Who wants to live forever?

Looking at the advancements of science and medicine, it’s not hard to imagine that we are only a few short steps away from fixing everything that can go wrong with a human body. We have stem cell technology, tissue engineering, robotics, biofabrication, nanotechnology… All pieces of the puzzle seem to be there, so why can’t we simply ‘recreate nature’ and produce organs or devices that make a broken body work properly again? Because such a body could potentially live forever.  

Pee in a jar, get a new heart

‘It might sound like science fiction, but we can actually derive any cell type of the human body from urine,’ says Robert Passier, Professor of Applied Stem Cell Technologies, explaining that this method exists thanks to human pluripotent stem cells, discovered in 2007. ‘Induced pluripotent stem cells (iPSCs) can be derived, for example, from blood, skin or even urine. This means you can literally pee in a jar, get the cells, culture them and reprogram the urine cells into stem cells. Those can be used to make any cell type, therefore any organ cell. We even use this method to produce cardiomyocytes, meaning heart cells.’

'We can actually derive any cell type of the human body from urine' 

Yes, we can make heart cells from urine. Hearing this, one can’t help but ask: can we make the entire heart? ‘We know that we can make the right cell types, so naturally you can speculate about their use in regenerative medicine. But that is the next step,’ answers Prof. Passier. ‘Stem cell technology currently focuses on disease modelling and drug discovery. We try to model complex diseases and see if we can find the mechanism that causes the failure, and therefore see if we can postpone the damage or repair it. Stem cells can also contribute to better and safer drugs.’

Organ structure

Although Robert Passier stresses that we first need to understand diseases and capacities of stem cells before we attempt to replace or repair organ function, he admits that regenerative medicine comes with exciting prospects. Some of which could eventually lead to the replacement of complete organs. ‘There are different types of stem cells and some indeed have a self-organizing capacity to create structure resembling organ structure and function. For example, you can isolate specific cells in intestines, culture them and make specialized cell types, which are organized in such a way that they form the structure of the intestine. Sadly, not all cells and organs have this capacity. For example, we can’t automatically create heart structure.’ 

‘However, we could help nature – for instance by using 3D bioprinting,’ adds Passier. ‘That way we can make a structure that truly resembles the real organ. We naturally can’t start with the whole organ, but we can start with smaller units and move to bigger ones. In the end, there might be a possibility for structures that are so well organized that we can use them for regenerative medicine. Maybe we can even make an exact copy of an organ or its part.’

We can make tissue. Now what?

While he mentions that ‘reconstructing’ and replacing entire body parts that consist of many different structures, such as legs or hands, might always be too complex and costly to accomplish in a clinical setting, Jeroen Leijten, Assistant Professor of Complex Tissue Engineering, also believes that the development of organs might be feasible. Feasible, but exceptionally challenging. Because, despite the fact that we are capable of making tissues, the right tissue isn’t all you need. The engineered tissues don’t necessarily function as well as their naturally grown healthy counterparts.

‘There are three types of tissue,’ says Leijten. ‘First one is flat tissue, for example skin, which we are very good at recreating. The second type is hollow tissue. That includes blood vessels, for instance. We can now engineer blood vessels, we can make a simple bypass graft and that works beautifully. But creating vascular trees within tissues remains tricky. Tissue engineering can contribute to overcoming this, but substantial financial investments would be required.’

Besides the high costs, Leijten points out other difficulties. ‘The third type of tissue is solid: liver, kidney, bone, brain etc. To recreate those, we’d have to master a high level of complexity. You’d need multiple tissues at the right place and they’d need to be integrated with each other as well as the whole bodily system. If you engineer an organ, you need a blood vessels network to provide the implant access to the patient’s blood, which keeps the implant alive. Furthermore, the tissues should be innervated, compatible with the immune system, and function for decades within the human body.  In short, a remaining key challenge is: how do we connect engineered organs to the human body?’

