The creation and shaping of the international team and the Friendzymes Project was born out of an
online class with more than 400 people from around the world; this unique beginning causes
Friendzymes’ Integrated Human Practices to be a little unusual when compared to many other iGEM
teams.
After beginning in the class,
Friendzymes has evolved into a team with people from 10 countries on 5 of the 7 continents of the
world, and is constantly mixing with the knowledge and enthusiasm great researchers and
bio-enthusiasts not of our team have for Synthetic Biology. Our vision is to build a frugal
biofoundry, to bring the technology and application of biological sciences to the level of the
community, and to make friends — as our name suggests! By working with various communities, we can
achieve our vision.
The seed of the Friendzymes Project was born in August 2020 in the Frugal Science online class taught
by Bioengineering Assistant Professor Manu Prakash from Stanford University. Manu is a
world-renowned, innovative scientist whose work focuses on frugal innovations to make medicine,
computing, and microscopy accessible to more people across the world.
The spirit of the class was for people to come together during hopeless times, such as the pandemic,
and try to look at the bigger picture, define world problems, and discuss potential solutions. This
class had two parts: frugal engineering guest lecturers and group projects where students united
based on similar interests. This built an international community of those wanting to tackle
problems of our times. The global issue of democratizing biotechnology was raised and the solution
of tackling it via enzyme production was proposed by Isaac Larkin, a team leader of the Friendzymes
project.
When thinking about this issue, Isaac wondered what we would need to build in order to frugally build
a bio lab. He was already working on an Open Enzyme collection for COVID diagnostics and this idea
was a broader scheme of frugal biotech. The things he thought might be necessary were: “a frugal
bioreactor for culturing microbes to manufacture enzymes and other biological reagents, a frugal
thermocycler for copying/amplifying DNA (and incubating reactions at set temperatures); a frugal
pipette to enable people to do liquid handling and set up reactions in the lab; a frugal
electrophoresis apparatus aimed at measuring the weight of molecules; a frugal optical measurement
device for probing the structure of molecules; a frugal French Press instrument, for popping cells
and accessing their intracellular contents; a frugal centrifuge like paperfuge or handyfuge, for
separating heavy/insoluble materials and liquids from less dense and soluble solutions; and at least
two ideas devoted to cheap manufacturing of enzymes/biomolecular reagents required to perform
biochemical/biotechnological reactions and transformations. This is a great start on a roadmap for
building a frugal bio lab. To summarize, we'll need: (1) frugal ways to grow cells and make
wetware/reagents, (2) frugal ways to set up reactions, (3) frugal ways to
separate/concentrate/purify things, (4) frugal ways to run reactions at specific temperatures, and
(5) frugal ways to measure the results of experiments, including potentially the
size/structure/concentration of molecules, cells and product materials.” - Isaac L
The scope of this problem was very large and further discussions with others as a part of the class
helped to prune out the unnecessary goals and focus on the most important thing, frugal bioreactors.
Leron Perez, a graduate student from Stanford University, who was part of the class, strongly
suggested that a frugal bioreactor will be one of the most important components in this pursuit. We
explored the diverse frugal bioreactor designs and decided it would be an important component in the
pipeline we would set up. For information regarding our progress on the frugal bioreactor, check out
our Hardware section.
Divij Kinger, a former member of the team, is a Biotech/Genetic Engineer who was working on
Gene
Drives to prevent transmission of Dengue in mosquitoes, saw the need to store, transport, and use
plasmids, DNAs, and enzymes as a necessary component of any biolab. He suggested that minimizing
transportation barriers would help local communities in making and sharing biological constructs
among themselves. Therefore, we started looking for organisms that can withstand uncertain
environmental factors and can be easily shipped.
Luckily, we were able to talk to Keoni Gandall, who had a solution ready because he ran a company
that specialized in creating genes and packaging them as spores to the end consumer. It seemed
magical without having to deal with any storage facility where you can mail your genetic constructs
because the spores can be transferred to paper. The only catch was that protein production wasn’t
very abundantly done in Bacillus subtilis, the organism forming those spores. The standard was, and
is, Escherichia coli because everyone has been thinking of ways to make protein production better in
E. coli, instead of thinking out of the box and going with less conventional model organisms.
Another benefit of B. subtilis was that the cells didn’t have to be popped, this reduces the
hardware component estimates that our (Isaac’s) crude idea began with.
