“If we
want to make the best products, we also have to invest in the best ideas...
Every dollar we invested to map the human genome returned $140 to our
economy... Today, our scientists are mapping the human brain to unlock the
answers to Alzheimer's... Now is not the time to cut these job-creating
investments in science and innovation. Now is the time to reach a level of
research and development not seen since the height of the Space Race”
“It’s all in the mind” seems to be one of humanity’s age-old
mottos whose meaning has only grown more persuasive against the test of time. Ailments
previously deemed peripheral based purely on their symptoms are being exposed
for having deep roots in the brain as quickly as our knowledge of grey matter
is expanding, so much so that many of over 600 known neurological disorders now
top the leading disease list in the developed world (Table 1). In Europe, 38%
of the population is said to be affected by brain disorders annually[i],
whose burden in 2010 was estimated to be €798 billion, taking into account
treatment costs as well as lost productivity. And the general consensus among
physicians is—incidences of neuro-disorders, such as migraine, autism,
Parkinson’s disease and multiple sclerosis is visibly on the rise. Over the
coming years the European Brain Council has forecasted a further 20% increase
in neurologic illness in the EU[ii].
To exacerbate the problem, ageing populations have never
before borne so much impact on the global total. As cardiovascular, infectious
and oncology treatments ameliorated, so has survivability and thus the
incidence of diseases of the “old age”, such as dementia and Alzheimer’s
disease, strokes, Parkinson’s disease and progressive hearing loss. Alzheimer’s
disease and stroke have been identified as the fastest-growing threats to US
health, ahead of autoimmune disorders and diabetes[iii].
And perhaps the worst news is—Big Pharma has so far yielded
sub-optimal treatments for neurological disorders, as success rates of
neuropharmaceuticals in costly clinical trials have been excruciatingly poor in
recent years. For instance, Alzheimer's disease (AD) researchers and patients
had to face a long string of disappointments, as one promising AD therapy after
another have failed to stop, or even slow down the disease. 2012 witnessed a
fascinating race to the finish line between two anti-β amyloid monoclonal antibodies -
Pfizer/Johnson&Johnson's Bapineuzumab ("Bapi") vs. Eli Lilly's
Solanezumab ("Sola"). Both contenders tried to make history by
altering the Alzheimer's disease treatment paradigm, but ended up failing in
two of the biggest phase III studies of the year, having likely spent at least
$400 million each on the drugs’ development.
TABLE 1. LEADING NEUROLOGICAL DISORDERS IN THE US, 2010/11
Disease
|
Prevalence/
Incidence
|
Economic
Burden (incl. prod. loss) (US$)
|
Available
treatment(s)
|
Chronic
pain
|
50 million
|
635 billion
|
OTC pain relievers, anti-inflammatory
steroids, therapy (physical & psychological), Medical Devices: Neurostimulators,
Patient Controlled Analgesia
|
Depression
(major)
|
46.4 million
|
16 billion
|
Medication: Selective serotonin reuptake
inhibitors (SSRIs), Serotonin and norepinephrine reuptake inhibitors (SNRIs),
Norepinephrine and dopamine reuptake inhibitors (NDRIs), others; Medical
devices: deep Transcranial Magnetic Stimulation (TMS), Vagus Nerve
Stimulation (VNS)
|
Migraines/
cluster headaches
|
37 million
|
20 billion
|
OTC pain relievers, anti-inflammatory
steroids, tripans, ergotamines, triptan+anti-emetic combination therapy,
Botulinum toxin (Botox)
|
Hearing
loss/deafness
|
37 million
|
14.75 billion
|
Hearing aids, cochlear implants
|
Bipolar
disorder
|
5.7 million
|
42 billion
|
Mood stabilizers: Lithium, anticonvulsants,
antipsychotics; Antidepressants,; Medical device: deepTMS (under
investigation by Brainsway Israel)
|
Alzheimer’s
disease
|
5.4 million
|
216 billion
|
Cholinesterase inhibitors: donepezine, rivastigmine, galantamine;
Glutamate blocker: memantine
|
Autism
spectrum disorders
|
3.5 million
|
35 billion
|
Virtually no medication – antidepressants
occasionally used to treat symptoms; educational programs
|
Schizophrenia
|
3.4 million
|
32 billion
|
Typical antipsychotics, Atypical antipsychotics; Medical device:
deepTMS (under investigation by Brainsway Israel)
|
Epilepsy
|
3 million
|
17.6 billion
|
Anti-epileptic drugs (AEDs): sodium
valproate, carbamazepine, lamotrigine, topamax, vigabatrin; Medical device:
VNS
|
Brain/head
injury
|
1.7 million annually
|
48 billion
|
Neurosurgery, physical therapy
|
Blindness
|
1.3 million
|
Retinal prosthesis, visual cortex
neuroprosthesis (under development), stem cell therapy (under development)
|
|
Stroke
|
795,000 annually
|
38.6 billion
|
Hemorrhagic: anticoagulants, surgery; Ischemic: clot busters,
surgical clot removal (3-4-hour window); Sphenopalatine Ganglion (SPG)
stimulation (24-hour window—under investigation by BrainsGate Israel)
|
Parkinson’s
disease
|
500,000
|
23 billion
|
Levodopa; Dopamine agonists: pramipexole, ropinirole;
Catechol O-methyltransferase (COMT) inhibitors, Monoamine oxidase-B (MAO-B)
inhibitors; Medical devices: Activa® implanted brain stimulator, deepTMS
(under investigation by Brainsway Israel)
|
Multiple
sclerosis
|
400,000
|
10 billion
|
Interferon-beta-1a and -1b, glatiramer acetate, mitoxantrone,
natalizumab, fingolimod, teriflunomide, dimethyl fumarate; Stem Cell therapy:
currently in clinical trials
|
Spinal
cord injury
|
12,000 annually
|
14.5 billion
|
Neuroprosthetics, Stem Cell Therapy,
antioxidant medication (methylprednisolone, lazaroids)
|
Amyotrophic
Lateral Sclerosis (ALS)
|
5,600 annually
|
6 billion
|
Riluzole (only FDA-approved medication); Clinical trials:
Arimoclomol, tirasemtiv, NurOwn™-adult stem cell therapy (under investigation
by BrainStorm Cell Therapeutics Israel)
|
Perhaps the most significant contributing factor to the Golden Age of Neuroscience has been the rapid advancement of our understanding of this field at the basic level. Rapidly growing annual numbers of academic neuroscience publications bear testimony to the intensification of research in this sphere (fig. WE KNOW MORE
Perhaps the most significant contributing factor to the
Golden Age of Neuroscience has been the rapid advancement of our understanding
of this field at the basic level. Rapidly growing annual numbers of academic
neuroscience publications bear testimony to the intensification of research in
this sphere (fig. 1), but neuroscience success is even more evident in the
highly-publicized neuro-breakthroughs of late, and in the number of academic
and government initiatives which have been launched in recent years.
Vital signs seem to point towards the fact that the
neuroscience revolution happening today bears striking resemblance to the
biotechnology revolution circa 2000, which witnessed the tremendous
efforts to sequence the human genome and resulted in colossal leaps in spheres
such as genetic engineering and bacterial- and plant-derived production.
The President of the USA is a heavy investor this time
around, with US$ 100 million to spend in just one year on novel
neuro-technologies and brain mapping—outshined only by the EU, whose commitment
to a novel EU Brain Project was recently unveiled with a whopping €1.19 billion
pledge. One needn’t be an expert in the field to sense that something big is
happening.
FIGURE 1. NUMBER OF
NEUROSCIENCE PUBLICATIONS, 1950-2012, PUBMED[1]
The SOCIETY FOR NEUROSCIENCE (SfN) was founded in Washington, D.C. in 1969, and is now the largest professional society for basic neuroscientists and physicians in the world. SfN has been a strong advocator of academic neuroscience and has played a pivotal role in funding and investment in the basic research of grey matter.
The society receives government grants, stages annual high-profile
neuroscience meetings of over 30,000 attendees from 75 countries, and runs The
Journal of Neuroscience - the world’s most cited neuroscience journal which
publishes more research than the next five leading neuroscience journals
combined. It is of no surprise that the health of SfN is often cited as a key
indicator of the success of the scientific field itself. Over the past decade
the society has gained nearly 20,000 members from across the world, and has
grown its revenue, 23% of which originates from the scientific journal, by 10%
in just eight years (fig. 2).
FIGURE
2. SOCIETY FOR NEUROSCIENCE MEMBERSHIP & REVENUE GROWTH, 2000-2012
Basic neuroscience indicators tell a tale of a rapidly
growing R&D environment which is continuously gaining new members and
producing qualitative output. The Journal of Neuroscience has doubled
the number of publications it contains since 2001—a growth rate which is
unmatched by any other journal in the life science field, but what are the
emanating breakthroughs which scientists are so eager to share with the world?