Medicine focused on the West

Integrating engineered tissue or organ parts into the body is one of the main challenges, indeed. Nonetheless, technical challenges don’t represent the full picture. Lengthening the human lifespan and being able to ‘fix’ everything - that also comes with ethical dilemmas. ‘Ethical considerations are often framed as drawbacks, and ethics as a brake on new technology,’ says Marianne Boenink, Associate Professor in Philosophy and Ethics of Biomedical Technology. ‘But the development of new technology already has a moral motive driving it, like the desire to realize better health or wellbeing. Because when we are developing a new technology, we do it because we think of improvement. However, we have learnt from experience that new things can lead to unexpected consequences, and so it is good to think of these upfront.’ 

Boenink suggests examining the ethics of medical technology from a different standpoint. What is it we aim to achieve with new technology? ‘It’s not about limitations, but about the priorities we set. For example, look at developing countries; medical progress has a huge impact on the people there. The issues in those countries are massive, but require a completely different approach. The problem is that medical technology still tends to be geared entirely towards the West these days.’

According to Boenink, we often consider circumstances here in the West to be the default. ‘It is important for us to examine the context,’ says Boenink. ‘Medical experiments are often carried out on young, male students who are not representative of the global population. There is no single standard human body. Of course we draw inspiration from nature, but which kind of body are we trying to ‘imitate’ in the field of medical technology?’

Boenink herself conducts research into the influences of predictive technology. New technology helps discover potential diseases earlier on and a prediction or diagnosis can have massive consequences. ‘It can affect people’s self-image,’ Boenink explains. ‘It changes the way people look at themselves. Moreover, if you can predict illnesses based on someone’s DNA, what happens when a potential employer of theirs gets hold of that information? These are highly relevant political issues.’

Biological inks

Even though other scientists certainly don’t disregard these ethical and political issues, they are also driven by the prospect of new, innovative technology. And, although it might not have only positive impact on human lives, engineering fully functional organs is a challenge that many researchers want to tackle. ‘Perhaps we can’t make an entire heart that functions as well as a normal healthy heart, but we can make its different layers,’ says Leijten and, once again, bioprinting is mentioned as the possible way forward. However, it also comes with obstacles: ‘We can recreate the general shape of the human heart or another organ with some of the right cells in it, for example, using bioprinting. However, we need more than just the macrostructure. You also need the right micro- and nanostructure to allow the engineered organ to function properly. So the question is: can we also make biological inks that have the right nanostructure? Creating the right biological inks to print organs could be the future.’

Creating the right biological inks to print organs could be the future

There are also other approaches scientists are considering in order to fix our failing organs. One of them is so called bottom-up tissue engineering. ‘This refers to going from nano- to macrostructures, creating different modules and inserting them into bigger organ systems,’ explains Leijten. ‘Challenge is: how do we make these tiny modules to reassemble into the right bigger structures? How do we create a self-organized system?’ Because this question is unanswered, there is another path to consider: ‘It might be better if we let the tissue develop by itself inside the body. After all, we developed from a single fertilized egg cell. If you have the right biomaterials and stem cells, you could perhaps create a suitable organ template and stimulate our bodies to organize and mature the replacement organs. Even though we can’t yet say this is indeed the ideal way forward, the human body as a bio-reactor is an interesting and viable concept.’

Cybernetics

Yet, both Robert Passier and Jeroen Leijten agree that biology alone will not cut it – we will need to combine it with technology as well. ‘If it comes to recreating parts of a human body, cybernetics will play an important role,’ claims Leijten. ‘We already have robotic hands, robotic hands that can do beautiful things, but the question is, how do you hook it up to your nervous system so it works as an integral part of your body? Maybe such a seamless integration can’t be achieved in the near future, but pursuing this challenge is relevant. Cybernetics is more likely to provide a cost-effective and durable solution for creating complex body parts, compared to engineering of purely biological tissues.’

