Inari: Joining a Start-up of Gene Editing and Innovation

(Disclaimer:  I want to state that what I write below are my personal opinions and views.)

I like to use this forum as way to not only share some of my thoughts, views and hobbies for others but to help document my own life experiences for myself.  I may be wrong but I am guessing one day when I am old I will enjoy going back through the story of my life to remember some of the details I will probably have forgotten.  So here goes the story of where life is taking my family in 2019.

I have not been as active blogging lately because my family and I have been preparing to move from the place we have called home for 17 years.  We will be moving from Cary, North Carolina to West Lafayette, Indiana where I will take on a new job.

One of my biggest passions beyond my family (and other than space!) has always been in agriculture biotechnology.  I have had the privilege of working for two very large agriculture companies since graduating from college.  These are companies that employ thousands and thousands of people.  They are companies where I have made friends and learned everything I know in ag biotech field.  I can say that I have loved every minute of it.  So the biggest question I get from everyone on my decision is  "why did you leave?"  Some of you reading this may be going through the same decision of whether to leave a job where you are comfortable and try something where there are many unknowns.    I also questioned myself for weeks on why I should try something different if I am comfortable and happy.   Why take a risk when staying put could be the better decision?

Abraham Maslow said, "In any given moment we have two options, step forward into growth or step back into safety."

I think ultimately I wanted to continue to grow by learning new things completely out of my comfort zone.  There are some days I am still petrified of leaving the job I knew so well and leaving the friends I made in NC.   However after much thought and reflection as well as a lot of family discussion we took the leap and I joined a company called Inari.  Inari is a small start-up based in Cambridge, Boston.  As they continue to grow they opened up a site in West Lafayette, Indiana (right beside Purdue University) and this is where we will be moving. 

Here is our new building in West Lafayette, Indiana.

If you want to learn more about Inari you can visit their website:  www.inari.com  I went into this job with the task of building a team in these new and empty labs in Indiana.   I have only been there for close to 3 months and in just this small amount of time I have learned much about this small start-up company.  Here are just a couple things that really excite me for the future of this company.

1.  We are working on gene-editing

When I say I wanted to continued to grow, I really wanted to keep learning new ways to make an impact in agricultural biotechnology.  Inari is a company focused on gene-editing technology.  They want to use gene-editing technologies to improve crops faster than traditional breeding by targeting precise changes that unlock the plants inherent potential for improvement.  I fully believe that gene-editing is the technology of the future and I was starting to worry that the technology was leaving me behind.  Many companies are working on gene-editing including the ones I have left.   In my past jobs I was also trying to make plants better with a biotech approach, but we were applying a technology(transgenesis) that is slightly different.  Inari as an entire company is focused on using gene-editing to create new products and this was a major reason for my decision to join Inari.

I know the term "gene-editing" scares some people, but I can at least try to give a very simplified primer on the subject.  The terms gene-editing and CRISPR/Cas are just some of the terms that get thrown around in the papers, news and social media.  There are some great resources online that go into much more detail than I am now, but gene-editing begins with one thing.  If you are gene-editing then you are able to cut DNA.  Scientists can use "molecular scissors" to make this cut.

https://geneticliteracyproject.org/2018/02/23/universal-genetic-scissors-crispr-cas-9-sister-protein-can-cut-dna-rna/

DNA is the code that defines who you are and likewise it is the same code that defines what a plant is,  or for that matter any living thing.   I liken DNA to computer code.  It exists unseen, yet gives rise to everything you see.   A DNA sequence (like a computer code) may say a flower color should be purple.

https://www.khanacademy.org/science/high-school-biology/hs-molecular-genetics/hs-rna-and-protein-synthesis/a/intro-to-gene-expression-central-dogma

Now what if someone thought the flower would be much prettier if it was white.  Well  plant breeders have been crossing plants for hundreds of years to do just this.   They have figured out that by combining DNA from different plants then you get different combinations of DNA until you eventually get what you want.  However it takes time to figure out the right crosses that show the output you want.  And when you cross plants, you may get the color you want but now you may get other bad stuff that also came in with the DNA.  For instance maybe you finally get that exact shade of red rose you want, but it meant your roses completely lost that great smell that makes a rose a rose.  The human analogy would be that you got the prefect hair texture from your mom and the tallness from your dad, but you also got a gene for sickle cell disease.

