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First Drafts: The Ugly, The Bad and The Good

Writing first drafts sucks.

For the past few months, I’ve been co-writing What’s Your Bio Strategy? with SynBioBeta founder John CumbersWe just completed the first draft. It feels monumental.

The process of writing a first draft is an epic like Sergio Leone’s classic spaghetti Western The Good, The Bad and The Ugly – one of my all-time favorite movies.

The Ugly

In the movie, Eli Wallach plays Tuco. A vicious criminal who will double-cross his partners at the drop of a hat. He’s eager for revenge and enjoys mocking and insulting his adversaries. He represents “The Ugly.”

Tuco made famous the phrase,

“There are two kinds of people in this world.”

And there are two kinds of people in this world: Those who have ideas for books and those who write the books.

Writing that first draft is Ugly.

John and I spent six months outlining What’s Your Bio Strategy? We formulated questions. We drafted lists of people to interview. We discussed and argued over business strategy books, articles, and methods. We got feedback from agents and publishers, friends and colleagues.

Once we started the interviews and the writing, I had a lot of doubts. There’s a little voice that loves to say, “Why are you writing this? It’s not very good.” I can usually avoid this with my business writing by delivering outlines, getting feedback, and keeping my clients involved in the process.

Eventually, I gave that voice to an ex-boss. Every time he appeared, I would say “Shut up. I’m writing the book and you’re not.” 

Also Ugly: I had a very unexpected health issue. I woke up one morning with double vision. I went to the emergency department, spent a night in the hospital. I underwent months of tests. The diagnosis? The auto-immune disease myasthenia gravis. I had to wear an eye patch for two months and am still on medication. 

The Bad 

In the movie, Lee Van Cleef plays “Angel Eyes” a ruthless, cold-blooded, sadistic psychopath. He takes pleasure in carrying out assasinations and “always gets the job done.”

Writing takes up all your time.

For us, the Bad took the form of schedules and travel. John and I were always on the road. In fact, John circled the globe during the writing. He traveled to Borneo, Germany, Denmark, London, San Diego and Singapore. My own travels to Basel, Boston, Los Angeles and Montreal look feeble compared to John’s. Without Skype and GoogleDocs, there would be no first draft.

That travel had an impact on interviews – we couldn’t schedule everyone. It required massive coordination. We couldn’t have done it without SynBioBeta’s Kristin Sorrentino, Claire Besino, and Marianna Limas.

Plus, both us of run our own business. For me that means business development and execution – often writing for clients. John joined the venture fund DCVC and launched a seed fund – that required a significant time commitment.

We both have families. During the writing, my son Alejandro went through the college application process, was accepted to Cornell, and graduated high school. My youngest graduated fifth grade.

I am a disciplined writer but to make word counts and deadlines, I got in the habit of waking at 4:30. Every time one of us missed a deadline, the other would call or send an email or text.

In the end, we got the job done and didn’t have to resort to being cold-blooded, sadistic psychopaths. There were a few times that we both had to be driven and ruthless.

The Good

In the movie, Clint Eastwood plays “Blondie, The Man With No Name.” He had made this character famous in A Fistful of Dollars and For a Few Dollars More.

He is calm, calculating, merciless, and keeps his eye on the prize – a coffin full of gold.

The time we invested in our outline and the book planning paid off. It made a huge difference. It made it easier to stay focused.

As the first draft started to come together, we made significant changes to the structure and flow. Those made the draft stronger. Without the planning, the book would’ve been a bowl of (western) spaghetti.

The people we interviewed were the Good. Every time we would end an interview, we would call each other to high-five virtually. We now share deeper insights into the field of synthetic biology and are happy to share them with you.

Having a co-writer was excellent. Writing is lonely business. It can be isolating. Having someone to speak with, someone to crack the whip on deadlines, accelerated the writing. Plus, we came up with a novel idea that we think is going to be big – Biology as a Service – and James Hallihan of Cambridge Consultants spoke to us about the concept of the Chief Biology Officer.

Finally, the best of the Good is completing the epic first draft. By time you read this, we’ll probably be on the twelfth or twentieth draft. But there is nothing more satisfying than sharing a drink – even if it’s via Skype – when you finally know the first draft is finished.

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Tim Gardner: “There Is Almost No Physical Problem That Can’t Be Solved With Biology”​

I’m co-author of a book called What’s Your Biostrategy? With SynBioBeta’s John Cumbers, we’re writing about the impact of biotechnology on ALL business. Over the next few months, I’m going to publish interview summaries from the book. For more information, scroll to the bottom of the post.

