Category: Research

EU logoAs various articles on this blog (Search: EU) have demonstrated over the past couple of years, the EU has been more proactive than the U.S. in targeting potential health and environmental risks posed to consumers by nanomaterials and seeking to generate and compile relevant and helpful information with an eye toward appropriate regulation.  The EU scientific panel is now calling for comments on opinions of the EU Scientific Committee on Consumer Safety (SCCS) on several nanosubstances used as sunscreens in cosmetics.

The opinions posted for comment indicate what is known about these substances and point to the gaps in the studies.  For example, with regard to dermal absorption of titanium dioxide nanoparticles, SCCS states, in part: 

            “[T]here is a body of open literature on this subject. The evidence from these studies supports the conclusion that TiO2 nanoparticles are unlikely to penetrate across the skin to reach viable cells of the epidermis. . . . Studies have also shown that TiO2 nanoparticles do not penetrate the (simulated) sunburnt skin.

            – Despite the extensive database showing a general lack of TiO2 nanoparticle absorption via the dermal route, there are a few gaps in the knowledge. For example, it is not clear whether TiO2 nanoparticles will be able to penetrate through cuts and bruises, or over repeated or long term applications of a sunscreen formulation.

            – A number of studies have indicated that TiO2 nanoparticle can enter the hair follicles and sweat glands, and that they may remain there for a number of days. This is a scenarioin which TiO2 nanoparticles are likely to get and remain in a close proximity to the living cells for a length of time. A photocatalytic nanoparticle in such a situation may cause . . . potential harmful effects when exposed to sunlight. . . . [M]ore data would be needed to justify the use of those TiO2 nanoparticles in skin applications that have a considerablelevel of photocatalytic activity.”  (Scientific Committee on Consumer Safety SCCS,Opinion on Titanium Dioxide (nano form), p. 97)

The document also indicates the need for study of the potential of these substances of the nano-related properties of the substances to be mutagenic or genotoxic.  (p. 97-98)

These few small examples of the more extensive information contained in the opinions gives a sense of where the SCCS’s attention is currently on nanosubstances in cosmetics, which is one of the most pervasive uses of nanosubstances in consumer use.  With study of such materials moving along in laboratories around the world, it is essential that the information be collected and evaluated to determine what risks, if any, may be presented to consumers by the nanoscale properties of the substances.  The EU is moving in the right direction.

All of the SCCS opinions are available at


nano 3The National Nanotechnology Initiative (NNI) recently held a Stakeholder Workshop for the purpose of assessing and strategizing in anticipation of the next version of the NNI Strategic Plan, a draft of which is due in late 2013 or early 2014.  Stakeholders from industry, government, and academia attended the workshop.  Participants considered questions related to technical challenges; commercial nanotechnology; environmental, health, and safety considerations; infrastructure needs; and ethical, legal, and societal implications of nanotechnology.

On the subject of environmental, health, and safety considerations, one report from the workshop indicated that NIOSH officials have recommended folding these matters into the other goals, rather than maintaining a separate approach.  The officials noted that of the $1.65 billion in federal funding allocated in FY2013 for nanotechnology research and development, environmental, health, and safety initiatives constituted only 7.6% of those funds.

Some of the other issues addressed, according to the report were:

1.  Improving communication among researchers.

2.  Balancing availability of research with confidentiality of proprietary information.

3.  Developing a common dose metric for research.

This news report may be found by subscription at:

Robert Iafolla, Include Safety, Environmental Concerns in Strategic Plan, Nano Researcher Say, 115 BNA Daily Env’t Rep. A-8 (June 14, 2013), available at


Whatever steps may be necessary to ensure that environmental, health, and safety concerns are at the forefront of the discussion about nanotechnology should be made a priority.


A detailed presentation of the Questions for Stakeholders for discussion at the 2013 NNI Strategic Planning Stakeholder Workshop, with further links, may be found at:

Lab beakerOne of the hallmarks of scientific knowledge is the ability of researchers to replicate results.  This has eluded scientists studying the health effects of exposure to nanomaterials for a variety of reasons.  Among the factors are:  the unavailability of standardized engineered nanomaterials for testing; differences among the many manufacturers of nanomaterials; lack of standard protocols; and variations in toxicity among particles due to the way the particles behave in certain situations. 

To attempt to resolve these problems, dozens of researchers from universities and NIOSH participated in what has been called the NanGo Consortium to conduct health studies on engineered nanomaterials using the same materials and developing standard protocols.  The program was developed by the National Institute of Environmental Health Sciences (NIEHS).

