Medical innovation holds out prospect of longer life, if you can afford it

The world’s tallest bridge, the Milau Viaduct, is in southern France. It reaches 336,4 m. The tallest building, with the antenna excluded, is the Taipei 101, at a height of 508 m.

Humankind has always striven to go higher and further. From here to the sky; even into space.

The human body has not been neglected in the primordial quest for improvement. It has become one of humankind’s most amazing feats of engineering. We live longer than ever, we can deftly replace nearly any organ or limb, and we could be on the brink of being able to prevent or cure diseases by controlling our genes or through breakthroughs in stem-cell research.

Never before has it been as possible to outwit the fiercely-ticking biological clock for longer.

Living longer
In Australia, the US and most of Europe, life expectancy reaches around 80 years. This has risen dramatically in the last century – life expectancy in the US was 49 in 1901. In contrast to this, life expectancy in modern-day Mozambique is only around 40 years – according to the United Nations Development Programme and Development Bank of Southern Africa 2005 Development Report.

Human life expectancy has been increasing in developed countries at the rate of about two years a decade for the last 200 years, says University of Newcastle-upon-Tyne (UK) Institute for Ageing and Health codirector Professor Tom Kirkwood. The Durban-born Kirkwood is also the author of Time of Our Lives: The Science of Human Ageing.

The rise in developing countries began a little later but, in most cases, is also increasing fast.

The only exceptions are regions where HIV/Aids is having a major impact on life expectancy or where there has been sudden adverse change in socioeconomic circumstances, such as a civil war, he adds.

The initial increases in life expectancy mainly came from the containment of infectious disease. Mortality from infections used to be the dominant cause of death, but a series of advances through sanitation, housing, nutrition, vaccines and antibiotics have transformed this picture, says Kirkwood.

These days it is usually diseases linked to ageing that cause most deaths in the developed world. “The last few decades have surprised many because it was expected that, when infectious diseases had been brought under control, life expectancy would reach a plateau. “This has not happened, though. It seems that people are actually reaching old age in better shape than previously.” Kirkwood says a growing amount of research is being done on the human ageing process, although “the volume is still tiny compared with the effort directed at, say, cancer”.

Are we programmed to die young?
Probably the most significant change in the thinking on ageing is that researchers now realise that there is no biological programme for death, notes Kirkwood.

“Rather, the body is programmed for survival but, in our evolutionary past, when most of us died young, there was little pressure to evolve survival systems that might make us live for ever. “In this view, ageing is caused by the lifelong accumulation of subtle faults in the molecules and cells that make up the body. “The change of understanding was catalysed by a theory I proposed back in 1977, called the ‘disposable soma theory’.” According to this theory, human genes provide for sufficient bodily maintenance to survive the all-important reproductive years in good shape. However, more than this is viewed as unnecessary, and a potential waste of energy. “The good news is that this tells us that the ageing process is much more malleable – susceptible to modification – than used to be thought,” says Kirkwood.

He notes that people’s genetic endow-ment accounts for about a quarter of what will determine their length of life. It does this through genes that set the levels of DNA repair or antioxidant enzymes, for example. “However, this means that three-quarters is under our own control through factors such as nutrition, lifestyle and so forth.”

Stem-cell research as the new frontier . . . hosting the new ethics war
Stem cells have the remarkable potential to develop into many different types of tissue in the body. When a stem cell divides, each new cell has the potential to remain a stem cell or become another type of cell with a more specialised function, such as a muscle cell or a brain cell.

In fact, researchers are trying to find ways to grow and manipulate stem cells and then to generate specific cell types so they can be used to treat injury or disease. For example, they could be used to form insulin-producing cells, which means a possible cure for diabetes type 1, or to generate healthy heart-muscle cells in the laboratory and then transplant these cells into patients with chronic heart disease.

There are different types of stem cells, though – leading to several heated ethical debates on the prudence and legality of research on these tiny cells with their potentially huge impact.

One of the least-controversial types are adult stem cells.

According to the US National Institute of Health (NIH), adult stem cells maintain and repair the mature organs and tissue in which they are found. (The NIH is a part of the US Department of Health and Human Services and acts as the primary federal agency for conducting and supporting medical research.) Stem cells are thought to reside in a specific area of each tissue, where they may remain quiescent (nondividing) for many years, until they are activated by disease or tissue injury. The adult tissues reported to contain stem cells include the brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver.

However, adult stem cells do pose some problems: they are generally limited to differentiating into only the different cell types of their tissue of origin; and they are also rare in mature tissues, with therapy unfortunately requiring a large number of cells.

A second type of stem-cell research, which has given rise to a storm of resistance, especially in the US, is embryonic stem-cell research.

