Revisiting Bonner 1947

In 1947, John Tyler Bonner published a paper in the Journal of Experimental Zoology presenting results of his experiments that suggested that a form of “chemotaxis” was the mechanism underlying aggregation of cells in slime molds . Sixty-nine years after the paper was published, I asked John Bonner about how he got interested in slime molds, memories of lab work, and what we have learnt since about this topic.

Citation: Bonner, J. T., & Savage, L. J. (1947). Evidence for the formation of cell aggregates by chemotaxis in the development of the slime mold Dictyostelium discoideum. Journal of Experimental Zoology Part A: Ecological Genetics and Physiology, 106(1), 1-26.

Date of interview: Questions sent by email on 6th December 2016; responses received by email on 15th December 2016.

 

Hari Sridhar: This work formed a part of your PhD, which, I came to know, was completed in a really short time. What motivated you to do the work presented in this paper?  Also, stepping back a bit, what got you interested in slime molds?

John Tyler Bonner: This paper was indeed my PhD thesis.  It was my first attempt to do experiments.  I had become interested in using lower organisms to attack problems of development and by sheer luck ran across Kenneth Raper’s PhD thesis and decided cellular slime molds were ideal, and they ended up a lifetime pursuit.

Slime molds are interesting because of the way they develop: cells come together to form a multicellular organism. Normally, that is not the way it works. Normally, a fertilized egg, divides many times, grows in size, and slowly turns into an organism. So when I started working on them, the first question that interested me was why do these cells come together? Why do they aggregate to produce an organism that has a front and a hind and produces spores at the top and stalk cells at the bottom? This question had been open for a long time, to as early as 1900. What attracts them to the central collection point? That was mysterious. There were lots of theories about the mechanisms of aggregation, but none that explained it satisfactorily. That became my PhD thesis.

 

HS: In the paper you say “This work was carried out at Harvard University, under the auspices of the Society of Fellows”. Could you tell us a little more about how the Society of Fellows helped?

JTB: I was a Junior Fellow in the Society of Fellows which provided a generous 3 year fellowship.

 

HS: Am I correct in saying that Kenneth Raper’s papers formed an important part of the background to the work presented in this paper? Did you know and interact with Kenneth Raper during your time at Harvard?

JTB: Yes, indeed!  He was a patient and supportive mentor who became a good friend.

 

HS: Today, nearly 70 years later, it is impossible to imagine what it must have been like to do these experiments at that time. Could you give us a sense of that, especially how different it was from the way labs function today?

JTB: Very different.  It was considerably before molecular biology and the experimental methods at the time seem remarkably antique.  It might be described as the kitchen phase of experimental biology!

 

 HS: Where did you do these experiments? Would you know what that space is being used for today?

JTB: As a graduate student, I had a small room to myself with simple furniture, right next door to the communal autoclave room.  (It always delighted me that its door had, in big gold letters, the one word CULTURE: that was the easy way to become cultured).  My room is probably still a student room today, but not just for one person.

 

HS: Would you remember when and where you wrote this paper?

JTB: Yes, right there in my room, longhand, and for a fee it was typed by some kind secretary.  No computers!

 

HS: Unlike the papers of today, this paper doesn’t have a separate ‘Acknowledgements’ section. At that time, who were the people who you were discussing ideas with? Were there people who helped you do these experiments or did you do them all on your own?

JTB: No, I did everything on my own, including washing the glassware.  My mentor, Prof. Weston, complained to me that I did not consult him very often, but I felt it was important that I stand on my own two feet.

 

HS: Could you also share with us how the collaboration with L.J. Savage come about?

JTB: We were both at the Marine Biological Laboratory in Woods Hole, Mass. one summer and he became interested in what I was doing and unleashed his extraordinary mathematical skills.

 

HS: Would you remember why you decided to submit this paper to The Journal of Experimental Zoology?

JTB: I felt strongly that the separation of Botany and Zoology, still prevalent then, was a big mistake.  My first paper was in a botany journal and I was eager to include slime molds equally between the two.  Slime molds were neither plants nor animals.

 

HS:  You say “during the aggregation of Dictyostelium there is some type of chemical substance (which is not necessarily homogenous but might consist of a group of compounds) produced continuously or at frequent intervals by the center, which freely diffuses, and the myxamoebae move in the resulting gradient of this substance towards the point of its highest concentration.” Today, 70 years later, could you reflect on this conclusion, and tell us whether you would change it in anyway?

JTB: Yes, I would delete the parenthesis saying “a group of compounds” because we now know it is cyclic AMP, one small molecule.

 

HS: You say “The final proof of the existence of the substance (and an important problem for future research) must be its isolation in vitro”.

Did this form part of your research subsequently? When and by whom was this substance isolated in vitro?

JTB: Yes, the substance was identified as cyclic AMP by David Barkley and Theo Konijn in my laboratory in 1947.

 

HS: Is the term you coined – Acrasin – still used?

JTB: And, yes again, because different species have different chemicals for their acrasin.

 

HS: Could you reflect a bit on how doing this work on your PhD influenced the trajectory of your research career?

JTB: I continued to enjoy doing this kind of experiment that is mostly at a level above the molecules.  Experiments on the behaviour of cellular slime molds.

 

HS: In the 70 years since this paper was published, have you ever had the opportunity to read it again? If yes, would you remember in what context?

JTB: Only recently; to answer your questions!

 

HS: Would you count this as one of your favourite pieces of work, and why?

JTB: It got me started in experimental biology and was well received, which was a tonic for a beginner.

 

HS: What would you say to a student who is about to read this 70 -year old paper today, given all that has happened in the field since then? Would you ask them to keep any caveats in mind as they are reading?

JTB: I don’t think so.  The message is so straight forward.

 

HS: If you think back to the time when you did this work and wrote this paper, what are your most striking memories?

JTB: I knew a brilliant embryologist called Paul Weiss at the Rockefeller University. He kept warning me, ‘Check everything else before you say it’s chemotaxis, because it probably isn’t chemotaxis.’ His theory was that it was some form of ‘contact guidance’, i.e. they sort of feel their way along. My thesis was to try to demonstrate that it was chemotaxis. When I got out of the army, I had a few months to complete my thesis. Early in that period, I hit on the solution. My Eureka moment had me dancing in the lab and punching the air. I looked through the microscope and knew it was chemotaxis. I saw a bunch of aggregates in a round dish and a slow current created by a stirring rod. Since I didn’t anticipate much to happen, I would go into another room to do something else. But when I looked through the microscope 20 minutes later, I nearly hit the roof. The amoebae up above had no idea where the centre was, but the ones down below were forming these long trails that go towards it. I knew I would get my degree then.

 

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