A new blood test could detect more than 20 types of cancer, allowing the detection of cancer in the earlier stages.
The Blood test spots changes in the genes, as cancer develops. This would allow early screening of cancer, according to scientists allowing sooner treatment.
The New Blood test for cancer has 99.4% accuracy meaning just 0.6% of cases were misdiagnoses of healthy patients. The test was able to detect one-third of patients with cancer in the first stage, and three-quarters of those with stage two disease.
Scientists have pledged to speed diagnosis so that by 2028, three-quarters of cancer patients are diagnosed at these two stages. Currently, 50% of patients receive a diagnosis before they reach stage three or four.
The New Blood Test For Cancer is advancement by US scientists. This blood test looks for abnormal patterns of methylation in the DNA. According to the researchers, this is an indication of cancer.
The study found the New Blood Test For Cancer could even highlight the cancer source with 90% accuracy. It includes cancers such as ovarian and pancreatic cancer which are some of the most difficult to spot.
In the study, researchers analyzed more than 3,500 blood samples. They were in a lookout for cell-free DNA. These are a kind of DNA which enters the bloodstream after becoming detached when its parent cell dies.
The samples were taken from more than 1,500 cancer patients and more than 2,000 from healthy people without cancer.
The patient samples comprised more than 20 types of cancer, including colorectal, hormone receptor-negative breast, ovarian, gall bladder, oesophageal, gastric, lung, head and neck, multiple myeloma, lymphoid leukemia, and pancreatic cancer.
The New Blood Test For Cancer accurately detected 76% of high mortality cancers.
Within this group the test accuracy was 32% for patients with stage one cancer; 76% for those with stage two; 85% for stage three; and 93% for stage four.
According to Dr. Oxnard detecting, even a modest percentage of common cancers early could translate into many patients who may be able to receive more effective treatment
Widespread antibiotic use is largely to blame for the emergence of antibiotic resistant bacteria, which is currently one of the biggest threats to global health. Not only does antibiotic resistance already cause an estimated 700,000 deaths a year, it’s also made numerous infections, including pneumonia, tuberculosis, and gonorrhoea, harder to treat. Without knowing how to stop bacteria from developing antibiotic resistance, it’s predicted that preventable diseases could cause 10m deaths a yearby 2050.
Some of the ways that bacteria become resistant to antibiotics is through changes in the bacteria’s genome. For example, bacteria can pump the antibiotics out, or they can break the antibiotics down. They can also stop growing and divide, which makes them difficult to spot for the immune system.
However, our research has focused on another little known method that bacteria use to become antibiotic resistant. We have directly shown that bacteria can “change shape” in the human body to avoid being targeted by antibiotics – a process that requires no genetic changes for the bacteria to continue growing.
Virtually all bacteria are surrounded by a structure called the cell wall. The wall is like a thick jacket which protects against environmental stresses and prevents the cell from bursting. It gives bacteria a regular shape (for example, a rod or a sphere), and helps them divide efficiently.
Human cells don’t possess a cell wall (or “jacket”). Because of this, it’s easy for the human immune system to recognise bacteria as an enemy because its cell wall is noticeably different. And, because the cell wall exists in bacteria but not in humans, it’s an excellent target for some of our best and most commonly used antibiotics, such as penicillin. In other words, antibiotics targeting the wall can kill bacteria without harming us.
However, bacteria can occasionally survive without their cell wall. If the surrounding conditions are able to protect the bacteria from bursting, they can turn into so-called “L-forms”, which are bacteria that don’t have a cell wall. These bacteria were discovered in 1935 by Emmy Klieneberger-Nobel, who named them after the Lister Institute where she was working at the time.
In a lab, we often use sugar to create a suitably protective environment. In the human body, this change in form is typically triggered by antibiotics that target the bacteria’s cell wall, or certain immune molecules – such as lysozyme, a molecule that’s present in our tears which helps protect us from bacterial infections.
Bacteria without a cell wall often become fragile and lose their regular shape. However, they also become partially invisible to our immune system, and completely resistant to all types of antibiotics that specifically target the cell wall.
Scientists long suspected that L-form switching might contribute to recurrent infections by helping bacteria hide from the immune system and resist the antibiotics. However, it was difficult to find evidence for this theory due to the elusive nature of L-forms and lack of appropriate methods to detect them.
By- Ms. Rabia Sarvar. BSc Biotechnology. Meerut College
A still from the virtual reality system gameChange — developed to treat people experiencing psychosis. Credit: University of Oxford/Oxford VR
I’m standing in a doctor’s waiting room. A few
distressed-looking people are seated on chairs lining the walls. I turn
around to see a man blocking the entrance behind me. Suddenly, I hear
the receptionist exclaim as several paper slips are blown by a fan into
the air above my head. I grasp them and return them to the reception
desk.
For a moment, I consider walking over to the other side of
the room. But this isn’t real. I’m actually in the office of clinical
psychologist Daniel Freeman at the University of Oxford, UK, wearing a
virtual reality (VR) headset and brandishing a motion-tracked controller
in each hand. Were I to attempt to explore, I’d run into one of the
very real walls of Freeman’s office — or worse, his computers.
