Our founder and president Helge Zieler, PhD, began Primordial Genetics in 2011 with the goal of building the premier company for genetic improvement of microbes. Since then, the company has developed its Function Generator™ technology and is busy rapidly boosting microbial productivity for renewable products. Today, we dive in to hear more of Helge’s Primordial Genetics story.

What led you to start Primordial Genetics?

I formed Primordial Genetics after observing that the biotechnology industry did not seem to have adequate tools to improve microbes for higher productivity and efficiency. We live in the age of genomics, in which the genetic content of any genome can be precisely determined. This has led to the accumulation of thousands of microbial genome sequences in public databases. In each case, the genome is the master blueprint of the organism. It brings incredible insights and potential for efficiency improvements. However, I did not see this newfound knowledge being put to use in a systematic manner. Many old methods were in use that are inefficient. Newer approaches were in development but were not ready to be applied to real-life problems of microbial strain development.

Function Generator, the technology that we created at Primordial Genetics, was designed to meet this shortfall and fill a critical technology gap. It is a whole-genome approach, meaning that we make direct use of the entire genome sequence of an organism. It creates collections of novel genes that have a high likelihood of dramatic improvements in any property of the microbe. It is rapid and relatively inexpensive; and most importantly, it is highly effective.

How long was it before the Function Generator was created?

It took two and a half years from founding Primordial Genetics in late 2011 to providing the validation of our technology. Because the technology idea had not originated in a parent company or university, there was no obvious institution to look to for funding. We spent 18 months applying for grants and searching for seed investments to get our work started.

In mid-2013, Primordial Genetics had a breakthrough with a grant from the National Science Foundation. With this grant came important validation – a team of outside experts had looked at our idea and decided that it was worth giving a try. This prompted Greg Mitchell, a professor at the local Scripps Institution of Oceanography, to match the NSF funds. His early support was critical, because we would not have been able to launch Primordial Genetics on the grant alone.

I hired Sabrina Baffert, a talented college graduate with extensive laboratory experience in molecular biology. Five months later we had our first promising results. A year after our launch we had shown that the technology produced very interesting, novel and completely unanticipated advances in our first test organism, baker’s yeast, a widely used industry production host. That initial success, in June of 2014, represented the birth of Primordial Genetics’ Function Generator technology.

What industries do you see benefiting from this technology?

Microbes are used very widely in multiple industries, and their applications are almost limitless. They produce food and feed additives, such as amino acids and vitamins; pharmaceuticals, such as antibiotics and therapeutic proteins; industrial enzymes used in animal feed and consumer products such as laundry detergent; cosmetic ingredients; commodity chemicals and fuels such as ethanol (alcohol); agricultural chemicals, such as insecticides; specialty chemicals such as flavors & fragrances, and many other products. Every industry uses microbial products.

Each of these applications, however, requires a microbe to be optimized for high efficiency in a bioreactor where the microbe grows and secretes its product. These optimization steps are very challenging, and in the past took decades to develop highly productive microbial strains. With modern genetic tools such as Function Generator, these improvements are greatly accelerated.

What is one thing you want readers to know about Primordial Genetics?

Our technology is the best in the industry for altering and shaping organisms for useful purposes. Biology is complex and its control mechanisms are poorly understood. That means we cannot yet engineer an organism the way we build a car or a computer, with each part designed to perform a very specific function. Organisms need to be shaped with specialized methods that allow the biology to sort itself out and present the best solutions. This is what Function Generator does to perfection. We create optimal biological solutions, not through an engineering design process, but by evaluating tens of millions of entirely novel sequence combinations that are new genetic parts, selecting the best ones, and then combining these to build a new strain. If a challenge needs a genetic leap, Function Generator is one of the few ways to achieve it.

How can you tell that your technology is better than others?

First, we have compared Function Generator to other advanced genetic methods, and it has come out well ahead each time, with superior and faster improvements, and bigger gains per improvement cycle. Second, we look at the newly discovered solutions from our Function Generator library and see that none of them are obvious or predictable. They could not have been designed based on current knowledge. Our novel genes tell a story, and give us new understanding and new tools to attack a microbial trait in the future.

It also helps to give a perspective of how our technology is differentiated from the computational methods that are gaining power and attention. We believe that computational approaches cannot compete with empirical technologies for the foreseeable future. They can produce useful models and insights but cannot predict the best solutions a priori. The simple reason is that computational methods rely on existing knowledge in some form or another. The only way to find the best solutions to biological optimization problems is to let the cells sort out the solutions themselves from large number of sequence combinations and genetic interventions at the start. This requires a technology like Function Generator at the front end. Once an initial set of effective genes or genetic changes have been identified, computational methods can be very effective to add predictive power to the existing data.

How can a non-biologist relate to these modern genetic technologies?

Just like humans, who don’t make full use of our brain capacity, microbes do not put their entire genome or genetic capacity to work. Much of it lies inactive, in wait for tough situations that require the microbe to harness its latent resources. At Primordial Genetics, we put these resources to work now, for our purposes. We maximize the microbe’s genetic potential, and allow it to use its entire genome’s worth of function in a more efficient manner. We allow it to be all it can be.

What are the next steps Primordial Genetics; needs to take to get to the next level?

We need to demonstrate that our methods can create an industrial organism that is used in commercial production. We are working on creating bacterial strains that make methionine, an essential amino acid and key ingredient in animal feed. These strains will be able to make methionine biologically, meaning better and cheaper than the current, chemical process. In other words, we are trying to displace an established industry.

This is a difficult problem to solve, particularly for methionine, which cells don’t readily produce in large quantities. But we have a technology advantage with Function Generator and all of our results to date are looking very promising. It will take us some funding and one to two years’ of additional work to accomplish this goal. Once we do, we will have established ourselves as one of the premier companies for microbial engineering and improvement.

What impact do you see Primordial Genetics having on the world in one year? 5 years? 10 years?

We want to help develop the bio-economy. The entire world is shifting from use of oil (petroleum) as the starting material for everything synthetic that is made and used in our world, to plant-derived chemicals and sugars as natural raw materials. This is a challenging transition, but one that will bring many benefits, among them more diversified and more environmentally friendly production, reduced greenhouse gas emissions, and a greener world in general. Biotechnology, and the synthetic biology industry to which we belong, will expand dramatically during this process. Primordial Genetics wants to help build this new world and be an integral, productive part of the future of bio-manufacturing.

 

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