Embryonic stem cells are derived from embryos.

Specifically, embryonic stem cells are derived from embryos that develop from eggs that have been fertilised in vitro – in an in vitro fertilis- ation clinic – and then donated for research purposes with the informed consent of the donors. Ethics currently require that they are not derived from eggs fertilised in a woman’s body.

The big advantages of embryonic stem cells are that they are plentiful and can become all cell types of the body. The range of diseases that might be treated by embryonic stem cells is wider and includes Parkinson’s disease, traumatic spinal-cord injury, muscular dystrophy, heart disease and vision and hearing loss – according to the NIH.

As embryonic stem cells are isolated from human embryos that are a few days old (in some cases, in the US, stem-cell lines have also been developed from foetal tissue older than eight weeks of development) prolifers have slammed research on these cells, arguing that an embryo is already the start of life.

Another means of creating these early-stage stem cells – therapeutic cloning – has even further heightened this already pyretic debate, attracting the anticloning lobby.

This very promising but controversial method makes use of nucleus material from a person’s cell, transferring it to a nonfertilised egg and then inducing the egg to grow, thereby creating a clone from which to harvest embryonic stem cells.

The South African government’s view on stem-cell research in general is that it must have sole control over stem-cell research in the country. Health Minister Manto Tshabalala-Msimang said at a Maputo meeting of regional health ministers earlier this year that the use of stem cells for research is currently still a matter of discussion within the South African Cabinet.

She also noted that the South African govern- ment views cloning of humans, along with the World Health Organisation, as ethically unaccept- able.

It is also important to note that stem-cell researchers worldwide are still negotiating several rather complex issues before they can claim success – such as finding adequate means of switching cell differentiation and growth on and off.

Stem cells in South Africa
A third type of stem cell, housed on the safer side of the Big Debate, is cord-blood stem cells.

Cord blood is generally defined as blood contained within the umbilical cord and contiguous placental circulation. It is seen as the richest source of stem cells, as it aids the embryo in the womb to develop into a fully-grown baby.

Stem cells can be harvested from the umbilical cord of new-born babies for a limited period after birth. It is reported to be a painless procedure.

Newly-formed South African biotechnology company Lazaron Biotechnologies specialises in the harvesting and cryogenic storage of cord-blood stem cells.

Director Harry Minnie says it is important to note that the main driving force in government’s attempts at stem-cell research regulation relates to embryonic stem cells and the inevitable ethical issues surrounding cloning.

“We are in continuous consultation and inter-action with the South African government; but note that we do not conduct embryonic research.” Cape-based Lazaron was formed by business people as well as several University of Stellen-bosch scientists.

The company already has several specimens stored in liquid nitrogen, at –196 ˚C. Each specimen is stored in two localities so as to better ensure its survival of any act of nature.

Lazaron harvests the stem cells at the request of the parents of newly-borns, at a cost of R6 500, with an annual storage fee of R120.

It is hoped that the stored stem cells may be used to cure diseases the child or its immediate family may suffer from in future.

“Cord-blood stem cells remain a perfect match for that baby. They have a high probability of being a viable match for a sibling and can potentially be used by parents and grandparents in the treatment of over 40 diseases, including a wide range of cancers, genetic diseases, immune-system deficiencies and blood disorders,” explains Minnie.

The uptake in the company’s storage facility has been overwhelming so far, he adds.

Getting it out of your genes
Genetic disorders, along with those conditions we unfortunately inherit from the biological line we come from, are common occurrences.

They can vary from albinism, Down syndrome and high cholesterol to hypertension. Other examples include the fact that a chromosome abnormality is present in 40% to 50% of all recognised first-trimester pregnancy loss. Genetic disorders account for 50% of all childhood blindness and 50% of all childhood deafness. And between 5% and 10% of common cancers, such as breast, colon and ovary cancer, have a strong hereditary component. (From Emery’s Elements of Medical Genetics).

A programme to map the entire human genome, which started in 1990 and wrapped up work in 2003, has, however, potentially changed the outlook for those suffering from genetic diseases or disorders.

The study revealed that there are around 30 000 coding genes that provide the blueprint for human life.

The immediate benefits of the sequence data is being realised in research that is leading to better diagnosis for families suffering from a genetic disease, as well as the development of new strategies for the prevention and treatment of genetic disorders.

However, the future use of the human-genome mapping project, to a great degree, lies in gene therapy, explains Dr Engela Honey, of the University of Pretoria Department of Genetics.

Most genetic diseases are resistant to conventional treatment, so genetherapy – or successfully modifying the genetic code in a patient’s cells – is an attractive option to combat the disease.

