Wednesday, 23 March 2011

The Future Is Behind Us: Tissue Engineering, the State of the Art by Ilyas Khan

The following is a piece written by Dr. Ilyas Khan - a research scientist at the Cardiff School of Biosciences - and relates to our sciSCREENing of Never Let Me Go tonight.

Human ingenuity knows no bounds, if we consider even just casually the achievements of mankind and the depth of understanding we have acquired of the nature of being in this universe, it beggars the mind to comprehend. The last man who could rightfully claim ‘all knowledge as his domain’ was the polymath Athanasius Kircher who died in 1680. To cope with the avalanche of new knowledge generated since, science and technology has fragmented to such an extent that separate fields of specialised study have emerged in order to facilitate advancement. Occasionally, these separate fields collide and fuse to generate new amalgamated sources of knowledge, one such example is Tissue Engineering (more commonly referred today, if as a scientist you want to be funded that is, by the funkier name of Regenerative Medicine).

Tissue engineering is the science of using human cells, engineering know-how and materials to maintain, repair, improve or even replace organs or tissues in the human body. Viewed from the perspective of the arts, particularly cinema and in near-science fiction novels, the technology of tissue engineering is merely in the process of catching up with the imaginations of their respective creators.

It is my contention that the reverse is true, that in fact, many of the imagined technologies for tissue engineering are already here and we are on the frontier of unforeseeable changes that will require reimagination of the future capabilities of man.

Both artistic mediums (cinema and sci-fi) conceive of near-futures where injured or diseased organs or appendages could be replaced by superior metallic or composite implants or limbs. An example of the depiction in the arts of the superiority of artificial limbs and organs was the 1970s television hit ‘The Six Million Dollar Man’, where Steve Austin the ‘Bionic Man’ had robotic legs, and one arm and one eye. An interesting aspect, possibly psychological in part, was the symbiotic nature of these implants with the human body, such that they integrated perfectly with surrounding biological tissue; a clinical aspect of implant bioengineering that is difficult to achieve in reality. Was this a tacit acceptance that man was inherently weak? By the latter half of the twentieth century practically every bone in our bodies had an artificial counterpart from metallic plates for the skull, spinal plates and prosthetic implants for the ribs, hips, knees, fingers and toes. In addition, fixation of bones using plates and wires is also in effect an indirect attempt at tissue engineering.

Professor John Charnley (1911-82) was probably the prototype first generation tissue engineer. Born in Bury, England, he was an orthopaedic surgeon, who in 1962 designed the replacement hip, conceived the surgical methods to place it in the body free of infection and fix it to the femur using thermoplastic cement. The success of this procedure is highlighted by the fact that hip replacement is the most successful orthopaedic procedure, with 97% of patients reporting improved outcomes.

Tissue engineering was borne primarily from the absence of any evidence of symbiosis between the robotic and biological circuitry, by this we mean that synthetic biocompatible materials were incompatible with the normal functioning of the human body. Therefore, although technology had advanced to such a degree that it was possible to keep a person alive using an artificial heart, kidneys or lungs it was becoming clearer, through an increased volume of research, that the cells of the body had an inherent capacity to heal or regenerate organs and tissues. Combined with technological advances in the production of biomaterials and bioreactors, even if patients were incapable of making replacement tissue, fabrication of organs and tissues could be performed in a lab prior to implantation.

Organisms are made of cells, and it wasn’t until the early 1900s that the technologies were developed to grow them reliably in the lab. The impetus for this particular research was to try and grow the poliovirus that needed cells to replicate, in order to produce enough vaccine to rid the world of this scourge of humanity. The workers who developed these methods received the Nobel Prize as an indication of the enormity of their enterprise. Further research in the following decades identified immortalised (cancer) cells and through analysis of these cells we learned more about human embryonic stem cells, which at their most potent, are also immortal and can generate any tissue of the body. Stem cells can be derived from embryos, but given ethical considerations it is now possible using scientific trickery to reprogram an adult's skin cell to behave as embryonic stem cells. These cells can then be pushed, by sequentially adding different chemicals, to become practically any cell in the body, such as cardiac cells. Cardiac cells can be added to a biomaterial in the shape of a heart valve or even heart, then grown and matured in a bioreactor (a glorified tumbler) under highly controlled conditions, until a functional valve or beating heart is produced.

