Life Blood

Programme Outline

The heart, together with all the veins and arteries and the contained blood, is to be regarded as the beginning of all things that are in the body: the creator, fount, and spring, and the prime cause of life.

This is a story of exploration and revelation. The English physician William Harvey lived in the 17th century and was perplexed by his observations of the heart and the movements of the blood around the body. What he saw didn't tally with what he'd always been taught: so he decided to investigate what was really going on.

Harvey asked some fundamental questions about the workings of the human body. The answers he found transformed our understanding of medical science, and are remarkable because they still hold true today.

William Harvey was a scientific 'rebel'. While his fellow scientists clung to the teachings of the ancient Greeks and Romans - ideas that had gone unchallenged for 1400 years - Harvey used observation and careful reasoning to discover the truth about how the human body worked.

He began by asking a few simple questions:

• What really happens when a heart beats?
• How does blood travel around our bodies?
• How does blood nourish our body?

Although these questions may seem simple now, they had baffled the greatest thinkers. The first to put forward firm ideas that gained popular acceptance was the Roman philosopher Galen. He proposed that the heart is a kind of furnace, a place where air and blood are mixed to create a 'life-giving warmth' that nourishes the body.

Galen thought that the vigorous beating heart actually sucked in life-giving air and expelled 'vile' sooty vapours. He described the flow of blood as being like the tides of the seas, believing that when blood arrived at the furthest reaches of the body it was transformed into flesh. Despite some obvious errors in his reasoning, Galen had grasped a crucial idea - that some form of combination between air and blood, coupled with the action of a beating heart, is essential to life.

It was not until William Harvey published the results of his experiment in 1628 that Galen's ideas were fully replaced. In his classic work on the 'Motions of the Heart and Blood' Harvey describes his theory:

'The animal's heart is the basis of its life, its chief member, the sun of its microcosm: on the heart all its activity depends. From the heart all its liveliness and strength arise.'

Harvey just couldn't accept the magical ideas of furnaces and sooty vapours. Instead he turned to what he could actually see in the bodies of living animals:

'I have demonstrated the first beginning of the chick in the form of a little cloud, after removing the egg shell and putting the rest into clear warm water. In the middle of the small cloud the throbbing point of blood is so tiny that it disappeared from view on its contraction, to reappear as a red point during its relaxation, and thus between being visible and invisible, or so to speak, between existing and not existing, it gave a representation of the heart beat and the beginning of life.'

By the observation of chick embryos and their gradual development into chicks, Harvey realised that the heart was not the magical furnace that Galen believed, but simply a device for pumping blood around the body. He was fascinated by the regular and endless beats: where was the blood coming from and where was it going?

'I then began to wonder if blood moved, as it were, in a circle.'

Harvey realised that as the heart contracts, blood is expelled into the arterial system from the left side and into the lungs from the right side. He also realised that blood returned, through veins containing one-way valves, to the heart. This led to his conclusion that the blood must circulate. We now understand this process in more detail: blood enters the upper chambers of the heart, the atria, from the vena cava on the right and the pulmonary veins on the left. As the atria fill and pressure builds the heart valves open and blood flows into the lower chambers - the ventricles. When full to capacity, the ventricles contract. Blood is forced out into the arteries, the pulmonary artery on the right and the aorta on the left. The heart is actually a double pump, simultaneously pumping blood from the right side of the heart to the lungs, and from the left side to the rest of the body.

Although Harvey observed the double beat of the heart and the action of the valves, he could only speculate about what caused the heart to beat. He knew that physical exertion caused the heart to beat faster, but he did not know how it beat in the first place.

The answer lies in two clusters of specialised cells commonly known as the 'pacemaker cells'. An individual pacemaker cell, when extracted from the heart, will still beat to its own rhythm. Combine two cells and they start to beat together. It is these cells that stimulate the rest of the heart muscle to contract. As the body increases its demands for oxygen, the pacemaker cells become more active. The heart beats faster.

Harvey maintained:

'Since that birthday of the circuit of the blood there has of a truth been scarcely a day in which I have not heard both good and ill reports of the circulation I discovered. Some think that by my experiments, my observations, my own visual experience, that I have established the circuit of the blood against the whole strength and force of arguments, the others that it is scarcely as yet sufficiently elucidated...'

Harvey's problem was that he couldn't complete the circle. He couldn't see how blood passed from arteries to veins - he only knew that it did.

Today we know of the millions of tiny connecting blood vessels - the capillaries. Capillaries are the almost invisible hair-like threads that transport blood to reach every cell in the body. Only one cell thick, they form an impressive network of tubes.

In coming so close to the truth, both Galen and Harvey had wondered what life-giving force blood actually carried. The answer, we know today, is oxygen.

As each individual red blood cell squeezes through Harvey's elusive capillaries, they release oxygen into the surrounding tissues: oxygen that is vital in the production of energy.

In 1962 Max Perutz was awarded the Nobel Prize for his work on discovering the structure of a protein called 'haemoglobin'. This was the answer to Galen's and Harvey's question: haemoglobin was the elusive oxygen-carrier found in blood.

Perutz said:

'If you prick your finger and draw a drop of blood - that contains about 3000 million red blood cells, which you can see under a microscope. Each of those red blood cells contains 250 million molecules of haemoglobin.'

Haemoglobin is the red stuff of our blood. Without it we couldn't live because couldn't get the oxygen. But how does haemoglobin transport oxygen, and what does it look like?

William Harvey really laid the foundations by discovering the circulation of the blood. But of course, when William Harvey made this discovery, oxygen hadn't been discovered yet - that took another 130 years.

Today our knowledge is more complete. Using modern technology we can separate blood into its many components. We find that blood is actually a mixture of many parts, including agents that prevent infection and others that aid clotting. Digested foods and wastes are also transported in the blood. Together with the oxygen-carrying red blood cells, all these materials are suspended in a liquid plasma.

Because red blood cells carry life-giving oxygen bound to haemoglobin, doctors are able to transfer blood from one person to another. In emergencies blood transfusions save lives. But it is not without its problems.

There is a very real shortage of blood, a shortage made worse by the risk of donor infection with HIV and hepatitis. Calls for clean and uncontaminated forms of blood have never been greater.

The real prize for scientists who have followed in the footsteps of William Harvey is the creation of an artificial oxygen carrier: a replacement for natural haemoglobin. We now know the detailed structure of a haemoglobin molecule, and as a result we can now produce haemoglobin outside of our body by a process of simple fermentation.

Dr Kiyoshi Nagai leads a research group at the Cambridge Laboratory of Molecular Biology. Dr Nagai has picked up where William Harvey and Max Perutz left off. His main interest is in using modern techniques of genetic engineering to help in making artificial haemoglobin - artificial blood.

Theoretically, using simple bacteria that have been genetically engineered, we should be able to make unlimited amounts of human haemoglobin by simple fermentation. In the United States, Dr Nagai's vision is being realised. Vats of artificial blood are being made. Dr Nagai was able to isolate the genetic code for human haemoglobin and insert it into E.coli bacteria. Then by growing large amounts of E.coli he can make an infection-free supply of artificial blood.

Clinical trials are now being carried out to ensure that this artificial oxygen carrier is not toxic in our body. Showing that it actually works as expected may be a few years away, but it is hoped that one day it will be possible to use this artificial oxygen carrier in place of donated blood.

The discovery of the function of the heart and blood came about by people asking simple questions:

'I then began to wonder if blood moved, as it were, in a circle...'

Dr Nagai is driven by the same kind of curiosity as Harvey. People today are as passionately interested as they were in the past to find out what's going on, how Nature works.