Knowing nano and when to say "no"

Knowing nano and when to say "no"

Technology and medicine at the nanoscale has the potential to solve countless issues from climate change to cancer. But the uncertainty surrounding this area also poses serious questions for regulators about if and when to draw a line.

Clothing, household appliances, food packaging, sunscreen and cosmetics are examples of everyday objects seen and used so often that we barely pay attention to them. They are useful, sure, but are they exciting? No, not usually. But what about when each of these items is made or infused with technology on the nanoscale? That’s when things get interesting. Carbon nanotube-infused graphite can make very strong but light tennis rackets. Silver nanoparticles can prevent any bacteria from reaching a wound. And that’s just what nanotechnology is achieving now. The potential for what nanoparticles and nanotechnology could achieve in the future is astounding - from providing better alternatives to cancer treatment to achieving multiple environmental goals by combatting issues in solar energy technology, pollution and water treatment.

But before understanding even the basics of what nanomedicine is, an introduction to the nano world in general is necessary (especially if you’re like me and have a limited understanding of science). All around the world scientists from every field are working together to study these tiny worlds that can have huge, unfathomable impacts on almost every aspect of life. While scientists have been working with these nanoparticles for centuries, the recent invention of new tools, especially the scanning tunnelling microscope, has made it much easier to work with nanomaterials. This is because the technology I am talking about is small – so small, in fact, that the human eye alone can’t see it. To provide some perspective: one strand of human hair is approximately 80,000 nanometres wide and one nanometre is one billionth of a metre. This means it would take 800 100-nm particles, side by side, to match the width of a human hair.

“There are nanoparticles floating around in the environment, like volcanic ash, but we’re not so interested in the naturally occurring ones,” Dr Jennifer Moore tells me after I sit down with her for a discussion on nanotechnology’s incorporation in medicine. “We’re interested in the human made, manufactured nanomaterials, which happens in labs right here on the Otago campus.” Jen is a lawyer, social scientist and health scientist with qualifications and training in all these disciplines. She has work experience as a legal and policy advisor for the New Zealand Law Commissioners and lectured in the Public Health Department at Otago and the Health Sciences Department at Monash University. Jen is now a Senior Research Fellow in the Faculty of Law and the Acting Director of the Legal Issues Centre. It’s safe to say that Jen knows what she is talking about.

Although the definition of nanotechnology itself is contested, most commentators agree that nanotechnology refers to a multidisciplinary field involving the manipulation of matter at the atomic and molecular scales. Engineered nanomaterials have greater surface area to volume ratios than at larger sizes, which increases their potential for biopersistence and reactivity – which also means that a sufficiently manipulated element can have several different properties at the nanoscale. A common example of this nanotechnology is sunscreen. Zinc oxide, the central ingredient for sun protection, at its bulk size, goes on the skin white or pink, but zinc oxide at the nanoscale appears clear when applied to the skin. The change in the optical properties of zinc oxide at the nanoscale is an example of the uniqueness of the nanoscale. “If we look at an element from the periodic table like gold, for example, when it is bulk it appears yellow but when it is at the nanoscale it appears red. The difference is due to the different optical properties of gold nanomaterials.”

Another example of an engineered nanomaterial is carbon nanotubes. This technology has raised concerns, particularly when people are exposed to it in the workplace. Research of carbon nanotubes suggests that their size and fibre shapes may lead to health effects similar to asbestos – prolonged inhalation of which can cause a myriad of serious illnesses, including malignant lung cancer. In one case Chinese workers who were exposed to nanoparticles in a factory started experiencing difficulties breathing. One worker died and several became severely ill. Later scans of the affected workers showed the nanoparticles in their lungs. Although these workers were not wearing personal protection equipment, he uncertainty about what caused these health problems means that this technology is still worth investigating. The trade and use of asbestos has been restricted or banned in many jurisdictions; whether the same will happen with the use of carbon nanotubes remains a pressing question.

