In the footsteps of Schrödinger: understanding the physics of life

It’s an old but unsolved problem that requires new ways of shared working between physicists and biologists

During malarial infection, parasites multiply within red blood cells and then egress to adhere and infect new red blood cells. This optical microscope image shows (false colours) a cluster of parasites (yellow) just released, and about to infect neighbouring cells (red). Photograph: A. Crick and P. Cicuta

During malarial infection, parasites multiply within red blood cells and then egress to adhere and infect new red blood cells. This optical microscope image shows (false colours) a cluster of parasites (yellow) just released, and about to infect neighbouring cells (red). Photograph: A. Crick and P. Cicuta

Athene Donald(*)
Erwin Schrödinger, the Austrian physicist whose eponymous equation lies at the heart of quantum mechanics, strayed beyond his normal disciplinary boundaries when he wrote a book called The Physics of Life in 1944. He was bringing concepts from physics – notably statistical physics – to bear on the complex behaviour of living organisms.

n his book, Schrödinger said how he had been influenced by another physicist, Max Delbrück, who modelled genetic mutations mathematically (work for which he was later awarded the Nobel Prize in Physiology or Medicine in 1969). Despite being a physicist, Delbrück ultimately went on to become a professor of biology at Caltech.

Schrödinger relied on Delbrück’s work to postulate that genes had to be some sort of aperiodic crystal; in other words, they lacked the regularity familiar from the packing of atoms or molecules in crystals. In turn, Schrödinger’s book influenced Francis Crick and Jim Watson as they tussled with the problem of the structure and coding role of DNA and its relevance to genetics, ideas which ultimately resulted in the famous 1953 model of the double helix.

So, physicists thinking about biology are nothing particularly modern, yet after Crick and Watson’s work and the founding of the science known as molecular biology, there seemed to be something of a parting of the ways between these disciplines in many places. In the intervening years, rather few physicists continued to work with biological colleagues, exacerbated in the UK by the way our education system favours early specialisation.

In Cambridge the geographical separation of the Laboratory for Molecular Biology – out near New Addenbrooke’s Hospital – and the centre-of-town site for the Cavendish Laboratory where Crick and Watson had originally worked, made this separation (of a mile or two) particularly vivid. Later the gulf was made all the worse by the subsequent move of the Cavendish to its present site in west Cambridge. Speaking personally, it now takes me around half an hour to cycle from one to the other; the bus is no faster.

There have always been some physicists who have worked closely with biologists, but funding mechanisms for research have not necessarily made this an easy path to tread, as I’ve discovered to my own cost. Recognising this, the Engineering and Physical Sciences Research Council (EPSRC) has recently set up, as one of its Grand Challenges, the problem of “Understanding the Physics of Life”. Initially all that has been funded is a network, but with the aspiration that this will lead to new collaborations and, one hopes, in due course to properly funded programmes to generate breakthroughs in the science.

Today sees the launch meeting of the network, whose goal is to bring researchers across the disciplines together to solve some of the “big” questions in the science of how our bodies (and those of other organisms) function. At the heart of the activity is a particular emphasis on integrating our understanding at different length scales, from single molecules via cells to whole biological systems and organisms.

The spirit of Schrödinger will be very much alive at this meeting. Sir Tim Hunt (Nobel prizewinner for Physiology or Medicine in 2001 for his work on cell cycle regulation) will be giving the plenary talk entitled “How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry? – Schrödinger at 70”. By my reckoning that book is only 69 years old, but nevertheless, the challenges Schrödinger saw remain, despite the passage of the years and despite the fact that our understanding of, for instance, what a gene is has come so far.

There are many challenges in making research work at this interface. Making sure both sides make their discipline’s jargon comprehensible to the other is vital. It is equally crucial that a physicist’s attempt to render a problem tractable does not lead to the baby being thrown out with the bath water. Oversimplification, of the sort captured in the old joke exam question which begins “a cow, which can be considered to be spherical …” (or massless, depending on the joke) can mean the essence of a problem is entirely lost if great care is not taken. But significant strides are being made, particularly when it comes to developments in quantitative modelling and in novel optical approaches that can permit sophisticated manipulation of individual molecules and cells as well as high-resolution imaging in both time and space.

A couple of specific examples of successful collaborations, where the physicist’s tools are being brought to bear on problems in human biology and disease, come from the work of my own Cambridge colleagues. The first deals with malarial infection, a huge problem for the developing world. One crucial stage in the spread of the disease within the body is the alignment of the infecting body from the parasite, known as a merozoite, with the red blood cell it is about to infect. This happens very fast, but at different times for different cells, so it is hard to focus a camera at the right spot at the right time and traditional averaging over the responses of a whole collection of red blood cells loses all the detail of the actual process.

