As one of the last graduate students in Sarah Hake’s lab in the Department of Plant & Microbial Biology (PMB), I am grateful to have the opportunity to work closely with such a remarkable female scientist. Professor Hake is a legend among plant geneticists—she famously cloned Knotted, a gene that led to morphological discoveries in many species, and the first developmental body gene identified in the plant kingdom. I recently sat down with Hake to hear her reflections on her journey as a scientist and her thoughts on the future of plant biology.
Sarah Hake on Gospel Flat Farm.
Nanticha Lutt: Where did you grow up and what led to your interest in science?
Sarah Hake: I lived in Iowa until I was ten, and then my family moved to California. I actually went back to Iowa to go to Grinnell College, partly to get away from the busy bay area, to be in a more rural place.
I think the tranquility in Iowa led me into science. I liked going out into the natural forest area, a bio-preserve that was owned by the college. It was a little piece of paradise in the midst of all these cornfields, and just being out there attracted me to plant biology.
I was also chosen by a plant taxonomy teacher as one of three students to accompany him to the Botanical Garden in St. Louis, and it was there where I thought, Wow, it’s decided; I’m going into plant biology.
Largely because of this teacher, I was inspired to think about plant taxonomy. I even later went to Washington University in St. Louis, because it was the only school I had ever visited with a graduate program—my knowledge of graduate schools was very limited back then. I thought I would study plant taxonomy; however, I realized it's really fun when you're out in the field collecting the tissue, but then you have to spend the rest of your time doing scientific analysis confined to a computer at a desk.
I discovered that experimental science might be more interesting, and earned my PhD with Virginia Walbot. Her research was focused on trying to understand the maize genome. We were using cot curves, where we were looking at how much repetitive DNA exists in the genome compared to single copy DNA. This was before genome sequencing.
NL: Woah. I don't really know what the world was like before genome sequencing. Can you explain that to me?
SH: About 80% of the maize genome is repetitive DNA. The way we discovered the repetitive DNA is by boiling it, where we would have it labeled and let it re-anneal and take measurements over time. It was very, very technical.
Sarah Hake examining plants on her farm.
In the beginning, it was just so hard
to clone a gene.
NL: Genome sequencing has made my life as a scientist easier—I've never had to do an experiment like the one you’re describing.
SH: At the same time I was doing this I met Jerry Neuffer and Ed Coe, who were at the University of Missouri at Columbia, and they were the first plant geneticists I had ever met. I remember feeling really excited. Just the way that they ran through the cornfield looking for genetic mutants in the rows was amazing. Somewhere along the line, I also met Mike Freeling, who was a professor at UC Berkeley. He was so so radical. He was just so far out of what was traditionally acceptable in genetics at the time!
I remember the first time I heard him talk, he was discussing how gene regulation wasn't an on-off switch, it was a rheostat. During the talk I remember these elder geneticists leaning over and saying to me, “do you have any idea what he's talking about?” I told them, “No! But it sounds very cool.”
So, I wrote a National Institute of Health postdoc proposal to work with Mike Freeling on the alcohol dehydrogenase (ADH) gene in maize. It looked like we could clone that gene because under anaerobiosis, where you drown maize seedlings...
Nanticha, it's so much fun to talk about this stuff.
NL: It's so much fun hearing about it. It's such a different perspective from my own science narrative, because it's a different generation.
SH: Yeah! It's before...any big technical discovery. So, under anaerobic conditions we knew that translation was shut off, and only a few mRNAs were translated. These were the anaerobiosis genes and ADH was one of them.
We cloned ADH because of its abundance in the maize genome, and found transposon aelles. Mike had an ADH mutant, and in the same family we had a Knotted mutant. These mutants led us to write a grant on Knotted. My National Institute of Health postdoc ended and we had this money on Knotted, and that's what propelled my career.
NL: What were some of the hurdles you faced during your graduate career and your postdoc?
SH: Honestly, it was pretty smooth sailing only because I never expected more out of my career than the immediate next step. In graduate school, I was thrilled to get a thesis idea and really own it.
Then I had two kids during my postdoc, and Mike was very supportive. I actually arrived with an 8 month old—so one hurdle could have been having kids and living an hour away in Bolinas—but my husband, Don, took care of the kids. Having a really supportive husband with that flexibility really helped.
NL: Did you ever feel that you were treated differently in academia because you are a woman, or that it affected the way people regarded your work?
Sarah Hake and her grandchild, Phoebe, on Gospel Flats Farm.
SH: Not really. Having a female advisor really changes the environment. The postdocs were 50% women, 50% of the faculty at WashU were women, a ton of really famous strong science women held positions there. I met Barbara McClintock [grandmother of corn genetics, the first person to discover that genes could ‘jump’] a few times.
During my postdoc Mike was strongly supportive of women. Half the postdocs were women in his lab as well, which is an unusually high percentage for that time.