The scene before me is one of several scenarios that make up
gameChange — a VR system that Freeman and his colleagues are developing
to treat psychosis. Because people experiencing psychosis often think
bad things will happen in social situations, such as people trying to
hurt them, they withdraw socially, leading to isolation and
strengthening of their beliefs. The idea behind gameChange is to put
people with psychosis in simulations of the situations they fear, to
help them to learn they are safe and, hopefully, to relieve their
symptoms generally.
GameChange is at the advanced end of a
spectrum of therapies that use digital technology to prevent, manage and
treat health conditions. As well as VR, the rapidly expanding field
also includes online therapies to help people to adopt healthy
behaviours, and social robots and smart pills that boost the
effectiveness of prescription drugs by improving people’s adherence to
dosing guidelines. Such technologies have the potential to transform
both physical and mental health care. But as the number of platforms and
devices claiming to provide health benefits balloons, medical
regulators and industry groups are scrambling to ensure that standards
of clinical evidence are met.
Remote guidance
“Digital
therapeutics have been on the market for about ten years, but there’s
only been a few of them,” says Megan Coder, executive director of the
Digital Therapeutics Alliance (DTA), headquartered in Arlington,
Virginia. Launched in 2017, the alliance is a global non-profit trade
association that aims to set standards and promote integration into
health care. “We look at the best practices and core principles all
these products should abide by,” she says.
One of their first
tasks was providing an official definition to distinguish digital
therapeutics from other digitally driven health innovations such as
telemedicine. “Digital therapeutics are part of the broader
digital-health landscape, but in order to be called one, a product has
to be software driven, evidence-based, and make a claim to prevent,
manage, or treat a medical disease or disorder,” says Coder. “They’re
different than diagnostics, telehealth, and all these others.” The
devices can be used alone, or with other therapies to optimize outcomes.
One
of the earliest advocates for digital therapeutics was Joseph Kvedar, a
dermatologist at Massachusetts General Hospital in Boston who in 1995
was tapped to lead Partners Connected Health, a joint initiative with
the nearby Brigham and Women’s Hospital, to explore the development and
application of technology for delivering care outside the hospital or
doctor’s office. Like many in the field, he is motivated by the need to
care for an ageing global population. He says that “2020 is a watershed
year in the history of mankind”. By then, there will be more people over
60 than under 5. People are living longer, but they are not staying
healthy for those extra years — and the medical profession cannot keep
pace. “The solution to that is what I call the one-to-many model of
care,” Kvedar says. The idea is to extend physicians’ reach by
overcoming time, place and personnel constraints that limit health-care
delivery. It’s about access, convenience and efficiency, says Kvedar.
“It’s more convenient to get care where you are, when it’s needed; it’s
more continuous,” he says. “We can take better care of you with fewer
resources, using this kind of approach.”
An area of particular
interest is the capacity of digital technology to effect behaviour
change at large scales. “We know from non-medical phone use how
addictive apps can be,” Kvedar says. “How can we use that to change
behaviour in the space of chronic illness?”
One of the earliest,
and still most prevalent, examples of digital delivery of behavioural
interventions has been in diabetes care. In 2002, a study1
showed that an intensive behavioural intervention targeting diet and
exercise could significantly reduce people’s risk of developing type 2
diabetes. In the United States, the finding has led to the development
of numerous lifestyle-change programmes that are accredited and promoted
by the US Centers for Disease Control and Prevention (CDC). Most of
these CDC-recognized programmes involve face-to face communication, just
as the 2002 study did. But some companies, such as Omada Health in San
Francisco, California, have sought to deliver the intervention digitally
— and in so doing, reach more people. “The vision with Omada was: how
do you take those evidence-based behavioural treatments, done in
traditional clinical face-to-face settings, and make them infinitely
scalable and accessible to millions of people?” says Cameron Sepah, a
behavioural health psychologist who spent five years with Omada between
2012 and 2017.
Omada’s programme involves a year-long educational
curriculum, personalized health coaching and support through a small
peer group using a social network. It also uses connected devices to
track people’s nutrition, activity and weight. “It’s hardware, software,
human coaching over a long time span; it’s throwing the kitchen sink at
people,” says Sepah, who is now a venture capitalist. In 2017, Sepah
and his colleagues reported2
that, after three years, participants with higher than normal blood
sugar on enrolment maintained a reduction in blood sugar, as determined
by A1c, the blood test commonly used to diagnose and monitor diabetes.
“On average, people regressed from the prediabetes range to the normal
range, which is pretty impressive,” says Sepah. They also maintained an
average 3% loss of body weight. “We shared our results with the CDC, and
they eventually approved online programmes as being comparable to
in-person programmes,” says Sepah. The CDC now fully recognizes online
diabetes-prevention programmes that meet its criteria from 14 providers.
