Download Aging with tech support – the promise of new

Aging with tech support
– the promise of new
technologies for longer
and healthier lives
September 2016
Authored by:
Amit Agarwal
Axel Baur
Martin Dewhurst
Tom Ruby
Pasha Sarraf
Shuyin Sim
2
Aging with tech support – the promise of new technologies for longer and healthier lives
4Foreword
5
Living longer and healthier lives:
A McKinsey perspective
12Infographics:
Breakthroughs supporting quality aging
14 Reading between the lines:
Unlocking the secrets of aging
with better data insights
18 Upgrading health:
Enhancing human longevity with
regenerative medicine
24
An interview with Michael May, CEO, Centre for
Commercialization of Regenerative Medicine (CCRM)
25 Inventing Cybermedicine:
Redefining “medicines” with
advanced technologies
29
An interview with Kris Famm, President, Galvani Bioelectronics
30 Rebooting the system:
Engineering cells to help the body fight disease
35
An interview with Christopher A. Klebanoff, M.D.,
Center for Cell Engineering and Department of Medicine,
Memorial Sloan Kettering Cancer Center
36 Changing the fundamentals:
Rewriting the source code to enhance lives
41Acknowledgements
Aging with tech support – the promise of new technologies for longer and healthier lives
3
Foreword
Amit Agarwal
Axel Baur
Tom Ruby
Pasha Sarraf
Shuyin Sim
In recent decades, medical science has shifted from curing the human
body to strengthening it. Diseases like smallpox and polio that once
plagued the world have been eradicated or are on the verge of being
eradicated. Since the 1800s, the average human life span has nearly
doubled. And the achievements of the past are quickly being dwarfed by
today’s advances. In some countries reaching 100 years old may soon
be commonplace. Science is rushing forward, not only in expanding
human longevity, but also in enabling healthier lives from crib to crypt.
Medical breakthroughs are taking human healthcare to new levels. For
example, scientists have been able to re-engineer immune cells and
direct them to help fight cancer. Looking ahead, a similar approach
could be used to treat a wide range of diseases. Genome editing has
the potential for combating and correcting genetic diseases, such as
sickle cell anemia, which cost hundreds of thousands of lives each year.
In addition, regenerative medicine, 3D printing, advanced sensors, and
data analytics are just some of the areas that can help medical science
deliver longer and healthier lives.
But as we rush toward these laudable goals, we must also consider the
broader implications. Already, a growing global population is straining
our vital resources, such as air, water, and space. Longer life spans
and healthier lifestyles may only exacerbate the problems. Developing
countries, which lag behind richer ones across all health metrics, could
benefit disproportionately from advanced medical technology, but often
don’t have the resources or infrastructure to provide access.
This compendium explores some of the exciting advances being
made in medical science that are already benefiting patients, as well
as breakthroughs that are likely in the coming years. It also brings into
the discussion some of the thorny topics around equitable access and
sustainability. Other systemic changes required to support longer lives
are also raised but are not the focus of this compendium. Our hope that
the conversations it helps to start can lead to some of the answers to
these difficult questions.
4
Aging with tech support – the promise of new technologies for longer and healthier lives
Living longer and healthier
lives: A McKinsey perspective
Amit Agarwal
Axel Baur
Tom Ruby
Pasha Sarraf
Shuyin Sim
In the science fiction universe of Star Trek, Mr. Spock exhorts those he meets to “live long
and prosper,” but are these goals mutually exclusive? Recent and expected breakthroughs
in medical science have moved such questions from the theoretical to the practical. Modern
medicine is allowing mankind to live longer and healthier, but unless broader implications – to
the environment and global society generally – are considered, prosperity might prove more
elusive.
Humanity stands at the cusp of a healthcare revolution that will eclipse the achievements of
past centuries in its speed and impact. Scientific and medical breakthroughs, often pushed
by big data analytics, have the potential to increase human life spans significantly while
improving the overall quality of life. Medicine is moving quickly from a focus on reacting to
disease and injury to one that emphasizes stronger and healthier bodies.
As medical and scientific researchers march forward the broader implications of longer,
healthier lives require questioning. Such questions must be considered not to halt or slow
progress, but to prepare for and mitigate any harmful consequences. Longer, more active
lives will consume more resources – food, water, energy, and space – and supply is not
infinite. In addition, the shift requires a different approach to how healthcare is delivered,
and businesses and other organizations must operate differently as well. Public health
officials, corporate leaders, investors, entrepreneurs, and other stakeholders must grasp the
relevance of such concerns to create a sustainable future for healthcare and the planet.
In this paper, we consider some of these longer range implications by first examining
advances that have already improved healthcare generally, as well as those on the brink of
significant breakthroughs. Second, we consider how best to distribute the benefits of these
advances to developing countries so that medical science can deliver the greatest overall
impact on longevity and quality of life. And, finally, we examine more broadly, the overall
impact of these advances on global sustainability.
Scientific advances enable longer and healthier lives
Over the past two centuries, the average human life span has almost doubled, increasing
from less than 40 years in 1800 to a global average of about 70 today. Human longevity was
given a sharp boost in the late 19th Century from a better understanding of the role of germs
in the spread of disease and, later, the discovery of antibiotics. Safer urban sewage systems,
more secure food supplies, and improved education, among other factors, contributed
greatly to longer, healthier lives during this period. Humanity, in general, has moved over the
past 200 years from a primordial fight for mere survival against external adversaries to an
internal battle to manage health and fitness.
Looking forward, modern technology will soon allow us to overcome diseases and
conditions considered incurable today (Exhibit 1). For example, regenerative medicine holds
the potential to recreate a spinal cord to overcome spinal cord injuries or malfunctions.
Advances in the understanding of the human genome and gene therapy are enabling and
accelerating the treatment of genetic mutations that was inconceivable only a few years
ago. Technologies being developed will enable 3D printing of lungs, hearts, and kidneys to
overcome organ failure.
Aging with tech support – the promise of new technologies for longer and healthier lives
5
Exhibit 1
Innovations that will
support longer lives
Gene therapy
Regenerative medicine
$30
795
Cost of editing 1 gene
using CRISPR;
conventional methods cost
more than $5,000
Sensor technology
6-8
months
Innovation cycle for new
and improved sensor
technology, compared to
3-4 years in the past
Regenerative medicine
therapies in clinical trials
for cell, tissue, organ
replacement
Artificial intelligence
40
million
Number of scientific
documents IBM Watson
can read in 15 seconds to
deliver a diagnosis
3D printed organs
20
People die every day waiting
for compatible organs for
transplant; 3D-printing uses
patients’ cells
Robot-assisted surgery
30
percent
Increase in number of robotic
procedures performed every
year
In addition, chronic diseases that are now difficult to manage will be fought with very different
methods. For instance, diabetes could be managed using an electronic skin patch that
detects glucose levels in sweat and automatically discharges drugs through micro-needles.
RNA-based technologies, taking advantage of the body’s natural machinery, could lead to
treatments that require much less administration, for instance injections only once or twice
a year for conditions as commonplace as high cholesterol, in effect creating a cholesterol
vaccine. Bioelectronics that selectively stimulate the nervous system are being developed
to activate a body’s own systems to manage autoimmune and neurological degenerative
conditions.
Modern data analytics also help practitioners break from the traditional approach to medical
care. A collaboration bringing together insurer WellPoint, the Memorial Sloan Kettering
Cancer Center in New York, and IBM, using its Watson computing system, offers a powerful
illustration. Sloan Kettering estimates that only 20 percent of the knowledge that physicians
use to diagnose a cancer patient and prescribe treatment relies on trial-based evidence.
The Watson supercomputer, on the other hand, can sift through millions of pages of medical
evidence covering decades of treatment history to provide a diagnosis and treatment options
within seconds.
The possibilities from these breakthroughs are wide-ranging. For example, genetic
fingerprinting, possibly at birth, could signal a predisposition for specific disorders or
syndromes. Constant monitoring through sensors that record vital statistics and biomarkers
could provide an early warning of some impending conditions, such as a heart attack or
stroke, and treatment could be delivered before the condition is triggered and permanent
damage inflicted. Post-treatment behaviors and conditions could be monitored to improve
treatment outcomes. Real-time feedback would help ensure that patients are following
6
Aging with tech support – the promise of new technologies for longer and healthier lives
their regimens and alert them and perhaps medical staff if there are any lapses. Evidencebased medicine, enabled by big data analytics, can reduce the levels of waste resulting from
incorrect or incomplete diagnoses.
These innovations will also raise new social and moral challenges that will need to be
addressed. For one, there are ethical risks from directly intervening in the genome. As
Siddhartha Mukherjee argues in his recent book, The Gene: An Intimate History, we cannot
be sure that as our ability to correct and coerce our DNA increases, society will show
restraint from trying to create superior versions of humans. Second, an older society will have
implications on economic productivity and the affordability of western social benefit systems.
Our ability to keep people alive might come much earlier than our ability to give older people
productive, higher quality lives, and the burden of an ageing society might get exacerbated
well beyond the levels seen today.
While it will still take several years for these advancements to reach patients, many are likely
to be available sooner rather than later. These advancements could help create healthcare
systems that not only react to problems as they appear, but incorporate preventive measures
and predictive models that help individuals and health authorities stay ahead of problems
before they develop. These advancements will also raise legitimate concerns, which need to
be addressed to manage unintended consequences.
Delivering true impact across the globe
Modern healthcare innovations will undoubtedly increase life spans and improve the
quality of life for the people they reach. In a practical sense, however, because of costs and
infrastructure shortfalls, these advances will likely arrive in the richest parts of the world
well before they get to the poorest. But to achieve the greatest impact – for instance, to
noticeably extend average life spans globally – modern medicine must find ways to reach into
developing economies, overcoming barriers to equitable access.
The benefits of bringing medical innovations to the developing world can be illustrated with
simple arithmetic. To increase global life expectancy by five years only by targeting the
developed world, the average life span in the richest countries would have to increase by
more than 20 years from an average that is already more than 80 years. In contrast, the same
result could be accomplished by increasing the average life span in the poorest half of the
world by just seven years, from 66 years to 73 years, which would still be much lower than
the current average life span in the richest countries.
Much of the medical technology needed to address the disease burden in developing
economies already exists. Governments are working to make this technology accessible,
but many developing countries lack the resources to deliver on their ambitions. For instance,
in 2012, there were three physicians for every 10,000 people in Indonesia, a country that
has resolved to provide universal health coverage by the end of the decade. This compares
to an average of 33 physicians per 10,000 people in member states of the Organisation
for Economic Co-operation and Development (OECD). Between 6,000 and 7,000 new
physicians are licensed each year in Indonesia, and at this pace OECD standards would
not be reached for decades. Similar infrastructure shortfalls are also seen in hospital beds,
nurses, diagnostics labs, and elsewhere.
