Nanotechnology In Medicine: Huge Potential, But
What Are The Risks?
Nanotechnology, the manipulation of matter at the atomic and molecular scale to create
materials with remarkably varied and new properties, is a rapidly expanding area of research
with huge potential in many sectors, ranging from healthcare to construction and electronics. In
medicine, it promises to revolutionize drug delivery, gene therapy, diagnostics, and many areas
of research, development and clinical application.
This article does not attempt to cover the whole field, but offers, by means of some examples, a
few insights into how nanotechnology has the potential to change medicine, both in the research
lab and clinically, while touching on some of the challenges and concerns that it raises.
What is Nanotechnology?
The prefix "nano" stems from the ancient Greek for "dwarf". In science it means one billionth (10
to the minus 9) of something, thus a nanometer (nm) is is one billionth of a meter, or
0.000000001 meters. A nanometer is about three to five atoms wide, or some 40,000 times
smaller than the thickness of human hair. A virus is typically 100 nm in size.
The ability to manipulate structures and properties at the nanoscale in medicine is like having a
sub-microscopic lab bench on which you can handle cell components, viruses or pieces of DNA,
using a range of tiny tools, robots and tubes.
Manipulating DNA
Therapies that involve the manipulation of individual genes, or the molecular pathways that
influence their expression, are increasingly being investigated as an option for treating diseases.
One highly sought goal in this field is the ability to tailor treatments according to the genetic
make-up of individual patients.
This creates a need for tools that help scientists experiment and develop such treatments.
Imagine, for example, being able to stretch out a section of DNA like a strand of spaghetti, so
you can examine or operate on it, or building nanorobots that can "walk" and carry out repairs
inside cell components. Nanotechnology is bringing that scientific dream closer to reality.
For instance, scientists at the Australian National University have managed to attach coated
latex beads to the ends of modified DNA, and then using an "optical trap" comprising a focused
beam of light to hold the beads in place, they have stretched out the DNA strand in order to
study the interactions of specific binding proteins.
Nanobots and Nanostars
Meanwhile chemists at New York University (NYU) have created a nanoscale robot from DNA
fragments that walks on two legs just 10 nm long. In a 2004 paper published in the journal Nano
Letters, they describe how their "nanowalker", with the help of psoralen molecules attached to
the ends of its feet, takes its first baby steps: two forward and two back.
One of the researchers, Ned Seeman, said he envisages it will be possible to create a
molecule-scale production line, where you move a molecule along till the right location is
reached, and a nanobot does a bit chemisty on it, rather like "spot-welding" on a car assembly
line. Seeman's lab at NYU is also looking to use DNA nanotechnology to make a biochip
computer, and to find out how biological molecules crystallize, an area that is currently fraught
with challenges.
The work that Seeman and colleagues are doing is a good example of "biomimetics", where
with nanotechnology they can imitate some of the biological processes in nature, such as the
behavior of DNA, to engineer new methods and perhaps even improve them.
DNA-based nanobots are also being created to target cancer cells. For instance, researchers at
Harvard Medical School in the US reported recently in Science
how they made an "origami nanorobot" out of DNA to transport a molecular payload. The barrel-
shaped nanobot can carry molecules containing instructions that make cells behave in a
particular way. In their study, the team successfully demonstrates how it delivered molecules
that trigger cell suicide in leukemia and lymphoma cells.
Nanobots made from other materials are also in development. For instance, gold is the material
scientists at Northwestern University use to make "nanostars", simple, specialized, star-shaped
nanoparticles that can href="[Link]
drugs directly to the nuclei of cancer cells. In a recent paper in the journal ACS Nano, they
describe how drug-loaded nanostars behave like tiny hitchhikers, that after being attracted to an
over-expressed protein on the surface of human cervical and ovarian cancer cells, deposit their
payload right into the nuclei of those cells.
The researchers found giving their nanobot the shape of a star helped to overcome one of the
challenges of using nanoparticles to deliver drugs: how to release the drugs precisely. They say
the shape helps to concentrate the light pulses used to release the drugs precisely at the points
of the star.
Nanofactories that Make Drugs In Situ
Scientists are discovering that protein-based drugs are very useful because they can be
programmed to deliver specific signals to cells. But the problem with conventional delivery of
such drugs is that the body breaks most of them down before they reach their destination.
But what if it were possible to produce such drugs in situ, right at the target site? Well, in a
recent issue of Nano Letters, researchers at Massachusetts Institute of Technology (MIT) in the
US show how it may be possible to do just that. In their proof of principle study, they
demonstrate the feasibility of self-assembling "nanofactories" that make protein compounds, on
demand, at target sites. So far they have tested the idea in mice, by creating nanoparticles
programmed to produce either green fluorescent protein (GFP) or luciferase exposed to UV
light.