 ‘Controlling wearable technology is indeed quite a challenge,’ says Herman van der Kooij, Professor of Biomechatronics and Rehabilitation Technology. He develops wearable robotics to help patients during the therapy stage, or if they have a permanent handicap. For instance, he works on exoskeletons intended for paralyzed patients. Meaning devices that can fix even ‘broken’ bodies and help them to move and function like their healthier counterparts.  

In fact, there is already a variety of exoskeletons out there that can help fully paralysed patients to walk again. A number of people use such devices in Nijmegen, although they do still need crutches to walk with these exoskeletons and, at 80,000 euros per skeleton, this new technology is still rather expensive. ‘Whether this technology will ever be affordable depends on the volume,’ says Van der Kooij. ‘The first automobile was incredibly expensive at the time, and yet now, almost everyone has a car. This technology too will become cheaper over time.’

Picking up brain signals

There are other challenges besides the price tag. How does the device know what the person wearing it wants, and how can the person know what the device is going to do? ‘It is all about the exchange of information,’ Van der Kooij explains. ‘This interaction can be controlled via brain activity, but these kinds of signals are very hard to pick up.’ One solution might be to input the necessary settings into the device beforehand, but that makes it hard for the patient to walk under varying circumstances, because each new situation would require new programming.

The biggest technological challenge is maintaining balance. ‘Without crutches, walking with an exoskeleton is still pretty much impossible,’ says Van der Kooij. ‘That is why we are performing extensive testing on how people maintain their balance. Our dream is to build an exoskeleton that will allow fully paralysed people to walk without crutches, and I believe that we can achieve this aim within one or two more years.’

Exosuits or Iron Man suits?

Wearing an exoskeleton is like wearing a robot, and so another issue is the hardware. ‘In a way, people don’t actually need the exoskeleton as long as they still have a skeleton of their own,’ Van der Kooij explains. ‘That is why we are working on a concept for activating people’s limbs using exosuits. An exosuit is a suit you put on and that activates your limbs for you. We are trying to keep the technology as small as possible, so that the suit could even be worn underneath people’s clothing.’

In the end, this robotic technology won’t make us immortal, but it could help us live much longer, supporting our worn down bodies. ‘It would be such a big help for industrial workers who perform manual labour,’ Van der Kooij states. ‘The additional support from an exoskeleton could really make a difference for them. People get older, but as for our bodies, they really wear and become strained.’ Moreover, such wearable devices could be rather fun. Whether healthy or disabled, exoskeletons could give people supernatural powers, like in science fiction. ‘Yes, an exoskeleton could help you achieve feats like jumping ten meters up into the air,’ says Van der Kooij. 

Replacement organs

If you have the funds, you can already get excited about the idea of becoming a real-life superhero, but we must disappoint you if it comes to the prospect of ‘replacement organs’ created from, let’s say, your morning visit to the toilet. Unfortunately it seems that we can’t expect any such developments in our lifetime. ‘If it comes to replacing whole organs, it certainly isn’t possible now,’ says Passier.

‘On the other hand, you should never say never. If you’d asked me ten years ago if we could make heart cells from urine, I would have said: ‘of course not’. So who knows. It also depends on the specific organ. There are already ongoing clinical trials for repairing eye disease using stem cells and they look very promising, but it is extremely complex to use stem cells in case of a heart failure, for instance. It is of course the dream to use stem cells to replace tissue and really repair organ function, whether that is by replacing the whole organ or parts of organs. But I think stem cell technology shouldn’t focus on that right now. There are many steps we need to take first. Because it also still is a dream to have really sophisticated models of diseases, and therefore develop better therapies and drugs. But this dream is feasible. I believe we can accomplish that within ten years.’