Aging with tech support – the promise of new technologies for longer and healthier lives
7
Given these challenges, developing countries will need to create a different model for
delivering healthcare than that used in richer nations. In Exhibit 2, we lay out a bolder vision
for what this might be. In this model, patients will still have access to universal healthcare
coverage, but they would be encouraged to track their activities and vital statistics using
monitoring devices issued by a public or private insurer. These devices would link to the
patient’s electronic medical records and the data would be used to predict emerging health
problems.
Exhibit 2
A bolder vision for
healthcare delivery
Diagnostic
labs
Physicians
Hospitals
Apps
Selfdiagnosis
tools
Health plans
Smart phones
Patient
Public health
managers
Sensors
Remote care
Genomic
data
Pharmacies
DIGITAL MEDICAL RECORDS
In such a system, healthcare practitioners would analyze the data and prescribe treatment,
focusing on preventative care and minimizing the need for expensive hospital stays. The role
of general hospitals would diminish further as home-based care becomes more feasible
under improved patient monitoring and remote care systems. Rural and remote populations
would also be connected and have access to higher quality physicians through telemedicine
or remote care tools. Health plans or insurance agencies would analyze the incoming data
more broadly to identify disease and health-risk patterns that might help practitioners detect
and treat conditions sooner and better.
A model like this could help to significantly improve healthcare quality across several
dimensions. It leans on evidence-based medicine, ensuring that services delivered are
founded on the best scientific knowledge and tailored to individual needs. Its primary focus is
on timely, preventative care, reducing delays that may permanently compromise health. The
model also does not require the expensive and time-consuming development of human and
physical infrastructure to reach underserved populations.
8
Aging with tech support – the promise of new technologies for longer and healthier lives
The challenges in realizing this vision are immense. Many of the technologies needed are
still several years away from the market. Although funding needs may ultimately be lower
than traditional models, public and private insurers may be unwilling to make the significant
upfront investments to build infrastructure in exchange for future savings. New or expanded
capabilities, including data scientists and medical specialists, would be needed, and
physicians would need to incorporate new capabilities into their roles, such as interpreting
data analysis and basing decisions on data. Ultimately, the biggest challenge may be in
shifting the attitudes of consumers to pay for and participate in such a model. Legitimate
privacy and safety concerns are raised by the prospect of an individual’s medical information
being available to public or private institutions, and consumers may distrust such a model
and balk at paying for it.
Perhaps surprisingly, developing countries may be in an advantageous position to overcome
these challenges. Many developing countries don’t have expensive legacy infrastructure,
which they might be reluctant to retire, and could invest directly into the new model. Several
developing countries already have widespread digital connectivity, a pre-requisite for such
a model. For example, The Future Health Index, published by Dutch medical technology
company Royal Philips, showed that developing markets have been faster to embrace digital
technology and data sharing than developed ones. And finally, the demand for affordable
universal healthcare amid funding and resource constraints could make compromises on
personal privacy more acceptable in developing countries, especially if strong safeguards are
in place to prevent misuse.
The impact on global sustainability
Even facing challenges of equitably allocating healthcare advancements, it is easy to become
dazzled by the potential for science and technology to improve and prolong our lives. But
advances in longevity and quality of life have a price. A more crowded planet with more
demands on its resources will likely exacerbate the strain on the environment. By taking a
step back, industry participants can consider the effect of healthcare advancements on local
and global ecosystems and even question whether these scientific advancements will truly
deliver longer and better quality lives.
Already under existing population projections, food and water will become constrained
resources in the medium term. The United Nation’s Food and Agriculture Organization
estimates that by 2030, humans will need almost 20 percent more food compared with
requirements in 2015 as a result of global population growth and dietary changes. To deliver
this, the supply of arable land must more than triple, but adding to the supply of arable land
means reversing the trend that’s seen the amount of arable land and agricultural yields
declining over the last several decades. Demand for water is expected to increase by more
than 50 percent by 2030, and meeting this demand will require a greater increase in supply
than realized in the last 20 years (Exhibit 3).
Aging with tech support – the promise of new technologies for longer and healthier lives
9
Exhibit 3
Challenges in
ensuring sufficient
food supply for
future populations
Demand
Food
Supply
Kcal consumption p.a.
Quadrillion (1015)
Incremental agricultural land needed to
meet increase in food demand1, Million ha
9
8
175-220
+18%
+178249%
63
Water
Incremental supply needed to meet
water demand1, Billion m3
Global water demand
Billion m3
2,200
6,900
+53%
4,500
Energy
World primary energy2 demand
Mtoe
13,300
2015
16,500
2030
+139%
900
Incremental supply needed to meet
energy demand, Mtoe
+24%
4,400
1990-20103
3,300
-26%
2010-20303
1 Calculated as incremental supply plus replacement rate; does not tie to total demand as it does not include efficiency gains
2 Energy form found in nature that has not been subjected to any conversion or transformation process
3 For energy supply, data reflects 1990-2012 increase and 2012-2030 increase respectively
SOURCE: McKinsey analysis
Further, human development has caused unprecedented environmental damage. The World
Wide Fund for Nature (WWF) estimates that 230 million hectares of forest will disappear by
2050 under current trends. Some also argue that irresponsible land and water use, pollution,
and overharvesting could lead to a sixth mass extinction, with half the world’s species of
plants and animals potentially going extinct between 2000 and 2100.
The loss of biodiversity and environmental destruction will lead to large economic losses, for
instance by eliminating vegetation that contributes to flood control and hampering pollination
of crops. Other losses can also be significant, such as the opportunity costs of medications
based on plant and animal substances left undiscovered. Also, biodiversity provides direct
benefits to mental and physical health, with an increasing number of studies demonstrating
improved health outcomes and cognitive abilities for individuals exposed to nature.
Several ideas are being explored to improve resource use, such as the circular economy
in which governments and companies strive to create a closed loop for resources where
everything is reused rather than discarded. Rotterdam, for example, has established a fresh
seafood distribution hub, using new technology that helps avoid spoilage losses. The city
has built networks of manufacturers, producers, and recyclers to improve recycling rates
and ensure greater reuse of copper found in discarded electronics. These circular economy
initiatives and others have reduced waste levels with, for example, the amount of electronic
waste being incinerated in Rotterdam dropping by more than 50 percent.
10
Aging with tech support – the promise of new technologies for longer and healthier lives
Similarly, advanced analytics are being applied to optimize food production and supply
chains. In 2007, the amount of food wasted globally equated to yields from 1.4 billion
hectares of agricultural production. Cutting such losses would provide enough food to feed
a billion people. Improved weather forecasting, demand planning, and the management of
products near their expiration, among other areas, could bring enormous social, economic,
and environmental benefits. For example, the French start-up Phenix connects supermarkets
with expiring food stocks to agencies and consumers that could use them. The platform
allows supermarkets to save disposal costs, uses consumable products more effectively,
and alleviates some of the social and environmental burden of waste.
While such sustainability initiatives remain young, they should be pursued in parallel to
advances in medical science. History shows that human innovation has regularly stretched
our ability to make more productive use of the earth’s resources. As longevity and quality of
life slowly improve over the coming years and decades, sustainability innovations must also
be implemented to assure that mankind can survive longer and healthier lives.
Conclusion
It would be difficult to argue that healthier, longer lives are undesirable. But all participants in
the healthcare industry must understand and contemplate the broader implications of these
aspirations. To live long and to prosper, mankind must address resource constraints and
craft an equitable distribution of the many benefits of medical advances.
Amid exciting healthcare advances, leaders and investors cannot lose sight of opportunities
for global impact through investing in and spurring innovation in equitable and sustainable
development. Medical advancements are arriving quickly, and so must initiatives and
technologies that expand medical access to the developing world or clear obstacles to living
longer and better, such as improved food management, greater use of renewable energy,
and the development of smart cities.
Amit Agarwal is an associate partner in McKinsey’s Singapore office, Axel Baur is a senior
partner in the Tokyo office, Tom Ruby is a consultant in the Boston office, Pasha Sarraf is a
partner in the New York office, and Shuyin Sim is a consultant in the Singapore office.
¨
¨
¨
Aging with tech support – the promise of new technologies for longer and healthier lives
11
Infographics: Breakthroughs
supporting quality aging
Scientific
breakthroughs in
the past have been a
key factor of human
longevity increase
Expected lifespan at birth
Years
2003
Human
Genome
Project
90
80
70
60
50
40
1954
First organ
transplant
1870
Germ
Theory of
Disease
1796
First
vaccine
30
Today
Global avg.
~71 years
1998
Methods
for deriving
stem cells
developed
1928
First
antibiotic
MID1800s
Modern sewage
systems
Future
innovations
20
10
0
1800
And its role will be
even more important
for challenging future
ahead …
1900
Leading causes of death
2000
Present day
World’s aging population
In 2050, one person in three will be over 65
Ischemic heart
disease
and it comes with consequences
Stroke
Chronic obstructive
pulmonary disease
?
Growing
healthcare
spending
Increasing
incidence of
dementia
HIV/AIDS
Diabetes
mellitus
12
Aging with tech support – the promise of new technologies for longer and healthier lives
Growing burden on
social welfare
systems
Emerging medical
breakthroughs will
continue to support
longer lives
Gene therapy
Regenerative medicine
3D printed organs
7,000
795
20
Number of rare diseases
without treatment today
that could be addressed
by genome editing
Human genome sequencing
228
thousand
Stakeholders have
to come together
to bring out next
generation of
medicine
Estimated number of
human genomes
completely sequenced in
year 2014, by researchers
around the globe
Regenerative medicine
therapies in clinical trials
for cell, tissue, organ
replacement
Robot-assisted surgery
Artificial intelligence
40
million
30
Number of scientific
documents IBM Watson
can read in 15 seconds to
deliver a diagnosis
THE ENABLER
Encouraging development of
favorable environment for
facilitating and strengthening
partnerships within healthcare
innovation ecosystem
People die every day waiting
for compatible organs for
transplant; 3D-printing uses
patients’ cells
percent
Increase in number of robotic
procedures performed every
year
THE ACCELERATOR
Pushing through development of
solution for the remaining technical
challenges through broad network of
close partnerships with biotech /
pharma companies
COLLABORATIVE
INNOVATION
THE INVESTOR
Ensuring access to emerging
medical technology for all through
innovative business models and
collaboration with government, i.e., risk-sharing
Aging with tech support – the promise of new technologies for longer and healthier lives
13
Reading between the lines:
Unlocking the secrets of aging
with better data insights
Daniel Cohen
Tom Ruby
Robin Tang
Since the sequencing of the human genome first hinted at the promise of precision medicine,
the “quantified self”—the vast streams of data generated by consumers and patients—has
grown exponentially. We have come a long way in our quest to improve human longevity by
turning these data into more-precise care.
Drug doses could be calibrated to match an individual’s physiology; public-health
interventions, such as early disease screening, could be targeted at people with high-risk
genes; devices could spot the early-warning signs of conditions like arrhythmia and epilepsy;
and social-media data could reveal indications of depression. Prevention being better than
cure, the ultimate prize would be to nudge people toward wiser choices about food, exercise,
and the environment to help them live longer and healthier lives.
