There is a potent mix of fear and wonder associated with the term nanotechnology that makes it hard to write about in pragmatic terms. In the story below, which I wrote recently for a publication at the University of New South Wales, I tried to weave my way between the two poles of “tiny robots” and “grey goo”…and tell a story that explains why working at a nanoscale is ideally suited to applications in medicine.
Inevitably, of course, I had to mention grey goo, and the main picture accompanying the story was of some kind of imaginary robot that looks a bit like a man-made bacteriophage. Sigh…
Still, it was great fun to follow someone around as they demonstrated one of the really exciting things about nanotechnology–the way that it blends and transcends traditional disciplines. Nanotech PhD candidate Bakul Gupta literally spent her days walking between the physics, chemistry and medicine departments of the university. Now that sounds like a great field to work in.
(Btw: To accompany the story, I’ve included here some pictures I took at the Anish Kapoor exhibition at the Museum of Contemporary Art in Sydney right now. They seem to fit somehow.)
Nanotechnology has the power to change the way science solves our biggest health problems.
By Stephen Pincock
Bakul Gupta pulls a pair of safety glasses over her eyes and takes the 35 per cent hydrofluoric acid out of the lab fridge.
In a neatly labelled plastic bottle, the clear liquid looks innocuous. But looks are deceiving – it is corrosive enough to dissolve her bones. So the UNSW doctoral student treats it with care as she pours it into a round Teflon vessel.
Inside the dark-grey cylinder is a small square of silicon. It’s the same material used to make computer chips, but Gupta has another purpose in mind.
She secures a heavy lid on top of the container, in the process dipping a thin platinum electrode into the acid. Wires that lead from the top and bottom of the vessel are connected and through them she sends a jolt of electric current.
Half an hour later the acid will have etched scores of tiny pores into the metal. When it has, Gupta will push the glasses back up on to her head and set off from the physics lab across the UNSW campus with a collection of now-porous silicon squares inside a little box, heading to the chemistry department.
It’s a path she has walked often during the past two years she’s spent working on a PhD. “I basically walk all day,” she laughs.
Splitting her days between the schools of chemistry, physics and biology, Gupta says she identifies with all three disciplines, and none of them. Really, she says, she is a nanotechnologist.
Put simply, nanotechnologists occupy themselves with making very small things. The term gets its name from a tiny unit of measure, the nanometre – one-billionth of a metre, or roughly how much the hair on your head grows each second. This is the scale at which atoms come into play: a nanometre is about 10 times the diameter of a single helium atom.
There are countless particles floating around the world that are in the nanometre ballpark, from volcanic dust in the air to molecules in your bloodstream. Nanotechnology deals with man-made items at this size – objects engineered for a specific purpose.
In Gupta’s case, she plans to pulverise her porous silicon into nano-scale particles and use them to detect infections in the eye long before they cause damage, and perhaps even to deliver anti-inflammatory drugs at the same time.
Enter the relatively new discipline of nanomedicine.
From molecular-sized structures that can deliver drugs to diseased tissue or switch off a disease-causing gene, to science- fiction scenarios of nano-robots performing the role of the surgeon, the new technology “has the potential to completely change the way we practise medicine”, says Scientia Professor Justin Gooding.
Gooding is one of three co-directors of the Australian Centre for Nanomedicine (ACN) – an Australian-first centre established at UNSW last year that is already investigating strategies to better diagnose and treat illnesses such
as cancer, diabetes, multiple sclerosis, Alzheimer’s and Parkinson’s disease.
“This is the next frontier in medicine,” he says. “Where we can actually help the human body perform its own natural functions to fend off and treat disease.”
A visionary question
Many nanotechnologists trace the origins of their field back to a Californian winter’s day in 1959, and a lecture delivered by theoretical physicist Richard Feynman.
“What would happen if we could arrange the atoms one by one the way we want them?” Feynman asked his audience. “I can hardly doubt that when we have some control of the arrangement of things on a small scale we will get an enormously greater range of possible properties that substances can have.”
This often-cited talk, dubbed “Plenty of Room at the Bottom”, was delivered at a time when computers filled entire rooms. It wasn’t until the end of the 1980s that Feynman’s imaginings started to become reality. In 1989, physicists Don Eigler and Erhard K. Schweizer used a newly developed microscope to manoeuvre 35 xenon atoms
on the surface of a nickel crystal, spelling out the name of their employer, IBM.
This loyal flourish marked the first time atoms had been precisely positioned, “one at a time, on a flat surface, like dominoes on a playing table”, as a New York Times reporter noted at the time. It wasn’t the last.
Soon enough, scientists and engineers began discovering more practical uses for nanoscale materials, making self-cleaning paints and LED televisions with nanostructure films to allow wide-angle viewing. As of today, the US-based Project on Emerging Nanotechnologies lists more than 1000 nanotech consumer products on its website.
In the late 1990s, the medical applications of nanotechnology began to gain attention. When they did, it became apparent the fields of nanotechnology and medicine were a perfect fit, says Patrick Boisseau, head of business development in nanomedicine for the French Alternative Energies and Atomic Energy Commission.
