When Biology Met Physics…

A photomontage showing helicoidal-shaped strands of DNA superimposed on a background of physical equations.The Emergent Field of Biophysics

Ever since Francis Crick and James Watson brought Physics and Biology together in 1953 to unveil the molecular structure of DNA, the boundary between the two disciplines has continued to become increasingly blurred.  In this genomic new era, ever more principles from Physics are being applied to living systems in an attempt to understand complexity at all levels.  Although sometimes the best solution to a Physics problem lies in the macroscopic world of Biology… 

The earliest studies in Biophysics were conducted in the 1840s by a group known as the Berlin School of Physiologists.  Among its members were pioneers such as Hermann von Helmholtz, Ernst Heinrich Weber, Carl F. W. Ludwig, and Johannes Peter Müller.  Although really, biophysics might even be seen as dating back to the studies on bioelectricity of Italian physicist Luigi Galvani (1737-1798).

 

Luigi Galvani and the Discovery of Animal Electricity

 

The popular legend about the beginning of Galvani’s experiments with bioelectricity has it that Galvani was dissecting a frog on a table where he had been conducting experiments with static electricity.  As Galvani’s assistant touched an exposed sciatic nerve with a metal scalpel that had picked up a charge, the scientists saw sparks and the dead frog’s leg twitched and kicked as if still alive.

An etching illustration showing Luigi Galvani's experiments on frog legs.
Galvani coined the term animal electricity to describe the force that activated the muscles of his specimens.  With his contemporaries, Galvani regarded their activation as being generated by an electrical fluid that is carried to the muscles by the nerves.

This observation made Galvani the first investigator to appreciate the relationship between electricity and animation – that is to say life.  His finding provided the basis for the new understanding that the impetus

behind muscle movement was electrical energy carried by a liquid (ions), and not air or fluid as in earlier balloonist theory.

The phenomenon was dubbed galvanism on the suggestion of his peer and sometime intellectual adversary Alessandro Volta.  Galvani is properly credited with the discovery of bioelectricity.  Today, the study of galvanic effects in biology is called electrophysiology.

At first, Volta embraced the idea of animal electricity, being among the first to repeat and check Galvani’s experiments.  Nevertheless, Volta started doubting that the conductions were caused by a specific electricity intrinsic to the animal’s legs or other body parts.  In fact, he believed that the contractions depended on the metal cable used to connect the nerves and muscles in his experiments.  Volta’s investigations soon led him to the invention of an early battery – the voltaic pile.

 

Biology – A Physical Science?

Three computer models demonstrating the differences and shape similarities between living cell organisms and physical molecules.
Biophysics is a bridge between Biology and Physics.

Biology studies life in its great variety and complexity.  Biology describes how organisms go about getting food, communicating, sensing their environment, and reproducing.

On the other hand, Physics looks for mathematical laws in Nature, and makes detailed predictions about the forces that drive idealised systems.  Spanning the distance between the apparent chaos and complexity of life and the simplicity and elegance of physical laws is the challenge of Biophysics.

Looking for the biological patterns in life and analyzing them with mathematics and physics is a powerful way to gain insights.

 

Biophysics and the Structure of DNA

A black and white photograph showing Watson and Crick posing next to the 3D helical DNA model.
Watson & Crick’s DNA Helix Model

Fast forward to the 1940s.  Experiments showed that genes are made of a simple chemical.

DNA is a nucleic acid – DeoxyriboNucleic Acid.  Along proteins and carbohydrates, nucleic acids compose the three major macro-molecules essential to all forms of life as we know it.

How such a simple chemical could be the molecule of inheritance remained a mystery until two biophysicists discovered the DNA double helix structure in 1953, using X-ray diffraction and the mathematics of a helix transform.

The discovery of DNA structure was a scientific watershed.   Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix.  It demonstrated how simple variations on a single chemical could generate unique individuals and perpetuate their species.

Biophysics showed how DNA serves as the ‘book of life’.  Inside living cells, genes are opened, closed, read, translated, and copied, just like books.  The translation leads from DNA to proteins – the molecular machinery of life.

 

What is Life?

 

A reproduction of the front page of Erwin Schrödinger's book "What is Life? - The Physical Aspect of the Living Cell".The popularity of the Biophysics field of study arose when the book “What is life?” by Erwin Schrödinger was published in 1944.

The book was based on a series of public lectures by Schrödinger in February 1943, at Trinity College, Dublin.  The audience of about 400 was warned “that the subject-matter was a difficult one and that the lectures could not be termed popular, even though the physicist’s most dreaded weapon, mathematical deduction, would hardly be utilized.”  Schrödinger’s lectures focused on one important question:

“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?”