Where are we? Starting out, with challenges ahead
As we start out along the path to precision medicine, we face three main challenges. First
we must collect data through electronic medical records, genome databases, mobile health
devices, and other means. Then we must connect the data, both by aggregating data silos
to achieve scale and by linking data of different kinds, such as clinical records with genomes.
Finally, we need to make sense of the data, through powerful algorithms and analytics as well
as through healthcare systems that can translate insights into interventions.
Collecting the data. Massive amounts of data are being created as hospitals adopt
electronic records, payors amass claims data, DNA sequencing costs fall, and consumers
adopt devices. But these data have only yielded limited clinical insights. First, step counts
and self-reported questionnaires do not provide real clinical information; better ways of
Exhibit 4
Integrated databases
will increase insights
exponentially
Only large, integrated databases will lead to a deep understanding of the multiple causes of a disease
High
In classic trials, only very obvious disease
causes can be detected, such as causes of
preventable mortality after surgery or from
hospital complications such as pneumonia
In registries and large cohort studies,
subtle causes can be detected, such as the
impact of hormone-replacement therapies on
cancer rates
Today’s large databases may be able to
detect weak but significant causes, such as
genes that increase the risk of diabetes or
schizophrenia or predict a patient’s response
to medications
When population-scale integrated data
become available, it may be possible to
perceive the link between diseases and
behavior, diet, and environment
Level of
confidence
in link
between
disease
and its
causes
4
3
2
1
Confidence
level needed
for clinical
decisions
Low
Low
High
Strength of link between a disease
and its causes
14
Aging with tech support – the promise of new technologies for longer and healthier lives
measuring symptoms and progress are needed to make data actionable. Next-generation
health devices show great promise, providing information on vital signs (Xiaomi iHealth),
invasive measurements (CardioMEMS), brainwaves (SmartCap, EMOTIV), or posture (Lumo
Lift). Second, more data needs to be collected on non-Western populations through systems
such as the China National Genebank and Japan’s Tohoku Medical Megabank. If these
databases could be made as clinically robust as classic clinical trials, their size would drive
powerful insights (Exhibit 4).
Connecting the data. Getting to the necessary kind of scale calls for data-sharing alliances.
Genomics players have led the way with global partnerships such as GenomeAsia 100K and
the Global Alliance for Genomics and Health, but other kinds of data lag. For example, most
electronic health records cannot be shared between hospitals, limiting the ability to analyze
them at scale. Connecting internationally is more challenging; even the European Union,
which has encouraged data interoperability, lacks coordinated standards for health data.
Next, different kinds of data must be linked. Large databases linking genomics and clinical
data are necessary to generate insights on the causes of diseases. But deep-seated
cultural barriers have meant that partnerships between the various owners of healthcare
data—hospitals, insurers, pharmacos, and diagnostics companies—have been rare. Some
genome databases, such as Human Longevity’s and Genomics England’s, are tied to
medical records, and some pharmacos are working with hospitals, as Regeneron does with
Geisinger Health System (Exhibit 5). But many more such partnerships are needed, as are
technological solutions. Even the leading electronic-record provider in the United States has
no field for entering a patient’s gene variant, for instance.
Exhibit 5
Databases with highquality genomic and
clinical data are being
created
NOT EXHAUSTIVE
High-pass
whole
genome
Million Veteran Program (US)
Garvan Institute (Australia)
Veritas (US)
Korea Biobank Network (Korea)3
Completeness
of genome
sequence
Genomics England (UK)
GenomeAsia 100K (Singapore)
China National Genebank (China)
Low-pass
whole
genome
Exome only
Human Longevity (US)
Regeneron (US)
Tohoku Medical Megabank (Japan)
Oncology Precision Network (US)5
WuXi NextCODE (China)
ExAC (many sites)1
Kaviar (many sites)2
Database size
(individuals)
Limited
panel or
microarray
Ancestry (US)
Molecular
data only
Limited
(eg,
questionnaires)
deCODE (Iceland)
Popgen (Germany)
Genomic Data Commons (US)4
23andMe (US)
Partial
clinical
records
Population
diversity
Complete
clinical
records
Current
(10,000)
Low
Projected
(100,000)
Medium
Extensive
monitoring
(eg, from
clinical trials)
High
Next
generation
data (e.g.,
microbiome)
Comprehensiveness of clinical data
1MIT-based consortium of 17 US and EU databases
2Includes UK10K, 1000 Genomes, the Wellderly Project, Genome of the Netherlands, and others
3Based at Korea National Research Institutes of Health
4National Institutes of Health and University of Chicago partnership
5Syapse, Intermountain, Providence, and Stanford University
Aging with tech support – the promise of new technologies for longer and healthier lives
15
Making sense of the data. Finally, connected data must be analyzed to detect subtle
signals. Which genes predispose patients to diabetes? What constellation of labs and vitals
can spot hospital-acquired infections? Which behaviors might presage addiction? The
volume and complexity of these data call for machine-learning algorithms, which is why
Hangzhou Cognitive Care in China, Bumrungrad International Hospital in Bangkok, and
Manipal Hospitals in Bangalore have partnered with IBM Watson, and why many artificialintelligence start-ups have focused on healthcare. Some players concentrate on special
populations, which may increase signal detection; examples include Biogen’s use of Fitbits
with multiple-sclerosis patients and Novartis’s introduction of ViaOpta apps for the visually
impaired. But algorithms for handling complex data are in their infancy, so making sense of
data is likely to present an even greater challenge than collecting and connecting it.
What’s needed? Roles in quantified healthcare
Different players will take on a variety of roles in collecting, connecting, and making sense
of data.
Who’s collecting the data. Data will come from many sources. First, hospitals and
physicians must take the lead in adopting electronic records, especially interoperable ones.
Second, device companies must develop applications that deliver value to patients, such as
St. Jude’s CardioMEMS for heart failure or Apple’s Gliimpse for viewing health records. Third,
as the cost of sequencing plummets, makers of machines will become providers of answers,
as Illumina demonstrates with its investment in GRAIL and its Illumina Accelerator. Finally, all
these players will increasingly partner with aggregators of behavioral data, such as socialmedia and search companies.
Who’s connecting the data. Key roles in bringing together complex data will be played by
alliances such as the Oncology Precision Network and tech innovators like IHiS, GeneInsight,
and Health Catalyst. Some companies will provide analytics as a service for payors and
providers, as IBM Watson and Flatiron Health do, while others—especially the makers of
diagnostic tests —will work on a pay-for-insight basis. New business models may emerge,
such as equity partnerships and outcomes-based risk-sharing agreements.
Who’s making sense of the data. The translation of data into health interventions will largely
be done by the physicians writing the prescriptions and the hospitals that are the sites for
procedures. Pharmacos will pursue smaller but more valuable markets for personalized drug
discovery, as Amgen did in buying deCODE, an Icelandic genome database. Consumers—
and not just patients—will be able to shape their health decisions through platforms like
Welltok that create personalized wellness plans. In turn, payors and governments can offer
people data-driven incentives to nudge them toward better choices.
Who can help? Policy makers and business leaders
There are three main ways that governments, health authorities, and businesses can promote
the development of precision medicine.
Changing incentives. National health systems, large employers, and private insurance will
need to shift toward value-based care, which incentivizes doctors and hospitals to monitor
16
Aging with tech support – the promise of new technologies for longer and healthier lives
patients more closely. For example, Singapore’s Agency for Integrated Care, encourages
care coordination and monitoring. Others include the National Health Service in the United
Kingdom and the Veterans Health Administration in the United States, both of which are
building large genome databases.
Enabling partnerships. Governments should continue to structure incentives to encourage
providers to use electronic health records, especially ones that are interoperable or shareable
between systems. They can also help quantified populations to reach scale by convening
groups of business leaders and other stakeholders to develop data-sharing models.
Businesses, especially pharmaceutical companies, should look to build creative partnerships
that reduce the incentives to keep databases siloed, perhaps through arrangements to split
the royalties from any products of a combined database. Extending all these partnerships
internationally will have even more impact for patients and businesses.
Shifting attitudes. Public health systems could save money and increase impact by
sponsoring data-driven approaches to one-size-fits-all healthcare policies such as screening
and vaccination. Governments can encourage citizens to participate in efforts to collect
genome and clinical data by explaining the potential benefits. Both they and business leaders
must bolster patients’ confidence by being transparent about privacy practices and investing
in cybersecurity. Finally, health-education systems can teach new generations of physicians
how to work in a quantified healthcare system.
Where are we heading? The impact on human longevity
The ultimate goal is to link all these data streams, including genomics, with electronically
enabled healthcare providers that are integrated with payors and others across the
healthcare continuum. This would create a learning healthcare system, in which algorithms
continuously observe the results they achieve and refine themselves in real time. Quantified
selves would feed data into a quantified population, which in turn adjusts the way it takes
care of each individual. Through such tailored precision healthcare, we may be able to
improve both longevity and quality of life.
Daniel Cohen is a consultant in McKinsey’s San Francisco office, Tom Ruby is a consultant
in the Boston office, and Robin Tang is a consultant in the Southern California office. Pasha
Sarraf is a partner in the New York office who assisted in editing the compendium.
¨
¨
¨
Aging with tech support – the promise of new technologies for longer and healthier lives
17
Upgrading health:
Enhancing human longevity
with regenerative medicine
Angela McDonald
Eric Soller
Yukako Yokota
Regenerative medicine promises to be a game changer for the treatment of a wide range of
conditions and diseases—from diabetes and heart disease to spinal cord injury. Scientists
have made important breakthroughs in using bioengineering and human stem cells, placing
a flood of commercial products within reach in the next decade. Harnessing the potential
of regenerative medicine could reduce patient morbidity and mortality, driving significant
quality-of-life and economic benefits around the globe.
Many credit the ancient Greeks with first describing the ability of the adult human body to
spontaneously regenerate, or recover its normal structure and function, after severe injury.
Prometheus the Titan, immortalized in Greek mythology, was punished by the gods for
stealing fire and doomed to have an eagle tear at his liver every day—only to have his liver
restore itself every night so the torment could be repeated. Today, we know that a human
liver can completely regrow itself after injury, starting with as little as 25 percent of its original
mass1.
Unlike the liver, in most cases when a human adult organ suffers a traumatic acute or
chronic insult, it leads to a devastating loss of function and, in many cases, death. Recently,
the convergence of several important technological advances—including a deeper
understanding of the biological conditions that lead embryonic stem cells to “follow their
fate” and differentiate into fully functioning adult cells, as well as the sequencing of the human
genome—have pushed medicine into a new era, in which advances in bioengineering and
other therapeutic approaches promise to extend regenerative capabilities.
The nature and pace of scientific advances in regenerative medicine are creating immense
excitement, and their projected long-term implications on human health are being recognized
globally. In 2012, Dr. Shinya Yamanaka, a Japanese scientist, was awarded the Nobel Prize
in Medicine for his discovery of the ability to convert an ordinary human skin cell into a stem
cell, from which new cells can be grown to rebuild injured, damaged, and diseased tissue
in the body. Researchers are now experimenting with regenerative therapies for diseases
ranging from macular degeneration to alopecia. And, in the next 10-20 years, we may see
regenerative medicine therapies for complex degenerative diseases, including Parkinson’s
and Alzheimer’s diseases (Exhibit 6).