A sheet of Proteus’s ingestible sensors. Each sensor is the size of a grain of sand. Credit: Proteus Digital Health
Omada plans to move into management of existing diabetes, an
area in which some companies have made headway already. Digital-health
company Welldoc, based in Columbia, Maryland, has BlueStar — an app that
helps people to log their blood glucose, medications, activity, diet,
blood pressure and weight, either manually or through Bluetooth-enabled
gadgets. The data can then be shared with the person’s care team. “They
showed they could lower A1c by two full points in patients with high
enough A1cs,” says Coder. This is a greater effect than drugs typically
manage. “The fact their product outperformed that of a drug caught a lot
of people’s attention,” she says.
Digital delivery of behavioural
therapy is not limited to diabetes, or even physical health. More and
more digital therapeutics are emerging that tackle mental health. The
most common application is digital delivery of cognitive behavioural
therapy (CBT) for depression and anxiety disorders, but the area is
diversifying rapidly. Pear Therapeutics in Boston partnered with Sandoz,
a division of Swiss pharmaceutical company Novartis, to develop an app
called reSET that delivers CBT for substance-abuse disorder. Pear also
has plans to develop a product for schizophrenia, and is collaborating
with the University of Virginia in Charlottesville to develop a
treatment for insomnia and depression, called Somryst. The leading
player in this area is currently London- and San Francisco-based
digital-health company Big Health. Its Sleepio system is an online
self-care programme based on CBT for insomnia, which has been shown to
improve both insomnia symptoms and mental well-being.
Whether
treating physical or mental health, developers need to take care that
the design of their interventions does not wholly displace the human
contact that is an essential part of health care, says Kvedar. “If you
use technology in a way that people feel less cared for, they typically
don’t like that,” he says. For some applications, including therapy for
complex problems such as trauma, digital solutions might not be able to
replace face-to-face therapy. But, says Eva Papadopoulou, a psychologist
and implementation manager based in London at digital mental-health
company Minddistrict, replacing therapists is not the aim. “What we want
is to release capacity for therapists and care teams to focus on the
people who need them most,” she says. “There’s a massive campaign to
battle stigma and have people coming forward, then we don’t have the
people to help them.”
Digital drugs
As well as being
treatments in their own right, digital therapeutics are also proving
useful in helping people to gain the maximum benefit from conventional
pharmaceutical therapies. “Efficacy is what a drug can do; effectiveness
is how it works in the real world, and right now we have a large
efficacy–effectiveness gap,” says George Savage, a physician and
co-founder of Proteus Digital Health in Redwood City, California. The
main issue is that, worldwide, between one-quarter and one-half of
people do not take their medications as recommended. In the United
States alone, this has been linked with 125,000 deaths and is estimated
to cost up to US$289 billion annually. “We have the potential to get a
lot more value out of existing medical treatments,” says Savage. “It
strikes me as low-hanging fruit.”
Provisions in the Affordable
Care Act to make reimbursement dependent on outcomes, have given
health-care providers in the United States an incentive to tackle
adherence. Together with the adoption of electronic health records,
this has driven an explosion in the field, Kvedar says. One effort,
developed by Catalia Health in San Francisco, is a robot called Mabu,
the main purpose of which is to nudge people to take their medications.
More than a simple medication-reminder system, Mabu uses artificial
intelligence and psychological modelling to tailor conversations to
individuals and build relationships with them, to keep them adhering to
dosing regimens for longer. Mabu is currently being used for people with
kidney disease, rheumatoid arthritis and congestive heart failure, but
Catalia plans to adapt it for other conditions.
Another approach
to reducing non-compliance is to make the pills themselves report when
they are taken. Savage, Proteus co-founder and engineer Andrew Thompson,
and their colleagues have developed an ingestible sensor that can be
incorporated into pills. The sensor is the size of a grain of sand and
coated on one side with copper and on the other with magnesium. When a
pill is swallowed, the liquid in the stomach connects the two sides,
generating an electrical signal that can be picked up by a sensor patch
worn on the person’s skin3. A digital record is sent to a mobile app and, with the person’s consent, shared with health-care providers.
“By
building in feedback and engaging the patient, they can do a better job
of taking the medication,” says Savage. “And, as importantly, the
physician can discern between failure to respond and failure to adhere,
and therefore make a better next decision.” The patch also monitors the
user’s activity, heart rate, sleep quality and temperature, which means
it can record people’s responses to the medication. “You can think of
this as a digital nurse,” Savage says.
Proteus’s system is
currently used to monitor people with type 2 diabetes, hypertension and
hepatitis C, with investigations under way for its use in HIV prevention
and treatment. The company is also beginning studies of potential
applications in oncology. “Quite often, cancer drugs carry very
challenging dosing schedules,” Savage says. “We expect patients to do
all this perfectly with no feedback, no measurement, no cues, no
rewards, nothing.” Digital-health company etectRx in Gainesville,
Florida, has developed a similar system using radio technology; others
have developed systems that log injections for multiple sclerosis and
inhaler activations for asthma and chronic obstructive pulmonary
disease.