In 2000, Tim Gardner wrote one of synthetic biology’s seminal papers: Construction of a Genetic Toggle Switch in Escherchia Coli. At Amyris he led the engineering of yeast strains and pioneered process technologies for the large-scale bio-manufacturing of renewable chemicals. He founded Riffyn to create tools to accelerate innovation in research and development. My co-author John Cumbers and I interviewed Tim for What’s Your Bio Strategy? Here’s a few excerpts from the interview:

“To increase the size of the bio-based economy, we need to reduce the cost of developing bio-based products that would have been made from petroleum and chemistry. If we can do that, then developing more specialized products will be acceptable. We’ll stop searching for billion dollar blockbusters. We’ll have more entrepreneurial successes and investors will be happy because we’re delivering on the promises of the bio-based economy.”

[“At Riffyn, our] thesis is that the solution to faster, better, cheaper drugs, and faster, better, cheaper bio-based products is the predictability of information. It’s about integrating information to make better, informed decisions. It’s not necessarily about fancy robots or magical tools.”

“Engineering has more science in it than people realize.”

“The idea that scientists are being paid more or are delivering more value or are in greater demand is not entirely true. It’s hard to hire engineers.”

“Value tends to accrue to people and organizations that can reduce uncertainty.”

“There are organisms that can detect light or transform electricity into energy for survival. Muscles are incredibly efficient compared to the hydraulics or batteries that you might put into a robot. If we want to use those properties to make the world a more efficient, higher performing, more enjoyable place, then we need to learn how to learn from nature.”

Want to read the full interview? Visit What’s Your Bio Strategy?

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iGEM is the Future of Biotechnology

Jennifer Lopez and Zachary Quinto.

Biotech is going mainstream in a big way.

That was the message to the more than 5,600 high school and college students crowded into Boston’s Hynes Convention Center for the 2016 International Genetically Engineered Machine (iGEM) competition. Lopez’s production company is producing CRISPR, a near-future crime drama named after the gene-editing tool that Science Magazine dubbed 2015’s Breakthrough of the Year.

Quinto, star of Heroes and the Star Trek-reboot, is producing and starring in BioPunk, a drama based on the book of the same name. It explores the world of DIY-scientists and garage biohackers.

Standing in front of the crowd, FBI Supervisory Special Agent Ed You pointed out that, unfortunately, Lopez’ and Quinto’s shows will likely continue Hollywood’s long-standing war against science – a disservice to young people worldwide who might consider careers as scientists [1].

That disservice, he said, also presents a great responsibility to the students in the audience. Those students and the iGEM alumni that number in the thousands spread widely around the globe still are, according to Stanford synthetic biologist, Drew Endy, “one in a million. And that isn’t enough.”

Unexpected applications of biotechnology today

A biological material that can absorb uranium.

Plants that generate electricity.

Proteins engineered to respond to sound.

These were a few of the synthetic biology applications created by the nearly 300 teams that traveled to iGEM from as far as South Africa, Pakistan, China and Australia, as well as from universities across the European Union and the United States.

In 2009, I had been told that if I wanted to see the future of biotechnology, I needed to attend iGEM. It’s where kids develop biological solutions that use functioning bits of genetic information (BioBricks) to solve real-world problems. Sometimes those solutions are audacious and function. Often, they do not.

Students learn how to think and work like scientists, and must engage their communities.

Over the summer, my son, Alejandro joined the GenSpace iGEM team. The Brooklyn team would be competing in the overgraduate category as team members ranged in age from high school juniors to grad students.

Since I write about the rapid advance of life science technologies, I was interested in how the young scientists participating in iGEM would tell their stories. I also wondered what storytellers could learn from the competition.

Here are a few of the things that I learned.

Standing on the shoulders of giants.

The term “synthetic biology” is more than a hundred years old, but published pieces discussing the creation of biological circuits date only to 2000. Modern biotechnology is not even fifty years old.  

iGEM is now twelve years old. From the beginning, it has given students the opportunity to leverage all of biotechnology’s history, as well as synthetic biology’s recent history of applying engineering and design principles to biology.

What iGEM doesn’t give is design constraints.[3]

It gives them BioBricks – interchangeable standard biological parts, pieces of DNA, the computer code of life, that have been developed to build biological systems in living cells.