The inter-laboratory, multi-investigator Consortium defined some of the challenges it faced as follows:

“In addition to dose, there are multiple factors that influence the toxicity of ENMs, including surface characteristics, charge, and shape. Size alone is a major determinant as many bulk materials that are relatively inert become toxic when produced at the nanoscale. . . . Determination of which ENMs will present the greatest potential threat to human health depends on relative toxicity, and on the potential for exposure.”  (pp. 5-6)

The Consortium conducted two broad sets of studies.  The first involved rats and mice exposed to carbon nanotubes and titanium dioxide, and measured pulmonary inflammation.  The Consortium concluded:  “The results presented and discussed herein demonstrate that a standard protocol can be used across multiple laboratories to yield similar results in the pulmonary inflammatory response.” (pp. 6-7)  The researchers are optimistic that with this start, there will be opportunities to determine the impact that exposure to nanomaterials may have on human at the preventive stage.

The second study examined the effects of carbon nanotubes, titanium dioxide, and zinc oxide in vitro in laboratory container studies.  The Consortium noted:  “A significant finding of this study was that the development of harmonized in vitro assay protocols made it possible to achieve reproducible results among different laboratories.” (p. 16)  This study, the Consortium concluded, “provides new information on the relative in vitro bioactivity of a large group of diverse ENM that can be used to inform future strategies for in vitro testing and predicting in vivo outcomes.” (p. 6)

These studies move researchers in the direction of being able to replicate results and ultimately draw reliable conclusions about the potential health hazards of exposure to nanomaterials, leading to effective regulation.

The NIEHS NanoGo Consortium reports are available at


On March 20, 2012, the U.S. Supreme Court handed down its decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S. Ct. 1289 (2012).  A year ago, when the Court decided to hear the case, I wrote about it in this blog.  Now – a little belatedly – I am discussing the Court’s decision, as it has given the biotech industry reason to be concerned about its scope.

Prometheus was the sole and exclusive licensee of certain patents on methods for determining the optimal dosage of thiopurine drugs used to treat autoimmune diseases.  When Prometheus sued Mayo for patent infringement, Mayo argued that the patents in question were invalid because they claimed subject matter unpatentable under the Patent Act, 35 U.S.C. § 101. Specifically, Mayo argued that the patents impermissibly claimed natural phenomena – i.e. the correlations between drug metabolite levels and efficacy and toxicity – and not patentable inventions.  The district court had agreed with Mayo, but the Federal Circuit Court of Appeals reversed and held the patents valid.  In a unanimous opinion written by Justice Breyer, the Supreme Court reversed the Federal Circuit, stating that the Prometheus patents were invalid under § 101 because the process incorporates the unpatentable laws of nature and “well-understood, routine, conventional activity previously engaged in by researchers in the field.”  (p. 1294)  The Court stated:

    “If a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself.” (p. 1297)

The Court determined that the patent in question in this case did not have such “additional features.”  The Court was especially concerned that future innovation could be stifled by allowing patents on certain uses of the laws of nature.  The Court said that the measurement processes at issue in this case stated such a broad use of conventional procedures that they could be read to monopolize the field, making them unpatentable subject matter.  The Court stated:

    “We need not, and do not, now decide whether were the steps at issue here less conventional, these features of the claims would prove sufficient to invalidate them. For here, as we have said, the steps add nothing of significance to the natural laws themselves. . . .The presence here of the basic underlying concern that these patents tie up too much future use of laws of nature simply reinforces our conclusion that the processes described in the patents are not patent eligible . . . .” (p. 1302)

Not surprisingly, the decision has raised red flags in the biotech industry, particularly in the areas of medical diagnostics and personalized medical treatments.  In an article in the most recent issue of the ABA Journal, author Steven Seidenberg examined the impact that the Mayo decision is likely to have on such innovation.  The experts consulted for the article all had concerns about the breadth of the decision and the chilling effect it might have on future innovation.  See Steven Seidenberg, New Laws of Nature Law:  Ruling Questions Scientific Patents,ABA Journal (Jul. 2012), at 20-21.

There are some issues that may need resolution going forward:

●  When a procedure is “less conventional” than the procedure at issue in Mayo, will it be patentable?  Or must it be “unconventional” to be patentable?

●  What exactly is a “conventional procedure”?

●  To what degree does the case represent a broadening of the “laws of nature” exception to §101?Those in the biotech industry will need to mull over this decision as new innovations are developed.