Technologies such as these could also allow people to
access drugs that they would usually struggle to get. People at high
risk of non-adherence, such as homeless people, are typically denied
access to expensive treatments. In a pilot study, 28 high-risk patients
were given treatment for hepatitis C that incorporated Proteus’
technology. On average, 94% of prescribed doses were taken, and 26
participants were cured4. “We got a very high cure rate in a very challenging population,” says Savage.
Virtually treatable
Improvements
in VR technology and falling costs are raising hopes that its use might
become more widespread in medicine. “VR has been used for 25 years, but
only for very few conditions, in specialist centres,” says Freeman. The
technology has seen most use in delivering exposure therapy for
post-traumatic stress disorder, and this is still the leading
application. But it also has potential uses in depression, anxiety,
phobias, obsessive–compulsive disorder, eating disorders, addiction and
psychosis.
Freeman is currently investigating its use for treating
schizophrenia. Initially, he used VR as a research tool to assess
paranoia by presenting people with neutral social situations and seeing
whether they perceived hostility. Now, he is aiming to use simulation to
allow people to learn by experiencing real-world situations. “The
really good treatments aren’t talking therapies, they’re action
therapy,” says Freeman. “You go into situations and learn how to think,
feel and act differently.”
The gameChange clinical trial, which
launched in July, is the largest trial of a VR therapy for schizophrenia
so far. Participants first choose from six scenarios, such as visiting a
pub or catching a bus, that were proposed by a patient group
coordinated by mental-health charity The McPin Foundation in London,
which promotes the involvement of people with mental-health conditions
in research. The 432 participants then set some parameters for the
session, including how challenging they want it to be, which affects the
numbers and proximity of other people. Additional stressors can also
crop up, such as the papers that blew into the air as I stood in the
doctor’s waiting room.
After three hours of self-paced treatment,
researchers will assess participants’ avoidance and distress in
real-life situations, and again at a six-month follow-up assessment. As
with other digital therapeutics for mental-health disorders, however,
the aim is to supplement clinicians, not replace them. “We need more
therapists, not fewer,” says Freeman. “But given the numbers of people
who aren’t getting the help they need, we’re going to need solutions
like VR.” And with consumer systems becoming cheaper and more
widespread, Freeman hopes that therapy could ultimately be delivered in a
person’s home. “That would be a very appealing way to access help,” he
says.
Regulation questions
As digital treatments
proliferate, the need for scrutiny of the various medical claims being
made becomes ever more important. “You have the App Store, which has
something like 300,000 health apps, but doctors are afraid they’re going
to recommend the wrong one,” says Kvedar. “Some of them have
high-quality clinical research behind them, some do not, and the
regulatory bodies in the United States are struggling to keep up with
the volume to make sure no one is making false claims.”
Catalia Health’s Mabu uses AI to build relationships with patients, helping them to stick to drug plans.Credit: Catalia Health
The DTA industry group, which companies join voluntarily,
expects members to adopt certain principles and best practices, to
reassure users that they take robust evidence and regulatory clearance
seriously, says Coder. “That’s part of our goal as an alliance, to
ensure companies know that these are the standards for our industry,”
she says. These include publishing trial results with clinically
meaningful outcomes in peer-reviewed journals, and incorporating
adequate privacy and security protections.
Digital therapeutics
can also run into government regulation. In the United States, they
usually fall under the Food and Drug Administration’s (FDA’s) definition
of a medical device, which is anything other than a drug that is
“intended for use in the diagnosis of disease or other conditions, or in
the cure, mitigation, treatment, or prevention of disease”. Most must
therefore follow the regulatory pathways set up for medical devices. In
these cases, “the FDA applies regulatory oversight since they could pose
a risk to patient safety should they not function as intended”, says
Coder.
The precise path a digital therapeutic must take, and the
level of clinical evidence its maker must provide, is dependent on the
novelty of the product and how great a risk it poses should it
malfunction. WellDoc’s type 2 diabetes management tool, BlueStar, was
granted FDA approval in 2010. Because BlueStar was similar to existing
therapies, this involved providing evidence of ‘substantial equivalence’
to existing diabetes-management software, rather than new clinical
evidence. Entirely new therapies, however, typically face bigger
hurdles. Pear’s reSET, for instance, had to submit results of a
randomized controlled trial (RCT) through the FDA’s de novo
approval pathway. The FDA approved it as a prescription-only product, a
designation that is independent of the level of regulatory control a
digital therapeutic requires.
However, almost regardless of the
type of claim being made, the FDA can exercise ‘enforcement discretion’ —
waiving regulatory oversight if it decides a product is low risk. For
example, apps that aim to prevent diabetes by helping people to change
their diet and to exercise, such as Omada’s programme, can be marketed
in the United States without providing safety and efficacy evidence to
the FDA.