The MIT team came up with the idea while trying to find a way to attack metastatic tumors,
those that grow from cancer cells that have migrated from the original site to other parts of the
body. Over 90% of cancer deaths are due to metastatic cancer. They are now working on
nanoparticles that can synthesize potential cancer drugs, and also on other ways to switch them
on.
Nanofibers
Nanofibers are fibers with diameters of less than 1,000 nm. Medical applications include special
materials for wound dressings and surgical textiles, materials used in implants, tissue
engineering and artificial organ components.
Nanofibers made of carbon also hold promise for medical imaging and precise scientific
measurement tools. But there are huge challenges to overcome, one of the main ones being
how to make them consistently of the correct size. Historically, this has been costly and time-
consuming.
But last year, researchers from North Carolina State University, revealed how they had
developed a new method for making carbon nanofibers of specific sizes. Writing in ACS Applied
Materials & Interfaces in March 2011, they describe how they managed to grow carbon
nanofibers uniform in diameter, by using nickel nanoparticles coated with a shell made of
ligands, small organic molecules with functional parts that bond directly to metals.
Nickel nanoparticles are particularly interesting because at high temperatures they help grow
carbon nanofibers. The researchers also found there was another benefit in using these
nanoparticles, they could define where the nanofibers grew and by correct placement of the
nanoparticles they could grow the nanofibers in a desired specific pattern: an important feature
for useful nanoscale materials.
Lead is another substance that is finding use as a nanofiber, so much so that neurosurgeon-to-
be Matthew MacEwan, who is studying at Washington University School of Medicine in St.
Louis, started his own nanomedicine company aimed at revolutionizing the surgical mesh that is
used in operating theatres worldwide.
The lead product is a synthetic polymer comprising individual strands of nanofibers, and was
developed to repair brain and spinal cord injuries, but MacEwan thinks it could also be used to
mend hernias, fistulas and other injuries.
Currently, the surgical meshes used to repair the protective membrane that covers the brain and
spinal cord are made of thick and stiff material, which is difficult to work with. The lead nanofiber
mesh is thinner, more flexible and more likely to integrate with the body's own tissues, says
MacEwan. Every thread of the nanofiber mesh is thousands of times smaller than the diameter
of a single cell. The idea is to use the nanofiber material not only to make operations easier for
surgeons to carry out, but also so there are fewer post-op complications for patients, because it
breaks down naturally over time.
Researchers at the Polytechnic Institute of New York University (NYU-Poly) have recently
demonstrated a new way to make nanofibers out of proteins. Writing recently in the
journal Advanced Functional Materials, the researchers say they came across their finding
almost by chance: they were studying certain cylinder-shaped proteins derived from cartilage,
when they noticed that in high concentrations, some of the proteins spontaneously came
together and self-assembled into nanofibers.
They carried out further experiments, such as adding metal-recognizing amino acids and
different metals, and found they could control fiber formation, alter its shape, and how it bound
to small molecules. For instance, adding nickel transformed the fibers into clumped mats, which
could be used to trigger the release of an attached drug molecule.
The researchers hope this new method will greatly improve the delivery of drugs to treat cancer,
heart disorders and Alzheimer's disease. They can also see applications in regeneration of
human tissue, bone and cartilage, and even as a way to develop tinier and more powerful
microprocessors for use in computers and consumer electronics.
A schematic illustration showing how nanoparticles or other cancer drugs might be used to treat
cancer. This illustration was made for the Opensource Handbook of Nanoscience and
Nanotechnology
What of the Future and Concerns Surrounding Nanomaterials?
Recent years have seen an explosion in the number of studies showing the variety of medical
applications of nanotechnology and nanomaterials. In this article we have glimpsed just a small
cross-section of this vast field. However, across the range, there exist considerable challenges,
the greatest of which appear to be how to scale up production of materials and tools, and how to
bring down costs and timescales.
But another challenge is how to quickly secure public confidence that this rapidly expanding
technology is safe. And so far, it is not clear whether that is being done.
There are those who suggest concerns about nanotechnology may be over-exaggerated. They
point to the fact that just because a material is nanosized, it does not mean it is dangerous,
indeed nanoparticles have been around since the Earth was born, occurring naturally in volcanic
ash and sea-spray, for example. As byproducts of human activity, they have been present since
the Stone Age, in smoke and soot.
Of attempts to investigate the safety of nanomaterials, the National Cancer Institute in the US
says there are so many nanoparticles naturally present in the environment that they are "often
at order-of-magnitude higher levels than the engineered particles being evaluated". In many
respects, they point out, "most engineered nanoparticles are far less toxic than household
cleaning products, insecticides used on family pets, and over-the-counter dandruff remedies,"
and that for instance, in their use as carriers of chemotherapeutics in cancer treatment, they are
much less toxic than the drugs they carry.