Those in the biotech industry will need to mull over this decision as new innovations are developed.

The Supreme Court’s decision is available at

 The ABA Journal article is available at

Many of the posts on this blog have addressed the regulation dilemma of whether to incorporate nanomaterials into the existing regulatory framework or develop separate regulations to manage their potential hazards.  This same dilemma is playing out in a slightly different way through a public-private partnership on exposures to carbon nanotubes in consumer products.

The NanoRelease project is engaged in this effort, with the support of numerous organizations, including U.S. EPA, Environment Canada, HealthCanada, and the American Chemistry Council.  Undertaken by the Government of Canada, the project has selected multi-walled carbon nanotubes in polymer to begin its study of the nature of exposures to nanomaterials.  The study includes determining likely release scenarios, evaluating release measurements, and considering needs for laboratory testing.  The research foundation has stated:  “The NanoRelease project will foster the safe development of nanomaterials by supporting development of methods to understand the release of nanomaterials used in products.”  Among other things, the group pledges to develop a “state of the science” report.

A summary of the project is available at

Both the National Institute of Occupational Safety and Health (NIOSH) and the Consumer Product Safety Commission (CPSC) are very interested in the ongoing process.  But will the ultimate result be “consensus standards” for nanomaterials that are efficient and effective?  Will consensus standards be followed by industry without a direct mandate?

Bloomberg BNA’s Daily Environment Reporter quoted John Howard, the director of NIOSH, as saying:  “We want to make sure that if we are developing consensus standards . . . that people are reading them and that people are adhering to them.  Otherwise heavy-handed government regulation – that industry always objects to – will come into fore and then we’ll have a less effective control system, a less efficient risk management system.”  (quoted in Pat Rizzuto, Regulators, Industry Sorting Through Potential Exposures to Carbon Nanotubes, 122 Daily Env’t Rep. (BNA) A-9 (June 26, 2012) (by subscription))

Will industry and governments agree on standards?  If so, some measure of regulation will be necessary, but probably not the “heavy-handed” sort that concerned Dr. Howard.  Consensus standards can be incorporated into existing regulatory regimes, perhaps rendering unnecessary separate extensive regulation for nanomaterials.  But essentially we are circling the same issue over and over again:  Is it possible to avoid separate, independent, and perhaps “heavy-handed” regulation of nanomaterials in the interest of public health and safety?  No question that it is an important issue.  And it remains unanswered.

white-house-south-2007-djIn my most recent entry, I noted that the National Academies would be releasing a report by the end of January that focuses on researching the health and safety aspects of nanotechnology.  The report, A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials, was released January 25 in prepublication (i.e. uncorrected) copy.  A download, with significant restrictions, is available at

The study was initiated by EPA, which asked the National Research Council of the National Academies to conduct an independent study with the goal of developing a research strategy.  The report sets forth a conceptual framework for research on the environmental, health, and safety impacts of engineered nanomaterials (ENMs).

 The report explains why ENMs are difficult to place into a system of risk analysis.  In this blog, I’ve discussed the fact that the tiny size of nanomaterials gives them characteristics and risks different from the same materials in larger dimensions.  The report points out the vast diversity of characteristics of ENMs, as well as the fact that those characteristics may behave differently depending upon the environment in which the materials are located, including changing characteristics as the nanoparticles migrate.  Furthermore, the uncertainty about risks in all sectors – among developers, regulators, and consumers – demands a uniform strategy for assessing risks.  The report points out that little research has been done to date, notwithstanding the fact that even more complex ENMs will soon be available.

In other words, we needed a research protocol for identifying, analyzing, and managing the environmental, health, and safety hazards of ENMs yesterday.

One of the most significant points made in the report was the identification of “critical research gaps” that must be addressed.  Examples of some of the gaps:

More is known about inhalation risks than other routes of exposure because of earlier research on the effects of particle inhalation on the human body.

Basic information is lacking on the chemical and physical properties of the ENMs currently out there.

Gaps in knowledge exist regarding how ENMs move through and interact with the human body and in the environment.

How research is conducted in the laboratory must be modified to provide accurate information about the risks.  Standard testing protocols must be developed.

 The report goes on, and in the months to come I will look at various aspects of the report in individual posts on this blog. 

 Consistent with its findings, the report recommended changing the structure of the National Nanotechnology Initiative (NNI), which is too vast and fragmented to be effective in the ways that are critical.  The NNI’s authority covers essentially only coordination functions.  The report recommends that the entity that manages and implements the report’s strategy be one with “top-down” management and budget authority over the research.  This may not be the NNI at all.  The report notes that the NNI’s objective of promoting the development and uses of nanomaterials may conflict with its role in identifying and appropriately managing the risks of the technology.  Accordingly, the report recommends separating those objectives and restructuring the NNI.