Many predict that the medical industry will be impacted the most by nanotechnology. “In medicine there are quite a few different applications of nanotechnology, many of which are at the clinical trials phase, but there are some products that are already on the market,” Jen tells me. These medicines have been reformulated with nanoscale materials to improve their absorption, bioavailability and to make them easier to administer. Nanotechnology is also being used as a delivery vehicle for medicines to target selectively specific cells such as cancer cells.

Although nanotechnology is available in a range of products, New Zealand has only approved two nanomedicines. The first, Rapamune, is an immunosuppressant for the prevention of organ rejection in renal transplant patients. The second nanomedicine is Abraxane, which is indicated for the treatment of metastatic breast cancer. However, because of the huge potential market for nanomedicines and the new or uncertain risks different products may bring, there is a need for adequate regulation to both avoid adverse health ramifications and following backlashes on research and innovation in science.

When I asked Jen if she knew of any other examples of nanomedicine about to enter the New Zealand market she told me that although she had checked with Medsafe about this recently, they reported to her that until they receive applications for approval from companies and manufacturers, they were unable to advise her. However, the knowledge that other regulators in jurisdiction like the USA have already approved eighteen nanomeds, means that it is “highly likely that there will be further nanomeds entering the New Zealand market soon.”

Another example of the application of nanotechnology in medicine is nanorobots specifically designed to target cancer cells. Nanorobots are programmed to attack and reconstruct the molecular structure of cancer cells and viruses, while leaving the surrounding healthy cells intact. While this is generating “a lot of excitement,” Jen asserts, “It is the same properties of nanomaterials, which cause concern in these products. For example, the potential for nanomaterials to cross the blood-brain barrier and react with brain tumour cells is both a concern and exciting. Some nanomeds are able to target the cancerous cells and leave the healthy cells intact by crossing the blood brain barrier [a membrane that protects the brain from harmful chemicals in the bloodstream] and target cells. But “barrier” is a crucial word here. Should nanoparticles be crossing it? Maybe we don’t want these things getting into that space? We just don’t know yet.”

Therefore, despite these innovations, Jen favours and encourages the precautionary approach when it comes to regulating nanotechnology. She is enthusiastic about nanotechnology research and development but believes that New Zealand is not spending sufficient money or resources to ensure that we have adequate regulatory regimes in place to protect public health: “the advances are exciting, but we do not want a repeat of other scares, such as asbestos or genetic engineering. If adequate protections are not in place, the science loses too. If harm happens, there might be a knee jerk reaction, which would stall scientific progress.” With the Chief Science Advisor on nanotech projects in the United States, Andrew Maynard, also forming similar conclusions, Jen is not alone in her beliefs.

So what is actually going on with the regulation of nanomedicine in New Zealand? While nanomedicines are not regulated by their own Act, they are instead regulated by the Medicines Act 1981. Because this existing legislation was drafted before nanomedicines entered the market and is not designed to deal with the novel and unique properties of some nanoscale chemical substances, nanoparticles are “illuminating” and “exacerbating existing legislative imperfections,” Jen wrote in her research. Furthermore, “rapidly developing nanomedicines using mechanical chemical and optical properties at the nanoscale will create classification challenges. Such products will integrate multiple modes of actions in a novel manner and blur the boundaries between mechanical and pharmacological actions.” Yet Medsafe (a business unit of the Ministry of Health) still do not single out nanomaterials as requiring special assessment.

The three categories of New Zealand’s regulation of medical products in the Medicines Act are: medicines; medical devices; and related products. The need to improve NZ’s regulation of medical products has been emphasised since at least the 1990s; however, proposed changes to NZ’s Medicines legislation in the Medicines Amendment Bill 2011 aren’t entirely achieving this purpose. There are commendable changes – the most notable being the establishment of the new Trans-Tasman Regulatory Agency as a single regulatory agency for Australia and New Zealand, which will, over the next five years, assume complete responsibility for the therapeutic goods regulatory functions currently undertaken in both countries. Arguably, however, the Medicines Act is so deficient that, as Jen writes, “simply making amendments is similar to sewing a new patch of fabric to an outdated tapestry.”