Most of the students working with the BioBricks probably don’t understand the molecular details of those parts – they don’t need to. They understand that the Bricks are like Legos and can be combined, arranged, recombined and rearranged in seemingly infinite ways. That simplifies the process of design and construction.

Many of those standard biological parts were created or characterized by previous iGEM teams. So, each competition can build upon the previous years’ and contribute the new parts they create to the registry that in turn will be used by future teams.

For example, Team Peking, the 2016 team behind the new biomaterial designed to absorb uranium, constructed a library of parts that they submitted to the BioBricks Foundation. They also offered experimental materials to other Chinese teams.

This is the way that science is practiced in the real world:

Science as a collaborative sport.

Over and over again, iGEM teams referenced the parts they used, as well as the other teams they asked for advice and advised.

Collaboration is considered an essential skill in the 21st century as it promotes the type of deep learning needed to identify and promote complex problems. Nearly every team I saw on stage was gender diverse and depended on older mentors.

For example, the  team from Brooklyn’s community lab Genspace consisted of high school, college, and graduate students. They were mentored by a biotech entrepreneur, a microbiologist, and biologist. There were 11 people onstage, plus their mentor in a tardigrade costume.

As part of the competition, all teams were questioned by a panel of judges comprising experienced academics and professionals. The questions asked were often difficult for the teams to answer. If the team pushed up against the limits of biosafety, the judges asked how risks were minimized.

Many teams also faced the additional challenge of having English as a second language. I watched teams struggle, passing the microphone, as they discussed the answer among themselves, until one team member felt confident enough to address the judges.

Sharing information dispels myths

One of the many teams from Mexico pointed out that 65% of Mexicans believe in magic.

(If you think that’s odd, remember that mistrust of science runs deep in the U.S. and has resulted in a surge of anti-vaccine sentiment and a government that wants to shut down most basic research-funding institutions. In the European Union, fears of genetic engineering have resulted in stringent controls on the use and growth of genetically modified crops, which have in turn prevented their adoption in many African countries where such crops could help feed a hungry population.)

To participate in the competition, iGEM teams are required to engage their local community in Human Practices: the study of how your work affects the world and the world affects your work.

Team Peshawar, the first ever iGEM team from Pakistan, traveled across their country visiting schools and college, running a roadshow to engage and educate as many people as they could about synthetic biology. They developed BioBrick trading cards for younger children and were featured on national television, in national newspapers, and on one international biotech web site.

The team, like many others, wrote a policy paper for the Pakistani government that contained recommendations for the development of synthetic biology in Pakistan, as well as its impact on science and education and the economy.

As a storyteller, I found this one of the most important parts of being in iGEM – you’re telling non-scientists about an important field that is rapidly growing and is quickly impacting all of our lives.

In his book Regenesis, Harvard genetics professor George Church wrote of iGEM,

“Some of the world’s most imaginative, significant, and potentially even the most powerful biological structures and devices [are] now coming not from biotech firms or from giant pharmaceutical companies, but from the ranks of university, college, and even secondary school students who were doing it mainly in the spirit of advanced educational recreation.”

When Professor Church visited iGEM this year, he was mobbed by students, following around like a rockstar. iGEMers have heroes, and those heroes are real scientists.

Let’s hope Lopez and Quinto follow iGEM’s lead by showing scientists are not crazy loners inspired to destroy world, but real people solving real problems by sharing information, collaborating, and dispelling myths.

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This post is a chapter from a book I’m co-authoring. If you’re interested visit, What’s Your Bio Strategy? and sign up for the newsletter.

[1] . Especially considering STEM jobs are growing three-times faster and pay 26 percent more than non-STEM jobs [U.S. Department of Commerce].

[2] My high school senior was on the GenSpace. They took the Overgraduate Award for measurement.

[3] The BioDesign Challenge, started this past year, offers art and design students the opportunity to envision future applications of biology. While the entries in the first year’s competition were more abstract than those at iGEM, students again, are not constrained by convention and could let their imaginations run wild.

[Thanks to Erum Azeez-Khan, Nat Connors, John Cumbers, Kristin Ellis, John Garrison, and Susan Rensberger for reading early drafts of this.]

 

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I Wanted To Be Right But Synthetic Yeast News Proved Me Wrong

I was wrong.

On Quora, someone asked:

How far are we from engineering a completely synthetic, self-replicating cell or organism?

