Craig Mello, who received the Nobel Prize in 2006 for the discovery of RNA interference (RNAi), together with Andrew Fire, visited Lund University and the Lund Spring Symposium, where he was awarded the “In Memory of Arvid Carlsson Award.” He emphasized that the information age has been ongoing since the dawn of life on Earth.
The genetic code is universal – the same language is used by all living organisms. But heredity is shaped by more than just parental inheritance. According to Mello, horizontal information transfer – genetic exchange between unrelated organisms – plays a crucial role in the history of life.
"Inside every germ cell, there is a fire of information burning," said Mello, pointing to images of glowing nuclei and mitochondria – organelles that were once free-living microbes but are now an integrated part of our bodies.
"It’s an incredible and beautiful story, really – that organisms can merge and incorporate information – information that has evolved independently."
He cited SARS-CoV-2 as an example: how it originated in China and spread across the global population.
"It also shows how information constantly flows horizontally – how microbes live in an inferno of information. They exchange genetic material all the time, even across species boundaries. And they’ve been doing this for billions of years."
From Roundworm to Nobel Prize
How does a cell defend itself against dangerous information? How does it recognize what belongs – and what threatens its survival?
It was when Craig Mello and Andrew Fire began exploring these questions that they made their Nobel-winning discovery: RNA interference. RNAi can be described as a type of genetic immune system. Instead of using antibodies, like our conventional immune system, the cell uses small RNA fragments to recognize and silence harmful information.
Fire and Mello discovered this when they injected double-stranded RNA – a kind of genetic information often found in viruses – into the tiny roundworm Caenorhabditis elegans. The worm’s cells somehow found genes that contained genetic information matching the information in the injected double-stranded RNA and shot those genes down. And not only that – the silencing was passed on to the next generation.
It’s worth noting that this worm is something of a celebrity in science, having contributed to many research awards and discoveries. It is transparent (no dissection needed to see what happens inside), every one of its cells has a name, its genes are easily edited using CRISPR, it lives only about three days – and it’s tiny and inexpensive.
An Ancient Immune Function
RNA interference (RNAi) is a mechanism in which cells use small RNA fragments to silence genes with matching sequences. Mello likens it to an immune system – but instead of fighting viruses with antibodies, the cell silences foreign genetic information.
"It’s like the cell has a search tool that scans everything being transcribed. If it matches something dangerous – like a virus – it gets silenced."
RNAi – The Cell’s Own Gene Guardians
The discovery opened up an entirely new research field and has revolutionized both molecular biology and drug development. Through RNAi, researchers can now shut off genes with high precision, which has led to new therapies for cancer and genetic diseases.
But Mello believes we’ve only scratched the surface of what cells are truly capable of.
Silencing – and Permission
RNAi is just one part of a complex network of information management in the cell. One particularly fascinating aspect of Mello’s lecture was his description of how certain genes are silenced – while others are licensed for expression.
"It’s not just that the cell knows what to turn off. It also has to know what to allow," said Mello.
In C. elegans, this is regulated through a balance of different types of Argonaute proteins – cellular "information guards." Some Argonautes silence transposons (self-copying DNA sequences that can otherwise wreak havoc in the genome), while others protect “self” genetic information by carrying memories of previously expressed RNA – a kind of molecular ID card.
"It’s as if the cell remembers which genes belong to it – and can therefore recognize foreign information as potentially dangerous," Mello explained.
Inheriting Memory
One of the most mind-bending insights is that this memory can be inherited. Mello showed examples of how silencing signals, in the form of small RNA molecules, can be passed from one generation to the next – even if the original gene that triggered the response is no longer active.
This means a cell doesn’t just inherit DNA, but also an epigenetic landscape of what has previously been silenced or expressed. This molecular inheritance shapes which genes are activated – and can influence the development of both individuals and species.
What Does This Mean for Humanity?
The lecture ended with a reflection on how humans manage information in our own age.
"Imagine if we could browse the internet and simply erase pages we don’t like. That’s what cells do all the time," Mello said with a smile.
But unlike humans – who often struggle to separate truth from falsehood – living cells have, over billions of years, evolved fine-tuned systems for evaluating, protecting, and filtering information. Perhaps, Mello suggested, we have something to learn from them.
"Organisms have been living in the information age since the dawn of life. We still have much to understand, and we must keep asking fundamental questions. That’s where the biggest discoveries lie."
