Monday, April 20, 2015

Better Know a Scientist: Interview with Plant Geneticist (now Human Geneticist) Sonya Clark

I've been working on a post about the Innate Potato for about a month and it keeps getting delayed. So this week, we have another edition of “Better Know a Scientist”, where I’m interviewing my boss!! Seriously. My manager, Dr Sonya Clark, has a PhD in Molecular Biology from the University of Canterbury in the faraway land of New Zealand. Like me, she moved to the US, where she did a post-doc at UC Berkeley in the Plant Gene Expression Center. Then, like me, she moved into the private sector where she’s worked for over 15 years, mainly in DNA sequencing companies. I wanted to learn more about the work she did in plants and also to score some brownie points :)

Q: Pretend I’m one of our interns: explain to me the work you did for your PhD. Why was it important?
My PhD was funded by a grant from a government agency in New Zealand that was directed toward improvement of crops.  At the time I did that work, onions were a significant export crop. The project was to clone the gene responsible for the flavor of onions, with the concept being that having that knowledge would facilitate the ability to adjust the onion flavor intensity (apparently New Zealand’s onions were too intense to be acceptable to overseas markets).  I did manage to clone the gene (turns out it was an interesting compartmentalized enzyme that acted on the substrates when the cells are broken to release all those pungent volatile sulfur compounds everyone is so familiar with!). Using it to modify the onion plant itself turned out to be the larger challenge and it took another 15 years or so until a commercial onion was released using the gene sequence to create a knockout line  (using RNAi technology - a ‘tearless’ onion!).  It was really nice to hear that the project did continue until that was achieved, and fun to know I had a part in making that happen.

[Biochica’s note: for more about RNAi, read this post about the Arctic Apple, which uses the same technology to make non-browning apples. The Wikipedia entry for RNAi is also quite good]

Q: What did you do for your post-doc in Berkeley? Why was it important?
My post-doc was in a lab funded by the Department of Energy to explore methods for phytoremediation (using plants to detoxify contaminated soils).  My project was to introduce expression gene libraries into a yeast model system with similar biosynthetic pathways to plant (Schizosaccharomyces pombe). I would build various types of gene expression libraries, transform them into the yeast and test how they grew on media plates infused with cadmium.  Whenever I found a yeast that would grow well in cadmium, I’d figure out which gene had been added (sequence the insert) and then test those genes in plants to determine whether a similar tolerance was capable of being created that way. Turned out there were lots of genes that worked in yeast and not any that had a big effect in plants. But it was an interesting project in that the genes that conferred tolerance in the yeast cells helped define how these detoxification pathways functioned. Basically, the metals are sequestered into cellular subcompartments, so the project provided a lot of knowledge of the various strategies that plant cells could potentially use.

Q: Why did you switch careers into human genetics? Was it an easy transition to make? Is it because you declined to participate in the ritual sacrifice that takes place when you sell your soul to Monsanto?
I switched out of plant genetic engineering mostly because it was so dominated by Monsanto and I didn’t want to be part of a monopoly around the use of the technology.  At the time I was thinking through where I wanted to go, there were very few ..(pretty much no..) other options to engineer plants in an industrial environment that would feel like a positive contribution.  As far as the transition, that was a matter of luck - other postdocs in the lab were joining a tiny startup working on engineering mammalian cell lines to produce enzyme therapeutics for a very rare childhood disease and the positive nature of that project was very motivating.  I got a  chance to work on something that was very novel at the time as well as technically challenging as well as the opportunity to learn an enormous amount about building a startup.

Q: Couldn't you make the same argument for human/pharma work, though? Getting a drug through trials costs so much that every start-up probably wants for a Glasko or Roche to buy them out. Isn't that comparable to plant work? Getting a plant through regulatory costs so much that you almost need a Syngenta, Dow or Monsanto to get through those hurdles?
At the time I switched plant genetics was being driven predominantly by profit margin motivations within large corporations even though plant engineering had the potential to offer many values in a less corporate way (such as the work going on within government funded labs to provide plant tools for countries where agriculture was a struggle). There seemed to be little opportunity for growth of startups in that field. However in the human disease treatment space new worlds were opening up with the appearance of the orphan drug program which allowed for startups to get traction and funding to work on the types of products that big pharma was not interested in addressing.  I guess it was therefore a lot about the type of environment (startup vs. corporate). I was interested in understanding how startup worked and how companies were created. Certainly as products mature and enter into the world of regulation having experience to get through that is critical to success, but a good partnership can achieve that just as well as a buyout.  I joined BioMarin in 1999 when they were just starting out, so got to live through a company being born in the orphan disease treatment space and successfully mature into a very successful company.

Q: Do you think that something as useful as a tearless onion will make anti-GMO activists change their tune?   
I’m not sure tearless onions are going to provide enough value to humanity to tip the balance in favor of GMO’s.  However I do think that a really valuable part of the GMO discussion is to appreciate that there are a lot of different motivations to use plant genetic engineering, some of which have the potential to be very important to human health and well being in the future (e.g. developing salt-tolerant crops).  It’s hard to support GMOs that are created primarily to generate profit for a large corporation.
A tearless onion would be awesome. I'd pay extra for that trait!
Image from Wikimedia Commons
[Biochica's note: An Iron Chef challenge using onions, where the challenger uses a GM onion and wins due to the time saved from not sobbing would show the true value of the crop]

Q: You seem to have mixed feelings about GMOs. You mention that some GMOs are hard to support when they're made mostly to generate profit for big Ag. But if they sucked, then farmers wouldn't buy them. So what do you think of current GMOs on the market? Do you think they're safe? What do you think of the next generation of transgenic crops, that are designed to benefit the end consumer?
The world of commercial GMOs is complex and there is no ‘one-size-fits-all’ answer.  We need to appreciate that the technology in and of itself is not the risk, it is how it is used that should be paid attention to.  Some uses are just fine and others may come with unintended consequences that have to be evaluated and understood in the same way all new technologies bring risk as well as value. So my opinion is that each one needs to be evaluated and accepted or rejected on its own risk-reward profile not in a dissimilar way to how we treat chemistries, after all we don’t believe all chemistry is bad and ban it all from our world.

Q: Do you miss plant genetics? Would you recommend it as a career path?  
I do miss plant genetics - it is a really fascinating technical area.  You get to tinker with a genome in a much more accessible way than with mammalian genomes and the understanding that is generated about how genes work is incredibly interesting.  A lot of the gene editing technologies that are emerging now for mammalian systems probably would not have come about without the learnings gleaned from the plant world.  The problem with it as a career path seems to be still the same - there are few jobs that would provide the ability to do positive work and provide a decent income.

[Biochica's note: recent articles suggest that the times are changing with respect to the demand for agricultural/plant researchers. See here and here]

Q: Last question: my readers here know that I dream of a peelable pomegranate. You and I have also chatted about my plans for early retirement, where I go back to school somewhere between the age of 42-45 to do a post-doc in plants. Or somehow I become CTO of a corporation. I still haven't decided which. But do you realize that by not doubling my salary annually, you're delaying my retirement and consequently depriving the world of a peelable pomegranate? How do you respond?
Apologies to the world for the deprivation….   That’d be one cool fruit. If you ever find a job with a doubling salary, let me know, I want one of those too!

[Biochica's note to POM: if you're reading this, contact me in 10 years when I retire, and you can sponsor my project]