were supported by the factory and their salaries went entirely to savings or disposable income. Also, all of the managers and even the boss lived together with the workers. I'm sure we were picking good factories to visit, but everyone seemed happy, open and very close.

After AQS, we visited King Credie, which made the actual printed circuit boards (PCBs). The PCB manufacturing process is a sophisticated process involving adding layers while also etching and printing all kind of materials such as solder, gold, and various chemicals involving many steps and complex controls. They were working on some very sophisticated hybrid PCBs that included ceramic layers and flexible layers --  processes that are very difficult and considered exotic anywhere else in the world, but directly accessible to us thanks to a close working relationship with the factory.

We also visited an injection molding plant. bunnie has been helping me with a project that requires some relatively complicated injection molding. Most of the plastic parts for everything from cellphones to baby car seats are made using an injection molding process. The process involves creating "tools" which are the huge steel molds that the plastic is injected into. The process is difficult because if you want a mirror finish, the mold has to have a mirror finish. If you need 1/1000th of an inch tolerance in production, you have to cut the steel molds at that precision. Also, you have to understand how the plastic is going to flow into the mold through multiple holes in the mold and make sure that it enters evenly and cools properly without warping or breaking.

The factory we visited had a precision machine shop and the engineering expertise to design and machine our injection molding tools, but our initial production volume was too low for them to be interested in the business. They wanted orders of millions of units and we only needed thousands.

In an interesting twist, the factory boss suggested that we could build the precision molding tools in China and then send these tools to a US shop for running production. Due to our requirement for clean-room processing, he thought it would be cheaper to run production in the US -- but the US shops didn't have the expertise or capability that his shop in China had to produce the tools; and even if they did, they couldn't touch his cost for such value-added services.

This role reversal is an indicator of how the technology, trade, and know-how for injection molding has shifted to Shenzhen. Even if US has the manufacturing capacity, key parts of the knowledge ecosystem currently exist only in Shenzhen.

bunnie then took us to the market. We spent half of a day there and only saw a very small part of the huge network of buildings, stalls and marketplaces. The market was several large city blocks full of 5-10 story buildings with stalls packed into each floor. Each building had a theme or themes ranging from LEDs to cellphone hacking and repair. I realize it's cliché to say this, but it REALLY felt like blade runner in a way that even Akihabara never did. I think it had a lot to do with the fact that many of vendors were selling to factories so were focused on wholesale and not retail and the volumes were huge and the interfaces were rough.

We started in the section of the market where people were taking broken or trashed cellphones and stripping them down for all of the parts. Any phone part that conceivably retained functionality was stripped off and packaged for sale in big plastic bags. Another source of components seemed to be rejected parts from the factory lines that were then repaired, or sheets of PCBs in which only one of the components had failed a test. iPhone home buttons, wifi chipsets, Samsung screens, Nokia motherboards, everything. bunnie pointed to a bag of chips that he said would have a street value of $50,000 in the US selling for about $500. These chips were sold, not individually, but by the pound. Who buys chips by the pound? Small factories that make all of the cellphones that we all buy "new" will often be short on parts and they will run to the market to buy bags of that part so that they can keep the line running. It's very likely that the "new" phone that you just bought from ATT has "recycled" Shenzhen parts somewhere inside.

The other consumer of these parts are the people who repair phones. Phone repair starts with simple stuff like replacing the screen to full-on rebuilds. You can even buy whole phones built from scrap parts -- "I lost my phone, can you repair it for me?"

After this market where phones were "recycled" we saw equivalent markets for laptops, TVs, everything.

Next we went to another kind of market. When we walked in, bunnie whispered to me, "EVERYTHING here is fake." There were "SVMSMUG" phones and things that looked like all kinds of phones we know. However, the more interesting phones were the phones that weren't like anything that existed anywhere else. Keychains, boom boxes, little cars, shiny ones, blinky ones -- it was an explosion of every possible iteration on phones that you could imagine. Many were designed by the so-called Shanzhai pirates who started by mostly making knockoffs of existing phones, but had become agile innovation shops for all kind of new ideas because of the proximity to the manufacturing ecosystem. They had access to the factories, but more importantly, they had access to the trade skills (and secrets) of all of the big brand phone manufacturers whose schematics could be found for sale in shops. These schematics and the engineers in the factories knew the state of the art and could apply this know-how to their own scrappy designs that could be more experimental and crazy. In fact many new technologies had been invented by these "pirates" such as the dual sim card phone.