Below are some examples of what neuroscience has accomplished in recent years.
MIND READING
Using electrodes to detect spikes in brain activity,
scientists have been able to map areas of the brain responsible for a plethora
of thoughts, actions and emotions. Back in 2007 scientists were able to predict
with astonishing accuracy whether a subject would decide to add or subtract a
number based on their brain activity in an fMRI scanner. However, already at
the dawn of the new decade fMRI brain mapping achieved a much more incredible
feat: reading and replicating vision. Subjects were asked to watch short clips
inside an fMRI scanner, whose output scientists used to externally replicate clips
of what the person was seeing. With this level of accuracy, it is only
a matter of time before mind-reading becomes as easy as, well, reading.
STILLS FROM ACTUAL CLIPS SHOWN TO SUBJECTS (TOP)
AND THE EQUIVALENT FMRI READINGS OF THE BRAIN (BOTTOM)
Image source; shinji nishimoto
Neuroscientists demonstrated their mind-reading prowess by quite literally communicating with a comatose patient with the use of an fMRI scanner. A man believed to be in a vegetative state for 12 years was able to communicate to doctors that he was not in pain, kick-starting what has since become a revolution in our understanding of the comatose state.
The occurrence caused medical books to be rewritten, as it
gave us the ability to communicate with thousands of patients previously
“trapped in their own skulls”, like Israel’s ex-PM Ariel Sharon, who has been
in a coma following a stroke seven years ago.
In January of 2013 physicians at Beersheba’s Soroka Medical Centre
announced that fMRI scan results of Sharon’s brain demonstrated significant
activity, as MRI spikes were documented in response to images and voices of
family members shown and played to the patient.
To advance fMRI matters further, researchers at Bar-Ilan
University in Israel have used the scanner to read motion signals from a
student’s brain and wirelessly transmit them to a thought-controlled robot
thousands of miles away—at a laboratory in France. The development is part of an international
initiative called “Virtual Embodiment and Robotic Re-Embodiment” (VERE). The
fMRI scannee could see a video relayed from a camera attached to the
robot, and direct the robot as he wished by thinking motion, and thus creating
certain discernible activity spikes for the robot to obey.
NEUROGENESIS and STEM CELL TRANSPLANTS FOR NEUROLOGICAL DEFICITS
"For more than a century, medical
science firmly believed that our brain
could not repair itself and that we
were born with all the brain cells we would ever have."
-Society for Neuroscience, 2007
Just six years ago aspiring neuroscientists would have been taught
that brains are born with a set amount of neurons, and, whilst new synapses (or
neuronal intersections) are able to form throughout a lifetime, new nerve cells
are no longer generated within the brain. But researchers have recently
delivered more uplifting news: neurogenesis has been documented to occur in
several brain areas: the hippocampus, responsible for memory formation, the
olfactory bulb, responsible for the sense of smell, and the subventricular
zone, which has been likened to the neuro-stem-cell “breeding ground” in the
brain. About 10,000 new neurons daily are now said to be born in the olfactory
and hippocampal areas.
Rapidly putting the newfound knowledge to use, researchers
at the University of Wisconsin-Madison have accomplished a notable feat in stem
cell research, having transformed human embryonic stem cells into
neuro-regenarative cells in the brains of neuro-deficient mice. Following
transplantation, the mice were able to regain their abilities to learn and
remember.
Once we know that adult neurogenesis takes place, it is
likely to be a matter of time before scientists elucidate the mechanisms which
guide new neuron formation, and are able to apply these to other, non-neurogenerative
areas of the brain—an accomplishment which would have tremendous implications.
NEUROPROSTHETICS and THOUGHT-CONTROLLED ROBOTS
Basic knowledge of the motor cortex has reached the level of
excellent in recent years, with thought-powered robot limbs not only doing
their owners’ precise bidding, but also offering their brains sensory input in
return. In other words, whilst neuroprosthetic wearers had to rely solely on
their vision when reaching for an item with, for instance, a thought-powered
arm, scientists are now beginning to devise cunning ways of allowing the users
to feel the object their prosthetic is interacting with. Sense-able
neuroprosthetics could utterly revolutionize this field, and have
wider-reaching implications in sectors such as gaming and technology.