“The nanoscale is really the ideal scale in medicine,” says Boisseau. “Biologists and chemists realised that everything in the human body happens at the nanoscale. It means we can engineer molecules that work at the scale of our own molecules.”
Over the past 15 years or so, there has been a boom in nanomedicine investment. The US Food and Drug Administration has already approved more than 40 nano-medical products, and there are in the region of 70 more products in clinical trials around the world.
“All advanced economies are investing,” says Boisseau. By 2015, the value of the world’s nanomedicine market will exceed $US160 billion, according to market research firm Global Industry Analysts.
Investing in breakthroughs
Standing amid the flasks and tubes of another laboratory bench, this time in the chemistry department, Gupta holds a centrifuge tube up to the light.
Resting at the bottom is a faint coating of brown-green dust: a thousand or so of her silicon nanoparticles. It doesn’t look like much, but these particles are a prime example of how nanomedicine combines technologies, in this case polymer technology, surface chemistry, materials science and clinical research.
Each of the tiny pores etched into the silicon by the hydrofluoric acid has now been filled with a polymer designed to only break down when it comes into contact with a specific molecule released in the eye in response to inflammation.
In the future, if all goes to plan, these silicon particles could be incorporated into contact lenses, Gupta says. Then, if the eye becomes inflamed, the polymer will be broken down changing the optical signature of the particles, serving as a visible indicator to the wearer that their eye is fighting off an infection and that they’d better see a doctor.
Later, Gupta plans to add anti-inflammatory drugs into the pores as well, so the silicon nanoparticles not only diagnose the infection, but treat it, too. In the world of nanomedicine, this is known as a “theranostic” – a device that detects a disease (a diagnostic), and treats it at the same time (a therapeutic).
I’ve come to visit Gupta at a crucial stage in her PhD project. In the next few days she is due to begin testing whether her nanoparticles can detect inflammation in laboratory animals. It is her chance to see if she has made something that could be of medical benefit.
“This is what I really love about my project,” she says. “I get to interact with all these different disciplines and I want to do something that has an endpoint that helps people.”
Some of the biggest investors in nanotechnology are pharmaceutical companies, who are using nanotechnology approaches to deliver drugs more safely and effectively to the right place in the body.
According to Gooding, Gupta’s supervisor, drug delivery accounts for around 60 per cent of the current global effort in nanomedical products.
Wrapping drugs in various kinds of nanoparticles can protect them from attack by the body’s multitude of defence mechanisms, and help target them to where they need to go to minimise side effects, explains Gooding.
A prominent example of this is the cancer drug Abraxane, developed by US firm Cellgene. In this drug, the chemotherapy drug paclitaxel is bound to albumin, the most abundant protein in the body. Paclitaxel is not normally blood soluble, but a nano-engineered connection between it and albumin allows it to be transported via the bloodstream to tumours. In 2011, Abraxane earned the company $US390 million.
Nanotechnology is also making an impact in technology used to diagnose and monitor diseases. This includes the use of nanotech surfaces for in-vitro testing such as diabetic blood-glucose monitoring, and the use of nano-encapsulated materials to improve the resolution of imaging techniques such as MRI.
In France, Boisseau’s group has developed its own clever nano-diagnostic. It found a way to coat a slender metal rod with nanometre-long pillars that can be slid delicately between the lobes of the brain to assess the spread of the brain cancer glioblastoma. “We can put the rod between lobes of the brain, and collect proteins and cells that can be analysed without needing to biopsy,” he says.
Imagination beats knowledge
The coffee cup sitting on Professor Maria Kavallaris’s office table in the gleaming new Lowy Cancer Research Centre at UNSW bears her favourite quotation from Einstein: “Imagination is more important than knowledge.”
And she’s not afraid to dream big: “Imagine if you could build nanoparticles loaded with metals that improve the sensitivity of imaging to detect cancers, target them to the tumour and use the same package to deliver chemotherapies or gene-silencing technology. There’s a long way to go in terms of making that a reality. It won’t be easy, but I do believe we’re well positioned to make a difference.”
UNSW established the ACN in July 2011 with Kavallaris, Gooding, and engineering professor Tom Davis sharing
the helm [see breakout box]. The centre’s approach starts with a medical problem that needs solving, Kavallaris explains. “Ultimately, we want our ideas to be applied in the clinic.”
Kavallaris is primarily a cancer researcher, so it isn’t surprising the centre is strong in that clinical area. There are projects underway to use nanoparticles in the treatment of lung cancer, and Kavallaris has other hard-to-treat cancers such as neuroblastoma in her sights.
“In many ways, engineering is the lynchpin,” says Tom Davis. “It bridges the gap between the fundamental science, and clinical medical application. We’re engineering new materials and drugs that perform very specific functions inside the human body and our cross-faculty approach not only gives us a broader pool of expertise, it fosters idea-sharing and creative solutions to very complex problems.”