The other amazing thing was the cost. There is a very low cost chipset that bunnie talks about that seems to be driving these phones which is not available outside of China, but they appear to do quad-band GSM, bluetooth, SMS, etc. on a chip that costs about $2. The retail price of the cheapest full featured phone is about $9. Yes. $9. This could not be designed in the US -- this could only be designed by engineers with tooling grease under their fingernails who knew the manufacturing equipment inside and out, as well as the state of the art of high-end mobile phones.

While intellectual property seems to be mostly ignored, tradecraft and trade secrets seem to be shared selectively in a complex network of family, friends and trusted colleagues. This feels a lot like open source, but it's not. The pivot from piracy to staking out intellectual property rights isn't a new thing. The United States blatantly stole book copyright until it developed it's own publishing very early in US history. The Japanese copied US auto companies until it found itself in a leadership position. It feels like Shenzhen is also at this critical point where a country/ecosystem goes from follower to leader.

When we visited DJI which makes the Phantom Aerial UAV Drone Quadcopter we saw a company that was ahead. They are a startup that is growing at 5X / year. They have one of the most popular drones ever designed for the consumer market. They are one of the top 10 patent holders in China. They were clearly benefiting from the tradecraft of the factories but also very aware of the importance of being clean (and aggressive) from an IP perspective. DJI had the feel of a Silicon Valley startup mashed together with the work ethic and tradecraft of the factories we had been visiting.

We also visited a very high-end, top-tier mobile phone factory that made millions of phones. All of the parts were delivered by robots from a warehouse that was completely automated. The processes and the equipment were the top of the line and probably as sophisticated any factory in the world.

We also visited a tiny shop that could assemble very sophisticated boards in single-unit volumes for a price comparable to a typical monthly cable TV bill, because they would make them by hand. They place barely visible chips onto boards by hand and had a soldering technique that Americans will tell you can only be done by a $50,000 machine. What amazed me was that they used no assisted vision. No microscopes, magnifying lenses, etc. - workers in the US can do some of what they do, but they need assisted vision. bunnie posits that they do it mostly by feel and muscle memory. It was amazing and beautiful to watch.

We visited PCH International where we saw supplies coming in just in time to be assembled, boxed, tagged and shipped. What used to take companies three months from factory to store, now only took three days -- to anywhere in the world.

We visited the HAXLR8R, a hardware incubator in the middle of the market district run by a pair of French entrepreneurs.

What we experienced was an entire ecosystem. From the bespoke little shop making 50 blinking computer controlled burning man badges to the guy rebuilding a phone while eating a Big Mac to the cleanroom with robots scurrying around delivering parts to rows and rows of SMTs -- the low cost of labor was the driving force to pull most of the world sophisticated manufacturing here, but it was the ecosystem that developed the network of factories and the tradecraft that allows this ecosystem to produce just about anything at any scale.

Just like it is impossible to make another Silicon Valley somewhere else, although everyone tries -- after spending four days in Shenzhen, I'm convinced that it's impossible to reproduce this ecosystem anywhere else. What Marty, Reid, bunnie and I talked a lot about was what could we learn from Shenzhen to help the Boston and Silicon Valley (and more broadly the US) ecosystems and how can we connect more deeply with Shenzhen.

Both Shenzhen and Silicon Valley have a "critical mass" that attracts more and more people, resources and knowledge, but also they are both living ecosystems full of diversity and a work ethic and experience base that any region will have difficulty bootstrapping.

I do believe that other regions have regional advantages - Boston might be able to compete with Silicon Valley on hardware and bioengineering. Latin America and regions of Africa may be able compete with Shenzhen on access to certain resources and markets. However, I believe that Shenzhen, like Silicon Valley, has become such a "complete" ecosystem that we're more likely to be successful building networks to connect with Shenzhen than to compete with it head on.

-

I recently did a TED Talk where I provide a higher level context for my trip to and observations about Shenzhen.

Recent Media Lab grad Drew Harry and co-founder Frances Yun have launched a site called Six Questions. I recently participated and answered my six questions. Here they are.

last.fm


Monthly Archives