Alex Zhavoronkov is the author of THE AGELESS GENERATION: How Advances in Biomedicine Will Transform the Global Economy ($27, Palgrave Macmillan).
Over the past 50 years, our way of life has changed more than in the previous ten thousand years. We are now living in the most exciting era in the history of humanity, the era of great change and accelerating innovation.
Average lifespans in the developed countries more than doubled in the 20th century due to increases in welfare, improvements in healthcare, decreases in child mortality and the advent of antibiotics and improved hygiene. What lies ahead however is dramatically different. There are several megatrends and specific technology trends already in the making, and they will undoubtedly make us live significantly longer than our parents and grandparents.
Here are 13 reasons why we will experience dramatically enhanced longevity:
1. Propagation of Discoveries into Clinical Practice
Real life-extending potential lies in the pipeline of drugs and medical procedures that are already discovered but have not yet propagated into mainstream preventative use.
Some of the most popular drugs on the market today were discovered many decades ago. For example, the first cholesterol-lowering drugs called statins (e.g. Crestor, Lipitor, Zocor, etc.) were discovered in the 70s and did not reach the market until late in the 80s. In 1998, the global sales of all statins were under $5 billion as doctors started prescribing them for elevated levels of cholesterol. However, it took these drugs that were relatively harmless (as compared to oncology drugs) until 2006 for sales to peak at over $20 billion as the industry picked up the pace.
Statins are just one example, but there are hundreds of drugs that are either gaining clinical popularity or getting through the pipeline today. In addition, there are hundreds of drugs slowly transferring into the preventative medicine markets. For example, many countries are considering recommending low-dose statin, beta-blocker and aspirin for prevention of cardiovascular diseases in old age.
Some readers may have already tried anti-influenza drugs like Tamiflu and Relenza that can substantially accelerate the recovery and even prevent flu. These drugs went into mainstream clinical practice over the past decade and have already had a positive impact on decreased mortality from influenza.
2. The Big Data Revolution
The scientific environment has never been as exciting as it now is. Advances in computing and telecommunications forever changed the way science is conducted. There are significant streams of valuable biomedical data available freely or by way of license agreements that may be analyzed and computed to produce life enhancing results.
There are many sources these days for this valuable data, including genetic sequencing, patient and molecular imaging, patient records, clinical trial data, scientific publications, high-throughput screening data and more. Microarray and genetic sequencing experiments are becoming cheaper and broadly used. Also, Beijing Genomics Institute (BGI) recently launched an ambitious million genome project intended to sequence a million people.
Genetic sequencing data alone however has limited value. It comes to vibrant life when it has corresponding patient records, epigenetic data, gene expression data, time series blood work analysis, drug response and the like. Many parameters can be correlated from these sources of data to find new disease markers, develop preventative programs, personalize treatment protocols, find new drugs and improve doctors' decision making.
It says a lot that almost every large multinational computer company has a department focused on healthcare and medicine. IBM launched a unique supercomputing project called Watson to apply novel techniques in data processing and machine learning to improve decision-making in almost every area of knowledge. Watson became most famous for winning the "Jeopardy" competition in 2011 against some of the most proficient humans on the planet, although one of the program's main applications will be in the healthcare field. One day it may be possible to show Watson the patient's record and ask for a diagnosis and a treatment strategy.
And in the not so distant future we will have AI-like machines that not only provide advice on how to treat a patient but also develop personalized therapies. Improved decision-making will certainly lead to better outcomes, increased survival rates and, by extension, longer lifespans.
3. Accelerating Funding Trends
Most of the advances in biomedicine start with a government grant or corporate funding. After the project is funded, it goes through years or even decades of experiments before the results are published and move into pre-clinical validation. The publication process itself may take a year and pre-clinical validation may take another few years. But the real holdup lies in the several phases of clinical trials that may last decades and cost billions. An average new cancer drug has six years of research behind it before it gets into clinical trials and spends eight to nine years in clinical trials before it reaches the clinic. But even after the clinical trials, the drug may be prescribed only for certain conditions, and it will take decades to propagate into other clinical uses.
To study the coming revolution in biomedicine, we developed one of the largest online databases of published biomedical grants that typically precede scientific publication and clinical trials by many years. We classified the projects in this database by their relationship to aging research (www.agingportfolio.org), and we were stunned at how much money had been pouring into aging and age-related research over the past 20 years.