For those digital therapeutics that do have to take the
long road, the process is not a rapid one. “An RCT takes about three
years, in which time there’s been new research and evidence published,
and we have improvements,” says Papadopoulou. “All the digital providers
say it’s too slow,” she adds. “The digital world moves fast.” Iteration
after approval can also be a pain point. “You can’t change your product
so much that it’s no longer doing what it was cleared to do,” says
Coder.
The FDA’s regulatory pathways for medical devices took
shape in 1976, and the agency has acknowledged the need to modernize its
procedures to better foster innovation, particularly in light of the
iterative nature of digital products. In December 2017, the FDA issued
new guidelines clarifying types of product that will no longer be deemed
regulated medical devices, such as apps that promote general wellness.
The guidelines also outline the kinds of change to existing software
that will require fresh approval, and those that won’t. Earlier that
year, it also outlined a pilot scheme for a ‘pre-certification’
programme that assesses companies, rather than products. Pre-certified
companies deemed to have demonstrated excellence in software development
and validation could market lower-risk devices without further
oversight, or through a more streamlined process. Real-world performance
data, which are generally much easier to collect for digital
therapeutics than for pharmaceuticals, could then be used to affirm a
product’s regulatory status, as well as supporting its evolution. The
idea is being tested in a pilot scheme involving nine companies that are
undergoing the new process alongside conventional review, to check that
they produce the same decision. One of those participating is Pear,
that in July became the first company to apply for authorization through
the scheme, for Somryst.
In the United Kingdom, the National
Institute for Health and Care Excellence (NICE) assesses the clinical
and economic efficacy of treatments. Although commissioners in the
country’s National Health Service (NHS) are not bound by NICE
recommendations, they carry enormous weight. In an effort to accelerate
NHS uptake of digital innovations, NICE, in collaboration with
stakeholders such as NHS England and NHS Digital, published guidelines
last year aimed at helping manufacturers to understand the kinds of
evidence they should be providing, and what commissioners should be
requesting. “The NHS has done a fantastic job with their
evidence-for-effectiveness guidelines,” says Coder. It provides guidance
for classifying a product according to its function or the type of
claim being made, with corresponding recommendations for minimal and
ideal types of supporting evidence, as well as appropriate economic
data.
NICE is also working with the NHS to expand its provision of
digitally enabled therapy for common mental-health conditions, such as
depression and anxiety disorders, through a new assessment programme. To
be eligible, the digital treatment must mirror a NICE-recommended
psychological therapy for the relevant condition, be designed to be used
with therapist assistance, and be backed by at least one RCT. NICE
assesses content, evidence, and cost and resource impact, before
potentially recommending a treatment for ‘evaluation in practice’, where
performance will be assessed during use in NHS services. The scheme
aims to assess up to 14 treatments by March 2020. Twelve assessments
have been published so far, of which three recommended the therapy for
evaluation in practice: Space from Depression, for depression, from
SilverCloud in Boston, which is currently one of the biggest providers
of digital mental-health treatments to the NHS; Deprexis, also for
depression, from GAIA in Hamburg, Germany; and BDD-NET, for body
dysmorphic disorder, developed by researchers at the Karolinska
Institute in Stockholm. Another digital therapeutic from the Karolinska
Institute — OCD-NET, for obsessive–compulsive disorder — was also
assessed, and although not accepted yet, the researchers were encouraged
to apply for development funding from NHS England to address some
technical issues, including around security and privacy, that the
assessors had identified.
With gameChange still in its early days,
Freeman and his colleagues have all this to come. They are attempting
to get a head start, however, by involving the NHS early on. The team is
assessing the system’s cost-effectiveness and overall value to the NHS.
“We’re talking to commissioners and staff in services, and collecting a
lot of health economic data,” says Freeman. But he is not just looking
for cost savings. Like many developers of digital therapeutics, he wants
the system to provide a transformational shift in how health care is
delivered. “GameChange could show how you can automate psychological
treatment and get it out to health-care systems at scale,” he says. “If
we crack that, it will show the way for many other conditions. That’s
the hope.”
Japan helped to bring stem-cell technology to the
world. Its regulatory policies threaten its hard-won reputation.
These heart cells on an electrocardiogram chip have been derived from human embryonic stem cells.Credit: Volker Sterger/SPL
In the global race to create companies offering stem-cell
therapies, one country is looking to stand out from its competitors —
Japan.
It is five years since Japan passed laws regulating
stem-cell clinics; in that time, some 3,700 treatments have received the
green light. From Hokkaido to the islands of Okinawa, companies in
Japan can extract stem cells from skin biopsies and use them in
injections for complex conditions such as heart disease.
But the vast majority of these therapies have not passed a randomized, controlled, double-blind clinical trial,
the global standard to prove that interventions are safe and effective,
and the foundation for most medical regulation. Instead, Japan’s 2014
Act on the Safety of Regenerative Medicine and a second law, the 2014
Pharmaceutical and Medical Device Act, provide a fast track to market
approval.
These laws were passed following the award of the 2012 Nobel
Prize in Physiology or Medicine to Kyoto University stem-cell biologist
Shinya Yamanaka. The government of Prime Minister Shinzo Abe decided to
establish one of the world’s more liberal regulatory environments for
regenerative medicine.
