John Brockman's EDGE asks a tough question every year. For 2017 the question was "What scientific term or concept ought to be more widely know?" My answer was:

Neurodiversity

Humans have diversity in neurological conditions. While some, such as autism are considered disabilities, many argue that they are the result of normal variations in the human genome. The neurodiversity movement is an international civil rights movement that argues that autism shouldn't be "cured" and that it is an authentic form of human diversity that should be protected.

In the early 1900s eugenics and the sterilization of people considered genetically inferior were scientifically sanctioned ideas, with outspoken advocates like Theodore Roosevelt, Margaret Sanger, Winston Churchill and US Supreme Court Justice Oliver Wendell Holmes Jr. The horror of the Holocaust, inspired by the eugenics movement, demonstrated the danger and devastation these programs can exact when put into practice.

Temple Grandin, an outspoken spokesperson for autism and neurodiversity argues that Albert Einstein, Wolfgang Mozart and Nikola Tesla would have been diagnosed on the "autistic spectrum" if they had been alive today. She also believes that autism has long contributed to human development and that "without autism traits we might still be living in caves." Today, non-neurotypical children often suffer through a remedial programs in the traditional educational system only to be discovered to be geniuses later. Many of these kids end up at MIT and other research institutes.

With the discovery of CRISPR the possibility of editing the human genome at scale has suddenly become feasible. The initial applications that are being developed involve the "fixing" of genetic mutations that cause debilitating diseases, but they are also taking us down a path with the potential to eliminate not only autism but much of the diversity that makes human society flourish. Our understanding of the human genome is rudimentary enough that it will be some time before we are able to enact complex changes that involve things like intelligence or personality, but it's a slippery slope. I saw a business plan a few years ago that argued that autism was just "errors" in the genome that could be identified and "corrected" in the manner of "de-noising" a grainy photograph or audio recording.

Clearly some children born with autism are in states that require intervention and have debilitating issues. However, our attempts to "cure" autism, either through remediation or eventually through genetic engineering, could result in the eradication of a neurological diversity that drives scholarship, innovation, arts and many of the essential elements of a healthy society.

We know that diversity is essential for healthy ecosystems. We see how agricultural monocultures have created fragile and unsustainable systems.

My concern is that even if we figure out and understand that neurological diversity is essential for our society, I worry that we will develop the tools for designing away any risky traits that deviate from the norm, and that given a choice, people will tend to opt for a neuro-typical child.

As we march down the path of genetic engineering to eliminate disabilities and disease, it's important to be aware that this path, while more scientifically sophisticated, has been followed before with unintended and possibly irreversible consequences and side-effects.

See the answers from everyone else on Edge.

This year, the Shuttleworth Foundation asked me to be the honorary steward of the September 2016 fellowship intake. This meant that I would help review and recommend the people who would receive the Shuttleworth Fellowship which funds the fellow's salary as well as their project up to $250,000. It's one of the most interesting and successful fellowship programs that I know for funding unique, provocative and unconventional individuals and their ideas. I'm a huge fan.

We saw some great applications and I was really happy with the three fellows selected for the round that I worked on, Achal, Isha and Ugo. Through the process I got to know their work quite well and I was excited to get a chance to meet Isha when I was in New York last week.

Isha Datar works on cellular agriculture research, the science of growing animal projects in cell cultures instead of farmed herds. It's a very new field with a lot of challenges including questions about how to make non-animal based nutrient systems, how to make it taste good, how to make it energy efficient, how to scale it, etc. At her non-profit organization New Harvest, Isha is working on the core research as well as funding and coordinating research across the world. What's exciting and important to me is that she's decided to do this in an open source and collaborative non-profit way because she and her colleagues believe that the field is still very early and that it would be advanced most effectively through this non-profit structure.

When I became the director of the MIT Media Lab three years ago, my previous primary "occupation" was investing in and advising startup companies. I invested in mostly Internet-related software and service companies (e.g., Twitter, Flickr, Kickstarter). Joining the Media Lab and MIT was bit of a "pivot"-academia was a fundamentally different model for impacting the world, focused more on fundamental science and technology that wasn't as easily commercialized.

In order to focus on the Media Lab after joining, I decided I would stop investing in startup companies. (I invested in Media Lab alumni companies, Littlebits and Form Labs, before I officially started at the Lab.) As I immersed myself in learning about the Lab and MIT, I continued to learn and think about how different types of science and technology made their way into the world. In particular, I was intrigued by how biomedical research, which has a major impact on human health, seemed to have an extremely different profile, requiring a great deal of upfront investment. I knew very little about biomedical research but was very interested.

Even before I arrived at MIT, I had heard about Bob Langer. He is famous for his impact on commercializing biomedical research, and for helping to substantially advance the field of bioengineering. He has 1,050 patents and a group of dozens of researchers. Bob is one of the 11 Institute Professors at MIT who are recognized by the Institute for their outstanding contributions and who report directly to the provost and not a dean.

Last June, David L. Lucchino, a former student of Bob's who had run a startup coming out of Bob's lab, invited me to my first Red Sox game together with Bob Langer and a few of his friends. I got to sit next to Bob and he offered to teach me about his field and show me how to do things at MIT. Since then, Bob has become a true mentor and now has an affiliation at the Media Lab, working with the Center for Extreme Bionics, an Institute-wide initiative based at the Media Lab to work on a wide variety of technologies focused on eliminating human disabilities.

Recently Bob told me about a related project that he has been working on as a co-founder and senior partner at a company called PureTech. PureTech focuses on taking science and engineering, primarily in the healthcare area, and developing innovative products and companies. It provides a base for researchers and funds the early development of both the technologies and the companies.

A team of senior partners, researchers, and entrepreneurs is currently working on 11 projects at various stages of development. The company is run by Daphne Zohar, its founder and CEO. On the surface, it looks like an incubator, but it really is a new model in many ways. There is actual translational research going on within PureTech, where the PureTech team is actively both acting as founders and also operating labs and running experiments.

Bob told me that more and more of the PureTech companies had software and Internet elements, and that they were looking for more expertise in that area on the board. This sounded like the perfect opportunity for me-participating in conversations about healthcare, bioengineering and biomedical technology with the best in the field while being allowed to contribute an area of business where I had some experience.

Healthcare is universal: we are all patient-consumers on some level and the patient will increasingly be at the center of healthcare decision making. We will also be immersed in technology that can measure our physiology in real-time as shown by the emergence of wearables. As technology and clinical practice converge, digital technologies will also increasingly enter the world of mainstream medicine, creating an entirely new area increasingly being referred to as "electronic medicine," which has the potential for incredible growth. Vast amounts of data that Internet and tech companies use to make decisions can also be leveraged for healthcare, opening opportunities for real-time disease monitoring and new targeted patient engagement opportunities.

I recently joined the board and PureTech announced a new funding round today. I have been working on two companies in particular, Akili - a cognitive gaming company that aims to diagnose and treat cognitive problems, and another cross-disciplinary digital health project that is still in stealth mode.

I think that healthcare and bioengineering are exciting spaces that are growing quickly, and thanks to many amazing labs in this field in the Kendall Square/Cambridge area, we have a regional advantage. I hope that PureTech can help create an effective pathway to impact health in new and positive ways, and that I can help contribute to this while continuing to learn.

Photo: via Alkili

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.