Out of about one trillion dollars spent on research over the past 20 years, at least $60 billion are expected to yield some longevity dividends. And in 2011, China announced a program to invest the equivalent of over $300 billion into biomedicine over the next five-year period, making the US and European funding pale in comparison.
These longevity dividends will prolong the lifespans of the majority of the people in developed countries, including the two generations that are due to retire within the next twenty years.
4. China Assumes a Lead Role in the Race
China tends to build things on a grand scale, and this particular project is no exception. Construction of a massive medical research center, dubbed "China Medical City," is taking place in Taizhou, a city on the banks of the Yangtze River, about 150 miles northwest of Shanghai. When completed, China Medical City will span over approximately 25 square kilometers (about 6,000 acres, or 10 square miles). That's a little less than half the size of Manhattan, or roughly the size of San Francisco from the Golden Gate Bridge east to the Bay Bridge and south to Golden Gate Park. It will be a hub for international research, and will house centers for R&D, international conferences, exhibitions, manufacturing and related support facilities. Several international hospitals will be integrated into the project to attract patients from around the world -and new learning through the patients.
The China Medical City is just one example. The largest genetic sequencing center, BGI, mentioned earlier, led by a brilliant Chinese scientist, Huanming (Henry) Yang, is located in Shenzhen. Located in three factory buildings provided by the government, it not only provides contract sequencing services to Harvard, Stanford, MIT and other top academic and commercial institutions in the U.S. and around the world, but it is also working on ambitious projects of its own, including genetic modification of plants and animals, drug development and innovative diagnostics. To provide another example that demonstrates the aggressive mindset of the Chinese and how fast they have caught up, the nascent field of non-invasive prenatal diagnostics was pioneered by the US-based company Sequenom, which launched its test commercially in November of 2011. At around the very same time, if not a little earlier, BGI launched a similar test and performed more prenatal tests based on next-generation sequencing technology than all of the US companies combined.
While most regenerative medicine advances have originated in the United States and the European Union, future advances are more likely to come from China, the same nation that brought us some of the world's oldest medicines. Zhou Qi, chief scientist with the stem cell research project at the Chinese Academy of Sciences, says they have progressed faster in stem cell research than any other nation over the past 10 years. "We are now close to the day when we will be able to hail a breakthrough in this important technology. China needs five to 10 years to shift from basic research to clinical application and another 10 years to realize a large-scale clinical application."
5. Massive Convergence of Technologies
In 1993, only two decades ago, if I were to put a phone on a table -plus a photo and video camera, a desktop PC, a calculator, a voice recorder, a cassette player, a TV and a VCR- and tell you that all of those will one day fit into a tiny glass box that you can carry in the palm of one hand, you will probably simply smile incredulously. Your smile would widen even further if I then told you that this small crazy gadget would put you in touch with billions of other "gadget" carriers all around the globe.
In biomedicine, we already have all the tools that are necessary to extend life. We are at the stage where we are laying all our components on a table, just as we did in 1993. All of the life-extending biomedical discoveries that will be put to clinical use will result from the massive convergence of technologies. Cellular reprogramming and tissue and organ engineering incorporate thousands of biomedical discoveries made in the narrow areas of science and technology. These range from the fields of refrigeration and bioreactors to reagents and materials.
3D Bioprinting, which is a revolutionary new field which endeavors to build new organs using the patient's own cells, uses a device similar to the inkjet printer. It is a prime example of the many areas of scientific research converging and evolving in tandem. It brings together materials scientists to produce biopolimers and gels, molecular biologists to regulate the cellular processes, cell biologists to grow cells, tissue engineering scientists to design the organ structure, robotic engineers to build bioprinting machinery, programmers to write software, imaging professionals to ensure quality control and medical doctors from many fields to facilitate clinical application.
At the risk of this sounding like science fiction, a U.S. publically-traded company called Organovo already demonstrated viability (proof of concept) of applying 3D bioprinting technology to produce some of the most complex tissues such as liver. Vladir Mironov, one of the pioneers of 3D bioprinting and head of a group called Center for information Technology Renato Archer, Campinas in San Paolo, Brazil, brought together a multidisciplinary international team to develop a machine to print bone and cartilage right on the operating table. The project not only resulted in a working prototype undergoing pre-clinical testing, but it also brought into the fold many experts from seemingly unrelated fields who are now striving together for yet more ambitious projects.
