«If you ask people if they would like to live 200 years, in the first instance all say ‘No’. They think they will become very old and diseased, being in a wheelchair for at least 100 years. But if you ask the question differently, if you ask if they want to become 200 years and still look as if they are 30 years old, much more people are interested». We met Kris Verburgh during the recent SingularityU Italy, the visionaires’ forum discussing how to apply exponential technologies to create positive changes and economic growth  in the current model of society, where the Belgian trend watcher and biotechnology expert gave a lecture on the new vision of life that is emerging as a consequence of the next-generation biotechnologies able to manipulate the genome, epigenome and transcriptome. Future years may see the effective possibility to cure many diseases that up to now seemed to represent a true obstacle to the prosecution of life, such as cancers. Born in Belgium in 1986, Dr. Verburgh graduated in Medicine at the University of Antwerp; he is currently a researcher at the Center Leo Apostel for Interdisciplinary Studies (CLEA) at the Free University Brussels (VUB) and a member of the Evolution, Complexity and Cognition group at the Free University of Brussels.

The new perspectives on human evolution

The traditional, nature-based model of human evolution might be experiencing its last days, as with next-generation biotechnologies the reaching of a sort of immortality – which in all times has been the ‘demon’ aspiration of the human being – is closer than ever. A new baby born today has already more than 50 percent change of becoming 105 years old, according to Kris Verburgh. With the aid of new biotechnologies,200 and more years might be a further plausible target to be reached in future. “People want to survive: it’s an evolutionary instinct, in fact. I think a lot of people would be interested in extending their lifespan, on condition they can still enjoy life a lot, still look healthy and ideally even young”, tells Kris Verburgh to NCF.

Next-generation technologies might have a dramatic impact on the concept of life itself, that might be reprogrammed to include the new opportunities for life extension and enhancement offered by medical interventions and artificial intelligence, taking the role traditionally played by natural selection and evolution. These are the core principles of transhumanism, a new thinking movement according to which the human species is living a relatively early phase of development: technologies are today available for humans to act directly to further accelerate and evolve towards an “intelligent life beyond its currently human form and human limitations by means of science and technology, guided by life-promoting principles and values” (Max More, founder of trans humanism in 1990) (Box about Transhumanism)

A complete change of perspective is needed to better perceive the opportunities of the proposed new paradigm, starting from overcoming the worries about getting older and being less active. According to Kris Verburgh, nature is not always a good guide, as it also creates terrible diseases that kill  many people, like cancer or viruses. “Some people believe we should not improve the genome because they fear we would create “perfect beings”. But we are far from perfect beings. We bear many mutations and faults in our DNA and design. Trying to fix some of these would considerably alleviate human suffering. On the other hand, even nature doesn’t abhor immortality, as it creates some species that seem not to age, like some polyps or the jelly fish”, adds the trend watcher.

How to enjoy the extend life

It might be argued that an extended lifespan would provoke a huge increase of the earth’s population, which might represent a critical danger for the planet, already under an excessive pressure for the use of its resources. “It’s an interesting topic – tells Dr. Verburgh.- If people live much longer, but have much less children than ever before, on the long term perhaps the overpopulation won’t to be that a problem. In the next 100 years global population will indeed increase. But in the next 300 years, we will see a huge population decline because the birth rate is too low to maintain the population”.

Artificial intelligence and virtual technologies would be also of help in making this extended life much active and full of new sources of entertainment, thus preventing boredom. “Also the traditional division of life – graduating, growing a family, working, then going on retirement – would change. You will have enough time to start doing many new and different things. If you look at psychological research, living much longer is not going to be really a big issue”, explains Kris Verburgh. The average lifespan was 45 years in the 19th century, is his reasoning, and it had already almost doubled. But this doesn’t mean we don’t know what to do with so much time. How can thus look a typical life in the 22nd century? Maybe it will be made of a periodic turnover of education, working and retirement periods, where one might exert all the different jobs of his dreams. “We are often very occupied, even  when we have already been living for a long while This is how the human mind works: we live a lot in the current present, we enjoy things most when we are doing things, and we forget time”, adds Dr. Verburgh.