The first wave of regenerative medicine has already proved the capacity of stem cells to
rejuvenate human tissue and cure disease. In recent years, more than 50 regenerative
medicine related products have been used in the clinic2. These are predominantly basic
forms of regenerative therapy that do not rely on bioengineering or genetic manipulation
of stem cells. For example, more than one million patients suffering from cancer and other
blood disorders have received bone-marrow transplants, which contain resident stem cells
1Michalopoulos, G.K., DeFrances, M.C., et al., “Liver Regeneration,” Science, April 4, 1997, Number 5309, Volume 276, pp. 60-66.
2Preparing for Regenerative Medicine, McKinsey Quarterly (2015).
18
Aging with tech support – the promise of new technologies for longer and healthier lives
Exhibit 6
Projected evolution of
regenerative medicine
therapies: New
therapies will target
more complex organs
and diseases in the
next 10-20 years
Regenerative medicine today
(today and over the next 5 years)
Regenerative medicine tomorrow
(in the next 10-20 years)
Affected
organ system Disease
Skin
Alopecia
Eye
Wet and dry
age-related
macular
degeneration
Stargart
macular
dystrophy
Retinitis
pigmentosa
Eye
Eye
Teeth
Dental
implants
Skin
Burn
treatments
Bone
Bone injuries
Cartilage
Cartilage
injuries
Problems that have been solved
▪
▪
▪
Ability to grow and manipulate stem cells
Generation of patient-specific stem cells (i.e., iPSCs)
Genetic modification of cells
Disease
Parkinson’s
disease
Huntington’s
disease
Amyotrophic
lateral sclerosis
(ALS)
Affected
organ system
Brain
Brain
Brain
Cystic fibrosis
Chronic obstructive pulmonary
disease
Lungs
Lungs
Myocardial
infarction and
heart failure
Heart
Crohn’s disease
Intestine
Spinal cord injury Spinal cord
Spinal muscular Spinal cord
atrophy
Liver failure
Diabetes
Liver
Pancreas
Osteoarthritis
Cartilage
Problems that need to be solved
▪
▪
▪
Overcome cell immunogenicity
Delivery of cells into complex organ compartments
Functional integration of cells into complex organ tissue
(e.g., neural networks within the brain)
capable of re-creating the entire human blood system3. Skin stem cells are also being used
to treat burn victims, expediting the wound healing process. Additionally, scientists have also
developed “spray on” skin approaches to treat large wounds (a small sample of the patient’s
own cells are placed at the wound site enabling wound healing to occur in days versus weeks).
Another promising area of research is in the treatment of Type 1 diabetes. Researchers
have previously demonstrated that transplanting pancreatic islet cells from cadavers into
human patients can restore insulin production. However, donor material is scarce. Eventually,
cadaver tissues could be replaced with pancreatic islet cells created from stem cells. Using
stem cells as a starting material, doctors could create a large supply of islet cells that would
be immunologically matched to an individual Type 1 diabetes patient. Restoring pancreas
function in Type 1 diabetes patients using islet-cell transplantation could provide a cure for
these patients, dramatically improving quality of life, and relieving them of daily insulin injections.
Diabetes is only one of many diseases being targeted by regenerative medicine applications.
Several advances—including a better understanding of different stem cell classes present in
the adult body, the discovery of human embryonic stem cells in 1998, and the subsequent
development of cell reprogramming technology—have led to an explosion of experimental
regenerative therapies. Nearly 800 stem cell-based regenerative therapies are in clinical trials
today (Exhibit 7)4. In the next ten years, many regenerative therapies will enter the market,
potentially changing the course of treatment for a range of diseases that today often lead
to disability and early death. The global R&D pipeline grew by approximately 15% per year
3Fred Hutchinson Cancer Research Center.
4clinicaltrials.gov.
Aging with tech support – the promise of new technologies for longer and healthier lives
19
Exhibit 7
Regenerative
medicine therapeutic
pipeline
795
Regenerative
medicine therapies
in clinical trials
40% in
oncology
10% in
cardiovascular
disease
(including human neural
stem cell treatment for
Parkinson’s Disease)
212
Phase II
492
91
6 bone regeneration
trials
13 ophthalmology trials
(including human embryonic
stem cell-derived treatment
for AMD)
25 rare
disease trials
14 trials in cartilage
degeneration
16 trials in cardiovascular disease
Phase III
10% in CNS
11 pulmonary disease
trials
22 CNS trials
Phase I
48 oncology trials
>500
6 CNS trials
Regenerative medicine
therapies in preclinical
development
SOURCE: Clinical Trials.gov; Alliance for Regenerative Medicine; PharmaProjects; Nature Reviews
from 2006 to 2013, demonstrating a strong pipeline of future potential therapies 5. Growth
observed in the regenerative medicine clinical trial pipeline over the past 10 years has been
enabled by four critical scientific and technological advances:
1. The ability to grow and manipulate stem cells in the laboratory. Processes are
improving to create differentiated cellular “products” (such as pancreatic islet cells) of
sufficient quality to be transplanted into human patients.
2. Genomic approaches. Advances in our understanding of genetics have allowed
scientists to manipulate the human genome and create patient-specific stem cells, using
the patient’s own skin, with the ability to turn into any cell type in the adult body.
3. A greater understanding of cellular-level processes. Technological advances have
allowed scientists to understand how specific cells function and thus have enabled them
to create functional cells that mimic cells in our bodies (for example, stem-cell-derived
heart cells that beat in a petri dish).
4. The development of more sophisticated delivery approaches. Next-generation
biomaterials allow scientists to move beyond creating single-cell layers in a petri dish to
creating complex, three-dimensional “living tissue” that can be implanted using minimally
invasive surgical techniques.
5Preparing for Regenerative Medicine, McKinsey Quarterly (2015).
20
Aging with tech support – the promise of new technologies for longer and healthier lives
Multiple regenerative medicine strategies are being tested in clinical trials. Cell replacement
therapies aim to treat disease by replacing damaged tissue with stem cell-derived tissue
(for a patient with heart disease, for example). Alternatively, “trophic” therapies can be used,
in which stem cells are implanted into a patient to deliver therapeutic factors to damaged
tissues. Cell replacement therapy is the holy grail of regenerative medicine—and science
is getting closer. Preclinical and early clinical trials are providing proof-of-concept support
for this approach. For example, US researchers have shown heart function improvement
following a heart attack in nonhuman primates 6. Additionally, researchers working for the
London Project to Cure Blindness at Moorfields Eye Hospital recently reported positive
results for the first two macular degeneration patients treated with retinal tissue generated
from human embryonic stem cells.
Additional advancements are being made to drive the regenerative medicine industry forward
(Exhibit 8) including advances in cell manufacturing, which will accelerate the transition
of regenerative medicine therapeutics to large-scale human clinical trials. To this end, the
Canadian government has partnered with GE Healthcare to construct a $40 million cell
manufacturing center, aimed at commercializing cell therapies. Regulators have also begun
to prepare for regenerative medicine products by designing explicit regulatory pathways.
In late 2014, Japan passed a number of regulations that could shorten the approval process
for regenerative medicine products to three years, versus the standard seven- to ten-year
development timeline for conventional drugs. The European Medicines Agency’s advanced
6James J. H. Chong et al., “Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts,”
Nature, June 12, 2014, Number 510, Volume 7504, pp. 273-7, nature.com.
Exhibit 8
Growing global
regenerative medicine
activity: timeline of
important events
Government
investments
California
electorate passes
Proposition 71,
providing $3B to
establish the
California Institute
for Regenerative
Medicine (CIRM)
2004
Scientific/
clinical
advances
2005
Yamanka
and
Thomson
labs derive
iPSCs
Connecticut
approves
$100M
in funding
for stem cell
research
over 10 years
2006
New York establishes
NYSTEM with $40 M
Korea establishes the
Global Stem Cell and
Regenerative
Medicine Acceleration
Center with an annual
budget of $47M
2007
2008
Provenge (Dendreon), prostate
cancer product marketed in the US
Geron initiates human embryonic
stem cell clinical trial for spinal
cord injury; and first pluripotent
stem cell therapy injected in
humans
Canadian government
invests $16M to
establish the Centre
for Commercialization
of Regenerative
Medicine (CCRM)
Stem Cells Australia
receives $21M
2009
2010
Trinity
Evolution –
musculoskeletal
defects
(allogenic)
ACT receives IND for human
embryonic stem cell therapy for
macular degeneration
Regulatory
EMA establishes a
regulatory framework for ‘Advanced
Therapy Medicinal
Products’
President Barack
Obama reverses
Bush ban of
federal funding for
human embryonic
stem cell research
Innovate UK
establishes
£70M Cell
Therapy
Catapult
network
2011
2012
Yamanaka
receives Nobel
Prize for creating
iPSCs
First report of
safety and
potential efficacy
of pluripotent
stem cell-derived
cells in humans
Japan invests
$1B into the
Research
Center Network
for Realization
of Regenerative
Medicine
2013
Approval of
first clinical
trial using
iPSCs; RIKEN
Institute’s
(Japan) iPSCderived
treatment for
age-related
macular
degeneration
2014
Canadian Federal
government,
CCRM and GE
Healthcare
announce $40M
investment in cell
manufacturing
facility
2015
2016
Viacyte’s Phase I trial
for human embryonic
stem cell based Type I
Diabetes treatment
approved
Asterias’ Phase I/II trial
for human embryonic
stem cell based spinal
cord injury therapy
approved
Japan passes the Act on the Safety of Regenerative
Medicine, and the revised Pharmaceuticals, Medical
Devices, and Other Therapeutic Products Act
Health Canada releases cell therapy ‘guidance
document’ for the preparation of clinical trial
applications for the use of cell therapy in humans
EMA releases report
outlining concerns
and regulatory
changes for cell and
gene therapies, and
tissue-engineered
products.
Recommendations
SOURCE: Nature Reviews Molecular Biology; Nature Biotechnology
Aging with tech support – the promise of new technologies for longer and healthier lives
21
therapy medicinal products scheme is creating a pathway to market for regenerative
medicine therapies developed by small and medium-size companies that would otherwise
have trouble finding the resources to satisfy the conventional regulatory process.
Significant financing and infrastructure hurdles remain. Regenerative medicine therapies
need to move beyond the “valley of death”—the phase between preclinical validation
and proof of concept where many new therapy ideas falter, usually because they lack
financing. Stakeholders, including federal and state governments around the world, are
coming together to nurture a global regenerative medicine ecosystem, in which clusters
are working together to tackle these hurdles (Exhibit 9). Organizations such as the UK Cell
Therapy Catapult, Canada’s Centre for the Commercialization of Regenerative Medicine,
and the California Institute of Regenerative Medicine are supporting translational research
to help commercialize regenerative medicine products. Integrated approaches to financing
regenerative medicine involve governments, universities, philanthropists, venture capitalists,
and biotechnology and pharmaceutical companies.
