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.
Conclusion
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.