But it isn’t only Japanese companies that
are in a rush to commercialize stem-cell treatments. The country is
becoming a magnet for scientists and entrepreneurs from around the world
who are seeking a rapid route to commercializing products and therapies
.
Japan’s attractiveness to regenerative-medicine entrepreneurs
is prompting other countries to look closely at its regulatory changes.
There is undoubtedly a competition under way, and unless something is
done, it risks becoming a race to the bottom.
Supporters of
Japan’s laws justify the fast-track approvals system by arguing that
more conventional regulations would drive clinics underground, and
regulators would constantly have to work to catch up — as is the case
for the US Food and Drug Administration. Japan’s solution, they argue,
means that companies are compelled to operate in the public eye, which
is itself a form of transparency, because clinics are visible and not
hidden.
Moreover, the law requires stem cells to be processed in
high-quality, certified cell-processing centres, and treatments to pass
through an independent ethical-review board — there are 100 of these. An
official in Japan’s Ministry of Health, Labour and Welfare told Nature
that double-blind clinical trials are expensive, and that there are
ethical issues involved in giving placebos to people with illnesses.
It
is possible that some of these justifications have a degree of merit,
but there’s still no denying that the majority of commercially available
stem-cell therapies have not been tested in more rigorous phased
clinical trials.
That leads to a second concern. As with all medical
therapies, people regard government approval for stem-cell clinics as
reassurance that treatments they offer are both safe and viable. Unless
people have read the text of the law, they will not know that stem-cell
products and therapies have a low barrier to regulatory approval. One
doctor told Nature that, from a patient’s perspective, an approval is an approval, and “everything else is just details”.
Japan’s
dilemma is a global one. Every government can see a pot of gold at the
end of the stem-cell rainbow, but countries know that these riches
cannot come at the expense of increased risks to patient safety.
Regulators
in the United States, who have also struggled with these issues, are
adhering to the international regulatory consensus for medical
therapies, and seem to be getting the upper hand in their battles
against treatments that have not been rigorously tested.
Japan’s
government must rethink its approach, and those looking to the nation’s
present laws as a regulatory role model must also think again.
The
world needs the pioneering research that Japan and other countries
conduct in stem-cell biology — and it needs promising therapies for
chronic disease. But getting from one to the other takes time, and
rigorous safeguards should not be circumvented. Policymakers,
regulators, researchers and entrepreneurs taking short cuts are
potentially putting people’s health at risk.
Imagine trying to paint a forest when all the
artist has is a leaf and a piece of bark versus having a living,
growing tree as a model. Seeing how the parts fit together can make all
the difference.
That's the level of advancement in organoid science that researchers
at Cincinnati Children's have achieved with findings published today in
the journal Nature. Instead of growing mini human organs
independently in separate lab dishes, a team led by Takanori Takebe, MD,
succeeded at growing a connected set of three organs: the liver,
pancreas and biliary ducts.
Organoids, grown from stem cells, are tiny 3D formations of human
tissue that actually perform the functions of multiple cells types found
in full-sized organs. Organoid experts at Cincinnati Children's have
already grown intestines that feature nutrient-absorbing villi, stomach
organoids that produce digestive acids, and more.
By themselves, human organoids already provide a sophisticated tool
for research. But this advance allows scientists to study how human
tissues work in concert. This major step forward could begin reducing
the need for animal-based medication studies, sharply accelerate the
concept of precision medicine, and someday lead to transplantable
tissues grown in labs.
"The connectivity is the most important part of this," Takebe says.
"What we have done is design a method for producing pre-organ formation
stage tissues so that they can develop naturally. We are maximizing our
capacity to make multiple organs much like or body does." A 5-year quest achieves key goal
Takebe, age 32, joined Cincinnati Children's in 2016 and holds a dual
appointment at Tokyo Medical and Dental University (TMDU) in Japan. He
graduated from medical school in 2011 with plans to become a liver
transplant surgeon. But as he learned about the yawning gap between the
supply and demand for donor organs, Takebe shifted gears to focus on
organ supply.
In previous research, Takebe has demonstrated a method to produce
large supplies of liver "buds," an early-stage form of a liver organoid.
He also has grown liver organoids that reflect disease states,
including steatohepatitis, a dangerous form of liver scarring and
inflammation that occurs in some people with obesity.
His work to date has been hailed by the Imperial Prince of Japan, who
presented Takebe with an honor in 2018 from the Japan Society for the
Promotion of Science. Discover magazine also listed Takebe's organoid work as No. 5 in its list of the top 100 science achievements of 2013.
But Takebe says this project is his highest-impact work yet.
"We noted this point in organ differentiation some time ago. But it
took five years to tune up the culture system to allow this development
to occur," Takebe says. How three proto-organs grow in concert
The hardest parts of the process were the earliest steps. Takebe
worked for many hours with colleagues at Cincinnati Children's including
first author Hiroyuki Koike, PhD, now at Nippon Medical School in
Japan, to perfect the process. They started with human skin cells,
converting them back into primitive stem cells, then guiding and
prodding those stem cells to form two very early-stage "spheroids" of
cells loosely termed the foregut and the midgut.