This problem of mixing DNA by crossing and getting so many changes at once (some bad and some good) is where gene can shine.  Gene editing at its simplest form can solve that problem by only changing the exact DNA sequence you need to get the result you want while leaving everything else alone.  In the plant example we could target one gene to get the color we want while all the other DNA stays the same.   Don't let the word gene editing scare you.  When a plant breeder crosses plants they are in a sense editing too, but they rely on much more random DNA recombination to get the desired trait.  Gene editing on the other hand just targets the exact DNA you need to target to get the right color.

I really think of gene editing as surgery but at a super small scale.   Just like in surgery, gene editing is all possible by precisely cutting the DNA where you want it to be cut.  A Doctor makes exacts cuts  when they do surgery and gene-editing uses the same precision.  We can target the exact location of a gene and cut the DNA.  Living organisms are extraordinary and so when that DNA is cut the plant says Uh-oh and tries to fix it.  The problem is the cells machinery fixes the DNA  incorrectly and the gene will no longer work after that cut.

So how do you even make the cut to begin with?  There are multiple "scissors" that can cut DNA.  You may hear words to describe these "scissors" including "TALENS" and "Meganucleauses".  The most common "scissor" used now is called "Cas" and is a protein found in bacteria that is relatively easy to use.  Here is a look at the "scissors" in real life actually cutting DNA!!!   Amazing!  The big orange blob is the Cas protein cutting DNA.

https://www.nature.com/articles/s41467-017-01466-8

If we go back to our flower color example, a real life example of gene editing of this is by a Japanese group who targeted a single gene and cut the DNA of that gene.  The plant repaired the DNA but not correctly and that gene no longer worked.  So without that one gene, the flower color went from purple to white.

https://www.asianscientist.com/2017/09/in-the-lab/morning-glory-color-violet/

Using tools to cut DNA and disrupt a gene is called a knock-out (loss of function) and is the simplest form of gene-editing.   Here is a graphic I picked up at a conference that does a great job summarizing.

Gene-editing can become much more complex as you may target multiple genes at once. However the concept is all the same.  You cut DNA at a precise location that you designate in order to get the exact change you are trying to make.  DNA is amazing stuff.  It defines every living thing, but it can also code some detrimental effects like human genetic diseases or disease susceptibility in plants.  By being able to modify the existing DNA in a plant (and some companies are trying to cure  human diseases the same way) the possibilities become very promising for humanity.

Inari is applying the gene-editing technology to commercial crops and I am enjoying seeing this story unfold in front of me.  I can't wait to see the future!  Here is the Inari model taken right from the website.

2.  We are innovating:  Strong interpersonal relationships lead to strong innovation

I have always been fascinated with innovation and how companies innovate.  Some companies are better than others at coming up new and novel ideas and then implementing them.   I am sure there are many strategies to become better at innovation, however I really think that innovation is directly linked to strong interpersonal relationships.  I think any size company can innovate, but it has to establish a culture of strong relationships among and across teams.

I had read one paper on this in the past that shows a model I personally think holds up very well.  It sure looks like common sense and looks easy, but as an organization grows it can be much harder to maintain this.  This may be one reason small companies seem to innovate so well, although that does not mean a large company cannot innovate well.

For people to innovate, there must exist communication from multiple directions in which all parties share a sense of psychological safety.   Psychological safety is the shared belief that a team is safe from interpersonal risk taking.

Psychological safety starts with positive interpersonal relationships.  These positive interpersonal relationships lead to strong communication within the organization on the good and the bad and is an enabler for people to meet and talk.   These pieces all come together to allow employees to innovate because they feel supported by those around them.   The biggest barrier to innovation is when there is no psychological safety; people don't innovate well when they are worried about the consequences (or lack of support) from risk taking.

I think Inari excels at innovation on a couple of fronts and has a been a great place to observe and work.  First they understand the concept that communication is key.   I had never been in an environment where the entire company sits together for lunch every single day.  This interaction over times builds positive interpersonal relationships and that is a catalyst to innovation.  Secondly Inari focuses on celebrating failure.  Celebrating failure is critical to achieve psychological safety since it supports boldness across the community.  It also encourages fast decision making since the community accepts failure in order to learn and do better the next try.  Two of Inari's core values sum up this discussion:  "Open" and "Boldness."

While packing and moving is a job in of itself, I am genuinely enthusiastic about tackling the upcoming challenges head on and seeing the possibilities that open up.