May 2014 - Revolution Bioengineering
26 May

Why does Genetic Engineering call himself Synthetic Biology?

One day Genetic Engineering started calling himself Synthetic Biology.  It was weird, but I let Genetic Engineering do it because he is an angsty teenager with something to prove to the world.

But then everybody started calling Genetic Engineering by his nom de Pubmed—Synthetic Biology.  Even people who have known Genetic Engineering since the 80s started calling him this.  Everybody knows who Genetic Engineering is.  Nobody can tell you (or at least nobody can agree on) who Synthetic Biology is because he doesn’t exist.

Black is the new LB

Black agar allows the yeast to fully comprehend the futility of its existence.

(Caption, Crabgrass; Photo from Sylvia Huttner’s bioart at Pavillion35 – please visit her site for original context)

Somehow Genetic Engineering thinks that just because he is now “applying engineering principles” to biology (what do you think he was doing before?), or getting codon optimized DNA synthesized, that he is all of a sudden doing something totally different.  Let me be the one to tell you.  He isn’t.  Genetic Engineering is on the same trajectory he has always been on. He’s just learned a few new tricks he is inordinately proud of.

Genetic Engineering has always been learning things from his buddies Molecular Biology and Biochemistry, then rationally designing and testing novel biological systems to introduce new functions in living organisms.  Remember back in the 70s and early 80s when Molecular Biology told him all that stuff about promoters and what a lactamase is good for? Genetic Engineering used that information to make a whole bunch of cloning plasmids with antibiotic selectable markers, and he threw in a pretty sweet multiple cloning site too.  Then, after Biochemistry figured out how to make DNA in a cell-free system by adding polymerase, a pinch of nucleotides, and some temperature cycles (That was so totally like Biochemistry to invent that)– Genetic Engineering was on a roll and to this day is still exploring the applications of this technology.

30 year old science, still impressive today.

Could we do this without synthetic biology? Well…yes. This picture was taken in 1986.

See the original paper and this timeline from GlowingPlant

Genetic Engineering has so much lot to be proud of – he’s made some huge advancements – but now he’s hiding behind this new name. Rather than rtPCRing off of some mRNA to grab a gene, he’s calling up a DNA synthesis company and getting codon-optimized genes mailed to him—and calling himself Synthetic Biology.  Now that Molecular Biology has given him a whole palette of characterized promoters and repressors, Genetic Engineering is making a toggle switch—and calling himself Synthetic Biology.  Now that Biochemistry has learned so much more about protein folding that he can create novel enzymatic activities, Genetic Engineering is popping these genes into a pathway—and calling himself Synthetic Biology.

What’s fundamentally different about what Genetic Engineering is doing today and what Genetic Engineering was doing 10 or 20 years ago?  There are more pieces involved now, and the supporting technologies are better, but it’s essentially the same thing. Genetic Engineering is growing up, and he doesn’t need to call himself something different just because he has some new toys.

So lets all agree to call Genetic Engineering by his real name, and not this contrived nonsensical name.  Take off that mascara too.  You look ridiculous.

20 May

Revolution on Regulation

NOTE: This is a behind the scenes look at the discussions in RevBio about the importance of regulatory compliance. There will be additional installments to this conversation. We are not doing any biological work at this time.

The Problem:

Revolution Bioengineering was accepted into a biotech business accelerator to create color changing flowers, or to at least demonstrate the technology that will bring that about. The accelerator program only lasts three months, which is a pretty short timeframe to get biological science done. We are now beginning our third week and we have a problem: we do not have regulatory approval to move forward .

A researcher must get their individual project approved by the Irish EPA. This requires detailing the specifics of the genes used and the organism to be transformed, i.e., putting yeast genes into bacteria to study a particular metabolic pathway. Even simple transformations of an empty pUC vector into a DH5a are not permitted unless approval is sought beforehand . The Irish EPA website states that the timeline for approval is 45 days, but the UCC biosafety chair told us that the process is rarely that long. Two or three weeks is typical for a thorough review and approval. This approval was filed last week.

To summarize our current situation: We have made significant sacrifices in our lives to be in Cork, Ireland for the summer. We have a lab space that suitable for everything we want to do, and we have all the genes and the plasmids and the enzymes and the materials we need to start working. However, we have no regulatory approval.

The Options:

1. Wait around until EPA approval comes through before starting science work.

There is a lot of outreach and networking we can do in the next 2 to 3 weeks instead of biology. We can prepare videos and materials for our website to “build our profile” and generate interest in the project. This keeps us in line with the regulations, but prevents us from accomplishing our ambitious scientific goals.