My original answer was three years. 2020.

My answer was based on research I’ve been conducting for What’s Your Bio Strategy?

Then last week, Science ran an issue on the creation of synthetic chromosomes.

The yeast genome is being reimagined as a synthetic chromosome

Scientists have synthesized five of the 16 chromosomes that comprise baker’s yeast. – Saccharomyces cerevisiae.

We have a long relationship with that species of yeast. We use it to make wine, brew beer, and make bread. It’s the microorganism we most use for fermentation. It’s also one of the most studied model organisms in molecular and cell biology. It is relatively easy to modify genetically and be grown at scale. That’s important for industrial applications.

Since s. cerevisiae is well-characterized, it made sense that scientists would choose to create a synthetic version.

It’s not the first, synthetic organism. [1]

That distinction goes to the researchers at the J. Craig Venter Institute. In 2010, they created a replica of Mycoplasma mycoides, a parasite that causes pneumonia in goats. They called that new entity syn1.0.

In 2016, Venter’s group streamlined (or “defragged”) the M. mycoides genome to create what they termed “the first minimal synthetic bacterial cell.” The original synthesis in 2010 caused a bit of an uproar. Last year’s news, not so much.

Here's how undergrads are reconstructing yeast, creating a synthetic genome

Let’s get back to yeast.

Back in 2014, New York University yeast geneticist, Jef Boeke announced that he and a group of undergraduate researchers had synthesized the first baker’s yeast chromosome. (Remember, yeast has 16 chromosomes.)

It was a significant development because it only took a few years. And undergrads did most of the work. (In contrast, Craig Venter and his team took 15 years and US$40 million to synthesize syn1.0.)

Boeke and a team of researchers started the SC2.0 project to “synthesize a modified version of the genome chromosome by chromosome, from the bottom up.”

In last week’s announcement, the researchers announced they had “untangled, streamlined and reorganized the genome of the most studied of all eurkaryotic genomes.”

Ultimately, the synthetic organism they create will be yeast reimagined. At the same time they’ll add features “to facilitate chromosome construction and manipulation.”

When will synthetic yeast be finished?

By the end of 2017.

Researchers will complete the construction of an entire synthetic yeast genome by the end of 2017. – Click to Tweet.

My prediction was wrong by three years. Oh well.

[1] In an email, Andrew Hessel one of the scientists behind the Genome Write Project, wrote, “People tend to split hairs about synthetic organisms… They argue the organism itself (yeast) isn’t synthetic.” I wrote back, “if you take an organism (yeast), delete a bunch of stuff that doesn’t seem to do anything (or defrag, per Craig Venter), and it still works, then it’s a synthetic organism. Because it doesn’t exist in nature.” Andrew wrote back, “I think any genome that is produced de novo via synthesis and boots up a replicating organism makes that organism by definition a synthetic organism.” Your mileage may vary.

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Interview: John Cumbers of SynBioBeta | Passionate Entrepreneurs Using Biology to Improve the World

Here’s John Cumbers, founder of SynBioBeta.

In this interview, John reveals SynBioBeta’s origin story, the challenges he faced in starting the company what big companies don’t understand about start-up synthetic biology companies. It’s an excellent read. Enjoy.

johncumbers

John Cumbers of SynBioBeta. Photo by David Kong.

Introduction

Stories about synthetic biology make news every day. Called “the next stage of genetic engineering,” synthetic biology brings to market tools and products predicted to reach approximately $16 billion in sales within the next two years.

To better understand the people and companies active in this marketplace, I interviewed John Cumbers, founder of SynBioBeta, a company that supports a conference series, online community, newsletter, education, and research for the community of entrepreneurs, investors, and policymakers who are defining the field.

John and his team have held conferences in Boston, London, San Francisco, Edinburgh, Cambridge, Malaysia, and Singapore; this year he will take the SynBioBeta community to three Chinese cities — Beijing, Shanghai, and Shenzhen. During our phone interview, I asked John about his company, experience, and industry perspectives.

How did SynBioBeta originate?

CUMBERS: I started my first synthetic biology company, Universal BioMining, around the idea of improving mining with biology. That startup failed, so I went to work at NASA while I started an incubator, the Synthetic Biology Launchpad.

There, I interviewed emerging synbio companies and even funded a few. I learned there were a lot of small companies with interesting ideas, but there was no ecosystem to support them. That was the inspiration for SynBioBeta.