Tissue engineered implants have many advantages over their synthetic non-biological counterparts. First and foremost, these implants can restore the function of damaged or diseased tissues and organs, and secondly, because stem cells (even from an unrelated donor) are not rejected, or can be engineered to be this way, a daily Smartie tube full of tablets to lower the power of the immune system to stop rejection is unnecessary. Also, the implanted tissue or organs integrate with the patients’ own blood supply thus providing the energy and feedback for optimal function.

So far we have touched on aspects of Regenerative Medicine, but this field emerged hand-in- hand with reconstructive surgery that is practised in many cases simply for aesthetic appeal. Walking down along the Santa Monica beach in Los Angeles it is hard as a bearer of a y-chromosome to not marvel as the semi-lunar protuberances disturbingly oblivious to the gravitational forces projecting from the chests of otherwise beautiful women. Similarly, one is entranced by the age defying, wrinkle-free, lip busting, facial features of celebrity septa- and octogenarians. These enhancements which owe more to first generation tissue engineering are merely the first wave of what will be a tidal wave of second generation body engineering. An example; doping is common in some sports, however even sportsmen and women are not oblivious to the detrimental side effects of drug taking, such as embarrassment, loss of earnings or the possibility of becoming a social pariah. But what is there to stop an athlete from harvesting muscle stem cells, expanding their numbers in the lab and then re-injecting them back into the limbs. In short, nothing. These technologies are available, are being used today and since this type of muscle modification is undetectable as yet, there is no downside for the athlete. I am in no doubt that athletes and coaches are unscrupulously using these types of techniques to gain unfair advantages on their rivals. It is likely that body modification through tissue engineering, rather than the cure of medically relevant diseases will be the big commercial thrust for large pharmaceutical companies in the coming decades.

As with most scientific studies, the detailed methods to replicate the latest advances in tissue engineering are all freely available online. The ubiquity of companies that generate materials for bioengineering could allow an enthusiastic amateur to accomplish almost anything, as the basic building blocks for any tissue are literally at hand. Website and blogs, especially those dedicated to muscle building, go into extraordinary scientific detail of the basic biology of growth and development of tissues. It is only hubris on the part of scientists to believe that they are the only ones engaged in tissue engineering.

As a teenager my personal epiphany of the extent to which the human body could be remodelled or indeed be repaired came through a decidedly grainy video of Ridley Scott’s magnum opus ‘Bladerunner’. In this very loose depiction of Phillip K Dick’s novel: ‘Do androids dream of electric sheep?’ androids called ‘replicants’ escape an off-world colony and try to find their designer on earth, a genius bioengineer, Dr Eldon Tyrell. Their hope is that he can override their in-built safety feature of a three year lifespan. Whilst my friends digested the philosophical implications of the films basic premise, I was personally entranced by the ubiquity of biological engineering throughout the film, such as artificial animals and human organs such as eyes that could be bought ‘off the shelf’. Bladerunner’s debt to the cyberpunk movement that depicted near-future dystopian societies in the midst of technological ferment led me to the novels of William Gibson, Bruce Sterling and Neal Stephenson. It was in these novels that the nexus between cell biology as I knew it then and the future of tissue engineering was most obvious. In these novels the hubs of tissue engineering were based in South East Asia, principally from what I could deduce, to the absence of any Health and Safety regulations (an entirely plausible scenario). These books were also littered with examples of body modification based primarily on tissue engineering such as, fangs, claws (think Wolverine from ‘X-Men’) and also chimeras. Making fangs and claws is old hat in terms of what science has achieved, just google ‘hen’s teeth’ if you don’t believe me.

Chimeras are animals with cells from two genetically distinct organisms. In our age of greater sensitivity to green issues and fuel economy how useful would it be to have the legs of a kangaroo? Impossible? Just consider these two facts, firstly; the kangaroo genome is known and from it we know that our last common ancestor was ‘hopping around’ 150 million years ago and that large chunks of both kangaroo and human genomes are essentially no different from each other. Secondly, you may be surprised or indeed shocked to learn that chimeras have already been created, such as the goat/sheep chimera known as the ‘geep’ and the quail/duck chimera known as the ‘quck’. In 2007, scientists from the University of Nevada created an embryo that was composed of 85% sheep and 15% human cells. Would the embryo have survived if implanted, and what would the creature have looked like. We will never know, or will we?

I titled this essay, ‘the future is behind us’, because I had the sense that as a tissue engineer we had forged ahead and met the expectations of this and previous generations and in some cases wildly exceeded them. If occasionally, I have the time to slip into an introspective mood, I am truly in awe of the possibilities that lie ahead of us.

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