Image credit: Rehabilitation Institute of Chicago
|
Every wireless technology started with a wire, and
neuroprosthetics are no exception. Normally bulky neuroprosthetic electrodes
have to be implanted into the brain, but scientists at the National Institute
of Biomedical Imaging and Bioengineering (NIBIB), part of the NIH in the US,
have built a compact, self-contained sensor which can record and relay the
activity of small groups of cells wirelessly (and invisibly). The sensor is the
size of a baby aspirin and is made of silicon containing 100 hair-thin
electrodes[i].
Not only is this technology much more compact and aesthetically pleasing than
its predecessors, but it also offers unfathomable opportunities for
thought-control of—pretty much anything—in stealth mode.
CURING BLINDNESS
|
Image credit: Martin Cleaver/AP
|
In February of 2013 a monumental breakthrough testified to
neurotechnology’s legitimacy when the first ever bionic eye received marketing
approval from the FDA. The Argus II Retinal Prosthesis system, marketed by Second
Sight Medical Products, provides electrical stimulation to the retina in
patients suffering from retinitis pigmentosa—a degenerative disease which is
caused by dystrophy of the retinal pigment epithelium. The device is a retinal
implant which relays external images to the brain by stimulating cells in the
retina via implanted electrodes.
A step further in the technology may soon be taken by Israeli Nano
Retina Inc: the company’s artificial retina technology Bio-retina incorporates
nano-size components in a tiny, flat implant that is implanted by a small
incision and “gluing” of the device to the damaged retina. The sensors
transform naturally received light into an electrical signal that stimulates
the neurons, which send the pictures received by Bio-Retina to the brain. The
technology is due to embark on clinical trials by 2015.
Success of devices like Argus II and Bio-retina also provides
immense hope for people who have been affected by blindness since a very young
age. For some time now it has been known that blind people are able to “see”
just with their brains, and a prosthetic device which detects the external
environment and generates basic images in the brain, bypassing the retina, is
only half a decade away. Currently, a team of scientists at the University of
Texas are generating a detailed map of the visual cortex, and are hoping to
begin working on a visual prosthetic device which would communicate directly
with this brain area.
SAMSUNG’S THOUGHT-CONTROLLED TABLET
Researchers at Samsung’s Emerging Technology Lab, in collaboration with the University of Texas, are exploring users’ ability to launch applications with the power of their thoughts in a novel Galaxy Note 10.1 interface. The technology would require the user to wear an Electroenchepalography (EEG) cap which would translate thought into basic functions like powering a device on and off, selecting a contact or a song from a list, or launching an application, and much more refined actions in the future.
Although the company does not intend to make a
brain-controlled phone or tablet in the near future, Samsung’s goal is to
demonstrate and ameliorate the feasibility of such an interface, which would be
particularly useful to people unable to interact with devices due to mobility
issues.
AN electroencephalography (EEG) cap, able to read brain
activity and communicate it to an electronic interface
Image Credit: Samsung
|
Although we may not see EEG-clad commuters on the bus playing
telepathic Sudoku any time soon, the recent neurotech developments herald a
quiescent truth: in this lifetime we are likelier than not to witness a world
where thought alone suffices to command the electronic power around us.
[i]
"Wireless, Implanted Sensor
Broadens Range of Brain Research." U.S
National Library of Medicine. N.p., 19 Mar. 2013. Web. 11 May 2013.http://www.nih.gov/news/health/mar2013/nibib-19.htm
[1]
The number of annual publications was extrapolated based on a publication
search on the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed
– a National Center
for Biotechnology Information, U.S. National Library of Medicine
database), using the search term “neuron”
[i]
"Growing Brain Disorders Lead
to Call for More Research." British
Neuroscience Association. N.p., 7 Jan. 2013. Web. 11 May 2013; http://www.bna.org.uk/news/view.php?permalink=SIXTE0PS9P
[ii]
"Neurological Diseases on the
Rise." European-Hospital.
N.p., 21 June 2010. Web. 11 May 2013.; http://www.european-hospital.com/en/article/7274-Neurological_diseases_on_the_rise.html
[iii]
Fox, Maggie. "Alzheimer's
Fastest-growing Health Threat, Report Says." NBC News. N.p., 5 Mar. 2013.
Web. 11 May 2013; http://vitals.nbcnews.com/_news/2013/03/05/17196908-alzheimers-fastest-growing-health-threat-report-says?lite
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