We had brainstorming sessions with Manu Prakash which helped to narrow down our project into looking
for
the harder tasks. He suggested that quantifying and purifying the production of our enzymes would be
a
critical aspect, as well as building a frugal chromatographic column. We were very excited when we
got
to speak to Dushanth Seervaratnam, who had built a frugal chromatography column purifying
based on
Silica tags which can be readily, and frugally, made from Sand.
Much of our understanding about the important parts of the project came through interacting with
others who were just as passionate about biotech as we are. Also, many of the initial team members
didn’t know anything about biotechnology, but conversations with Scott (our PI) helped many learn
about plasmids and gene editing.
When the Frugal Science class ended, a lot of people dropped off the team due to other commitments;
however, 6 members of the class continued to collaborate and built Friendzymes, which has since
become a very dynamic team as more people from different communities got excited about this idea.
Clearly, we needed to tackle this problem globally, instead of in a specific region.
As we thought about how to push our team to the global scale, iGEM seemed like the best platform to
showcase our interests, so we joined iGEM 2021!
As one can imagine, when you bring together people from 10 different countries, all with different
backgrounds, every meeting and decision becomes very well discussed in its diverse aspects. This is
how we managed to have so many different areas within SynBio covered by Friendzymes. It is because
of the expertise of the group's Software Engineers and Bioinformaticians that we have been able to
develop work in the Software section that goes through different levels of programming knowledge:
The Friendzymes Cookbook, for beginner programmers, and Friendzymes Actions for large-scale circuit
design analysis for those more advanced (see Software and Education for more
details). This diversity also opens us to members who are interested in hardware development, which
has allowed us to build two different types of bioreactors. Once these two bioreactors are developed
and the problem areas fixed, we intend to analyze and compare their quality and feasibility (see Hardware ). Finally, it is
because one of the leaders (and creator of the project) and also our PI Scott were previously
associated with Free Genes and the Open Bioeconomy Lab that we already had a library available (see
the B. subtilis Protein Secretion Toolkit ), which also provides shipping around the world.
As you can see, the more our team grew in numbers and consisted of a wider audience, the more our
project began to develop a global perspective. During meetings and co-working, we noticed that a
single question arose time and time again: “what does democratized biotechnology mean?” While this
was a single question, there was no single answer. This was where we saw that “democratized
biotechnology” could mean different things, since each person saw it in a different light, depending
on where s/he was from.
Those from high-income countries viewed “Democratized Biotechnology” as a means to provide community
labs or biohacking spaces with cheaper alternatives for their work since they often don't have
funding from large institutions. This perspective is exciting as it can introduce many niches in
biotechnology.
However, that was a completely different view from our members who were from resource-constrained
areas (e.g. Brazil, Philippines) where the currency was weaker than the USD dollar - the most common
currency for purchasing laboratory supplies. For them, democratizing Biotechnology meant giving even
their biggest labs' possibility to have the very basic tools, as these places suffered not only with
the currency but also with a general lack of financing; the difficulty of importation (including
high shipping rates); and the difficulties of transporting biological materials, e.g. if the product
has to be kept at low temperatures. Thus, in these places, the amount paid can be around double in
comparison to what labs in the US/Europe pay for reagents; and the ability to manufacture some
reagents locally through synthetic biology relieves this problem.
Friendzymes as a whole soon realized the importance of those exchanges as both views provided insight
on what impact our project will have depending on the country; therefore, perspectives are taken
into consideration when attempting to democratize biotechnology for all. Given the international,
diverse, and heterogeneous nature of Friendzymes (see Diversity section ), we
were able to see this vividly. We found ourselves with priceless resources, our team. Everyone had
something they could teach, enthusiasm to learn, and diversity so beneficial as to help all learn
more about the world we live in.
The Frugal Science class was over, but our team's journey continued. We have discussed the
project with many people since then, only now in a more iGEM-driven manner, to develop the best
possible project. From here, we have categorized individual collaborations by theme.