For example, there remains no regulatory pre-market approval system for medical devices in New Zealand, even though most developed countries require this. While the pre-market approval process applies to medicines, including nanomedicines, it does not apply to medical devices. The Medicines Amendment Bill leaves this issue to be dealt with in an indeterminate time in the future. “This is an issue because it means that New Zealanders are using medical devices which have not been approved, which means that their safety has not been independently tested. This in turn means that there are potentially harmful products available for New Zealanders to purchase, creating a potential risk for consumers. My argument is that they should be dealing with it and dealing with it now.”

“We, in New Zealand, are far behind other jurisdictions that deal with these issues. I’m less worried about the medical devices that you can get in a pharmacy, what I’m worried about in particular are the nanomedical devices,” Jen clarifies. “Some of the best examples of these are a combination of devices and medicines like cosmetics that contain medicines with nano particles, supposedly to improve the product. All over the world these products are regulated differently; in New Zealand the question is: do they fall under our Medicines legislation or do they fall under cosmetics regulations? In the U.S. they have said this is a problem but they seem to be taking [a] hands-off approach. They do seem to be slipping through the cracks. I don’t want to be an alarmist – these products may be fine – but, for me, I would rather be prudent about it. I think science ultimately suffers if a product is harmful and we [don’t] have the appropriate regulation in place – often there’s a very immediate reaction to shut down the labs, stop the research, stop the innovation and then science can’t progress.”

Although Jen is “very hopeful” that the deficiencies she has outlined in her research will be met eventually, she provided me with a number of remaining deficiencies with the new Bill. There are no human and safety assessments for medical devices. There is no definition of combination product, which means that they may not be caught by legislation and consumers may be put at risk. There is insufficient mandatory labelling. The regulation under the Hazardous Substances and New Organisms Act is not sufficient because of trouble deciding whether nano is new or existing. Here Jen argues that they should be treating it as new because they would undergo more stringent safety assessment testing. “If nanogold,” for example, “is treated the same as bulk gold, it would be treated as ‘existing’ under the Act and it would just go through the normal procedure. But if it is treated as ‘novel’ then it would be treated differently. We still don’t know what could happen with these materials. We want to be prudent. It may be that it’s absolutely fine, but it’s better to be safe than sorry. I do really want to point out that not all nanomaterials are dangerous, however some have demonstrated properties that have the potential to be.”

But the regulation of nanotechnology isn’t totally unchecked. In fact, the University of Otago has a centre set up for this very purpose. The New Zealand Law Foundation Centre for Law and Policy in Emerging Technologies is the (very long) name for this research centre that examines the “legal, ethical and policy issues around new technologies,” which include biotechnology, nanotechnology, neurotechnologies and the Internet. The Centre’s overall vision is “to encourage the formulation of a framework for the systematic and comprehensive evaluation of emerging technologies, and to build New Zealand’s legal and policy capability in these developing areas.” The Centre is led by Director Associate Professor Colin Gavaghan (who also lectures a 400-level Law paper called Law and Emerging Technology). However, it was Lynda Hagen, the Director of the New Zealand Law Foundation, who contributed the funding to set it all up. “We’re really lucky in Otago because of this really amazing woman,” Jen remarks. “Lynda was sitting there one day watching the TV, seeing all this science happening, and she thought ‘where is the law in all of this? Where is the regulation?’ And now we have cool research being done on these sorts of topics. If it wasn’t for her, I wouldn’t be doing this. This centre is unique to Dunedin and the Law and Emerging Technology course is the only one I know of on this topic in New Zealand.”

The world of nanotechnology, particularly nanomedicine, is incredible. However, innovation can come at huge costs. As Jen stresses, “it is crucial to have a regulatory regime that can deal with the challenges presented by the influx of new nanoproducts onto the market.” But even for the experts, when it comes to regulating uncertainty, the “how” remains the big question.
This article first appeared in Issue 13, 2014.
Posted 2:07pm Sunday 25th May 2014 by Loulou Callister-Baker.