Gene therapy involves the replacement of a deficient gene product or the correction of an abnormal gene – having been made possible because the human-genome mapping project has ‘bagged and tagged’ all the genes in the human body. “If we know what the gene product is we will one day be able to replace the abnormality. I am not sure if it would be possible for all anomalies, especially for structural abnormalities already present at birth, such as a cleft lip and palate, but definitely biochemical abnormalities, such as diabetes or cystic fibrosis,” explains Honey.

It may also be possible one day to introduce conditionally toxic, or suicide genes, into the body to attack cancer cells – one of many examples of what the future could hold.

However, warns Honey, progress to date of gene therapy has been limited, with many practical difficulties still remaining and vast research necessary.

Popular ethical issues surrounding this branch of medical research include the possibility of genetic enhancement to supply certain character- istics, such as height and intelligence, or to predetermine gender.

A suitable replacement
Medical science, along with the engineering disciplines, are working towards finding increasingly suitable replacements for failing body parts.

Iqbal Parker, professor of medical biochemistry and director of research for the University of Cape Town (UCT) Health Science Faculty, says anything can be replaced if the technology is available.” “The brain is perhaps the most difficult one, both technically and ethically.” In Pretoria, the Materials Science and Manufacturing (MSM) unit of the Council for Scientific and Industrial Research (CSIR) is hard at work creating suitable replacements for certain parts of the human body.

A recent success – in fact, only entering commercial production this year – is the Eyeborn orbital eye implant.

The implant offers people who have lost an eye a substitute which, unlike unsightly glass or polymer eyes, provides for synchronised movement with the remaining unaffected eye, explains MSM unit project leader Dr Wim Richter.

This is because the implant is made of hydroxyapatite, a calcium phosphate compound, which has a similar mineral content to bone. Because it is a body-friendly material, the body ‘thinks’ it is part of it and joins the porous implant to the eye socket with tissue and muscle, explains Richter. This enables synchronised control of movement to the implant and, after insertion of a prosthesis (with a plastic covering cap with the appropriate artwork), the implant is almost indistinguish-able from a real eye.

Richter notes that the Eyeborn implant was developed in close cooperation with the Wits Health Consortium and the Pretoria Eye Institute, and with financial support from government’s Innovation Fund. To date, patents have been filed for the product, and 200 people have so far received orbital eye implants in South Africa.

Cerdak, in Kwazulu-Natal, is due to start commercial production of the eye implant this year, and also plans to export the product.

Richter emphasises that the aim of the project was also to provide for an affordable implant solution, as many people who have lost an eye are typically from poorer communities.

The MSM unit is also researching the de- velopment of biomaterials for the repair and reconstruction of other diseased, damaged or simply worn-out body parts, says biomaterials scientist Dr Roger Nilen.

The focus is again on using hydroxyapatite.

“When medical practitioners use something like titanium for a hip replacement, the body accepts it, but does not fully integrate the material.

“The body forms scar tissue around the implant, causing it to eventually loosen. However, bioactive materials, such as hydroxyapatite, are fully bonded into the body,” says Nilen.

For example, small ‘pellets’ of hydroxyapatite are currently used to fill cavities in bones, where, through a process called osteoinduction, it literally becomes part of the bone.

One problem, though, is that the product does not have load-bearing capacity as yet – which means it cannot replace an entire section of (load-bearing) bone, says Nilen.

However, he adds, the pro- ject the MSM unit is currently working on is developing a product which will see hydroxyapatite possibly combine with specialised polymers (creating a polymer/hydroxy-apatite composite), to allow for a flexible and load-bearing bone substitute.

Again, the project aims to develop – as with the Eyeborn product – a local manufacturing industry and to deliver a much more affordable product than the expensive dollar-priced imports.

A Southern (African) solution
Southern Implants MD Graham Blackbeard started his career as a mechanical engineer in the US, building mechanical hearts and heart valves while on a Rotary Foundation scholarship.

“Even before Chris Barnard did the first heart transplant, there were mechanical heart valve implants happening throughout most of the world,” he explains. “To put it simply, an implant is when something is placed within the body that is not from the human body, and a transplant is when one part of the human body is placed within another body.” Blackbeard returned to South Africa to establish the Pretoria-based Southern Group of medical companies in 1987, a knowledge hub which today employs eight mechanical and bioengineers. It is a prime example of budding bioscience and what it can achieve.

Southern Implants produces dental implants which are exported to seven countries. Southern Medical “produces the most revolutionary spinal-disc implant developed so far anywhere in the world, offering an alternative to spinal fusion which, contrary to our product, requires extended immobilisation following the operation,” explains Blackbeard.

The company also produces ankle-, elbow-, finger- and toe-joint replacements, making use of titanium, cobalt, chrome or polyethylene (a form of plastic).