These balls of cells form very early in embryonic development. In
humans, they form late in the first month of gestation. In mice, they
form in just 8.5 days. Over time, these spheres merge and morph into the
organs that eventually become the digestive tract.
Growing these spheroids in the lab was a complex process that
required using the right ingredients at the right time. Once they were
mature enough -- a timing step that required much work to pinpoint --
then came the easier part.
The team simply placed the spheroids next to each other in a special
lab dish. The cells were suspended in a gel that's commonly used to
support organoid growth, then placed on top of a thin membrane that
covered a carefully mixed batch of growth medium.
"From this point, the cells knew what to do," Takebe says.
The lab team simply watched as cells from each spheroid began to
transform upon meeting each other at the boundary between the two. They
converted themselves, and each other, into more specialized cells that
could be seen changing colors thanks to chemical tags the lab team had
attached to the cells.
Soon, the merging, changing spheres sprouted into branches leading to
new groups of cells that belonged to specific organs. Over a period of
70 days, these cells continued to multiply into more refined and
distinct cell types. Ultimately, the mini organoids began processing
bile acids as if they were digesting and filtering food.
"This was completely unexpected. We thought we would need to add
ingredients or other factors to push this process," Koike says. "Not
trying to control this biological process led us to this success." What does this advance mean?
Aaron Zorn, PhD, Director of the Center for Stem Cell and Organoid
Medicine (CuSTOM) at Cincinnati Children's says this advance will be
useful in multiple ways.
"The real breakthrough here was to be able to make an integrated
organ system," Zorn says. "From a research perspective this is an
unprecedented opportunity to study normal human development."
However, Takebe and colleagues were able to grow these organoids only so far.
For the long-term hope of growing organ tissues large enough to be
useful in human transplantation, Takebe says more work is needed. He and
his colleagues already have started working on ways to add in immune
cells along with cell lines needed to form blood vessels, connective
tissues, and more.
But for research and diagnostic purposes, this discovery may have more immediate implications.
In precision medicine, doctors are starting to use genomic data and
other information to determine exactly which treatments would work best
for patients with serious disease, at what dose, and with the least
amount of possible side effects.
A living "gut" of multiple organs would provide scientists with a
powerful tool for studying exactly how gene variations and other factors
affect organ development during pregnancy, and to develop better
targeted drugs to treat conditions after babies are born.
A connected system of "generic" human organoids would offer much more
information than having three organoids in disconnected dishes. Growing
a set of gut organoids for a specific patient could allow even more
precise diagnosis and customized treatment.
"Current liver regenerative medicine approaches suffer from the
absence of bile duct connectivity," Takebe says. "While much work
remains before we can begin human clinical trials, our multi-organoid
transplant system is poised to solve this issue and may someday provide a
life-long cure for patients with liver diseases." Someday may not be so far away
While much more work remains ahead, Takebe and colleagues already report one step toward a practical application.
The team already has grown a set of gut organoids that lack the gene
HES1. This is one of several known genes that play a major role in
triggering biliary atresia, a condition that destroys the biliary duct
system, which leads to liver failure and death unless a transplant can
be provided. This condition is the leading cause of liver transplants
for children.
The new study demonstrates how the gut organoids are harmed by the
lack of HES1. If scientists can find a way to compensate for that
genetic variation, they may be able to find a medication or cell
transplant that would preserve biliary function in newborns and possibly
avoid the need for hard-to-obtain liver transplants.
(Established vide Act No. 25 (2009) of Parliament)
Advt. No: Pro- 100 (2019)
Projects Title
"Role of Nischarin in regulation of
intestinal apical epithelial junction".
Principal Investigator: Dr. SOMESH BARANWAL
Assistant Professor (DBT
Ramalingaswami Fellow), Department of Microbiology,Central University of
Punjab, Bathinda, Punjab 151001.
No. of Post
(01)
Name of the Post
Junior Research Fellow (JRF)
Age
Below
30 years on date of interview (Relaxation in age is permissible for SC/ST/OBC
candidates as per Government of India rules)
Fellowship
Rs 31,000/- per month plus admissible HRA
Tenure
Initially
for Six month, extendable up to the duration of the project based on
performance and availability of the fund
Essential Qualification
•M.Sc.
Life Sciences/ M.Tech. Biotechnology or related subject with at least 55%
marks for GN/OBC (50% for SC/ST/PH) from UGC recognized University/
Institute.
•CSIR-UGC
or any other NET or GATE
Desirable Qualification
·Experience in Tissue Culture and Molecular Biology
Techniques
Last Date
September,
28th 2019
Interview
September, 30th 2019
Terms and Conditions
·Short listed candidates will be intimated by e-mail or
Phone.
·No TA/DA will be paid for attending the
interview.