It is early days, but bringing together chemists, engineers and biomedical researchers has already sparked exciting ideas, says Gooding. “The big question is how can we make a difference? Interdisciplinary research is the answer.”
Beware the grey goo
The flip side of excitement is often fear, and it’s fair to say nanotechnology has generated its share of concern over the years — some of it silly, like the Prince of Wales’ warning that swarms of rogue “nanomachines” could one day reduce all in their path to “grey goo”, and some more valid, such as questions about whether the use of nanoparticles in cosmetics has been properly evaluated.
When the French government launched a campus for research into nanotechnology in 2006, anti-riot police had to be called in, says Boisseau. The French prime minister ended up cancelling his planned attendance.
“To some extent this was activists feeding fear felt by part of the population,” he says. “This is especially true for industrial nanoparticles. People can live without the benefits of stronger [nanomaterial] tennis racquets or car tyres.”
Latent opposition to industrial nanomaterials remains, but most people make a distinction between nanomaterials and nanomedical products, says Gooding. He and Kavallaris stress nanomedicines are no different from any other medicine in that they need to be tested for safety and efficacy before regulatory authorities such as Australia’s Therapeutic Goods Administration will allow them to be used on patients.
If anything, past experience has shown that the novelty of nanomedicines exposes them to even tougher scrutiny, Kavallaris argues. In any case, she says, it is vital researchers are transparent about their work to help address the public’s concerns.
“I really feel as scientists that we have to communicate our findings to the general public in a way they can understand. Open communication is very important and can help dispel these panics,” she says.
A promise unconsummated
One person who seemingly needs no convincing about the potential of nanotechnology is Alan Trounson, the eminent Australian stem-cell researcher who was picked in 2007 to head the $US3 billion California Institute for Regenerative Medicine. Trounson was recently in Sydney to attend the 3rd International Nanomedicine Conference hosted by the ACN, and to deliver UNSW Medicine’s annual Dean’s Lecture.
Applying nano-techniques to regenerative medicine is a hot new thing in the world of nanomedicine, and Trounson spent a fortnight visiting the ACN to get a better idea for himself of how the two fields might work together.
“I haven’t interacted much with nanotechnology,” he says. “The Australian centre is newly started, and there’s a lot of enthusiasm. We’re learning from one another.”
When I ask him how he sees these two cutting-edge disciplines interacting, he scatters ideas around like sowing seeds: “What are the interfaces between regenerative medicine and nanotechnology? You start to think about very interesting ways you can move cells around. Can you make cells more aggressive against tumours?
“You could use nano-smart surfaces to get cells to interact with one another differently, or grow neurons vast distances on etched surfaces,” he continues. “You could grow cells on moving surfaces to mimic what’s going on in the body. Perhaps you can make the environment in a nanotech way that instructs the cell. Maybe we can stop inflammation raging. They are all opportunities … what we will end up doing I don’t know.”
Taking a breath, he slides in an important caveat: science takes time.
“The promise is enormous but it hasn’t been consummated yet. It’s often the way in the sciences. It just takes time and we’re not very patient, any of us. This field will blossom. Stand up to unwarranted fear and say that’s just not right. Walk through the wall of fire.”
AUSTRALIAN CENTRE FOR NANOMEDICINE
When he launched the Australian Centre for Nanomedicine (ACN), Australia’s Chief Scientist, Professor Ian Chubb, predicted big things for the University-based centre.
“The purpose of universities is to use our talents to make the world a better place. Nanomedicine will enable better delivery of drugs and vital therapies to individuals who would not prosper without that treatment,” he said.
Unique in Australia, the ACN brings together medical and clinical researchers with specialists in nanotechnology, engineering and chemistry to create new treatments for difficult-to-treat diseases.
The first ailments in the centre’s sights are lung cancer and chronic liver disease. The ACN is also investigating new pain management drugs derived from marine life and the use of nano-constructs to stimulate tissue regeneration.
The multidisciplinary centre comprises researchers from the faculties of Medicine, Science and Engineering, as well as the Children’s Cancer Institute Australia and the UNSW Centre for Advanced Macromolecular Design. It is led jointly by Professor Tom Davis (Engineering), Professor Maria Kavallaris (Medicine), and Professor Justin Gooding (Science).
Professor Kavallaris says steps towards the first nanomedicine breakthroughs have already been taken. They involve the use of organic nanoparticles to deliver gene-silencing therapy and drugs directly to cancer sites.
“Using nanomedicine we work with engineers and chemists to custom-design the vehicles that will deliver a treatment direct to the site of the disease. Imagine them as tiny cargo carriers,” Kavallaris says.
“As a cancer researcher, the possibility of being able to specifically target cancer cells and spare the normal cells
– which are often unintentionally affected by chemotherapy – is a major advancement.”
Apart from delivering improvements in health, another of the centre’s aims is to establish the International NanoMedicine Conference in Sydney as a leading conference in the Asia–Pacific region. In July, 240 of the world’s leading researchers in the field attended the third instalment of the conference, which organisers say was an “extraordinary success”.