The Backstory: Padmanabhan Babu and the isolation of the e912 mutant (lin-4)

7/30/2025

By Richard Behringer

The 2024 Nobel Prize in Physiology or Medicine was awarded jointly to Victor Ambros and Gary Ruvkun "for the discovery of microRNA and its role in post-transcriptional gene regulation". 

Their studies were enabled by mutations isolated in the lin-4 and lin-14 genes of the nematode worm C. elegans. These mutations alter cell fates and cell lineage. The lin-4 gene product is a microRNA that regulates the translation of lin-14 mRNA through an anti-sense mechanism.

 lin-4(e912) mutant worms (top and middle), showing “bag of worms” phenotype; wild-type (wt) worm (bottom). Image by Tokiko Furuta (Swathi Arur Lab).

lin-4 (e912) mutant worms (top and middle), showing “bag of worms” phenotype; wild-type (wt) worm (bottom). Image by Tokiko Furuta (Swathi Arur Lab).

 
Here we focus on the discovery of the lin-4 mutant worm. For many years there was only one lin-4 mutant allele (e912), and this single allele enabled the studies reported by Lee et al. (1993) from the Ambros lab, describing the first microRNA.

The e912 mutant was first reported by Horvitz and Sulston (1980) - “lin-4 (e912) was obtained by P. Babu”.

Who is P. Babu? Dr. Padmanabhan Babu came from India to work in Sydney Brenner’s lab at Cambridge University between 1970 and 1973. Dr. Babu performed a 32P decay mutagenesis screen in C. elegans for mutant phenotypes (Babu and Brenner, 1981).

Dr. Babu isolated the e912 mutant because it had a vulva-less phenotype, indicating altered cell lineages. The consequence of these abnormalities was a “bag of worms” phenotype in which eggs are fertilized but cannot be laid and remain inside and consume their mother.

Dr. Babu’s discovery of the e912 mutant on one of his plates in the early 1970’s in Cambridge led to developmental biology studies by others that identified a fundamental mechanism of gene regulation.

Dr. Babu is now retired, living in Bangalore, India.

 Dr. Babu (left), Anand Sarabhai, and Sydney Brenner (right) in Bombay, 1981.

Dr. Babu (left), Anand Sarabhai, and Sydney Brenner (right) in Bombay, 1981.

References:

Babu and Brenner, 1981. PMID: 7266559
Lee et al., 1993. PMID: 8252621
Horvitz and Sulston, 1980. PMID: 7262539

Last Updated 08/05/2025