An Intimidating Person

So [David Botstein] invited Sydney Brenner and invited Mark Ptashne at the same time [to give a lecture in the CSHL Gene Expression Course]. So, Sydney Brenner and Mark Ptashne were in the room together, and Sydney Brenner was holding court, and Sydney Brenner was the only person I've ever seen be able to silence Mark. Sydney Brenner is a very intimidating person, and Mark just behaved himself, and Sydney just took over the conversation.

Becoming Sydney Brenner’s Postdoc

Anyway, I decided to ask [Sydney Brenner] if I could postdoc with him. And so, because David Botstein was there and Mark Ptashne was there, he got personal references at that time. And so, he said, yes, you can come to my lab. And then he said, but you have to get your own fellowship, you can't come to- I can't support you. You have to get your own fellowship. And I said, okay. And he told me about some new experiments that Jonathan Hodgkin had done where there were mutations that could cause sex reversal of the nematode. You could have a hermaphrodite that genetically, by chromosome content could be a hermaphrodite, but it was transformed into a male. And I was really intrigued by that idea. And so, I went home and I wrote a postdoc proposal and sent it to Helen Hay Whitney Foundation and all the foundations. And I got every fellowship I applied for. So, I took my fellowship to England and started working with Sydney Brenner.

Postdoc with Sydney Brenner

And I realized that really what I wanted to discover was how the worm, I knew from work in the fifties from Nigon that the worm could count the number of X chromosomes relative to the sets of autosomes, the ploidy. That was the X to autosome ratio. And I really wanted to understand how that worked because, again, it was a genetic switch, and from lambda I wanted another genetic switch, but it was impossible to figure out how that might work. And there were no clone genes. Sydney was working to clone the myosin gene on 54, but there are no clone genes. And so, there were no genes on X that had been cloned. So eventually what I decided to do was I had to figure out what the sex signal, the X:A ratio, was controlling. And my now husband, who I didn't even know at the time, had discovered in drosophila that both the sex determination and the dosage compensation pathway were linked by a gene called sex-lethal. And I thought, oh, what if that's true in worms? I better prove whether there's dosage compensation. But to do that, I would have to clone, I'd have to get genes on the X chromosome. So, I made cDNA libraries and I probed the cDNA libraries by taking DNA from a male that had one X chromosome and DNA from a hermaphrodite that had a translocation of part of X onto an autosome, so there were four copies of a particular region of X. And I did differential probing to find genes on the X chromosome. And so, I was able to take those genes.

Working with Sydney Brenner

Sydney, the first year he had had this horrible accident and so we didn't see much of him. But when I was first his postdoc, I flew back to the United States to finish writing my papers with Mark Ptashne. And that took longer than it should have, it took a few months and so he was pretty annoyed. But he agreed to be the editor for JMB, and so I brought my papers to Sydney to be my editor. And at this point he was in the hospital and so his leg was up in the cast and he was in his hospital bed in Addenbrooke's and he served as my editor for my JMB papers. So, I'd go over and talk to him all the time about my JMB paper. So, I had all these crazy connections with him that I worked with him and in that connection, he was really kind to me. And he wasn't, he's not an easy person to be around. He's extremely smart and extremely witty and extremely cutting. And you always felt, you never knew when the story was going to change and all of a sudden you were the object of the story, not a co-listener to the story. He was a complicated man, but he was such a brilliant man. [May] never really came to the lab that much, and so I really never had an association with her, but obviously he had great respect for her. I never worked with easy people. That's true. Sydney could be tough on women. He can be very tough on women, but he was also a very generous person.

Becoming Friends with Sydney Brenner

When I was an assistant professor at MIT, Sydney Brenner came to give lectures at Harvard Med School and David Botstein invited Sydney over to dinner and invited me over to dinner and a bunch of people. And that's really the first time I was in a more social situation with Sydney and we had a lot of fun. And I was in charge of driving him to David Botstein's house and driving him back. We just became friends. No longer when I was a postdoc, I had my own job, so there was no responsibility. And at that point, when I first joined the MRC, he was in a terrible car crash and he had his leg broken in a lot of places and so he could hardly walk. And so, when he gave his seminar at Harvard and David invited me, he was limping very badly, so he was very kind to me. He took me to dinner afterwards and I said, let's go on a walk. And so, I had had knee problems from hiking too much and so I actually knew how to walk and I knew how to deal with knee problems and broken parts. And so, we would go on walks and I would show him how to walk, show him better ways to walk because he had terrible physical therapy and it helped him. So, we just became friends, we became friends and we trusted each other. And I always told him the truth. I think very few people will tell Sydney Brenner the truth, but I just always told him the truth and I think he valued somebody who would tell him the truth. So just we became friends and he was on the East Coast a lot and so I would see him. Eventually, when I came to Berkeley, I was famous enough to be invited all over the world to give seminars and so I would end up sometimes in Japan or Singapore and we just continued being friends. He was just an incredibly insightful and smart person to be around. He was such a brilliant man.

Dr. Barbara Meyer is a genetics, genomics and development professor in the molecular and cell biology department at University of California, Berkeley. She also serves as an adjunct professor in the biochemistry and biophysics department at University of California, San Francisco’s School of Medicine and an HHMI investigator. Dr. Meyer completed her undergraduate studies at Stanford University and began her PhD at the University of California, Berkeley and finished at Harvard University. During her post-doctoral work, she researched how chromosomes determined sex of C. elegans at the Cambridge University Laboratory of Molecular Biology with Dr. Sydney Brenner.

Dr. Meyer received her Bachelor of Arts in Biology from Stanford University in 1971, her Master of Science in Molecular Biology from the University of California-Berkeley in 1975, and her PhD in Biochemistry and Molecular Biology from Harvard University in 1979. She then began post-doctoral research at the MRC Laboratory of Molecular Biology to research how chromosomes determined sex of C. elegans. After completing her work at the MRC, she established her first lab at MIT to further analyze sex determination mechanisms.

Dr. Meyer was a tenured professor at MIT until 1990 where she became a genetics, genomics, and development professor at the University of California-Berkeley. In 1995, she became a member of the American Association of Cell Biology and American Academy of Arts and Sciences. She also became an investigator for the Howard Hughes Medical Institute in 1997, where she and her lab successfully identified the master gene involved in sex determination. This breakthrough has helped advance research on chromosome repression and X chromosome dosage compensation.

Dr. Meyer has received many awards for her work, including the Genetics Society of America Medal in 2010, the Francis Amory Prize in Medicine and Physiology by the American Academy of Arts and Science in 2017, the E.B. Wilson Medal by the American Society for Cell Biology’s highest honor for science, the Thomas Hunt Morgan Medal, and was also elected to the National Academy of Medicine all in 2018.