Hamburger; hot dog; ice cream. Five ordinary words, but with extraordinary significance. It was 1984. Gerry Merwin, MD, an ear-nose-throat surgeon at the University of Florida, whispered them into the ear of a young, deaf woman expecting her second child. She was desperate to be able to hear her new-born baby cry. She had become deaf after an infection had dissolved two of the three bones of her middle ear, and Dr Merwin had just inserted the world's first Bioglass implant during pioneering surgery. A big smile appeared on her face and she repeated, "Hamburger; hot dog; ice cream." The implant worked. Ten years later, it was still working.
The idea of replacing damaged body parts in humans is by no means new. Bio-inert materials have been used for this purpose for more than 3,000 years. In 1994, a team of researchers in Albany, New York, used X-ray radiography and computer tomography to study two 3,000-year-old Egyptian mummies. A radiograph of the female mummy revealed what appeared to be a highly crafted ceramic foot implant, attached directly to a bone of the big toe. Part of the implant replaced the other bones and restored the shape of the toe.
In Ancient Egypt, materials were also used routinely to replace teeth and segments of the jaw. In the 8th and 9th centuries BC, Egyptians and Etruscans used gold wire and gold soldered rings around groups of loose teeth to keep them in place. An investigation of a tomb in Capua, Italy, discovered a leg replacement made of bronze, iron and wood. Such replacements were vital as the inability to walk almost certainly meant the individual could not survive. Facial spare parts seem to have been developed at the start of the 17th century, when replacement noses and earlobes were crafted from papier-mache, silver or ivory.
During the past 30 years, it has become routine to use bio-inert materials to replace more than 40 parts of the human body. An important example is the total hip replacement, pioneered by Charnley in the 1960s, which uses a specially shaped titanium.
The first Bioglass device, implanted by Dr Merwin into his patient's middle ear, was designed to conduct sound waves from the eardrum to the cochlea (inner ear), and thus restore her hearing. Bioglass was the first man-made material that could bond to living tissue. Discovered in 1969 by one of the authors of this article, Professor Hench, it had been subjected to 15 years of safety tests. These had to determine many questions - would the new material work in a human? Would the implant bond to the soft connective tissue of the eardrum and the hard connective bone tissue of the stapes? Would it conduct sound?
Surgeons had previously used other types of middle-ear implants - usually made of metals and plastics because these were relatively inert and non-toxic - but these often failed, isolated from the body by a thin layer of scar tissue. The Bioglass implant tested a new concept in body repair: bioactive bonding. The special composition of glass contained compounds that are also present in bones and tissue fluids (sodium oxide, Na2O; phosphorus pentoxide, P2O5; calcium oxide, CaO; and silicon dioxide, SiO2). These are the very compounds used by the body to form new bone tissue. The Bioglass implant releases these compounds and the bone cells use them to form a bioactive bond. In the years since Dr Merwin's ground-breaking surgery, thousands of patients have had hearing restored with such implants, and new bioactive materials have been discovered as technology has advanced.
However, many deaf people cannot be helped in this way. They are deaf because of damage to the inner ear. The nerve cells of the cochlea are not able to convert the mechanical vibrations of sound waves to electrical pulses that travel to the brain. A man-made solution to nerve deafness also began with ordinary words - "Watson, come here," commanded Alexander Graham Bell in 1876 to his technician, who waited in another room. Thomas Watson heard, and the world changed. The words were converted by a microphone into electrical signals which travelled along a wire connecting the rooms and were converted by a speaker back into words. The telephone was invented.
In 1951, ear surgeons in Paris, working with an electrical engineer, used the concept of the telephone in an attempt to provide hearing to patients whose deafness was due to nerve damage in the inner ear. Their idea was simple: convert sound waves into electrical pulses to travel down a wire, as in a telephone. But, instead of connecting the wire to a speaker, it was implanted in the patient, in contact with the nerve that produces hearing.
Their second patient was a young woman with profound deafness. The French surgeon invited Ellis Douek, a distinguished young ENT surgeon in London, to observe the test. Mr Douek listened as the surgeon said into a microphone, "Allo. Allo. Tu m'entends?" ("Hello. Hello. Can you hear me?"). The patient smiled and nodded her head. What she heard no one knew, but the electrical pulses had surely stimulated action in the nerve cells leading to the auditory cortex of her brain. Hundreds of profoundly deaf people are now able to communicate more clearly through the use of inner-ear cochlear implants. Mr Douek at Guy's Hospital and Professor Adrian Fourcin at University College London performed several of the pioneering experiments that made electrical stimulation of hearing possible.
There have been attempts for the past 40 years to restore vision in blind people by transmitting electrical signals to the visual cortex of the brain. The effect is to produce bright spots of light in the mind's "eye". By sending electrical pulses to electrodes placed at different parts of the visual cortex, the spots can be moved to form an image that is similar to a very poor quality television picture. However, concerns for patient safety mean that such electrical stimulation is still experimental. The first device to restore sight will probably not be available to patients until after 2010.
