Ichiro Hirao talks about nucleic acid research, expanding the genetic code and the possibility of creating new life. Kathleen Too asks the questions

              

Ichiro Hirao is a team leader at the RIKEN System and Structural Biology Center, Yokohama, Japan. He is interested in the creation of unnatural base pairs towards the expansion of the genetic code and re-engineering DNA/RNA materials.

 

What inspired you to become a scientist?

From a very young age, I have been fascinated by science. When I was in elementary school I devised my own experiments. At the age of 11, I attempted the electrolysis of water to make hydrogen and oxygen gas on my own.

What motivated you to study the chemistry of nucleic acids?

I used to attend a technical college combining high school and university and came to be interested in organic chemistry. When I was 19 years old, one of my professors gave me a book called The Double Helix by James D Watson. I was very impressed by it and at the time I really wanted to create artificial genetic compounds by employing synthetic chemistry. Since then, I have used synthetic chemistry and applied it to nucleic acids research. In the US, I worked with Professor Andrew Ellington in Indiana, where we focussed on nucleic acid aptamers to study evolution. We wanted to synthesise new compounds to incorporate into DNA, RNA and proteins. At the time, Dr Shigeyuki Yokoyama at RIKEN started a project in conjunction with the Japan Science and Technology Agency to expand the genetic code, and called me back to Japan to lead the project.

You are currently working on unnatural base pairs for the expansion of the genetic alphabet. Can you explain why this is important?

If we create new base pairs besides the A-T and G-C pairs, we can add new compounds into nucleic acids and proteins. All creatures have only 4 bases: A, T, C and G. I often ask: why is this the case and can I challenge it? Can new bases be added into a new creature? For that purpose I want to test the expanded genetic system in a test tube. So, we managed to create a new base pair, different from the usual A, T, C and G. In 2002, we reported our first new pair, by which a non-standard amino acid can be incorporated into a protein using a chemically synthesised gene containing the new pair.¹  

What is going to be the next biggest development in your field?

In 1989 Steven Benner reported the first novel unnatural bases.² Since then a lot of unnatural bases have been made. However, precise replication is often too difficult for these unnatural base pairs. My second aim was to make sure that the unnatural base pairs can replicate as this is the most important function. After several years of struggle, we at last developed the other new pair and published this in 2006.³ The results, thus far, were obtained in a test tube and the next aim is to discover if the unnatural base pair works in the cell. I have also founded a venture company, TagCyx Biotechnologies, for applying the unnatural base pair technology.

What is the most rewarding achievement in your career?

Sometimes we find new things by serendipity. I consider working with my colleagues very rewarding. Often ideas and new methods arise from different people in the group and from foolish ideas but precise experiments. By working together, we aim to achieve a common goal and I am ever so grateful to have my own research group. 

What is the secret to running a successful research group?

We have to make sure that the correct control experiments are done and that all the data are reproducible. Obtaining reproducible and precise data is very important for the success and credibility of a research group. During the research process, we try not to miss very subtle things which could be of importance.

If you were not a scientist, what would you be?

I am a computer and board-game geek, so maybe I would be a game designer. I also like to play the classical guitar, so a guitarist would be another option.                                            

Which scientists do you most admire and why?

I admire all the researchers that I have ever met and have known through literature. They are always inspiring me to come up with solutions.