Physicist Pietro Cicuta has developed sophisticated image analysis techniques to make sure that filming of the cell occurs at just the right moment. As the red blood cell changes shape – which turns out to be a crucial step in the infection process – the camera remains in focus but moves onto another cell as soon as the infection process is complete for that cell. Being able to follow cell after cell, in detail, means that a highly detailed picture of the complete sequence of events can be built up – providing insight for the biologists (Teresa Tiffert and Virgilio Lew , also from Cambridge) as they strive to develop new vaccines and drugs to prevent the infection from occurring in the first place.

The second example relates to cancer. Here the work of Jochen Guck, originally carried out with Josef Käs in Leipzig, took the mechanism of optical trapping to explore the response of single cells when placed in crossed laser beams. Optical trapping was originally developed to move single atoms around close to absolute zero; a key early proponent of the technique was the erstwhile US Energy Secretary Stephen Chu (and for which he won the 1997 Nobel Prize in Physics) before he moved into politics.

These light beams trap the cell at centre stage; but if the light intensity of one is increased it causes a deformation of the cell. How large that deformation is depends on the mechanical properties of the cell and, since cancerous cells are softer overall than healthy ones, by closely following and analysing this deformation a way is provided to phenotype (and thereby sort) individual cells, without the use of histology or markers of any sorts.

Today at the launch meeting there should be many opportunities to initiate new collaborations – the ultimate point of the network – and learn about the wide range of problems looking for solutions and techniques looking for specific targets. My own role will be to talk about the Institute of Physics’ project aimed at producing teaching material in biological physics for undergraduate courses. I mentioned the importance of physicists and biologists being able to speak the same language above; by introducing some fundamental biological concepts into a physics degree, couched in the language of physics, and exposing our undergraduates to a modicum of biology to whet their appetite, this project hopes to inspire future generations that “Understanding the Physics of Life” has a huge amount to offer.

(*) Athene Donald is a professor of experimental physics at the University of Cambridge and, like Sir Tim Hunt, is a member of the European Research Council’s Scientific Council.

Read more: http://www.guardian.co.uk

What is life? The physicist who sparked a revolution in biology

Erwin Schrödinger introduced some of the most important concepts in biology, including the idea of a ‘code’ of life

Insights from biology and computing built upon Schrödinger's genius, changing our view of life forever. Photograph: Rick Sammon/AP

Insights from biology and computing built upon Schrödinger’s genius, changing our view of life forever. Photograph: Rick Sammon/AP

Matthew Cobb
Seventy years ago, on 5 February 1943, the Nobel prizewinning quantum physicist Erwin Schrödinger gave the first of three public lectures at Trinity College, Dublin. His topic was an unusual one for a physicist: “What is Life?” The following year the lectures were turned into a book of the same name.

One of Schrödinger’s key aims was to explain how living things apparently defy the second law of thermodynamics – according to which all order in the universe tends to break down. It was this that led my colleague Professor Brian Cox to use Schrödinger as the starting point of his BBC series Wonders of Life, leading to What is Life? shooting up the Amazon sales chart.

But Schrödinger’s book contains something far more important than his attempt to fuse physics and biology. In that lecture 70 years ago, he introduced some of the most important concepts in the history of biology, which continue to frame how we see life.

At a time when it was thought that proteins, not DNA, were the hereditary material, Schrödinger argued the genetic material had to have a non-repetitive molecular structure. He claimed that this structure flowed from the fact that the hereditary molecule must contain a “code-script” that determined “the entire pattern of the individual’s future development and of its functioning in the mature state”.

This was the first clear suggestion that genes contained some kind of “code”, although Schrödinger’s meaning was apparently not exactly the same as ours – he did not suggest there was a correspondence between each part of the “code-script” and precise biochemical reactions.

Historians and scientists have argued over the influence of Schrödinger’s lectures and the book that followed, but there can be no doubt that some of the key figures of 20th century science – James Watson, Francis Crick, Maurice Wilkins and others – were inspired to turn to biology by the general thrust of Schrödinger’s work.

The role of the brilliant “code-script” insight is less clear. Reviewers of What is Life? in both Nature and the New York Times noted the novel phrase, but despite the fact that in 1944 Oswald Avery published clear evidence that DNA was the genetic material, virtually no one immediately began looking for – or even talking about – a molecular “code-script” in DNA, although Kurt Stern suggested that the code might involve grooves in a protein molecule, like the grooves in a vinyl disc.

Part of the reason for this lack of immediate excitement and for Avery’s discovery not being widely accepted was that DNA was thought to be a “boring” molecule with a repetitive structure – exactly what Schrödinger had said a gene could not be. It took the work of Erwin Chargaff, inspired by Avery, to show that the proportion of the “bases” in the DNA molecule – generally presented by the letters A, T, C and G – differed widely from species to species, suggesting the molecule might not be so boring after all.

As early as 1947, Chargaff suggested that the change of a single base “could produce far-reaching changes … it is not impossible that rearrangements of this type are among the causes of the occurrence of mutations.” The culmination of this line of work was Watson and Crick’s double helix model, which was based on the experimental data of Rosalind Franklin and Maurice Wilkins.