2. Start doing work at UCC and not tell anybody.

We are in a foreign country and in this option we would be knowingly breaking their laws concerning GMOs. It’s unlikely to be reported to the EPA, per conversations with faculty and staff, and by choosing this we would be able to move our science project forward.

3. Start doing work at UCC and blog about it.

We started our company with the ambition to be very open about everything we do to demystify the scientific process and plant biotechnology in particular. Choosing this option would be keeping in line with our values, would allow us to get work done, but would be exposing ourselves, our accelerator program, and UCC to trouble.

4. Move our scientific operations to another country and clone there until UCC approval comes through.

Other countries don’t require individual project approval to do simple molecular cloning. We could move our operations there and do work until we get approval from Ireland, then move back to Ireland to do the plant work. This is the most expensive option.

The Discussion:

Keira: Regulations are important to retain the public trust – they should be respected. No biological work until regulatory approval is granted.

Let me start by saying that we are experts in our field. We understand the risks, how to mitigate them, and are confident in the safety of both our approach and our end product. We know this project inside and out.

However, we understand that GMOs are a complicated topic with some frightening associations for the public. Having an open scientific process and sharing detailed descriptions of the science behind the plant isn’t enough to unseat the skepticism and fear that has overwhelmed public debate on GMOs. Instead, those of us working in this field have an obligation take on these projects within an eye towards rebuilding the public’s trust in science and scientists.

One simple, easy way to do that is to adhere to the established regulatory framework. Working on this technology without the official regulatory approval will taint our project with the same arrogance people despise in larger companies like Monsanto. Our goal is to engage the public, not alienate them, and I believe regulatory compliance is essential to establishing trust with the public.

This is not to say that the regulations cannot be changed. But that effort should be conducted through the proper political forum with public input and widespread discussion on the merits and safety of synthetic biology. It is less convenient to do this – the conversations will be frustrating and circular, the work will take longer. But it restores integrity to a process that many have given up on as controlled by special interests.

I will add to this that it’s not only our project we need to worry about. There is a growing DIYbio community in Ireland who has taken the time to follow the rules. We would be undermining not only our own position as a company dedicated to open science and public engagement, but the efforts of the DIYbio community as a whole, and quite possibly the larger field of synthetic biology.

We have already had to adjust our experimental plan due to delays in shipping and synthesis. Waiting at least another three weeks for regulatory approval will set us back further, but it is the right thing to do. Alternatively, we can shift operations to Germany until we have regulatory approval. In this scenario we can both get the science started and maintain our integrity – the work we plan to do is allowed under German regulation, and we can import DNA to Ireland without restriction. While neither option is ideal, they both make clear that we are committed to furthering our business in a responsible way.

Nikolai: If we don’t start working now, there are no ethics to fret over because there will be no business

Keira and I are at an accelerator program that takes idea-stage projects and gives them time and money to develop a prototype which they can then pitch to investors. We have made significant life sacrifices to get to Ireland to take advantage of this opportunity, and we are fully committed to it. Without this accelerator, all we have is an idea.

Everything we are doing is safe, and the project falls well within the Irish EPA guidelines of biosafety level 1 work. Our application will be approved once the EPA gets around to sitting on the documents for a sufficiently bureaucratic amount of time. We just have to wait for that to happen.

Right now if we are not doing science, we are wasting our time. We are here to start a business, and if we have to do it by bending the rules, we need to do that. Following the rules to the letter is fine, but with such a short timeframe and ambitious scientific goals, we can’t afford to wait around to do work. If we don’t start doing science now, at the end of this accelerator we will still be at the idea stage and have nothing to show for it except some more blogs.

Since we have already wasted so much time moving to Ireland and getting equipped in a laboratory starting from scratch, I think temporarily moving our operations to a different country will be a further waste of time. Even if we show up in a fully functional lab, there will be additional time spent re-setting up, re-ordering things, re-acquainting ourselves with how things are done at the new facility and where everything is, not to mention time wasted for things outside the realm of science like getting another apartment.

The only two options I see available to us is to start working and blog about it as we had promised ourselves we would do (and worry about the consequences later, if there even are any), or start working and not blog about it and sacrifice our corporate principles from the very beginning in order to even have a corporation.

The EPA approval will come through at some point. They don’t have a deadline to approve our work. We do have a deadline to get work done. We need to come through with some scientific results, or our whole summer is fantastic waste of time and money.

05 May

First meeting with the Boss

Logo thought

We had our first meeting today with Bill Liao, the head of SOS Ventures and the entire Synbio Axlr8r summer program.  This was our first real conversation with anybody anywhere about business thinking and strategy for a science company.  It was really eye opening, and it made it clear that some of our scientific planning and preparation we did ahead of arriving in Cork was time wasted (but certainly not all).