Exhibit 9
Global regenerative
medicine ecosystem
2
3
Toronto 10
Boston
5
New York
9
13
14
6
Legend
1 California Institute for Regenerative
Medicine
2 Centre for Commercialization of
Regenerative Medicine
3 Centre for Advanced Therapeutic
Cell Technologies
4 CGT Catapult Manufacturing Centre
5 Harvard Stem Cell Institute
6 Harvard University Department of
Stem Cell and Regenerative Biology
NOT EXHAUSTIVE
7
8
9
10
11
12
13
14
15
Lonza Asia
Lonza Europe
Lonza North America
McEwen Centre for Regenerative Medicine
Kyoto University Centre for iPS cell
research & application
Progenitor Cell Therapy
Progenitor Cell Therapy
The New York Stem Cell Foundation
WuXi AppTec
Maryland
UK
4 8
1
12
California
15
11
Japan
7
Cell manufacturing
Companies
Network and
Consortiums
Research centers
SOURCE: McKinsey analysis
There are also business issues. Competing in regenerative medicine will likely require
global scale to optimize the cost of goods and manufacturing. New distribution models
for cell therapies, pricing optimization, and sophisticated approaches to modeling the
long-term economic benefits of these therapies will be critical for market access. Given
the complexities around these business issues in the context of regenerative medicine,
the global regenerative medicine ecosystem is coming together. Collaborative innovation
is building global momentum and will continue to expedite the development process of
regenerative medicine therapeutics (see interview box).
22
Aging with tech support – the promise of new technologies for longer and healthier lives
It has been nearly 30 centuries since the myth of Prometheus first celebrated the powers
of human tissue regeneration. Now that regenerative medicine is closer to reality, what will
the impact be? How many lives will be saved? How will the routine use of stem cells to repair
organ damage such as heart damage reduce mortality and extend life spans? By how much
will the human and economic toll of chronic disease be reduced? The global regenerative
medicine ecosystem is still working to answer these questions. However, now, 22 patients
die each day in the United States alone waiting for an organ transplant. With the advent
of regenerative medicine therapeutics, organs may be repaired before they need to be
replaced. Alternatively, we could one day “grow” replacement organs or tissues. Therapies
for spinal-cord injuries could help victims regain their mobility, reducing the $3.9 billion
annual global economic burden of spinal-cord-injury patients. Finally, it is estimated that 785
million men and women of working age are unable to work due to chronic disease or injury.7
Regenerative medicine may help some of these people get back into the labor force—driving
significant economic impact, and more importantly, improving quality of life, and driving
human longevity.
Angela McDonald is a consultant in McKinsey’s Toronto office, Eric Soller is a former
associate partner in the New York office, Yukako Yokota is an associate partner in the
Tokyo office. Pasha Sarraf is a partner in the New York office who assisted in editing the
compendium.
7International Labour Organization.
Aging with tech support – the promise of new technologies for longer and healthier lives
23
An interview with Michael May, CEO, Centre for Commercialization
of Regenerative Medicine (CCRM)
Why is now the time to invest in regenerative medicine?
The global healthcare market is stressed. People are getting older, costs are rising and we’ve been treating
symptoms of disease for decades. Regenerative medicine represents an evolution towards a new approach to
healthcare that involves combining molecules, with cells, and biomaterials. It is complex, but will enable us to treat
chronic disease and conceive of cures, which will drive significant quality of life improvement. It is the right time to
invest because we are seeing good clinical data and discussing issues like manufacturing and quality control, which
means we are truly at a point of industrialization.
How will a global regenerative medicine ecosystem advance this novel therapeutic class? What is CCRM
doing to build this ecosystem?
A global regenerative medicine ecosystem is a requirement of success, as this is one of the most complex endeavors
of human history, and happening in a capital-limited environment. A lot of expertise exists globally that can be
shared, reducing redundancy and creating synergy. Additionally, significant intellectual property exists around the
world, a lot of which gets orphaned in small markets. CCRM’s mission is about bundling intellectual property and
coordinating expertise. Our vision is to bring together top talent, and intellectual property so that it can be leveraged
into capital-efficiency and smart financing. To do this governments, academia and industry must work together to
drive the sector forward. In other words, a collaborative, global regenerative medicine network is required to bring the
promise of stem cells and cell therapy to reality.
How can we advance experimental regenerative medicine therapeutics past the valley of death?
Collaboration to achieve a “critical mass” of coordinated resources and funding is how we will get this done, built
on clinical evidence and the industrialization of excellent science. Scientists and engineers need to work together to
take the right biology and formulate it into a regenerative medicine product that can be manufactured at a reasonable
cost, with the right quality and in sufficient quantities. The global collaboration required to do this is happening now.
What aspects of the regenerative medicine business model need to be solved to advance regenerative
medicine therapies to the clinic?
First of all, each type of therapy will require a different business model. For example, patient-specific stem cell
therapies (i.e., therapies using a patient’s own cells) must address variable cell input, robust and cost-effective
scale-out of small processes for thousands of patients. These products will be hardware driven and depend on
close partnership between health delivery centers and service/tools companies. In contrast, “off the shelf” stem cell
therapies (i.e., therapies using donor cells) will have to manage scale-up, logistics and preservation issues. Global
scale-up will be different for each type. Given that many of these products will be cures, how will payors think about
reimbursement? There are still many common problems to solve. Working together as a global network is the most
capital-efficient and effective way to tackle them.
¨
24
¨
¨
Aging with tech support – the promise of new technologies for longer and healthier lives
Inventing Cybermedicine:
Redefining “medicines” with
advanced technologies
Inn Inn Chen
Colin Field-Eaton
Alexander Murphy
Bioelectronics hold great potential, but must overcome
several barriers to reach their full potential
Bioelectronics is an emerging area of medicine that uses miniaturized implantable devices to
deliver electrical stimulation to control a wide range of bodily functions. Bioelectronics and
electroceuticals, or bioelectronics aimed at replacing a pharmaceutical therapy, have huge
potential. For example, they can help in conditions such as spinal-cord injuries that cannot
be treated with conventional medicine or surgery. However, they still need to overcome
significant barriers. In particular, a much more detailed understanding of the anatomy and
function of neural circuits is needed to target treatments precisely in what can be viewed
as the neural equivalent of gene therapy. Recent advances, such as ultraminiaturized nerve
cuffs (devices that can decode and stimulate neural activity at the level of just a few nerve
cells), offer hope, but a step change in innovation will be needed to help electroceuticals and
bioelectronics reach their full potential. Although much progress can be expected over the
next five to ten years, translating this into meaningful clinical treatments for the patients with
the most complex disease states may take considerably longer.
The extent to which the electrical systems of the body contribute to healthy functioning
and disease remains underappreciated, even within the medical field. Beyond the obvious
example of defibrillating patients in cardiac arrest to bring them back to life, electrical
therapies already improve quality of life across a range of conditions. Pacemakers for
abnormal heart rhythms and electroshock therapy for depression have long been mainstays
of medical treatment.
However, the idea of using electricity to treat a wider range of complex conditions is relatively
new. It was only within the past two decades that researchers discovered the key role played
by the nervous system in immunological homeostasis. In the so-called inflammatory reflex,
the vagus nerve—the longest cranial nerve in the body—helps control the level of tumor
necrosis factor (TNF), which helps regulate immune pathways and cells.
Today, implantable electroceutical and bioelectronic devices that electrically affect this
inflammatory reflex are being tested as treatments for rheumatoid arthritis and inflammatory
bowel disease. And in the future, they could be applied to many other medical conditions
with an immunological component, such as multiple sclerosis. Just as the development
of pacemakers depended on a detailed knowledge of the electrical circuits and pathways
that lead to healthy function or disease in the heart, a better understanding of the electrical
circuits and pathways for other diseases should render them increasingly amenable to
bioelectric treatment. As this therapeutic approach is applied more widely, the lines between
medical technology and pharmaceuticals will continue to blur (see interview box).
In principle, the medical use of bioelectronics and electroceuticals (Exhibit 10) has several
advantages. First, and most important, it holds out the promise of treating conditions that
today’s drugs and medical procedures are unable to address, such as severe spinal-cord
Aging with tech support – the promise of new technologies for longer and healthier lives
25
injuries and blindness. Second, miniaturized electric stimulators have the potential to deliver
true precision medicine. Almost all drugs have a degree of systemic effect, but the precise
targeting permitted by bioelectronics could limit the number and extent of side effects.
Additionally, electrical dosing is much easier to adjust as a treatment’s effects on a patient
become clear. An electrical current can be increased or reduced far more easily than a drug
concentration, and unlike surgical procedures, the effects are reversible: the current can be
switched off.
Exhibit 10
Bioelectronics
have significant
potential and growing
investment
Definition
Bioelectronics is an emerging area of medicine that uses miniaturized implantable devices to deliver electrical
stimulation to nerves to control a wide range of bodily functions.
Electroceuticals are a type of bioelectronics aimed at replacing a pharmaceutical therapy
Illustrative examples (not exhaustive)
Restore
damaged
circuits
Replace
damaged cells
Range of
potential
applications
Select players
to watch
Modulate signals
for existing
applications
Spinal cord
injury
For patients partially or fully paralyzed, bioelectronics could be used to
bridge the injury site and restore function
Parkinson’s
disease
Dopamine-producing cells in the brain degenerate, leading to loss of
control over voluntary movements. Bioelectronics could be used to directly
communicate with dopamine-producing cells’ targets
Immunology Reduce cytokine production (cytokines help regulate the immune system)
applications and block inflammation in diseases such as Rheumatoid arthritis or
Inflammatory bowel disease
Entity
Key investors
Investment
Key objectives
Galvani
Biosciences
GSK, Verily
Up to $700M over
7 years (announced
Aug. 2016)
Develop devices to correct irregular electrical signals
underlying a number of chronic diseases (e.g.,
inflammatory, metabolic, and endocrine)
CVRx
J&J Innovation
$113M as of
August 2016
Improve cardiovascular function for patients with
heart failure
Reduce blood pressure for patients with hypertension
ElectRx
(military
program)
DARPA
$80M (announced
Aug. 2014)
Restore functionality for wounded service members,
including improving prosthetics and reducing chronic
pain
SOURCE: Company websites; press search; expert interviews
A wave of such technologies has established proof of concept and demonstrated quality-oflife improvements in select subsets of patients. However, significant advances will be needed
before bioelectronics can deliver widespread clinical impact. Exhibit 11 illustrates some
recent and ongoing efforts.