Southern Ear, Nose and Throat imports cochlea implants which can restore hearing in certain cases.

Southern Cryoscience conducts cryopreser- vation of human tissue. “For example, the best heart valve for many paediatric cases is an actual human heart valve taken from a donor heart. Cryogenics ensures the valve can be frozen and used when necessary. Traditionally, any donor organ has to be used within hours of being removed from the donor,” says Blackbeard.

Southern Biotechnology makes use of human tissue from a patient to culture (or grow) the tissue that is needed for reimplanting in that patient.

“This means we can take chondrocytes (cells that form cartilage) out of a diseased spinal disc and grow more of the right chondrocytes and then put it right back into the diseased disc. Or we can replace the disc with a mechanical disc, grow the necessary chondrocytes from the diseased disc and inject that into the other spinal discs to bolster them,” explains Blackbeard.

The last Southern Group company is Medika, which manufactures wound-care products, in particular ozone products that expedite the healing process.

As for what the future holds, Blackbeard says stem-cell research will one day make some implants redundant.

“For example, you will be able to grow a new tooth should you lose one. However, much research is still needed.” Blackbeard says the world- wide implant market is growing by a conservative estimate of 20% a year. One obstacle is that entry into that market is difficult, as barriers are extremely onerous. “You can typically look at paying millions of dollars to manage a product from concept through development to testing and approval by European and US regulatory authorities.” As for other local companies following in Southern’s footsteps, Blackbeard says there is not enough faith or funding available in South Africa to feed the biomedical industry. Southern has so far made use of funding from US venture capitalists.

Between 10% and 20% of the company’s annual turnover is spent on research.

Until we can grow bone then . . .
Shane Olfsen is a medical orthotist and prosthetist with the Orthotic and Prosthetic Centre at the Wentworth hospital, in Durban – which means he makes prostheses for those who have lost their limbs.

“The manufacture of prostheses is quite common in South Africa as we have a fairly high percentage of amputations throughout the country.” He says there are multiple reasons for manu-facturing a prosthesis for an amputee, for example diseases such as arteriole sclerosis, deep vein thrombosis or diabetes or trauma, such as car accidents or injuries sustained at the workplace.

Olfsen says there are two basic types of prosthesis.

An exoskeletal prosthesis (latched onto the body) is manufactured from wood, polyurethane foam and laminated resins.  An endoskeletal prosthesis (made to fit into the bone) has a laminated or draped plastic socket with a tube-frame construction. These modular components are interchangeable and allow for modifications to the alignment of the prosthesis.

The components could be made of aluminium, steel, titanium, or carbon fibre. The limb is covered with a cosmetic foam.

“Prostheses were originally handmade from basic materials such as leather, steel or wood. In the early nineteenth century, prostheses were divided into individual components, namely the prosthetic foot, knee, skin component, and individually fabricated socket.  “This was the basis for systematic and improved construction of prostheses, which eventually resulted in the industrial fabrication of components, still present in countries such as Germany, the US, UK and Japan,” explains Olfsen.

Materials used in the manufacture of prostheses are increasingly high-tech and the main function is optimum use with minimum weight.  As for the future of this division of medical science, Olfsen says technology is changing rapidly.

“From mechanical knees, hydraulic knees and pneumatic knees to computerised knee joints, one can only imagine what technology will appear next.  “Sadly, South Africa does not compare to overseas companies where the manufacture of com- ponents is concerned. We are not able to compete with overseas technology as research and development is very costly and resources are few.” The only components that are being manufactured locally are those on which the patents have fallen away. These designs are simple but very effective, leaving little room for improvement, says Olfsen.

The future . . . still imperfect
The UCT’s Parker says the body of the future “would be one where the immune system has developed resistance to a variety of diseases as we currently know them. “However, the downside is that new strains of pathogens (such as bird flu) would also have evolved and the body will face new problems.” He adds that improved healthcare in developed countries has indeed resulted in increased longevity.

“Their major concerns are, therefore, focused on diseases associated with ageing, such as Alzheimer’s and Parkinson’s disease.

“However, life expectancy in the developing world is generally lower as we have higher infant mortality.  “I do not see this picture changing much, unless the problems of infectious disease and malnutrition are solved. These two are linked, as malnutrition very often compounds the devastation caused by disease, and lowers the resis-tance to infection,” explains Parker.

The reality is that poverty will always separate the poor from the best possible medical care, and, as medical technology grows by leaps and bounds, it will create as much of a medical divide as the much-publicised digital divide. The developing world is still battling tuber- culosis, malaria and flu as killer diseases, while the developed world is able to focus on diseases associated with growing older . . . and older.

Those who will live ‘for ever’, will most likely be those with a healthy-sized back pocket.


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