6. Health Consciousness
Smoking and obesity are the major preventable contributing factors to the loss of function and to the preponderance of disease and mortality. Despite the continuing growth of the fast food segment and the dramatic increase in obesity in the United States from 1990 through 2010, the populations of the developed countries are finally reverting to healthier lifestyles. Government policies and public campaigns started paying off and, additionally, tobacco consumption has been decreasing steadily over the past 40 years. In the US alone the per capita cigarette pack sales have fallen steadily, and as of 2009, they were 35% lower than in 1999, per a report on smoking consumption by the Centers for Disease Control and Prevention.
Most fast food outlets also started providing energy value information for their foods and started introducing lower-calorie items into their menus.
The obesity epidemic in the US is likely to further curb down as the non-discrimination and acceptance campaigns make an increasing number of people take a full measure of the foods that have harmful effects to health.
It is likely that the trends towards healthier lifestyles will provide the populations of the developed countries with the time needed for the biomedical advances to catch up and extend their lives beyond the limits imagined by their parents.
7. Advances in Screening and Diagnostics
Genetics play a key role in our resilience to stress and disease. The past two decades brought a revolution in both screening and diagnosis, and the two areas that stand out and are rapidly entering our lives are genetic screening and electronic biosensors.
Perhaps the most famous example of the use of genetic screening for prevention is Angelina Jolie's decision to undergo a preventative double mastectomy after her test results indicated a near-certain risk of breast cancer.
One of the leaders in genetic screening is 23andMe, a company started by the wife of the founder of Google, Anne Wojcicki. The company managed to get the cost of screening of almost one million single nucleotide polymorphisms down to a very accessible $99. They also provide individual disease risk estimates, individual response to drugs and carrier status for a variety of diseases.
For some of the people born over the past two years, genetic screening was performed before they were even born. It is now possible to sequence the whole genome of the embryo at the prenatal level way before it is born -or even developed- using a simple draw of the mother's blood.
Thousands of electronic devices have been developed to monitor almost every aspect of our behavior and health. A regular smart phone can be used to diagnose diseases by analyzing a picture of the birthmark to recognize melanoma patterns, perform a time series analysis, monitor activity patterns and perform many other diagnostic and screening functions. The ubiquitous devices like Fuelband, Fitbit and UP help monitor movement, activity, sleep patterns and diet and exercise, while more advanced multi-sensor devices like the Basis B1 watch and Scandu Scout with multiple sensors can monitor heart activity, temperature and even moisture. As the amount of data gathered using these devices increases, it may be possible to predict diseases using activity and other patterns. It is only a matter of time before these devices add more advanced sensors performing biochemical analysis of sweat, saliva, blood and urine. They will help diagnose and prevent problems long before they occur.
8. Artificial Organs
Organ transplantations that were unimaginable to most people less than a century ago are already mainstream procedures. Heart, liver and kidney transplantations that were the prerogative of only a select few highly-skilled experimenting doctors at the top-tier medical university hospitals are now performed in thousands of hospitals worldwide.
Artificial limbs have been around for centuries although nowadays we see amputees not only performing mundane daily tasks, but successfully competing in Olympic sports. Artificial organs are already omnipresent and range from brain pacemakers improving the activity of the brain, to dialysis machines performing kidney functions.
Just as in every field of technology, we also see in biomedicine the convergence of countless technologies, with many experiments that combine cellular technologies with artificial implants. For example, the artificial heart valves may be incubated with the patient's own stem cells in a bioreactor before transplantation to improve the outcome.
The real low hanging fruit in aging research that will extend lives in the near future is regenerative medicine. Bioengineered organs made from patients' own cells, cell therapies and drugs that accelerate regeneration are already a reality in mice and even in humans.
In 2011, Dr. Paolo Macchiarini, working at the Karolinska Institute, recently gave a lecture to my students and performed several successful trachea transplantations. The tracheas were made using the decellularized scaffolds from diseased donors and repopulated with the patient's own cells. These procedures were successfully replicated in several countries, including Russia. Dr. Macchiarini and his collaborators also developed artificial scaffolds eliminating the need for donor organs.
Beating heart tissue, liver, kidney and bladder were all made in bioreactors outside of the patients' bodies over the past decades. Some of these organs were already successfully transplanted into animals.