It was kind of odd starting at the Plant Gene Expression Center at Berkeley, where the director would call the women— Barbara, Shelia, and I— his girls. And of course the men who worked here were not his boys. I chalked it up to another era, so I kind of just compartmentalized his way of dealing with us; he was just an old school kind of guy.
I haven't experienced sexism personally in science, and I think that plant biology is good for that—and developmental biology is really good for that. I always end up at conferences where there's such a powerful women presence and I love it.
I think it's just that plants are incredible—and wise people know that they're incredible.
NL: I've never really felt bias explicitly in plant biology either, but I've also heard and witnessed from women scientists in other biological fields that it is a significant problem that affects their day-to-day interactions and life. I wonder what it is about plant biology that makes this less of a problem.
SH: I think it's just that plants are incredible—and wise people know that they're incredible. And development is too. The fields of developmental biology or plant biology aren't filled with power-grabbing people.
NL: What do you consider to be the greatest challenge in your field?
SH: In the beginning, it was just so hard to clone a gene.
Today, the challenge is to make new discoveries. Honestly, scientists really should take advantage of all the genomic data out there and not just keep repeating the same thing.
We should really try to come up with clever ideas. I think of Annis's [a postdoc in our lab] modeling maize, and that's really new and different, and looking at mutants to see if this process is true or not. Or looking at Sam's [another postdoc in the lab] sorghum and maize work. So many people have done transcriptomes of sorghum and maize, but the way that he created a developmental comparison in his paper, I thought that was a really clever use of new technologies. It's important to think outside of the box.
Another challenge is life balance. How do we maintain productivity and balance everything else? Work-life-balance is essential to being a good scientist.
NL: What is the greatest reward in the field?
SH: Training people. Always. Don Kaplan, a former faculty member in PMB said “It's not what you do, it's who you train. That's what makes a difference.” I think that's very true.
NL: What was the most surprising to you about your career in science?
SH: I was surprised at how much fun it was! I saw so much of the world traveling for my career. Another sort of painful surprise is saying goodbye to the meaningful connections you make. You bond so closely with someone working together side by side for many years, and have dinner every night, and suddenly when they graduate or get a job, you have this absence. However, you always get to see them again, because they're your colleagues and maybe you write a grant together or hang out at a conference.
NL: Is there an achievement or contribution you are the most proud of?
SH: Having the tenacity to hold on to finding Knotted. It was not easy.
NL: Can you talk about the recent grants you've been awarded and the direction your lab is heading as you move towards retirement?
SH: I want to tie up a lot of loose ends. We just got a grant for research in which we’re trying to figure out the underlying genetic networks that can give a change in sex in some plant hormone mutants.
We already know a lot about how plant hormones can affect development, so we’re trying to tell a more concrete story and get some papers published as well. Those are the goals. I'm trying to look at broad, bigger pictures, and not just one part of the plant.
NL: Can you tell me a little bit about your farm in Bolinas?
SH: I love it. My parents bought this piece of land in Bolinas when I was coming to UC Berkeley do a postdoc, with the idea that we would all meet and camp near the creek there on the weekends. But the more time we spent there we decided we should really live full-time on this land.
So my husband started farming there. We named it Gospel Flat Farm. First he grew wild rice. He flooded the fields and formed rice paddies, so that was a really good way to help get the land going. The land had previously had horses on it, so the flooding was really essential to kill the weed seeds leftover in the ground. Then he diversified his vegetables, and farmed for 25 years.
I spend a lot of time on the farm. In the summertime all the peppers, tomatoes, flowers, and green beans are abundant and fertile— it's just so fun. When my son graduated from college, he decided he wanted to work the farm, so he started a Community Supported Agriculture subscription (as a way for consumers to buy local, seasonal food directly from local farmers). That quickly morphed into the farm stand.
So rather than having a box where someone buys a predetermined set of vegetables, we have a farm stand where they pick whatever they want. Rather than everyone getting the same thing, you get a diversity of options.
It was also too much trouble to actually sit there and collect money, so we decided to just use an honor system.
NL: And do people actually 'honor' the honor system?
SH: Sometimes I'll find notes, like the other day I found a piece of paper instead of a bill that said “I owe you $20,” and I thought, “Well, you left a note, maybe you'll come back and pay it.” So largely, it seems like they do, and I know there's money at the end of the day.
NL: What are you most excited about in retirement?
SH: Staying in Bolinas on beautiful days like today! But also having my time available to drop everything and help somewhere. I really want to be available for the 2020 election. So even if I haven't really retired, I'll absolutely go on leave.
I hope to be retired by September 2020, so I could maybe go to Nevada, or help in a swing state. And spend a lot of time with my grandkids.
NL: So you're going to stay really busy, that's not surprising to me at all.
SH: Really busy, I promise.