Good evening, and thank you for tuning in to our regularly scheduled program,
the Complete History of Science. The year is 1946 and this week, we will be delving into bacteria.
So please, enjoy this brief documentary about our current understanding of this mysterious organism.
Our story begins in 1876, when Robert Koch exposed the anthrax bacteria as an agent of infection,
carrying illnesses from one infected person to another - and for a few decades,
bacteria remained much of a mystery.
It was commonly thought that bacteria was distinct from the higher organisms like us animals,
and had a mystical, life-giving protoplasm that allowed it to reproduce by dividing.
Flash forward to 1928, when Fred Griffith observed the apparent transmission of genotypic changes,
converting the bacteria Streptococcus pneumoniae from non-virulent to virulent strains.
This transforming factor wasn’t discovered until 1944, when the trio Avery,
Macleod and McCarty identified this pneumococcal transforming agent as DNA.
Suddenly, the bacteria’s internal system was called into question. Did this DNA strand
carry genes? Did bacteria have genes? Were they able to reproduce? It still remains a mystery -
Sorry for the interruption. For those of you just tuning in,
we’ve recently received word of a disturbing sexual scandal regarding Bacteria.
We are joined today by the accuser, J. Lederberg and the defendent, Escherichia coli.
Thank you.
Thank you. And please, call me K-12.
So my understanding here is that Lederberg, you are accusing K-12 of engaging in sexual relations.
That is correct.
And completely inaccurate. I deny the allegations.
Well, how did you stumble upon this discovery? It’s a pretty bold claim.
Well, you know, it wasn’t that bold. Dubose’s monograph The Bacterial Cell
really revealed the flimsy evidence supporting bacteria’s supposed lack of sexuality.
Salmonella had somatic and flagellar antigens in different combinations,
implying the existence of random, or natural, recombination.
I met my mentor, Francis Ryan, in 1942, and tried to replicate DNA transformation in Neurospora.
When that didn’t work, I thought Why not test my hypothesis?
So I modelled recombination in E. coli.
So what was the experiment?
I’m glad you asked. My partner Tatum couldn’t be with us today,
but I actually recorded the experiment, so I’ll show you that now.
Using radiation, Tatum mutated our E. coli strain K-12 here into the two auxotrophic strains
Y-10 and Y-24, both with different nutritional deficiencies. Y-10 needed to be supplemented with
threonine, leucine and thiamine to grow, while Y-24 required biotin, phenylalanine and cystine.
When we combined these strains in mixed cultures of about a billion cells, we observed the growth
of one hundred colonies. And in those colonies was the original K-12 strain.
After eliminating transformation through control experiments with sterile filtrates,
we concluded that this strain arose from a sexual process between Y-10 and Y-24.
It’s ridiculous. How do you know I hadn’t spontaneously
reverted back to my original parental genotype?
It’s interesting, because I actually published a paper on this phenomenon in Neurospora with Ryan.
Spontaneous reversion to auxotrophy foiled my attempts to model transformation in
Neurospora before this. But you would notice here that I used triple mutants,
and the chance of spontaneous reversion for all three mutations was vanishingly small.
Now, that is interesting. E. coli, how do you respond?
Well, I actually brought a few of my lawyers. For instance, I have with me, Sir Cyril Hinshelwood.
You know, the Nobel Prize Laureate and famous physical chemist.
Thank you. My client here has been falsely accused. Bacteria are simply reaction systems:
they only adapt in response to their environment through spontaneous biochemical reactions.
How else can you explain the rapid response to nutrient sources?
Ah yes, Lamarckism. Well, it’s an interesting theory, this idea of holistic adaptation.
But only three years ago, Luria and Delbruck had proven that bacteria mutate not in response to
its environment, but randomly, disproving this idea of acquired characteristics.
And now, my study on genetic exchange explains the rapid spread of a favourable trait.
Well, that’s okay, because I actually brought another lawyer,
the microbiologist and Nobel Laureate, Andre Lwoff.
Yes, thank you. Mr Lederberg, how can we be sure that these results did not arise from,
say, the cross-feeding of nutrients between the mutant strains?
I did take careful pains in the experiment to avoid cross-contamination. But to be sure,
Dr Max Zelle helped me isolate the recombinant strains under the microscope, confirming single
cells with parental characteristics. Our paper should be out soon, maybe 1950.
Do you know what the implications could be if this scandal was released?
You’ve revolutionised our understanding of bacteria. Now that I have a genetic system, I’d
just be used for further experimental analysis. I’d probably help develop your understanding of
virulence and the transmission of antibiotic resistance, eventually improving vaccines.
I know. I should win a Nobel Prize for this.
Well, that about wraps up tonight. Thank you for
joining us for a historical moment at the Complete History of Science. Good night.