Once these advances converge and reach the clinic, we will, without a doubt, see significant increases in human lifespans.
9. Cellular Reprogramming
In 2012, Professor Shinya Yamanaka was awarded the Nobel Prize for Physiology or Medicine for his work on a method for reprogramming mature cells into the embryonic-like stem cells called the Induced Pluripotent Stem Cells (iPSC). Those can be turned into other cell types. Since the publication of this method in 2006, thousands of scientists from all over the world applied it in their laboratories and developed alternative reprogramming protocols. At present, using the iPSC in the clinic has proven risky as these cells tend to become cancerous, but the proof of concept for cellular reprogramming stands firm. Research is on the way to developing therapeutically-viable methods for taking cells all the way back to the embryonic state or taking just a few steps back -or to the side- without even getting to the embryonic state.
One of the brilliant and highly admired scientists from Scripps, Professor Kristin Baldwin, who considers herself a neurobiologist, created live mice from the mesenchymal stem cells. In 2008, she created mice from iPSC. The mice developed cancer and died early, but the proof of concept had been established. Cloning an organism from just one skin cell using iPSC became a reality.
I followed up with one of the outstanding scientists in China, who continued Prof. Baldwin's work running tens of expensive parallel experiments and managed to produce mice cloned from iPSCs that lived just as long as the donors of the cells. It may be possible to produce therapeutically viable iPSCs using similar protocols, although the process can be greatly accelerated through increased funding, closer collaboration between doctors and scientists, and by allowing limited but accelerated and less expensive trials in patients that do not have any other choice.
Turning these technologies into therapeutic life-extending applications is just a matter of time.
10. Life Extension in Model Organisms
There are about 1800 genes that have been studied and linked to longevity in model organisms -about 300 human genes- out of over 20,000 genes. In reality, there are less than 100 gerontogenes that have been actively studied and that have demonstrated an increase in lifespan when overexpressed or mutated. Most of these known gerontogenes relate to the organism's ability to respond to stress and to survive starvation, heat, radiation and toxic chemicals.
For millions of years, evolution wanted living beings to reproduce, compete and take care of -and then vacate the place for- offspring. It favored species that could survive longer when starved and built in mechanisms to slow down metabolism and launch expensive damage control protocols that in many cases resulted in increased longevity.
While the primate experiments did not yield significant results, experiments in yeast, worms, flies and mice showed that animals live substantially longer on caloric restriction. Interventions in the metabolic regulatory pathways that are responsible for stress response produced organisms that live significantly longer.
Scientists are already close to understanding the genetic and molecular basis of several mechanisms for life extension in animals, and it will soon be possible to develop interventions to extrapolate these results into humans. In fact, some of these interventions may already be in clinical use. Metformin is a pharmaceutical that works on metabolic regulatory pathways. It shows life extending effects in model organisms, and it is today in the mainstream clinical use as a diabetic drug.
11. The Renaissance of Gene Therapy
The first revolution in genetics that occurred in the 1960s and 70s produced a generation of gene hunters who proceeded to clone genes at an accelerated rate. The promise at the time was that gene therapy will provide cures for almost every disease known to man. Just like with stem cells, gene therapy acquired a stigma following several early clinical failures, and just like with stem cells, this field is re-living a current renaissance and will result in life-extending treatments in the near future. Over a thousand trials involving gene therapy and genetically-modified cells were conducted worldwide over the past decade, and some of those treatments are already entering the clinic.
A major breakthrough was made in the late 1990s when Andrew Fire and Craig Mello discovered a novel mechanism for gene silencing called RNA-interference. This allows gene expression to be suppressed a-la-carte. Just like the discovery of the iPSC in stem cells, the discovery of the RNAi in 1998 resulted in one of the shortest time lapses between the discovery and the award of the Nobel Prize in 2006. Today RNAi is used to study genetics in thousands of laboratories worldwide, and there is little doubt that it will propagate into clinical use in the near future. Several companies are commercializing the technology, and new delivery methods are being developed.
One of the main causes of cancer and many age-related diseases is the accumulation of genetic instability. In some cases a mutation in just one gene can lead to fatal consequences, in others many genes must break to cause disease. As our understanding of the genetics of aging and longevity improves, it will be possible to use gene therapy not only to dynamically fight and prevent disease, but also to maintain genetic stability and combat stress.