Costs of innovative therapies won’t be a problem

In the current socioeconomic model at the base of most Western health systems the very high costs of innovative therapies – including genetic and cellular interventions, e.g. CAR-T therapies or immunotherapies – represent a burden difficult to overcome in order to improve a wider access to patients. But in future years, the cost will decrease, says Kris Verburgh, something that will happen anyhow when the patents will expire. «These therapies are often very expensive in the beginning, but I think that’s something that will resolve itself later on. Also, for specific therapies which are very expensive, like CAR-T therapy, we will see new treatments coming that are much less complex: I feel they will be much more cost effective». In the case of CAR-T therapy, for example, the current procedure implies getting the white blood cells out of the body, to then reprogramming them in the lab and injecting back to the patient. Kris Verburgh sees opportunities in new companies being created to vaccinate people against cancer, so that the receptors of the cytotoxic T cells have not to be artificially added like in the CAR-T approach. They may be created instead through specific forms of dendritic cell-targeting vaccines, for example.

 

 

There is still space for traditional pharmacology

But how does this scenario fits with the traditional approach to drug discovery and development, centred on the identification of the most promising candidate molecules? This approach still represent the core business model of biopharmaceutical companies, even if with many new improvements coming from the increasing application of data-mining and big data analysis technologies offered by artificial intelligence.

There is certainly room for the traditional approach and it will be still useful in the future, according to Dr. Verburgh. «I think one of the big problems with the current drug discovery is that it’s focused too much on artificial compounds – he tells NCF -. If we look more in databases of natural compounds, we often find more effective molecules compared to artificial compounds, because of bio-similarity. Aspirin, opioids, or taxanes are based on compounds found in nature. We can learn a lot from nature by trying to look more into databases of these natural molecules and toxins. Molecules found in a long-lived animals can perhaps be used to treat ageing and so on. Also, ethnopharmacy: looking at the pharmaceutical habits of tribes. I think with the advent of artificial intelligence and other technologies you can find or score the databases better to find these small molecules». Dr. Verburgh also mentions some small molecules that are under study to slow down the ageing process, and perhaps even reduce the risk of old age-related diseases, like metformin or rapamycin, that could probably extend life span (see the other article of the dossier). «You have also small molecules that change the epigenome, like specific nicotinamide-based substances. Biotechnology is some kind of mimicry of biological systems, and it will be in many cases more powerful than small molecules to really slow down, and even partially reverse, the aging process», tells Kris Verburgh.

The silver tsunami to be afforded by medical professionals

The new paradigm of life does not concern only the pharmaceutical industry working to find new treatments for many still orphan or incurable diseases. Medical doctors and health professionals would need also to completely rethink their activities and the vision itself of what is health and disease.

«Medical doctors often look at ageing as something natural, something too complex to treat. The problem is that in many different countries ageing gets not a lot of attention during medical education, that’s very unfortunate. It should get much more attention, because it’s the root cause of many diseases that medical doctors will have to treat. And more and more, because of the ageing population: we will have a ‘silver tsunami’», tells Dr. Verburgh.

Prevention is another pillar of the new paradigm to extend lifespan. With an healthy life style, it is substantially possible to reduce the risk of these age-related diseases, according to Kris Verburgh, who is also the founder of the new discipline of nutrigerontology (see below). «If you live healthy, you will get these diseases five or ten years later. But in the end you will get them anyhow, because they are age-related».

Smartphone older

Biogerontology to reverse ageing

The increased attention that medical doctors are called to pay on ageing and its related diseases also implies for Dr. Verburgh an improved education in the huge changes that are happening in the field of the discipline known as biogerontology. «There are now various studies showing that ageing can be partially reversed in animals, it’s not that difficult doing it. We know ageing is a very complex process, but you don’t have to unravel every mechanism. Some things can amazingly work, as we see with epigenetic modification. We don’t know exactly all the Yamanaka factor influences thousands of pathways. But we know it works, at least in mice. What these studies show is that ageing is a plastic process that can be reversed, at least partially», explains the trend watcher. The reference is to the discovery that awarded Shinya Yamanaka with the Nobel Prize for Medicine 2012, i.e. how intact mature cells in mice can be reprogrammed to become immature pluripotent stem cells (iPS) by introducing just a few genes. In one study, scientists cyclically and transiently activited Yamanaka factors in old mice, rejuvenating them: life span was increased, and muscle and organs could regenerate themselves better again.

Ageing to become a disease?

Next-generation gene editing techniques, such as CRISPR-Cas9, allow for the easy and cheap manipulation of genome. By now, it is still forbidden on the base of ethical consideration to use such techniques to modify germlines (which are transmitted to progeny), while the editing of somatic cells (on those the effects are limited just to the treated individual) is already in clinical trials to treat several genetic diseases, with the first products will be approved in the coming years.

