Innovations

Imaging the Future

What image in biology would you most like to capture if you could? Nobel Laureates reveal their wishlist of images.

 

The stories within Imaging Life reveal how advances in imaging during the course of the last century have changed our view of ourselves and the world around us – from the first X-ray images that revealed our bones to unravelling the complex machinery that lies at the heart of heredity.

Like all other aspects of science, however, the journey of discovery is far from complete; there are still many invisible territories to visit and many more sights to see.

To get a sense of what possibilities could lie ahead in imaging, we asked Nobel Laureates what image they would most like to capture if the technology was available, and why? Their answers illustrate the need to understand the fluidity of life – whether it is looking at the processes that allow life to begin, viewing the molecular or physiological engines that keep us alive, or seeing how these processes go wrong in order to prevent disease and death. Within the next century, these images will hopefully become as familiar as the images that we see today.

Michael Brown

Nobel Prize in Physiology or Medicine 1985
One important medical advance would be the ability to image early atherosclerotic deposits in human coronary arteries in a safe, non-invasive fashion. Recent improvements in computerized axial tomography (CAT, or CT scans) have approached this goal, but they are hindered by the large radioactivity exposure that is required. Additional methodologies should be developed. With such images in hand, we would be able to predict who may have a heart attack 20 years in the future. This would allow physicians to initiate cholesterol-lowering therapy at a stage where we would have a high likelihood of preventing the attack. Such images would go a long way toward eliminating heart attacks, the major cause of death in industrialized societies.

Richard Roberts

Nobel Prize in Physiology or Medicine 1993
For me as a molecular biologist I would wish to be able to dynamically view DNA and its associated proteins in real time and in molecular detail. This would permit one to see as a movie the actual initiation of replication and transcription and to know the exact mechanisms used to open the DNA helix and position the first nucleotides at the appropriate start points.

Ferid Murad

Nobel Prize in Physiology or Medicine 1998
It would be a major breakthrough to selectively image different inflammatory and disease processes in the body non-invasively with high precision, sensitivity and at a resolution of several nanometres or millimetres. If one had to administer agents to tag the diseased site before imaging, this would also be an acceptable alternative. Nanochemistry should make this a reality in the next decade. Nanoparticles could deliver tags such as antibodies or receptor ligands to home in on specific diseased sites and the payload could also include nucleotides, dyes and other agents for imaging.

Aaron Ciechanover

Nobel Prize in Chemistry 2004
A crucial advance would be made if we could follow dynamically the numerous biochemical reactions that occur in the cell. This will be important for understanding the mechanism of the reactions that could later allow the development of rational drugs to modulate them. High-resolution mechanistic analysis can be performed today using X-ray crystallography; however this technique requires – as the name implies – crystallization of the enzyme and its substrate, and therefore this method looks at a frozen rather than a dynamic state. Techniques such as nuclear magnetic resonance in solution suffer from relatively low resolution. All these techniques are limited in their ability to look at complex reactions, and are yielding acceptable results only when the substrate is a small molecule, or if it is a large protein, when only part of it – a short peptide – is used to mimic the entire substrate. Complex reactions such as ubiquitination of proteins and their degradation cannot be analysed using these techniques. Furthermore, we cannot look at several independent reactions occurring in parallel, or when a substrate is undergoing a successive chain of reactions. We need a “biochemical microscope” that will look at live cells at a resolution that is many orders of magnitude higher than the “microscopes” we have today.

Johann Deisenhofer

Nobel Prize in Chemistry 1988
I would like to see a high-resolution image of a small multicellular organism, such as the worm Caenorhabditis elegans, showing the structure of every molecule (for instance, protein, DNA, RNA, lipid, etc.) and its environment. This would provide us with insights into the detailed architecture of differentiated eukaryotic cells and their interactions. The information in such a picture would certainly be too much for human brains or contemporary computers to store and to comprehend, but this would set an ambitious target for the future course of biology.

Rolf Zinkernagel

Nobel Prize in Physiology or Medicine 1996
Since an image captures one particular time point, I would like to see a film – that is, a sequence of images – that shows how the T cell recognizes a virus-infected cell or a tumour cell, to learn how the recognition molecules, T-cell receptors and the accessary molecules change their structure when they interact with the target cell, and how these receptors and target antigens move on a living cell.

Paul Nurse

Nobel Prize in Physiology or Medicine 2001
I would like to be able to visualize the workings of multi-protein macromolecular machines in cells, such as the ribosome, the transcriptional machinery and the DNA replication machinery. At present it is difficult to acquire precise images of large macromolecular complexes at a scale between individual proteins (imageable by X-ray crystallography) and organelles (imageable by electron microscopy), and even more difficult to dynamically capture a time sequence of images of these macromolecular machines carrying out their work. Such images would greatly contribute to our understanding of how living cells function and operate.