12. Advances in Physical Chemistry and New Materials
We have all heard about the harmful effects of free radicals and how antioxidants may be helpful in scavenging these harmful molecules. But these free radicals are the byproducts of energy production and also regulate hundreds of vital processes in our cells. In 2006 the Oxford scientist, Dr. Michael Schepinov proposed a dramatically new concept for combating oxidative stress. Instead of using excessive amounts of antioxidants, it may be possible to fortify the organic compounds (lipids, amino-acids and sugars) that make up membranes, proteins and our DNA in different places. These could then resist the attacks of free radicals, but still maintain normal function.
The idea is as simple as coating the metal in your car with zinc and paint instead of keeping it away from air and water. It involves substituting some of the hydrogen in the organic molecules with the heavier isotope deuterium to strengthen the molecular bonds. Schepinov teamed up with the former director of the Human Genome Project, the world famous biophysicist Dr. Charles Cantor -as well as with several other brilliant scientists- to form a company called Retrotope, which tested the technology in yeast, worms and mice. Their starting point was to reinforce the essential organic compounds like omega-3 and some of the amino acids that we do not make by ourselves but only take through diet -i.e. the essential building blocks of vital proteins and lipid membranes.
When this and other technologies involving novel materials propagate into clinical practice, human lifespans will in all probability increase.
13. Patient Empowerment: Crowd Medicine, Personalized Science, Medical Tourism and Telemedicine
The Internet, social networks and globalization gave birth to the new concepts in medicine that were previously not possible. When faced with a medical condition, many patients turn to Google, social networks or patient forums to analyze the possible treatment options. And whether doctors like it or not, some patients will get educated about their conditions, and they will develop their own opinions about the treatment strategies they wish to pursue.
Just recently, Dr. Stephen Coles, a professor at UCLA and the founder of the L.A. Gerontology Research Group (GRG) -a forum and newsletter for gerontologists- was diagnosed with pancreatic cancer, the same kind of cancer that killed Steve Jobs. A task force was formed to investigate ways to combat his cancer and test the effectiveness of a variety of drugs on his type of cancer cells. A crowd founding initiative was set up in a matter of months, and research was undertaken in the US, Germany and France to help Dr. Coles and to identify new ways to tackle this rare but dangerous cancer.
Platforms like PatientsLikeMe not only enable patients to get a broader view of what is possible with regards to their disease, but to also act as massive clinical data aggregators analyzing clues to attain effective personalized treatments of diseases and diagnostic techniques.
Other trends include telemedicine and medical tourism that substantially increase our freedom to choose medicine and level the board for self-pay patients. For patients who can afford it, it is now possible to consult, evaluate and get treated by the doctors in the country of their choice -for example in Israel or China, where some of the advanced procedures may already be legal.
These new concepts help the patient take more control over his or her possible treatment options. They engage patients in research and increased medical knowledge so that in time there will be faster growth in citizen science, accelerated propagation of the discoveries into the clinical stage and increased lifespans.
Accelerating aging research that extends healthy productive lifespans seems to be in everyone's best interests. There are few people on this planet who, given the choice to live longer and healthier lives, would choose to age and gradually succumb to disease.
Up until recently however, the many failed promises of scientists made many of us weary of accepting the possibility of the interventions that may take us way beyond the lifespans of our parents and grandparents.
Well, now is a good time to open up to these possibilities and get actively involved. Accelerating aging research now springs from realities that are deeply embedded in the urgent needs of vast populations of aging people in the developed world.
Aging populations in the developed countries are now the single biggest threat to the global economy. People who are retiring today and who are due to retire in the next decade are going to live extraordinarily long lives due to the advances in biomedicine and the recent propagation of these advances into the clinical setting. But prior to these new realities of longer lifespans taking a strong hold worldwide, there will be a period of a decade or two where myopic, debt-burdened governments, continue with the current social security and healthcare systems. They will thus increase the burden of the retired population on the rest of the economy.
The developed countries, led by the US, EU and China must, in record time, start a coordinated program to increase healthy productive lives of the two generations that are nearing retirement. Failing to have success in that endeavor will result in the whole world experiencing several decades of economic decline and possible collapse. The need for a coordinated program to combat aging is no longer an altruistic initiative -it has become a real and vital economic necessity.
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