26
Aging with tech support – the promise of new technologies for longer and healthier lives
Exhibit 11
Several examples
highlight recent or
ongoing bioelectronic
efforts
“Let there be light”
Example: Second
Sight
“Tickling the
vagus nerve”
Example: SetPoint
Medical
“Hacking the
brain”
Example: Ohio
State University
Wexner Medical
Center
Description
Key lessons
Remaining barriers
Bioelectronic retinal implant
allows patients with a rare eye
disease (retinitis pigmentosa)
to regain a degree of lost sight
(e.g., perception of motion
and recognition of simple
objects)
The difficulty of developing
bioelectronics increases
exponentially with the
number of neurons or
signals involved; actual
amount of vision restored for
blind patients is relatively
modest to date
Fuller understanding of neural
circuitry at a systems level (specific
pathways and targets) is needed to be
able to more fully address complex
conditions via bioelectronics (e.g.,
restoring brain function after a stroke)
Electroceutical approach to
treat inflammation by
neuromodulation, stimulating
the vagus nerve to block TNF
production in rheumatoid
arthritis (in a pathway similar
to that of biologic drug
therapy)
Applications of bioelectronics are not just limited
to musculoskeletal
conditions like spinal cord
injury: nerves exert systemic
control over a huge range of
pathways and conditions
Devices will need further
miniaturization before they can hit
specific nerve fibers rather than the
entire nerve. Miniaturization is
particularly challenging for devices that
need to be able to sense and deliver
both excitatory (“turn on”) or inhibitory
(“turn off”) signals
Brain implant connected to a
sleeve of electrodes allows a
paralyzed man to play guitar
and perform other activities,
bypassing his damaged spinal
cord
It is likely easier to intervene
in cases where an element
of voluntary control allows
real-time feedback than in
cases involving peripheral
autonomic systems, which are
harder to influence
Even in systems that are easy to
monitor (e.g., a patient can move their
arm or they can’t), it can take years
and the support of highly specialized
expertise before interventions translate
into benefits for an individual patient
SOURCE: Company websites; press search; expert interviews; McKinsey analysis
Exciting as they are, these early examples also point to the kinds of challenges that the field
will need to overcome. However, significant progress has been made in the past decade, and
there is reason to expect still more over the next five to ten years. As we seek to understand
the basic biology of neural pathways, advances in imaging technology and computing power
have moved us closer to understanding electrical activity at a system level. Where once we
could measure activity only in a single neuron at a time, we can now monitor hundreds of
neurons, or even a thousand, at once. This allows us to understand increasingly complex
systems and points the way to new targets and pathways for therapies. But we are still a long
way from being able to fully understand extremely complex pathways, given that there are up
to 100 billion neurons in the brain.
Advances in device engineering have also opened up new frontiers for research and
therapy. For example, ultraminiaturized (~50-micron) nerve cuffs allow the targeting of very
small (dozens of axons) peripheral nerves and carry lower risk than traditional methods
of shredding or tearing fragile tissue. Advances in materials science, such as carbon
nanotubes, have allowed the production of soft, flexible electrodes that are easier and safer
to use on small peripheral nerves—like the end-organ nerves that control vascular tone and
blood pressure—because they transmit less mechanical force and are therefore less likely to
cause nerve or tissue damage.
Further technological advances will be needed to make these ultraminiaturized stimulators
practical to use. Apart from the challenge of which nerve fibers to target, it is difficult to
power and wirelessly control small devices that are used in deep tissues, as normal body
tissues cause signal attenuation. Novel approaches, such as using piezoelectric crystals
as stimulators, may be able to address this in time. However, at this early stage, most
Aging with tech support – the promise of new technologies for longer and healthier lives
27
bioelectronic applications are likely to be limited to bigger nerves that are relatively easy to
access surgically, like the vagus nerve.
Exciting times are ahead for the new era of bioelectronics and electroceuticals—and
for patients. Although considerable hurdles must be overcome, early successes have
established the potential of the promising new field of cybermedicine. It seems likely that
today’s applications have only begun to scratch the surface of what is possible (Exhibit 12).
Exhibit 12
Cybermedicine
applications will
evolve in the years
to come
Near-term
Simple, large nerves
(e.g., vagus for
autoimmune or
inflammatory conditions,
discrete spinal cord
injuries)
Example
applications
▪
▪
▪
Mid- to longer-term
Complex central nervous system
circuits (e.g., stroke, multiple
sclerosis, complicated seizure
disorders)
Smaller, relatively simple
peripheral circuits (e.g.,
blood pressure, insulin
release in diabetics,
chronic localized pain)
Device engineering hurdles
Device miniaturization to target increasingly smaller nerves
Wireless power and communication to overcome signal attenuation and
power loss in deeper tissue implants
Safety and durability (e.g., soft electrodes to limit damage to surrounding
nerves / tissues, designs to minimize heat delivery and device security /
anti-hacking)
Basic biology and medical side hurdles
▪
Problems to
address
▪
Mining and decoding neural language to enable
bioelectronic or electroceutical intervention (reading,
writing, and monitoring)
Medical understanding of diseased state neural
circuitry to identify intervention points/therapy
▪
▪
Systems level understanding of neural
circuitry
Pricing and regulatory model for
bioelectronics
SOURCE: Expert interviews; McKinsey analysis
Inn Inn Chen is a consultant in McKinsey’s Boston office, Colin Field-Eaton is a consultant
in the New Jersey office, and Alexander Murphy is a consultant in the New York office.
Pasha Sarraf is a partner in the New York office who assisted in editing the compendium.
28
Aging with tech support – the promise of new technologies for longer and healthier lives
An interview with Kris Famm, President, Galvani Bioelectronics
How do you define the field of electroceuticals and how is it different from current pharmaceuticals?
The field of electroceuticals or bioelectronic medicines is a new modality of therapeutic intervention and is a general
way to treat many diseases in a very precise manner by tapping the nerve that go to the organs that are central in that
particular disease. I see it as a new and complementary way with a whole new set of mechanisms that can be used
side by side with traditional pharmaceuticals.
Why is excitement in the field picking up now?
Many factors are coming together to make this the golden decade when we can potentially take bioelectronic
medicines from a promising biological concept to implants that can help patients: technology developments that can
lead to low power, miniaturized, wirelessly powered devices, insights that have emerged in the past two years (such
as brain mapping) which we can adapt to therapy relatively quickly, and the entry of companies (like GSK) who are
looking for the next class of therapies and willing to invest significant amounts of money over a long period of time.
What is the potential for electroceuticals in personalized medicine?
We have for so long associated personalized medicine with a patient’s genotype. But that is only one aspect of a
patient’s disease. For electroceuticals, we are closely looking at neural traffic and modulating the therapy in real
time. We are adjusting to a patient’s physiological state, not the genotype. In the long-term, when the devices are
embedded in the midst of pathophysiology, we can detect many signals and get longitudinal data to help make
better and better medicines.
What is the biggest challenge for the field?
There is a big question around how much physiology we can control with the nervous system. We have seen
significant effects in animal models, but we don’t know if this is relevant in 5% or 50% of human pathophysiology.
We have the genome sequenced down to the last letter, but we don’t have a detailed map of the nerves that go to
and from each organ. In the 21st century we will map this in one way or another and this will both open up many more
treatment opportunities and eventually define how big this field will become.
How are we bridging our basic biological understanding to create therapies?
There is a lot of innovation in this space that is getting us closer to understanding of how neural control functions.
By looking at turning up and down signaling in nerve branches and fiber sub-types in peripheral nerves we can
start gaining a better mechanistic understanding. These sort of experiments help optimize a first generation of
bioelectronics medicines.
What are some key challenges for adoption?
Electroceuticals will likely come with more risk up front, during surgery, and then a lower risk therapy profile
thereafter. Making that work for physicians and healthcare systems will be a challenge in the next 5-10 years. It’s
important to prove therapeutic benefit--that’s the first challenge. The other challenges can be pulled through if there
is convincing therapeutic benefit.
Why are you excited about electroceuticals?
Two things. When we look at the concrete biological data, it looks remarkable. The potential and line of sight to
patients is really exciting. Secondly, this is also something we believe can be catalytic. The prospect of working on
something that if unleashed in the right way will lead to many treatments and can be used over and over again is what
gets many of us out of bed in the morning.
¨
¨
¨
Aging with tech support – the promise of new technologies for longer and healthier lives
29
Rebooting the system:
Engineering cells to help
the body fight disease
Daina Graybosch
Guang Yang
In the past five years, decades of research on the immune system and its interaction with
tumor cells has paid off, as reengineered immune cells have achieved dramatic results in
treating cancer. These results have prompted huge investments that accelerated innovation.
Together, technical advances, investment, and collaboration are fundamentally changing
drug development, facilitating faster development cycles. Collaboration on a global scale
could further accelerate innovation for immune-cell reengineering, delivering benefits across
disease areas.
The computer industry offers a useful analogy to better understand what is happening with
cell reengineering. Leading computer companies have made the (often painfully disruptive)
transition from hardware to software. Today, sophisticated software codes (“patches”) can
fix hardware malfunctions, allocate hardware resources for optimal performance, and enable
even mediocre hardware to deliver high-quality results. But until now, the treatment of human
diseases has not been able to make a similar transition.
Think of the human body as hardware. Malfunctioning cells cause diseases, including cancer,
autoimmune diseases, and age-related diseases. Throughout our lifetime the body’s immune
system, our natural weapons to fight these malfunctioning cells, either prevent or correct
these malfunctions to avoid disease. Malfunctioning cells and immune failure are signs of
hardware breakdown. Remarkably, we can now successfully use simple DNA instructions
(which can be likened to software code) to reengineer human immune cells and direct them
to fight cancer cells—with spectacular results, including complete disappearance of cancer
in some cases.
These are called chimeric antigen receptor T cells (CAR-T) therapies. CAR-T involves
removing white blood cells (T cells) from a patient or a donor and adding chimeric receptors
that recognize cancer and activate white blood cells to divide and attack the tumor. The
modified cells are then returned to the patient. In effect introducing a software “patch” to
correct a hardware problem.
The evolution of CAR-T
The CAR-T process may sound easy, but it is the result of decades of trial and error in
modifying human cells. Over the past ten years, there’s been an explosion of experimental
immune-engineering therapies, with 142 in clinical trials today (Exhibit 13). Three critical
advances in science and technology led to this proliferation:
ƒƒ The enhanced ability to expand and manipulate immune cells reproducibly ex vivo
enables the production of enough stable immune cells to infuse back into the patient.
ƒƒ A sophisticated understanding of immune-cell interaction with tumors informs the
intelligent design of traits for engineered cells, including engagement with tumor cells,
efficient destruction of target cells, and measures that ensure safety.
ƒƒ Precise and efficient tools to modify genes let scientists engineer (sometimes
extensively) immune cells that have the desired constructs safely and reliably.
30
Aging with tech support – the promise of new technologies for longer and healthier lives
These advances have produced clinical benefits that stimulated further research and
investment in CAR-T therapies.