I named it SynBioBeta because of synthetic biology and “beta” because of beta testing — a play on the fact that we’re in beta testing. I worked on it one day a week while I was at NASA.

For SynBioBeta, I interviewed new companies that were seeking funding, introduced the science to venture capital firms around Silicon Valley, then educated the technology companies about this exciting, emerging technology. Eventually, I realized it was time to bring the companies and the investors together for an event, which took place in Menlo Park in November 2012. Shortly after that, we were invited to the UK to hold an event, bringing together members of the community. We call those brief events “Activate” and have held them in Singapore, Boston, and a number of other cities.

Very quickly, SynBioBeta became a full-time job. I left NASA last year, and I am doing everything I can to keep SynBioBeta growing by listening to entrepreneurs, finding creative solutions in media, and partnering events.

What challenges did you face in starting — and now running — the company?

CUMBERS: My biggest challenge in starting SynBioBeta was having the courage to do it. My biggest fear was that no one would come to the party (the first SynBioBeta conference). That’s only happened to me once before; I think it was my 13th birthday party. It’s an experience I never want to repeat. Luckily, it didn’t happen with the first conference, and we’ve grown ever since.

My biggest challenge, now, is learning how to manage other people. My previous careers in academia and government didn’t provide training in management. The other big challenge is going from being an idea generator to creative manager. It’s fun to create new event ideas, but, as a company, we must always execute.

In general, big companies underestimate the passion of young entrepreneurs and the impact they will have on the world.

To date, what has been the biggest lesson?

CUMBERS: You have to move from thinking about it to doing it. You have to be willing to drop your 9-to-5 job as quickly as you can and become your own company. Then, you have to learn to manage people, run your company, and control your own destiny.

We have a culture where education is all about getting a job — but that’s not the reality of Silicon Valley or our economy. Silicon Valley teaches you that taking risks is not a big deal — but explaining to your spouse or family that you’re going to do something that could fail is a big deal. That’s why you need a supportive environment.

When my first startup failed, my immediate reaction was, “I’m going to start another company.” That was probably a bad idea, but I was lucky enough to go back to NASA while I started SynBioBeta on the side. If I hadn’t had the NASA job, I would have had to either scramble to find another job or join another startup.

My advice to startup founders is to build a nest egg, a safety net. It’s critical to have six months to a year of savings so you can focus on the business instead of scrambling for money.

We’ve both been around many emerging companies, what do you think early-stage synthetic biology companies fail to do in their communications?

CUMBERS: Many synthetic biology companies come from the mission of making biology easier to engineer.

The biggest communication failures come from an inability to straddle the worlds of engineering and public perception.

Companies need to understand they have to communicate to two separate constituents — their customers and their own internal audiences. Even though end-users don’t necessarily care about the company and its culture, communicating those values clearly is essential to building a successful company because you also must communicate with investors, scientists, and engineers.

At the same time, you have to help the public — whether this public is consumers or other businesses — understand the benefits of your company. So, it comes down to having two communication streams — one for your company and one for your customers.

What do you think established companies — both in the biopharmaceutical space and outside it — do not understand about synthetic biology?

CUMBERS: In general, big companies underestimate the passion of young entrepreneurs and the impact they will have on the world. The dynamic that has played out repeatedly in the technology world will also play out in biotechnology, and the impacts of synthetic biology will touch most of our lives.

Big companies also don’t understand how the attitudes of young people toward genetic engineering are changing. I’ll be the first to admit I may not totally understand those changes, either, but I do see shifts in terms of understanding and adoption.

You’re taking SynBioBeta to China this year. Why? What has been the reception from the Chinese synthetic biology community?

With almost a quarter of the world’s population, China is a growing economic powerhouse. China’s recent strategic investments in the area of synthetic biology makes it an important place for SynBioBeta. In June, we’re running an event that spans Beijing, the political capital; Shanghai, the financial capital; and Shenzhen, the manufacturing capital of China.

Big companies also don’t understand how the attitudes of young people toward genetic engineering are changing.

What are your interests outside work?

CUMBERS: My passions are traveling and language. I speak fairly good Spanish and pretty good Chinese, but I am constantly learning new languages, and I can say a few sentences in many. Whenever I get an excuse to go to an exotic place, I go. I was in Lisbon last year, and I was just invited to Laos, where I’ll go for a conference later this year. I’m very excited about that.

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