Albert stain is a type of differential stain used for staining the volutin granules also known as Metachromatic granules or food granules found in Corynebacterium diphtheriae. It is named as metachromatic because of its property of changing colour i.e when stained with blue stain they appear red in colour. When grown in Loffler’s slopes, C. diphtheriae produces large number of granules
Principle of Albert Staining:
Albert stain is basically made up of two stains that is Toluidine blue’ O’ and Malachite green both of which are basic dyes with high affinity for acidic tissue components like cytoplasm. The pH of Albert stain is adjusted to 2.8 by using acetic acid which becomes basic for volutin granules as pH of volutin Granule is highly acidic.
Therefore on applying Albert’s stain to the smear, Toluidine blue’ O’ stains Volutin Granules i. e the most acidic part of cell and Malachite green stains the cytoplasm blue-green. On adding
Albert’s iodine due to effect of iodine, the metachromatic property is not observed and granules appear blue in colour.
Composition of Albert stain:Albert stain is composed of two reagents:
Albert’s A solution consist of
Toludine blue 0.15 gm
Malachite green 0.20 gm
Glacial acetic acid 1 ml
Alcohol (95% ethanol) 2ml
Dissolve the dyes in alcohol and add to the distilled water and acetic acid.
Allow the stain to stand for one day and then filter.
Add Distilled water to make the final volume 100ml
Albert’s B solution consist of
Iodine 2gm
Potassium iodide (KI) 3 gm
Dissolve KI in water and then add iodine. Dissolve iodine in potassium iodide solution
Requirements: Smear on glass slide, staining rack, Albert’s A solution , Albert’s B solution, blotting paper, immersion oil, microscope
Procedure
Prepare a smear on clean grease free slide.
Air dry and heat fix the smear.
Treat the smear with Albert’s stain and allow it to react for about 7 mins.
Drain of the excess stain do not water wash the slide with water.
Flood the smear with Albert’s iodine for 2 minutes.
Wash the slide with water, air dry and observe under oil immersion lens.
Result
If Corynebacterium diphtheria is present in the sample it appears green coloured rod shaped bacteria arranged at angle to each other, resembling English letter ‘L’, ‘V’ or Chinese letter pattern along with bluish black metachromatic granules at the poles.
Uses:
This helps to distinguish Corynebacterium diphtheriae from most of the short nonpathogenic diphtheroides which lack granules.
We are looking to Hire dynamic and aspiring candidates with B. Sc/ M.Sc in Chemistry, Micro- biology, Bio- technology, Diploma in Chemical Engineering / Chemical Technology/ Petroleum Refining, Diploma/PG Diploma in Plastic Processing & Testing as FIXED TERM PROJECT ASSOCIATES on Fixed Term basis at HP Green R&D Centre, Bengaluru. Interested candidates are advised to apply online in the prescribed format. Terms of reference and other details regarding engagement of Project Associates on fixed term basis are enumerated.
1. JOB DESCRIPTION FOR FIXED TERM PROJECT ASSOCIATES:
To assist Scientists carrying out research project(s).
Prepare samples for establishing methods of analysis & carrying out routine analysis related to the assigned project(s).
Monitoring batch reactions for optimizing reaction conditions
Running pilot plants in shifts.
Carryout any other job(s) assigned by the reporting scientists/Officers.
2. EDUCATION QUALIFICATION AND WORK EXPERIENCE:
Discipline Prescribed full time degrees BSc/MSc
Chemistry
Microbiology
Biotechnology
Last date of online application by candidates 10 October, 2019
ENGAGEMENT OF FIXED TERM RESEARCH ASSOCIATES FOR HP GREEN R&D CENTRE, BENGALURU
We are looking to Hire dynamic and aspiring candidates with Ph.D in Chemistry/Chemical Engineering/ Bio-Sciences/ Bio Technology OR M.Tech in Chemical Engineering/ Mechanical Engineering/Electrical/ Electronic as FIXED TERM RESEARCH ASSOCIATES on Fixed Term basis at HP Green R&D Centre, Bengaluru. Interested candidates are advised to apply online in the prescribed format. Terms of reference and other details regarding engagement of Research Associates on fixed term basis are enumerated.
1. JOB DESCRIPTION FOR FIXED TERM RESEARCH ASSOCIATE::
To prepare Project proposal including work plan on the specific research topic assigned to the candidate
To carryout research activities on the specific topic including literature search, set up experimental facilities, if required, carryout experimental/ pilot/ simulation studies.
Interpret results and undertake studies for further development/ improvement.
Prepare technical reports.
Carryout any other activities that are assigned from time to time.
2. EDUCATION QUALIFICATION AND WORK EXPERIENCE:
Ph.D., in Bio-Sciences /Biotechnology.
Candidates with research experience in microbial bioprocesses with experience of working on yeast or bacterial molecular biology will be preferred. In addition, candidates with research experience of working on bio-fuels such as 2G Ethanol and Algal Biofuels are desirable.
Last date of online application by candidates 10 October, 2019