Although the existence of DNA had been known since 1869, its role in reproduction and helical shape remained unknown at the time of Erwin Schrödinger’s lectures.  With hindsight, Schrödinger’s notion of aperiodic crystal can be viewed as a well-reasoned theoretical prediction of what biologists ought to have been looking for during their search for genetic material.  Both James D. Watson, and independently, Francis Crick, the co-discoverers of the structure of DNA, credited Schrödinger’s book with presenting an early theoretical description of how the storage of genetic information would work, and both acknowledged the book as a source of inspiration for their research.

Since 1957, biophysicists have organized themselves into the Biophysical Society which now has about 7,000 members over the world.

 

During the 2000s, biophysical inventions decoded all the genes in a human being – the human genome.  All the genes of nearly 200 different species, and some genes from more than 100,000 other species have been determined.  Biophysicists analyze those  genes to learn how organisms are related and how individuals differ.

 

What Do Biophysicists Study?

Two computer models showing the nanocage of a protein machine in their closed and open states.
Protein machines: An open and shut nanocage

Biophysicists study life at every level, from atoms and molecules to cells, organisms, and environments.  As innovations come out of Physics and Biology labs, biophysicists find new areas to explore where they can apply their expertise, create new tools, learn new things…

The aim is to find out how biological systems work.  Biophysics researches questions such as:

  • How do protein machines work?

Even though they are millions of times smaller than everyday machines, molecular  machines work according to the same principles – using energy to do work.  The kinesin machine shown carries a load as it walks along a track.  Biophysics reveals how each step is powered forward.

  • How do systems of nerve cells communicate?

Biophysicists invented coloured protein tags for the chemicals used by cells.  Each cell takes on a different colour as it uses the tagged chemicals, making it possible to trace its many pathways.

  • How do proteins pack DNA into viruses?

  • How do viruses invade cells?

  • How do plants harness sunlight to make food? 

 

Why Does Biophysics Matter?

Society is facing physical and biological challenges of global proportions.

 

A photograph showing an almost completely dry lake in India, where women go and fetch drinking water.
Water does not come on tap in many parts of the World…

How will we continue to get sufficient energy?  How can we feed the ever increasing World’s population?  How do we remediate global warming?  How do we preserve biological diversity?  How do we secure clean and plentiful water?

 

These crises require scientific insights and innovations.  Biophysics provides that insight and technologies for meeting these challenges, based on the principles of physics and the mechanisms of biology.

A photograph showing three jars filled with algae mush that is successively refined into something resembling crude oil, and eventually clear usable fuel.
From algae soup to bio-crude oil…

Biophysics discovers how to modify micro-organisms for biofuel (replacing gasoline and diesel fuel) and bioelectricity (replacing petroleum products and coal for producing electricity).

Biophysics discovers the biological cycles of heat, light, water, carbon, nitrogen, oxygen, heat, and organisms throughout our planet.

 

Biophysics Applications

Biophysics applies the power of Physics, Chemistry, and Maths to understanding health, preventing disease and inventing cures.  Biophysics is a wellspring of innovation for our high-tech economy.  The applications of biophysics depend on society’s  needs.

In the 20th century, great progress was made in treating diseases.  Biophysics helped create powerful vaccines against infectious diseases.  It described and controlled diseases of metabolism, such as diabetes.  And biophysics also provided both the tools and the understanding for treating diseases of growth, known as cancers.

A diagram showing the degradation by microbes of crude oil - a process known as aerobic bioremediation.
Aerobic Bioremediation

Nowadays, we are  learning more about the biology of health, and society is deeply concerned about the health of our planet.  Biophysical  methods are increasingly used to serve everyday needs – from forensic science to bioremediation.

Biophysics gives us medical imaging technologies including MRI, CAT scans, PET scans, and sonograms for diagnosing diseasesIt provides the life-saving treatment methods of kidney dialysis, radiation therapy, cardiac defibrillators, and pacemakers.

Biophysicists invented instrumentation for detecting, purifying, imaging, and manipulating chemicals and materials.  Advanced biophysical research instruments are the daily workhorses of drug development in the world’s pharmaceutical and biotechnology industries.  Since the 1970s, over 1,500 biotechnology companies, employing 200,000 people, have earned more than $60 billion per year.

 

How Essential is Biophysics to Progress in Biology?