Exhibit 13
There has been an
explosion of CAR-T
clinical trials, and
most of them are
targeting CD19
Target
Trials1
Ph. 1 Ph. 1/2 Ph. 2
CD19
66
31
HER2
8
Mesothelin
7
GD2
Indications
Non-academic sponsor
24
11
B cell malignancies
13
5
3
0
Brain, breast, sarcoma, multiple
1
7
0
0
Pancreatic, breast, multiple
1
6
5
0
1
Neuroblastoma, sarcoma, multiple
1
EGFR
6
3
3
0
Brain, multiple
1
CD22
5
4
1
0
B cell malignancies
1
CD30
5
2
3
0
B cell malignancies
N/A3
GPC3
4
2
2
0
Liver, lung
2
MUC1
3
0
3
0
Multiple
1
BCMA
3
3
0
0
Multiple myeloma
1
CEA
3
3
0
0
Liver, multiple
1
CD33
2
1
1
0
Acute myeloid leukemia
N/A
CD20
2
0
2
0
B cell malignancies
N/A
ROR1
2
2
0
0
Chronic lymphocytic leukemia, multiple N/A
Liver, stomach
EPCAM
2
0
2
0
Others2
20
13
7
0
1
N/A
1Only counting trials registered on clinicaltrials.gov as not suspended or terminated, as of Sept 3, 2016; Phase 0 trials are excluded
2Each with 1 trial, including ROR1, LeY, CD133, NKG2D, T1E, CD171, Kappa Immunoglobulin, PSCA, Tri-virus, FAP, CD123,
IL13Ra2, VEGFR2, CD138, MG7, CD7, CD70, EphA2, and one trial targeting both CD19 and CD20
3Indicates all sponsors are academic hospitals
SOURCE: clinicaltrials.gov; McKinsey Cancer Center; McKinsey Center for Asset Optimization
CAR-T has had particular success targeting CD19, a protein found on the surface of most B
cells, both malignant and healthy. A host of publications—including the New York Times and
a documentary, Cancer: The Emperor of All Maladies—profiled Emily Whitehead, the first
child to undergo successful CAR-T treatment for leukemia. This six year old, whom traditional
chemotherapy had not helped, was cured by CAR-T developed at University of Pennsylvania
and derived from her own body. In 2012, Novartis formed a strategic alliance with the
university to co-develop the therapy1.
In 2015, one-year-old Layla Richards, who had not benefited from chemotherapy and a
bone-marrow transplant to treat aggressive leukemia, became the first person to receive
“universal” CAR-T, or modified T cells derived from donors. These T cells required extensive
genetic modification to eliminate the risk of foreign cells attacking the host. Months later,
Layla was pronounced free of detectable leukemia. Cellectis, the company that had provided
the cells, signed a large deal with Pfizer and Servier for rights to the treatment2.
1http://www.uphs.upenn.edu/news/News_Releases/2012/08/novartis/
2http://www.cellectis.com/en/content/servier-exercises-exclusive-worldwide-licensing-option-cellectis-ucart19-allogeneic-car-t-0
Aging with tech support – the promise of new technologies for longer and healthier lives
31
Millions of dollars in federal grants and billions of investor dollars have been pouring into
CAR-T therapy. Vice president Joe Biden has designated the University of Pennsylvania as
the official launch site for the “moon shot” program to cure cancer.
Collaboration on CAR-T innovation
Just as anyone can join the software industry, CAR-T innovation is democratizing rapidly.
Any academic medical center in the world can participate and accelerate the development
cycle: after decades of research in molecular biology, academic institutions have extensive
experience managing complex cell procedures ex vivo and experimenting with sophisticated
DNA delivery tools, such as viral delivery vectors. While most hospitals have access to
patients and their white blood cells, recent advances in gene editing, including clustered
regularly interspaced short palindromic repeats (CRISPR) and transcription activator-like
effector nucleases (TALEN), have further broadened access to highly efficient and precise
gene-engineering tools.
Not surprisingly, almost all biotech and pharmaceutical companies involved in CAR-T
development to date have affiliations with sophisticated academic medical centers. We
expect these centers to continue playing an essential role in CAR-T innovation, as they
bring unrivaled experience managing the adverse reactions that systematic activation of
the immune system might trigger—very similar to bone-marrow transplants. Indeed, most
of today’s 66 clinical CD19 CAR-T programs are sponsored by academic bone-marrowtransplant centers (Exhibit 14).
Exhibit 14
Most CAR-T clinical
trials targeting CD19
are sponsored by
academia
Acute lymphoblastic
leukemia (ALL)
Diffuse large
B cell lymphoma
(DLBCL)
Phase 1
Phase 1/2
Phase 2
Hospital sponsored
Hospital–industry
collaboration
Industry sponsored
Chronic lymphocytic
leukemia (CLL)
Multiple
myeloma1
Multiple
Lymphoma
Note: Only counting trials registered on clinicaltrials.gov as not suspended or terminated, as of Sept 3, 2016; Phase 0 trials are excluded
1 Myeloma does not express CD19 but University of Pennsylvania patient achieved complete remission with CD19-CAR
SOURCE: clinicaltrials.gov; New England Journal of Medicine; McKinsey Cancer Center; McKinsey Center for Asset Optimization
32
Aging with tech support – the promise of new technologies for longer and healthier lives
Challenges to the commercialization of CAR-T
Despite easy access to CAR-T technology, clinical-trial enrollment and execution present
major challenges. For example, the initial CD19 CAR-T programs target acute lymphoblastic
leukemia (ALL), but the United States has only about 1,000 eligible patients if the treatment is
limited to relapsed or refractory patients (768 adults and 168 children each year) (Exhibit 15).
As more clinical trials launch and advance to phases 2 and 3, requiring more patients, access
to patients in cancer centers will likely become a serious bottleneck.
Exhibit 15
Need for global
collaboration to
accelerate cures
Adult
3,250
2,180
Transplant
eligible
970
650
320
200
130
70
1,070
3,000
2,090
710
1,400
560
150
20% died
during
induction
<34 years old
>34 years old
1,370
830
690
Cured in
1L (30%)
Pediatric
Cured by
transplant
270
80
540
Refractory/ Ineligible
20%
relapsed
elderly,
for CAR
37% young
(50%
elderly)
250
770
580
190
30% died
after
transplant
2,400
First line
cured
80%
120
Transplant
eligible
Cured by
transplant
480
240
20% died
during
induction
70
170
30% died
after
transplant
Note: Most induction- and postinduction- (including transplant) associated mortality is CAR-T-eligible patients because median
onset age for acute lymphoblastic leukemia (ALL) is very young
SOURCE: Patient number and age breakdown: National Cancer Institute Surveillance, Epidemiology, and End Results (SEER)
Program; cure rate: expert interview; mortality rate: literature search
Safe execution of clinical trials requires great technical know-how. One clinical trial was briefly
suspended after three patients died as a result of rapid immune expansion. Currently, CAR-T
clinical trials are restricted to medical centers that have cell-transplant expertise and wellestablished infrastructure for intensive care units. This means the clinical-trial footprint for
CAR-T is much narrower than for hematological-tumor trials using other modalities.
Manufacturing also represents an obstacle to scaled commercialization. CAR-T production
can happen on two platforms, each bringing their own set of challenges:
ƒƒ Point-of-care manufacturing requires commercializing devices. Most current clinical
trials use on-site manufacturing in academic medical centers to retrieve white blood
cells from patients, modify the cells, and reinfuse them into patients. Medical-technology
companies with regulatory know-how will play a critical role in commercializing
automated, compliant cell-processing devices.
Aging with tech support – the promise of new technologies for longer and healthier lives
33
ƒƒ Centralized manufacturing to increase scale and improve efficiency poses supply-chain
challenges. As major players invest in centralized manufacturing, they must develop an
individual batch for each patient, cope with zero tolerance for temperature deviations
during shipping, and adhere to tight timelines. Sophisticated supply-chain capabilities will
be critical to the cost-effective commercialization of CAR-T.
We are starting to see unprecedented collaboration among pharmaceutical companies,
academia, and medical-technology companies to address the complexity of ex vivo cell
therapies, primarily in Europe, the United States, and East Asia. Global acceleration of the
system reboot will require government incentives to encourage leading US companies
to expand their global footprint or to urge local companies on each continent to address
the challenges. We predict that increased global collaboration and investment will
prompt the next wave of innovation. If we can address all the challenges associated with
commercialization of CAR-T, the door is open to a whole different world of broad applications,
beyond just hematological malignancies (see interview: Immune reengineering beyond
CAR‑T). For example, great advances are already being made for T cells with reengineered
T cell receptors that are screened to recognize patient-specific tumor neoantigens but
also pose minimal cross-reactivity to healthy tissues3. We are also starting to reengineer
immune cells that act as a micropharmacy to deliver targeted drugs based on specific local
environmental cues4. The potential for immune system reboot is immense and immune
reengineering will surely lead to longer and healthier lives.
Daina Graybosch is a senior expert in McKinsey’s New York office, Guang Yang is a
consultant in the Charlotte office. Pasha Sarraf is a partner in the New York office who
assisted in editing the compendium.
3Christopher A. Klebanoff, Steven A. Rosenberg, and Nicholas P. Restifo, “Prospects for gene-engineered T cell immunotherapy for
solid cancers,” Nature Medicine, January 6, 2016, Volume 22, Number 1, pp. 26–36.
4Leonardo Morsut and Kole T. Roybal et al., “Engineering customized cell sensing and response behaviors using synthetic notch
receptors,” Cell, February 11, 2016, Volume 164, Number 4, p. 780–91.
34
Aging with tech support – the promise of new technologies for longer and healthier lives
An interview with Christopher A. Klebanoff, M.D.,
Center for Cell Engineering and Department of Medicine,
Memorial Sloan Kettering Cancer Center
Immune reengineering beyond CAR-T
ƒƒ CAR-T is just the first wave of immune-cell reengineering. Immune-cell reengineering can be applied broadly
beyond simply hematological malignancies.
ƒƒ T cells with reengineered receptors can be a truly personalized medicine that allows destruction of each
patient’s tumor cells based on their unique mutation profile. We have shown striking proof of concept in humans
for melanoma, as well as made great strides in gastrointestinal cancers with mutations that are an order of
magnitude lower than melanoma3.
ƒƒ Immune cells can also be reengineered to deliver payloads upon specific receptor engagement4. This has
immense application potential, including releasing immune-suppressive proteins, such as IL-10, to treat
autoimmune diseases, or factors that disintegrate artery plaques to prevent stroke.
¨
¨
¨
Aging with tech support – the promise of new technologies for longer and healthier lives
35
Changing the fundamentals:
Rewriting the source code to
enhance lives
Daniel Cohen
Tom Ruby
Robin Tang
The potential benefits of genome editing are broad, and could be especially important in
healthcare. But a number of challenges still need to be overcome to bring the benefits of
genome editing, and of gene therapy in particular, to a more global scale.
We are reaching a point where we can rewire nature in fundamental ways
Genetic engineering is not new: the first genetically modified organism was created in 1972,
and the first transgenic animal a year later. However, recent breakthroughs in genomeediting technologies—particularly transcription activator-like effector nucleases (TALENs)
and clustered regularly interspaced short palindromic repeats (CRISPR)—have significantly
improved our ability to edit the genome of living organisms. By reprogramming the
fundamental code of life, we can not only exert control over genes but also modify organisms
and species, and thus shape entire ecosystems.