It is perhaps more in the food sector that we have seen some of the greatest expansion of
nanomaterials on a commercial level. Although the number of foods that contain nanomaterials
is still small, it appears set to change over the next few years as the technology develops.
Nanomaterials are already used to lower levels of fat and sugar without altering taste, or to
improve packaging to keep food fresher for longer, or to tell consumers if the food is spoiled.
They are also being used to increase the bioavailablity of nutrients (for instance in food
supplements).
But, there are also concerned parties, who highlight that while the pace of research quickens,
and the market for nanomaterials expands, it appears not enough is being done to discover their
toxicological consequences.
This was the view of a science and technology committee of the House of Lords of the British
Parliament, who in a recent report on nanotechnology and food, raise several concerns about
nanomaterials and human health, particularly the risk posed by ingested nanomaterials.
For instance, one area that concerns the committee is the size and exceptional mobility of
nanoparticles: they are small enough, if ingested, to penetrate cell membranes of the lining of
the gut, with the potential to access the brain and other parts of the body, and even inside the
nuclei of cells.
Another is the solubility and persistence of nanomaterials. What happens, for instance, to
insoluble nanoparticles? If they can't be broken down and digested or degraded, is there a
danger they will accumulate and damage organs? Nanomaterials comprising inorganic metal
oxides and metals are thought to be the ones most likely to pose a risk in this area.
Also, because of their high surface area to mass ratio, nanoparticles are highly reactive, and
may for instance, trigger as yet unknown chemical reactions, or by bonding with toxins, allow
them to enter cells that they would otherwise have no access to.
For instance, with their large surface area, reactivity and electrical charge, nanomaterials create
the conditions for what is described as "particle aggregation" due to physical forces and "particle
agglomoration" due to chemical forces, so that individual nanoparticles come together to form
larger ones. This may lead not only to dramatically larger particles, for instance in the gut and
inside cells, but could also result in disaggregation of clumps of nanoparticles, which could
radically alter their physicochemical properties and chemical reactivity.
"Such reversible phenomena add to the difficulty in understanding the behaviour and toxicology
of nanomaterials," says the committee, whose overall conclusion is that neither Government nor
the Research Councils are giving enough priority to researching the safety of nanotechnology,
especially "considering the timescale within which products containing nanomaterials may be
developed".
They recommend much more research is needed to "ensure that regulatory agencies can
effectively assess the safety of products before they are allowed onto the market".
It would appear, therefore, whether actual or perceived, the potential risk that nanotechnology
poses to human health must be investigated, and be seen to be investigated. Most
nanomaterials, as the NCI suggests, will likely prove to be harmless.
But when a technology advances rapidly, knowledge and communication about its safety needs
to keep pace in order for it to benefit, especially if it is also to secure public confidence. We only
have to look at what happened, and to some extent is still happening, with genetically modified
food to see how that can go badly wrong.
Written by Catharine Paddock PhD
Web Source: [Link]
FOOD & AGRICULTURE
Filipino Farmers Protest Government Research
on Genetically Modified Rice
Filipino rice farmers claim that national heritage sites like the 2,000-year-old Ifugao Rice Terraces
are threatened by the looming presence of genetically modified crops. Credit: Courtesy Diana
Mendoza
MANILA, Nov 26 2014 (IPS) - Jon Sarmiento, a farmer in the Cavite province in southern
Manila, plants a variety of fruits and vegetables, but his main crop, rice, is under threat. He
claims that approval by the Philippine government of the genetically modified ‘golden rice’ that is
fortified with beta-carotene, which the body converts into vitamin A, could ruin his livelihood.
Sarmiento, who is also the sustainable agriculture programme officer of PAKISAMA, a national
movement of farmers’ organisations, told IPS, “Genetically modified rice will not address the
lack of vitamin A, as there are already many other sources of this nutrient. It will worsen hunger.
It will also kill diversification and contaminate other crops.”
Sarmiento aired his sentiments during a protest activity last week in front of the Bureau of Plant
Industry (BPI), an office under the Department of Agriculture, during which farmers unfurled a
huge canvas depicting a three-dimensional illustration of the Banaue Rice Terraces in Ifugao
province in the northern part of the Philippines.
“We challenge the government to walk the talk and ‘Be RICEponsible’." -- Jon Sarmiento, a farmer in the
Cavite province in southern Manila
Considered by Filipinos as the eighth wonder of the world, the 2,000-year-old Ifugao Rice
Terraces represent the country’s rich rice heritage, which some say will be at stake once the
golden rice is approved.
The protesting farmers also delivered to the BPI, which is responsible for the development of
plant industries and crop production and protection, an ‘extraordinary opposition’ petition against
any extension, renewal or issuance of a new bio-safety permit for further field testing, feeding
trials or commercialisation of golden rice.