The new paradigm addressing ageing to expand lifespan implies the application of these gene editing techniques to rejuvenate the whole organism, something which by now is far from reaching the clinical phase of testing.

«There is a huge potential in treating ageing, but it’s underfunded. The problem is that many governments don’t consider ageing as a disease. It’s very difficult to create a treatment against ageing because it won’t be reimbursed, which is very ironic as most diseases are in fact caused by ageing. It’s very difficult to get funding to create a therapy for ageing. This is also very unfortunate, because a molecule or therapy that can slow down ageing could be very valuable for pharmaceutical companies», says Kris Verburgh. The suggested approach would be able to address many age-related diseases at the same time – like cardiovascular problems and Alzheimer -, because it works on the underlying common cause: ageing.

Again, considering ageing as a disease is one of the principles of transhumanism, where the new evolution paradigm allows humans to fully exploit the potential of genetic engineering, nanotechnology and artificial intelligence to alter the natural fate and to extend their own life.

«There are some people in the ageing field who are lobbying at the World Health Organisation to categorise ageing as a disease. But there are also a lot of people against, because in doing so, first of all you give all elderly people a bit of sense of guilt, they would feel as if they have a disease. Secondly, it looks like something that needs to be treated. A lot of people say it’s too difficult, we shouldn’t give people false hope -, tells Dr Verburgh. – There are a lot of personal or emotional reasons why ageing is not categorised as a disease. But if you look at it from a biochemical or physiological viewpoint, aging looks very much like a 100 percent hereditary, 100 percent fatal multi-systemic disease caused by evolutionary negligence. A lot of ageing scientists call it as a disease: we see more and more a paradigm shift going on, ten years ago it was taboo to speak about trying to treat ageing».

The boundaries with human enhancement

There is a very thin line between the therapeutic applications of techniques such as gene editing and their use to enhance the physiological characteristics of the human being. A line that up to now has limited the boundaries of research in the sense to avoid manipulation, for example, of the somatic characteristics of an embryo in order to give birth to newborns with the desired features.

«We see more and more that the line between medicine and human enhancement will be blurred – tells Kris Verburgh – First of all, we will see treatments to address a specific diseases, but as side effect they will improve human ability. For example, you can make people immune to HIV using these new gene editing technologies, this can be quite easily done in a new future. Is it still medicine, or it is human enhancement?» The same might occur if specific genes would be changed in order to obtain a better cardiovascular system, resulting for example in more endurance capacities. «If the governments won’t allow it, we will see more and more people taking their own health and their own body in their own hands. Look at these biohackers, we already have some people who tried the gene editing technology – like CRISPR-Cas9 – on their own body to get more muscle mass, allegedly. Regulatory authorities strongly advise against this – continues the expert -. But in some countries it’s not forbidden to try a new therapy on yourself. We’ll see more and more happen, because it will become so easy and cheap to do so». No more need for a million dollar lab to run experiments, today it is quite easy and cheap to access gene editing tools. ‘Patient zero’ is claimed to be Liz Parrish, founder of BioViva, who in 2015 said she went to Colombia to have injected two gene therapies against muscle loss and telomere shortening.

The role of nutrition

Healthy nutrition represents a central pillar for the prevention of many diseases, e.g.diabetes or cardiovascular diseases. These are also among the main typical age-related heath issues, together with neurological disorders. The science investigating the influence of nutrition on the ageing process is one of the main research interests of Kris Verburgh, who defined this area of intervention with the term “nutrigerontology”. «You have two approaches to ageing – he explains -, the low tech approach and the high tech approach. The low tech approach is nutrition, and a healthy lifestyle in general. Currently, it is the best method we have to live longer. Unfortunately, there are many different, often contradictary diets. If we know how we age, we can better see what is the best diet in the long term. For example, one of the reasons why we age is because of the accumulation of proteins in our body. Knowing that, you know that the high protein diet it is not probably that healthy in the long term. There are all kinds of specific foods that could help slowing down ageing. We have seen in studies that if you eat healthy and have a healthy lifestyle in general, then you can live eight to fifteen years longer on average, you can become 90 years or 85 years in good health, and that’s great already. But if you want to push beyond this natural boundary of maximum lifespan of our species of 120 years, we need new biotechnology, like this cross-link breakers,epigenetic reprogramming, mitochondrial rejuvenation or lysosomal enzymes».

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