A picture describing the photosynthesis equation: Start with CO2 (carbon dioxide) + H2O (water), combine the Sun's energy to the plant's chlorophyll, and you get C6H12O6 (sugars) + O2 (oxygen).
Plants meet Quantum Mechanics: In Photosynthesis, sunlight is captured and transported by highly specialised antenna proteins. Surprisingly these proteins act as quantum machines and use a quantum transport mechanism to efficiently guide the light and finally store the energy in their reaction centres. Researchers from ICFO – the Institute of Photonic Science in Barcelona – have tracked this energy flow in individual proteins and discovered that the quantum coherences makes the light flow in the antenna protein immune to the ubiquitous external natural turmoil.

Biophysics discovers how atoms are arranged to work in DNA and proteins.  Protein molecules perform the body’s chemical reactions.  They push and pull the muscles that move your limbs.  Proteins make the parts of your eyes, ears, nose, and skin that sense your environment.  They turn food into energy and light into vision.  Proteins provide your immunity to illness.  They repair what is broken inside of cells, and regulate growth.  Proteins fire the electrical signals in your brain.  They read the DNA blueprints in your body and copy the DNA for future generations.

Biophysicists are discovering how proteins work.  These mysteries are solved part by part.  To learn how a car works, you first need to know how the parts fit together.  Now, thanks to biophysics, we know exactly where the thousands of atoms are located in more than 50,000 different proteins.

Each year, over a million scientists and students from all over the world, from physicists to medical practitioners, use these protein structures for discovering how biological machines work, in health and also in diseases.

Variations in proteins make people respond to drugs differently.  Understanding these differences opens new possibilities in drug design, diagnosis, and disease control.  Soon, medicines will be tailored to each individual patient’s propensity for side-effects. 

Biophysicists looks for principles that describe patterns.  If the principles are powerful, they make detailed predictions that can be tested. 

And yet, cultural differences still exist today between physicists and biologists, as is discussed in a set of articles in the journal Physical Biology, published by the Institute of Physics.  In “Perspectives on Working at the Physics-Biology Interface”, a group of eminent scientists gave their accounts of working at the interface of physics and biology, describing the opportunities that have presented themselves and outlining some of the problems that they continue to face when working across two fields with quite different traditions.

 

Cultural Differences

Many physicists recall collaborations that have yielded long-lasting friendships and significant scientific advances, yet some are more candid about their experiences of working with biologists.

Robert Austin, a physicist at Princeton University, states that he often uses biologists as a sounding board to test his ideas.  If they hate the ideas and tell him not to proceed, he forges ahead!

“The more I am told I am wrong by biologists, the more likely it is that I am on the right track.  Being unpopular and eating lunch by yourself is not necessarily a bad thing.”

A humoristic cartoon showing two concerned pet owners attending the vet, with them a man is inside a pet carrier. The caption says: "Doctor... We have this pet physicist and... Something's wrong. It keeps babbling about linguistics and neurology and climate science".Not all of the perspectives are as hard-hitting as that of Austin, but clearly many barriers still need to be broken down between Physicists and Biologists, specifically with regard to the terminology and language that both use to communicate with each other.  Kamal Shukla, of the National Science Foundation, believes that physicists are making a sincere effort to break down such language barriers, but that more needs to be done on the part of biologists to learn about the principle methodologies in Physics.

An example of this two-way communication is detailed in an entertaining article jointly written by a biologist  and a physicist, Bonnie Bassler and Ned Wingreen (both from Princeton), who have been collaborating for over 15 years after randomly bumping into each other at baggage reclaim in an airport in Mexico City on the way to a conference.

The perspectives throw up examples of similarly serendipitous meetings, such as the one described by physicist Herbert Levine, from Rice University, who was reading a biology book to learn more about a micro-organism he was studying when he realised that the book’s author was actually based in the building next door.  Together, they have now been collaborating for almost two decades.

From the University of Cambridge, Athene Donald is one of a number of scientists who believes that these encounters should not be left to chance, and that more needs to be done to bring physics and biology closer together:

“Many physicists see the interface with biology as an exciting place to be. However, not all universities – certainly in the UK – teach much about this to their undergraduates, still focusing on fairly traditional areas of condensed matter.  This absence of exposure in the undergraduate curriculum is a serious deficiency in my view.” 

So, it seems a lot of work remains to be done.  The onus is on researchers, as well as universities and institutions, to ensure that Biological Physics / Physical Biology continues to flourish and scientific advancements on the scale of Watson and Crick’s discovery are repeated.