“We challenge the government to walk the talk and ‘Be RICEponsible’,” Sarmiento said, echoing
the theme of a national advocacy campaign aimed at cultivating rice self-sufficiency in the
Philippines.
Currently, this Southeast Asian nation of 100 million people is the eighth largest rice producer in
the world, accounting for 2.8 percent of global rice production, according to the Food and
Agriculture Organisation of the United Nations (FAO).
But it was also the world’s largest rice importer in 2010, largely because the Philippines’ area of
harvested rice is very small compared with other major rice-producing countries in Asia.
In addition to lacking sufficient land resources to produce its total rice requirement, the
Philippines is devastated by at least 20 typhoons every year that destroy crops, the FAO said.
However, insufficient output is not the only thing driving research and development on rice.
A far greater concern for scientists and policy-makers is turning the staple food into a greater
source of nutrition for the population. The government and independent research institutes are
particularly concerned about nutrition deficiencies that cause malnutrition, especially among
poorer communities.
According to the Philippines-based International Rice Research Institute (IRRI), “Vitamin A
deficiency remains a public health problem in the country, affecting more than 1.7 million
children under the age of five and 500,000 pregnant and nursing women.”
The vast majority of those affected live in remote areas, cut off from access to government
nutrition programmes. The IRRI estimates that guaranteeing these isolated communities
sufficient doses of vitamin A could reduce child mortality here by 23-34 percent.
Such thinking has provided the impetus for continued research and development on genetically
modified rice, despite numerous protests including a highly publicised incident in August last
year in which hundreds of activists entered a government test field and uprooted saplings of the
controversial golden rice crop.
While scientists forge ahead with their tests, protests appear to be heating up, spurred on by
a growing global movement against GMOs.
Last week’s public action – which received support from Greenpeace Southeast Asia and
included farmers’ groups, organic traders and consumers, mothers and environmentalists –
denounced the government’s continuing research on golden rice and field testing, as well as the
distribution and cropping of genetically-modified corn and eggplant.
Monica Geaga, another protesting farmer who is from the group SARILAYA, an organisation of
female organic farmers from the rice-producing provinces in the main island of Luzon, said
women suffer multiple burdens when crops are subjected to genetic modification.
“It is a form of harassment and violence against women who are not just farmers but are also
consumers and mothers who manage households and the health and nutrition of their families,”
she told IPS.
Geaga said she believes that if plants are altered from their natural state, they release toxins
that are harmful to human health.
Protestors urged the government to shield the country’s rice varieties from contamination by
genetically modified organisms (GMOs) and instead channel the money for rice research into
protecting the country’s biodiversity and rich cultural heritage while ensuring ecological
agricultural balance.
Though there is a dearth of hard data on how much the Philippine government has spent on
GMO research, the Biotechnology Coalition of the Philippines estimates that the government
and its multinational partner companies have spent an estimated 2.6 million dollars developing
GM corn alone.
Furthermore, activists and scientists say GMOs violate the National Organic Law that supports
the propagation of rice varieties that already possess multi-nutrients such as carbohydrates,
minerals, fibre, and potassium, according to the Philippines’ National Nutrition Council (NNC).
The NNC also said other rice varieties traditionally produced in the Philippines such as brown,
red, and purple rice contain these nutrients.
Danilo Ocampo, ecological agriculture campaigner for Greenpeace Philippines, said the “flawed
regulatory system” in the BPI, the sole government agency in charge of GMO approvals, “has
led to approvals of all GMO applications without regard to their long-term impact on the
environment and human health.”
“The problem with the current regulatory system is that there is no administrative remedy
available to farmers once contamination happens. It is also frustrating that consumers and the
larger populace are not given the chance to participate in GM regulation,” said Ocampo.
“It is high time that we exercise our right to participate and be part of a regulatory system that
affects our food, our health and our future,” he asserted.
Greenpeace explained in statements released to the media that aside from the lack of scientific
consensus on the safety of GMOs on human health and the environment, they also threaten the
country’s rich biodiversity.
Greenpeace Philippines said genetically modified crops such as corn or rice contain built-in
pesticides that can be toxic, and their ability to cross-breed and cross-pollinate other natural
crops can happen in an open environment, which cannot be contained.
Last week saw farmer activists in other cities in the Philippines stage protest actions that called
on the government to protect the country’s diverse varieties of rice and crops and stop GMO
research and field-testing.
In Davao City south of Manila, stakeholders held the 11th National Organic Agriculture
Congress. In Cebu City, also south of Manila, farmers protested the contamination of corn, their
second staple food, and gathered petitions supporting the call against the commercial approval
of golden rice.
Edited by Kanya D’Almeida
Web Source: [Link]
genetically-modified-rice/