And it was also clear that the amount of work we have to do is staggering.  So much of success is going to be based on how much of a web presence we have, how many people are our tweet friends, (or however that works), how many people are seeing our webpage, and how many are talking about us in teh interwebs.

Developing a media/web profile for the company is a daunting task, and pretty far outside the skillset I have thus far developed as a scientist and in life.  However I have a summer to do nothing but devote all my time to developing this business in every dimension, so let’s see in three months how things have gone.

04 May

Taking a chance

Keira and I are at O’hare airport for a 7 hour layover. Denver to Chicago, Chicago to Dublin. Then a train ride to Cork.

We are taking a big gamble in a lot of different ways. Not only are we are trying to start a biotech business, we are flying to Ireland to do it. There are simpler businesses to start, businesses which require less capital, lower investment, and can be done in your spare time while you keep your full time job. We are jumping in with both feet into a high risk, high reward proposition. But being able to take this chance, uncertain as it might be is a victory for us.

Keira and I worked in the same lab at CSU, and we have a certain kind of enterpreneurial synergy. We spent lunches and evenings talking about businesses to start, what the next big thing is definitely going to be, and how we would ride that wave to riches.

Lots of ideas spun out of this collaboration. Many bad, some quite good. I tend to be pessimistic about ideas, Keira optimistic, so we ended up having lengthy discussions about ideas; the bad ideas always fall, and the good ideas rise. Eventually we started formalizing our daydreamy talk and began having regular journal clubs.

Our fledgling biotech startup limped along for a bit. I had full time paid employment, Keira was a graduate student, and we did what we could in our free time, but it wasn’t much. Keira graduated, and was able to devote a lot more time to our company. Things started moving at Revolution Bio, and then I got word that the contract at my job was ending.

Keira could manage to work for some period of time earning nothing trying to get our company going. I didn’t have that luxury. So when I heard that I only had 4 months left at my job, I had to devote my free time to a job search, not into company development. To find a job in the biological sciences, that likely meant that I would have to move far away from Colorado, ending this partnership before it really began.

Keira was also running out of steam – the first contract we landed was time-consuming, frustrating, and poorly compensated. Her husband had recently moved for a dream job in Ohio, and despite contacting multiple agencies and partners, we just hadn’t had any bites at that point for any of our ideas.

Then Keira came across SynbioAxlr8r, a biotech start-up accelerator program focusing on synthetic biology. It was right up our alley, and it was in Ireland. When she asked if I was interested into going to Ireland, I never responded to her email. We weren’t getting in anyway, so why bother thinking about it.

I barely had a hand in shaping the application– my free time was devoted to my job search. Still, when Keira forwarded me the application materials for the accelerator program, I made comments and corrections.
Lo and behold, we got an interview for the accelerator. A week later we got an email confirming our acceptance, and we were on our way.

So I quit my job a month-and-half before it was anyway slated to end, we got an apartment rented in Cork, and we came up with a three month science plan. We are flying there now.

I really hope this is the opportunity we were looking for, and leads to continued opportunities for us to grow our business. I think both Keira and I will be busting our tails this summer to make sure we give ourselves the greatest chance to succeed.

04 May

Ireland: Days 1-5

Logo thought

It’s been a busy several days, even though the accelerator hasn’t truly begun yet. We have spent a great deal of time getting our apartment cleaned up, and getting basic items purchased. It’s given us an opportunity to do a lot of walking around town and exploring the beautiful city of Cork.

We live on Blarney Street, and that makes both Keira and I happy. It is an old street, incredibly narrow and steep, with beautiful houses, shops, and pubs shoulder to shoulder along the length of it. So much of the city center of Cork is pedestrianized – you can walk anywhere you need to go – and there are shops of all sorts everywhere. There is a great temptation to purchase lots of things– I will probably walk away from this summer with a new tweed blazer– but we have limited money and can also foretell that our entertainment budget may have to be expanded because pubs can be fun.

We had a few meetings on Thursday and Friday with the accelerator program where we went over safety issues and the locations of things around the microbiology department. The main value in those meetings was finally meeting other participants in the program: the Austrians, working on low cost DNA synthesis technology, MuuFree, developing real vegan cheese by producing milk proteins in plants, Hyasynth, working on THC production in yeast, and UCC’s IGEM team, who will be working on a new biomaterial based on hagfish slime. Friday’s day of meetings and orientations of course culminated at a pub where great merriment was had.

This summer will be a ton of hard work, but I think it’s going to be really fun as well.