Stories from Christopher Wright
Posted by Helen Zenner, on 1 February 2023
At the Joint Society for Developmental Biology (SDB) – Pan-American Society for Evolutionary Developmental Biology Meeting in 2022, I spoke to Christopher Wright, the winner of the 2022 SDB Victor Hamburger Outstanding Educator Prize. You can read the interview in Development, but Chris shared some stories that we couldn’t squeeze in, so with his permission I have reproduced a couple of examples here. I selected these stories as they show the fun side of doing science and the excitement for biology that Chris expressed throughout our interview.
Science on a whim
“When I was in Eddy de Robertis’ lab for my postdoc, we decided to start probing the organizer region – the Spemann-Mangold organizer – for homeobox genes. We did this on a whim when Eddy went on vacation, and when he came back several people in the lab were running around clearly excited running old-school “high-throughput” DNA sequencing by hand. We told Eddy what we’d done and he was somewhat shocked. But, in the end, organizer molecules were what set his lab moving forward for the next 10 or 15 years. Out of that work came goosecoid. A huge amount of work went on after I had left, but finding goosecoid and naming it, based on part of its homeodomain sequence resembling the fruit fly gene gooseberry and the other part bicoid, was great. We decided that ‘bicberry’ sounded wrong but goosecoid stuck. It felt like we had just joined the Drosophila community and could name things crazily! There was an important lesson in this situation: when working with postdocs, the challenge for the PI is to understand that there are often things that are done outside of the PI’s undoubted own brilliance. Great postdocs should be semi-independent almost straightaway. You want them to cause (almost) paroxysmal change in the lab. I think Eddy learnt that. And Eddy was phenomenal to just talk to about science, he was always asking, “what do you think this means?” I remember looking down the microscope together, at the first Xenopus nuclei ever labelled with antibodies I’d made to the homeodomain proteins. He jerked me up from the microscope and gave me a huge hug!”
Seeing is believing
“It is wonderful to look down the microscope at new findings. One fun time was when Yoshiya Kawaguchi, a terrific Japanese postdoc with me, did an experiment that would be the first time that lineage tracing was combined with a gene knockout in the endoderm. He took the pancreas master transcriptional regulator called Ptf1A and hooked it up to Cre. The Cre replaced the protein, so was essentially a knock-in as a knockout, and we had a ROSA26-lacZ reporter in there too. One day he came bowling into my office and said, “Chris, Chris, Chris, you have to come right now and look at this embryo (which had been stained with X-gal overnight). The mutant is amazing”. And I said, “yep, okay, I’m coming right now. I’m really excited. Let me just tell you what I think you have found, I bet you found that all the cells that were going to become pancreas have now become duodenum”. He was shocked, asking “how can you know that?” I said, “don’t let that disturb you. Let’s go and look together.” As soon as I looked down the microscope, I knew this was an important result and we were so excited. It’s a memory that sticks with me, seeing that result for the first time!
Another result that really stuck with me was when we got involved in cloning Nodal, cobbling it together using various parts of the mouse gene, and isolating the frog orthologs. We injected the mRNA into Xenopus embryos and when we came back the next day, well – they had made notochord everywhere. This started our move away from homeobox genes. Left-Right asymmetry patterns came up from our Nodal work early on. This time I absolutely couldn’t believe the result to start with and I told my postdoc (the wonderful Karuna Sampath) that the pattern must be due to the side the embryos were lying down, having had some horrible glass reaction. She very kindly said “No, no, it’s all on the left-hand side of the embryo irrespective of which side they were lying”. Again, off we charged to look down the microscope straight away!
Overall, I have so many exciting moments in my career, and I feel very privileged and fortunate to have been born at the right time, landed in the right place and then to have done at least some of the right experiments!”