But in 1947 there was a missing component in biological thinking about the nature of the code, one which was at the heart of Watson and Crick’s decisive interpretation of their discovery a mere six years later – “information”. That idea entered biology through some applied research carried out to aid the war effort.

In 1943, the US National Research and Development Committee set up a group of scientists to study “fire control” – how to ensure accurate anti-aircraft fire, by the control of information from radar, visual tracking and range-finding. Two of the men involved in this project were Claude Shannon, a mathematician who developed what became known as “information theory” to understand how signals were processed, and Norbert Wiener, who thought there were parallels between control systems in machines and in organisms, and who coined the term “cybernetics”.

The first person to argue that a gene contains information was the co-founder of cybernetics, John von Neumann. In 1948, von Neumann described a gene as a “tape” that could program the organism – like the “universal Turing machine” described in 1936 by Alan Turing (intriguingly, Turing had discussed it with Shannon while working in New York in 1944). A few years later in 1950, geneticist Hans Kalmus deliberately applied cybernetic thinking to the problem of heredity and suggested that a gene was a “message”.

Cybernetics briefly became wildly popular, filling the pages of broadsheet newspapers all over the world and encouraging biologists to look for feedback loops in living things. Following the 1948 publication of Shannon’s dense book Information Theory (co-authored by Warren Weaver, who had chaired the fire control group and also coined the term “molecular biology”), the abstract concept of information percolated into the scientific mainstream.

Although the term had a precise meaning for Shannon, in the hands of the biologists it turned into a vague metaphor, a way of thinking about something they as yet had no real understanding of: the nature of the gene.

Ten years after Schrödinger’s brilliant insight, Watson and Crick’s second 1953 article on the structure of DNA provided the world with the key to the secret of life, casually employing the new concepts that had been created by cybernetics and propelling biology into the modern age with the words: “it therefore seems likely that the precise sequence of the bases is the code which carries the genetical information.”

These prophetic words – shorn of the conditional opening phrase – are uttered in biology classes all over the world, every single day.

In a decade of tumultuous discovery, insights from biology and computing built upon Schrödinger’s genius, changing our view of life forever. Life had become information, genes were the bearers of that information, carrying it in a tiny, complex code inside every cell of our bodies. And the breakthrough began in a Dublin lecture theatre 70 years ago this week.
Read more:  www.guardian.co.uk

Life in the Universe by Stephen Hawking

In this talk, I would like to speculate a little, on the development of life in the universe, and in particular, the development of intelligent life. I shall take this to include the human race, even though much of its behaviour through out history, has been pretty stupid, and not calculated to aid the survival of the species. Two questions I shall discuss are, ‘What is the probability of life existing else where in the universe?’ and, ‘How may life develop in the future?’

It is a matter of common experience, that things get more disordered and chaotic with time. This observation can be elevated to the status of a law, the so-called Second Law of Thermodynamics. This says that the total amount of disorder, or entropy, in the universe, always increases with time. However, the Law refers only to the total amount of disorder. The order in one body can increase, provided that the amount of disorder in its surroundings increases by a greater amount. This is what happens in a living being. One can define Life to be an ordered system that can sustain itself against the tendency to disorder, and can reproduce itself. That is, it can make similar, but independent, ordered systems. To do these things, the system must convert energy in some ordered form, like food, sunlight, or electric power, into disordered energy, in the form of heat. A laptopIn this way, the system can satisfy the requirement that the total amount of disorder increases, while, at the same time, increasing the order in itself and its offspring. A living being usually has two elements: a set of instructions that tell the system how to sustain and reproduce itself, and a mechanism to carry out the instructions. In biology, these two parts are called genes and metabolism. But it is worth emphasising that there need be nothing biological about them. For example, a computer virus is a program that will make copies of itself in the memory of a computer, and will transfer itself to other computers. Thus it fits the definition of a living system, that I have given. Like a biological virus, it is a rather degenerate form, because it contains only instructions or genes, and doesn’t have any metabolism of its own. Instead, it reprograms the metabolism of the host computer, or cell. Some people have questioned whether viruses should count as life, because they are parasites, and can not exist independently of their hosts. But then most forms of life, ourselves included, are parasites, in that they feed off and depend for their survival on other forms of life. I think computer viruses should count as life. Maybe it says something about human nature, that the only form of life we have created so far is purely destructive. Talk about creating life in our own image. I shall return to electronic forms of life later on…… Continue reading Life in the Universe by Stephen Hawking

‘It’s Alive! It’s Alive!’ Maybe Right Here on Earth

video: Life Out There: Eden in a Test Tube: To better recognize extraterrestrial life should they come upon it, scientists are working to create simple life forms in a lab. But, as Dennis Overbye reports, they first have to agree what life is.

Here in a laboratory perched on the edge of the continent, researchers are trying to construct Life As We Don’t Know It in a thimbleful of liquid…. Read more: http://www.nytimes.com/2011/07/28/science