How do we think and why are we self-aware?

Why do we need to sleep, and why do we grow old and die?

Those are some of the big, burning questions a Nobel Prize-winning scientist, visiting New Zealand this week, says he would love to see answered in his lifetime.

"Many, many questions linger in biology, some of them quite obvious," said Professor Bruce Beutler, who opened Queenstown Research Week, an annual summit of hundreds of leading Kiwi scientists.


Beutler, currently the director of the University of Texas Southwestern's Centre for the Genetics of Host Defence, jointly received the Nobel Prize in Physiology or Medicine in 2011 for a breakthrough that changed the course of immunology.

This work revealed an important family of receptors that allow mammals to sense infections when they occur, triggering a powerful inflammatory response.

Beutler achieved this by cloning mutations to discover how what are called "Toll-like receptors", or TLRs, act as molecular sensors of infection.

The immunologist and geneticist is also revered for having laid the foundation for a widely-used treatment for rheumatoid arthritis and other inflammatory diseases.

He and his colleagues try to learn more about immunity and other important biological processes through studying mice.

"We do this by making abnormalities - for example, immune deficiencies or autoimmunity - using a randomly-acting chemical mutagen," Beutler told the Herald.

"That way we can identify those genes that are essential for normal immune function."

By revealing these genes, scientists could gain a clear impression of how immunity normally operates in both mice and in humans, which were very similar when it came to immunity.


"Ultimately, we would like to understand living things as one might understand the workings of a machine of human construction."

Since the discoveries around TLRs - particularly that one of the proteins, TLR4, responds to bacterial endotoxin - work in this area had "grown enormously", he said, but there was much more to understand about them.

He wanted to know what it was that created and controlled endogenous ligands, an enigmatic form of protein produced within our bodies, and whether they recognised TLRs.

Answering such questions had been made easier through a surge in technology - namely advances in DNA that have now allowed scientists to edit genes and sequence, or download, our entire genome, or genetic make-up.

"In our laboratory today, we often find mutations that disrupt TLR4, and do so immediately and without any particular effort: an amazing thing considering how hard it was to find the first mutation," he said.

"This is due to several advances - sequencing is a million times faster and costs about one millionth as much as it did 20 years ago."

With new structural methods, notably one called cryo-EM, scientists could visualise large molecules and their interactions in ways that were not previously possible.

"All these advances synergise with one another, and make a qualitative difference in how biology is practised."

In the long run, he said, we might imagine synthetic biology will permit us to synthesise large genomes at will - perhaps even creating "designer animals" in a way that goes far beyond what we can currently accomplish with today's gene-editing approaches.

"We may be able to understand complex genetic diseases by creating them," he said.

We might also expect to see artificial intelligence begin to make a huge contribution to biological science, including immunology of course.

"This will be necessary to parse and assimilate the huge volume of data we may expect to gather - more data than any human beings can individually assimilate."