The line we won’t cross

Even though we might be light-years away from achieving it, the scientists agree that recreating organs isn’t unrealistic. Is there a line we won’t be able to cross if it comes to mending human bodies? ‘Probably the brain,’ thinks Jeroen Leijten. ‘Yes, even if – many years from now - we can print brain cells into an engineered brain that is indistinguishable from natural brains, and it might even function as a brain organ, but it is unlikely we can fully recreate all the unique connectivities that make us into the persons we are, including all our memories.’ But, with the exception of brain, Leijten doesn’t rule out a scenario in which everything in the human body is fixable. ‘Everything might become repairable, but not replaceable. Organ systems, such as our vascular system, will be difficult to fix, because they are too vast to be replaced. To fix these issues, we would need regenerative strategies.’

Robert Passier is also naturally skeptical about ‘brain replacements’, but he doesn’t want to put any limits on medical technology. ‘I don’t want to say ‘we will never be able to do this’, because who knows what might be possible in the future,’ he says. ‘Will we ever make a brain? That is an extremely complicated challenge. Can we make it now? Of course not. Can we make it a hundred years from now? Yes, maybe. Maybe we can even replace brain.’ 

Aging, a curable disease 

Even with the head transplant on the horizon, Leijten doesn’t think we can replace everything in our bodies, but he quickly adds that: ‘We could potentially rejuvenate bodies. There are enticing studies that suggest that we can rejuvenate cell behavior. If that is the case, is aging only a disease then? If we can keep repairing and restoring everything, aging is nothing but a curable disease.’

 'If we can keep repairing and restoring everything, aging is nothing but a curable disease.' 

Saving and prolonging lives, providing healthy organs or new limbs…. all that sounds like good things to do. However, nothing is black and white. ‘If we could stretch human survival to several hundreds of years, is that really something we should want?’ ponders Leijten. ‘How much life can we sustain on our planet, what effect would this have on potential food shortages and other issues. If we are able to do it, could longer lifespan become a commodity that is purchasable for the wealthy? There is a potential risk that we would inadvertently create two financial classes – the nearly immortal upper class and the dying working class.’

Marianne Boenink agrees that conquering old age would have huge societal consequences. ‘Imagine a world without old people; what would we be missing out on then?’ says Boenink. ‘What kinds of implications would the lack of old age have on the notion of wisdom? And should we even consider aging a problem or a disease? There are plenty of positive sides to aging. Moreover, the technology might not be affordable for all and might create a new class of privileged people who are able to conquer their old age, simply because they can afford it, unlike others. This could happen on an international level – the West versus developing countries. That makes you think of how we should regulate development in biomedical technology. Now we almost never forbid new developments, but maybe that is something to consider. But what if certain countries forbid a technology and others don’t? It is very hard to ban technology on a global level.’ 

Personalised medicine  

Back to the topic at hand, Marianne Boenink doubts whether humankind will be able to ‘fix’ everything related to its physique. Be that as it may, we are getting increasingly better at visualising diseases and at discovering them in earlier stages. ‘We might be able to create personalised medicine and get even better at predicting which diseases people will be affected by,’ says Boenink. ‘On the other hand, this might also mean withholding medication if we know that it isn’t going to make someone better.’

These issues also give rise to the questions of how people see themselves. If everything can be fixed, what is left for people to base their identities on? ‘You have to remember that people are very flexible,’ says Boenink. ‘Our bodies change continuously. People with prosthetics tend to become fully used to their new limbs, as if it were a pair of glasses. I would not rule out the possibility of people being able to get used to, say, a new head.’

Not yet, but…

At this point, there are many things we don’t understand about the human body, and that we therefore can’t fix. Still, ten years ago we didn’t have functional exoskeletons walking in the streets, we didn’t know heart cells could be derived from our urine and our 3D printers were still in diapers. Research and medical technology are moving at a rapid speed. In fifty years, even our wildest dreams could become reality. Maybe, just maybe, we will have Iron Man suits in our closets, 3D printed hearts pumping in our chests and a tuned brain running it all.