Although transplants of the cornea (the film that covers the iris and pupil and focuses light coming into the eye) are now possible, a functional implanted artificial eye is at least 50 years in the future. The same is true for other prosthetic senses - smell, taste and touch. However, sight is restored for more than a million patients annually who have cataracts removed, with very high success rates. In an inexpensive 20-minute operation, a fixed Perspex lens, which is stable for many years, is inserted into the eye.
Implants to provide electrical signals to aid the rhythmic pumping of blood by the heart are also very successful. Heartpacers have been used for 30 years to save millions of lives. This year, implantable electronic defribillators, which shock a sick heart back to normal rhythm, have been approved for use for heart attack victims.
The first successful heart transplant was performed on December 3, 1967 in South Africa, by Dr Christiaan Barnard. But there is now a shortage of donors for this procedure. In the US, 100,000 patients require heart transplants each year, but only 2,000 donors are found. Artificial heart valves preserve the lives of tens of thousands of patients every year. They are made of pyrolitic carbon and other bio-inert non-toxic materials that stimulate a minimal biological response from the body, but patients have to be continually administered with drugs that prevent blood clotting and maintain the blood flow.
An implantable battery-powered full-heart replacement (AbioCor) has been developed by Abiomed Inc (a US company). AbioCor is made primarily of titanium and polyurethane plastic and is equipped with a quiet motor. The only component that is outside the body is a rechargeable battery. AbioCor is undergoing clinical trials and one patient has recently celebrated a year of survival since implantation.
Most replacement body parts last for 10 years or longer. In the US, Berkley Advanced Biomaterials Inc has developed an artificial bone graft called Bi-Ostetic, which is available clinically in Europe for use as an artificial bone graft. Made from hydroxyapatite, the material bonds to bone. However, parts made from bio-inert or bone-bonding materials always have limitations. Man-made materials are not living. They cannot repair themselves. They cannot adapt to the continually changing environment in the body. Their mechanical and chemical properties never completely match the properties of the tissues they replace. Consequently, failures occur. A novel approach to human body parts is needed for this new millennium.
An innovative field called regenerative medicine is now developing. It is based on new biomaterials that help the body heal itself through interaction with cells and proteins that activate the body's own genetically programmed repair mechanisms. Studies at Imperial College Tissue Engineering and Regenerative Medicine Centre in London show that the latest generation of bioactive glasses activate seven families of genes present in human bone cells. These genes encode the proteins that control all phases of the bone-cell cycle, including growth, replication of DNA, mitosis (cell division), and apoptosis (programmed cell death). By activating the appropriate genes, the new bioactive materials enable the cells to quickly regenerate bone tissue. This happens in cell cultures even when the bone cells are obtained from patients aged 60 or older. More significantly, it also happens within the body and leads to rapid bone repair.
The development of these biomaterials is the basis for two new alternative routes to regenerative medicine. One is tissue engineering, where stem cells from a patient or another source are seeded onto "scaffolds" made from new biomaterials to grow in a bioreactor. The bioactive scaffold provides the three-dimensional shape required for cellular growth and, with time, the material dissolves and the cells form a living tissue. This is then implanted into the patient to replace diseased or damaged tissues. The authors have developed bioactive glass scaffolds that mimic bone's porous structure and have a high potential for growing bone tissue. New findings suggest that cartilage cells and lung cells will also colonise such scaffolds, paving the way for research into the engineering of various soft tissues. This could lead to the regeneration of tissue in the liver and heart, or repairing joint damage or muscular and ligament injuries.
The second approach is in situ tissue regeneration. This uses bioactive powders, such as Perioglas (developed by USBiomaterials), which can be used to fill a defect left by removal of diseased jaw-bone and stimulate localised bone repair. The powder dissolves at a controlled rate, releasing ions which activate the genes of cells in contact with it, and eventually leading to regenerated tissue.
The use of implants and prostheses is now the norm, with three million spare parts inserted into people every year. Our desire for increased life expectancy requires that we use the information contained in each of our unique set of genes to help repair ourselves. Stem cells are now used in the laboratory to stimulate tissue regeneration - the challenge now is to achieve this in patients and drive forward to an entirely new form of medicine.
We could be one of the last "mortal" generations, as replacement-part medicine advances towards self-healing technology. It is not unreasonable to predict that, in a few generations, humans could live to beyond 100 years, with all body parts functioning naturally and efficiently.
Larry L Hench is professor of ceramic materials in the Department of Materials at Imperial College of Science, Technology and Medicine, University of London. He is director of the Imperial College Centre for Tissue Regeneration and Repair and deputy director of the Imperial College Tissue Engineering Centre. Professor Hench is also author of a series of children's books featuring Boing-Boing the Bionic Cat
Julian Jones won the Lloyd's of London Tercentenary Foundation award this year. A graduate in Materials Science from Oxford University in 1999, he gained a PhD from Imperial College London, Department of Materials. He is now working as a Lloyd's fellow in the Department of Materials and the Tissue Engineering Centre, Imperial College London