Genome editing has the potential to affect our lives in many ways. It could improve the quality
of our environment by allowing us, for instance, to boost crop resistance to pathogens and
raise agricultural output, to limit the spread of pathogens by reducing the population of animal
carriers, and to manage waste more effectively. It could also have a more direct impact on
human life by enabling major advances in healthcare, including the development of cuttingedge gene and cell therapies for hard-to-treat diseases such as sickle-cell anemia (Exhibit 16).
NOT EXHAUSTIVE
Environment
Better water
management
Improved
water filtering
Pathogen
resistant produces
Cheaper
fabric
Higher
agriculture
throughput
Cheaper
diagnostics
Pathogen
population
elimination
Safer
animal feed
Accelerated
drug discovery
Cheaper
antibodies
Cell therapy
Gene therapy
Organ
replacement
Small
Indirect
Direct
Impact on human health
SOURCE: McKinsey analysis
36
Healthcare
Large
Size of population to benefit
Exhibit 16
Editing genomes of
living organisms will
have a wide range
of impact on human
longevity
Aging with tech support – the promise of new technologies for longer and healthier lives
In the next decade, genome editing will prove its tremendous benefit potential in
Healthcare and other areas, but only for a small portion of the population
The ability to modify the human genome will allow us to repair virtually any gene and thus
find a cure for rare genetic disease in particular. Curing these diseases will have a profound
effect not only on patients’ life span but also on their quality of life, reducing or even
eliminating symptoms and comorbidities. Caregivers, too, will derive tremendous benefits,
as treatment alleviates or even lifts the burden of care. For those diseases with costly existing
treatments, both patients and caregivers could also see a dramatic reduction in their financial
burden. Similarly, the healthcare system will benefit if rare-disease patients no longer need
expensive lifelong treatments: the median annual cost of treatment for an ultra-rare disease is
approximately $280,000 in the United States.
In addition, gene therapy has the potential to transform our approach to treating disease.
The components of gene therapy (DNA guide, endonuclease, viral vector) have become
commodities in Life Science research, which makes the manufacturing process faster,
cheaper, and capable of being customized to the needs of individual patients. In this way, it
holds the promise of removing the barriers to precision medicine. In time, medical centers
may be able to develop their own point-of-care manufacturing facilities close to their treatment
centers and gain the ability to move in a matter of months from diagnostics to the delivery
of a tailored, new gene therapy. By contrast, the development of a new biologic therapy
not tailored to an individual patient typically takes seven or eight years. A few large medical
centers such as Stanford University are already building their own Good Manufacturing
Practice facilities for cell and gene therapy.
However, although gene therapy is likely to become available to patients in the near future,
only a fraction of the population will likely benefit for two main reasons.
First, because only a small number of diseases will gain an approved gene-therapy treatment
in the next decade, because the molecular processes at play in replacing a gene are so
complex that few clinical trials will have successful outcomes. The first gene-therapy
procedure was approved in 1990, and the 500th clinical trial was submitted to the US Food
and Drug Administration (FDA) as long ago as 2001. Yet to date, only two gene-therapy
treatments have gained international market approval: Glybera in 2012 and Strimvelis in 2016.
Moreover, of the gene-therapy clinical trials currently under way, only 110—less than 5 percent
of the total—are late-phase (Phase II or III) trials that, if successful, could lead to market
approval in the next few years.
Second, most likely only a small population of patients will benefit from new gene-therapy
treatments within the next decade, as current trials are targeting a subset of rare diseases
such as hemophilia, lysosomal storage disorder, and adenosine deaminase deficiency (ADASCID). Two main reasons explain the focus on specific rare diseases
ƒƒ Only one gene is responsible for the disease and the organ or system to repair is readily
accessible such as the liver, eyes or blood. The technology is not yet mature enough to
allow multiple genes to be targeted simultaneously or to treat hard-to-reach organs
Aging with tech support – the promise of new technologies for longer and healthier lives
37
ƒƒ The level of risk associated with the development of gene therapy is tolerable for rare
disease due to the absence of treatment or the burden of existing treatments
Similarly, beyond healthcare, some applications also have high potential benefits but
will likely have limited impact in the short term because of ethical, environmental, or
technological challenges. For instance, the application of gene-drive technology (i.e., altering
genes to reduce reproductive capacity) to limit the spread of pathogens by reducing the
population of carrier animals has met resistance because of the potential harm to those
animals’ ecosystem. A case in point is the recent protest in Miami against reducing the
mosquito population to limit the spread of the Zika virus. Other technologies that engineer
microorganisms to improve waste management or produce biofuel have had limited impact
because of unclear economics or the technical challenges of deployment at scale.
All stakeholders need to collaborate to capture more value from these technological
advances globally
To capture more value from these advances globally, two steps need to be taken: first,
develop a favorable environment for investment and market access, and second, build large
coalitions and networks to accelerate learning and solve technical challenges (Exhibit 17).
Exhibit 17
Significant challenges
remain to unlock the
full potential of gene
therapy
Getting to market
Commercial
potential
Unlocking potential
Polygenic diseases
Inaccessible
monogenic
diseases
Accessible
diseases
Challenges
Regulatory
approval
▪ Regulatory
agencies
▪ Governments
Manufacturing, supply chain
▪ Biotech
▪ Medical Centers
▪ Governments
Technical safety and efficacy
▪ Biotech
▪ Academic Medical
Pricing model
▪ Payors
▪ Governments
Centers
Target identification
▪ Biotech
▪ Academic Medical
Centers
▪ Governments
SOURCE: McKinsey analysis
Before governments approve market access, gene therapies need to meet safety conditions
and satisfy ethical considerations. To facilitate those aims, countries around the world could
cooperate in developing a common regulatory framework that defines guidelines for safety
and long-term patient monitoring. Such a framework could be based on guidance from the
European Medicines Agency (which approved Glybera and Strimvelis) or the FDA (which is
38
Aging with tech support – the promise of new technologies for longer and healthier lives
expected to approve the first gene therapy for the United States early next year). In much the
same way, ethical questions about the use of and limits on genome editing in germline cells or
embryos also need to be addressed at a global level.
Governments will need to make significant investments to allow their citizens to gain access
to expensive gene therapies. One approach is to collaborate with manufacturers to define
a pricing model that allows risk to be shared. For instance, GlaxoSmithKline obtained
reimbursement for Strimvelis in Italy via a payback-guarantee model.
The technical challenges of targeting inaccessible organs and repairing multiple genes
simultaneously will need to be conquered before the number of disease candidates for genetherapy treatment can be increased. To accelerate the development of solutions to these
challenges, a broad network of close partnerships—like the existing alliances between the
University of Pennsylvania and Biogen, CRISPR Therapeutics and Bayer, Editas Medicine
and SR-TIGET, Spark Therapeutics and Pfizer, and Intellia and Novartis—should be further
developed among medical centers, biotechnology and pharmaceutical companies, and other
members of the gene-therapy ecosystem.
Another barrier to the global impact of gene therapy on genetic disease is our limited
understanding of the genes involved. For most genetic diseases, we do not yet know
which genes need repair; in addition, which sequence of a gene to repair may differ from
one population to another. To bring gene therapy to a global scale, we will need a granular
understanding of the genetic makeup of local subpopulations. Such a challenge again
calls for a global effort to develop networks of partnerships among governments, medical
centers, and biotech and pharma companies to collect the enormous amount of genetic and
clinical data needed. As we have seen in France, the United Kingdom, and the United States,
government investment will be critical in encouraging such consortiums to form and to cover
the full range of population types.
After over three decades of development, we are seeing gene therapy gaining market
approval. Moreover, recent technological advances are accelerating the impact of genome
editing technologies on human lives, in multiple ways. Although the impact will be likely limited
in the near term to a small population, we are seeing signals of broad collaboration between
the key genome editing stakeholders that would enable a more global impact.
Daniel Cohen is a consultant in McKinsey’s San Francisco office, Tom Ruby is a consultant
in the Silicon Valley office, Robin Tang is a consultant in the Southern California office. Pasha
Sarraf is a partner in the New York office who assisted in editing the compendium.
¨
¨
¨
Aging with tech support – the promise of new technologies for longer and healthier lives
39
About McKinsey & Company
McKinsey & Company is a global management consulting firm, deeply committed to helping
institutions in the private, public and social sectors achieve lasting success. For over eight
decades, our primary objectives has been to serve as our clients’ most trusted external
advisor. With consultants in more than 100 offices in 60 countries, across industries and
functions, we bring unparalleled expertise to clients anywhere in the world. We work closely
with teams at all levels of an organization to shape winning strategies, mobilize for change,
build capabilities and drive successful execution.
Authors
Amit Agarwal
Associate Partner, Singapore
+65 6586 4852
[email protected]
Axel Baur
Senior Partner, Tokyo
+81 3 5562 2667
[email protected]
Martin Dewhurst
Senior Partner, London
+44 20 7961 5864
[email protected]
Tom Ruby
Engagement Manager, Silicon Valley
+1 408 412 4070
[email protected]
Pasha Sarraf
Partner, New York
+1 212 446 8907
[email protected]
Shuyin Sim
Engagement Manager, Singapore
+65 6586 2690
[email protected]
40
Aging with tech support – the promise of new technologies for longer and healthier lives
Acknowledgements
“Aging with tech support – The promise of new technologies for longer and healthier lives” is
written by experts and practitioners in McKinsey & Company’s Pharmaceuticals and Medical
Products Practice.
To send comments or request copies of this publication, please e-mail us at
[email protected]
Editors: Tom Ruby, Pasha Sarraf, Jill Wilder
We would like to thank the following colleagues who contributed with their expertise: Inn Inn
Chen, Ph.D., Associate in our Boston office; Daniel Cohen, Engagement Manager in our San
Francisco office; Nicolas Denis, Expert Principal in our Brussels office; Colin Field-Eaton, M.D.,
Engagement Manager in our New Jersey office; Daina Graybosch, Ph.D., Senior Expert in our
New York office; Angela McDonald, Ph.D., Associate in our Toronto office; Alexander Murphy,
Ph.D., Associate in our New York office; Eric Soller, Ph.D., former Associate Partner in our
New York office; Robin Tang, M.D., Associate in our Southern California office; Guang Yang,
Ph.D., Associate in our Charlotte office; and Yukako Yokota, Ph.D., Associate Partner in our
Tokyo office. In addition, we would also like to recognize the contribution of the McKinsey
project team, comprising of Sharmeen Alam and Nadine Mansour.
Finally, we would like to acknowledge our colleagues Martin Dewhurst, Kevin Sneader, and
Oliver Tonby for their support and encouragement along the way.
Aging with tech support – the promise of new technologies for longer and healthier lives
41
Copyright © 2016 McKinsey & Company.
All rights reserved.
This publication is not intended to be used as the
basis for trading in the shares of any company or
for undertaking any other complex or significant
financial transaction without consulting appropriate
professional advisers. No part of this publication
may be copied or redistributed in any form without
the prior written consent of McKinsey & Company.