It’s another beginning.  The follow-up report, in which the committee promised to assess progress toward the goals set forth in this report, isn’t due for a couple of years.  In the meantime, ENMs will continue to proliferate.  My recommendation is that all sectors exercise all due caution until more is known.

ref1394_x180-fThe National Academies have promised a report by the end of January 2012 on priorities (both short- and long-term) for studying the health, safety, and environmental effects of nanotechnology.  According to the National Academies, this report will address the following matters:  the properties of engineered nanomaterials; methods and technologies for “detecting, measuring, analyzing, and monitoring” engineered nanomaterials; what studies are needed; what testing methods need to be developed; the models for predicting impacts that should be developed; research priorities; and the criteria for evaluating research progress.  In its “Statement of Task,” the National Research Council has explained:

“The committee will take into consideration current and emerging uses of engineered nanomaterials and the scientific uncertainties related to physical and chemical properties, potential exposures, toxicity, toxicokinetics, and environmental fate of these materials.”

I will discuss the report when it is issued.  More information on the National Academies’ research strategy is available at

This is a promising developing to look forward to, but as with all things, the proof is in the, er, nanopudding (sorry, couldn’t resist).  Initiating a task such as this is daunting, with the result a framework for assessment, not the ultimate assessment.  But it is a necessary step in what is certain to be a long process.

In a separate project, the National Academies are considering more than the health, safety, and environmental effects of nanotechnology.  Pursuant to the Nanotechnology Research and Development Act (Pub. L. No. 108-153), Congress has mandated triennial reviews of the National Nanotechnology Initiative (NNI).  The National Academies’ National Research Council convened a committee to conduct the second such triennial review, and its report is due in 2013.  Much of the review will entail examining the economic impact of nanotechnology and ways to measure the value of nanotechnologies.

Information on the triennial review project is available at

The two projects discussed in this post demonstrate the efforts to address the two important aspects of progress in the uses of nanotechnology – understanding the health, safety, and environmental effects, and measuring the economic benefits of nanotechnology.

chip-makerAn interesting and potentially revolutionary development in magnetic storage of data was announced a couple of weeks ago.  Researchers at I.B.M. have reported the development of a new class of nanomaterials that could lead to the development of new, significantly smaller memory chips and disk drives that will both hold vast amounts of information and use less power than the current class of silicon chips.  The report (Loth, Baumann, Lutz, Eigler, and Heinrich, Bistability in Atomic-Scale Antiferromagnets) appears in the journal Science at Vol. 335, no. 6065, pp. 196-99 (Jan. 13, 2012), and has been widely reported in the news media.  There is much excitement over this development, both for its inherent promise for data storage and for its potential in other areas.  Analysts have suggested that other new nanomaterials may be forthcoming using some of the same general methodologies and approaches of these researchers.

 Among other media sources, this development has been reported in the New York Times:

John Markoff, “New Storage Device is Very Small, at 12 Atoms,” N.Y. Times, Jan. 12, 2012, available at

So while we are wowed by such progress, it only begs the same old question of what should be done to determine the hazards that the technology might pose to workers, the general public, and the environment.  As with so many of the technological developments using nanomaterials, there is little discussion of potential hazards at this juncture.  But when will we give some serious thought to them?  After the products are developed and marketed?  After adverse effects are manifested?  So maybe there won’t be any adverse effects.  But do we know that as we continue to be dazzled by the potential technological developments in the nanoworld?  At the risk of sounding very non-technological, maybe we need to refer back to that old adage – better to be safe than sorry.

asbestos-fibreI have written here about various ways in which nanomaterials may be comparable to asbestos – both in the ways nanoparticles may impact the human body and the ways the law may respond.  So it’s not surprising that one more comparison has emerged recently.

 Scientists from Brown University have studied the impact of carbon nanotubes on mouse cells.  Their study, published in the September 19, 2011 issue of Nature Nanotechnology, showed that certain types of multi-walled carbon nanotubes enter cells in a way that causes an immune response and cellular inflammation.  The physical properties of the nanotubes are responsible for this reaction.  As the researchers stated in their abstract, “cylindrical one-dimensional nanomaterials such as carbon nanotubes enter cells through the tip first.”  Certain nanotubes – those with end caps or carbon shells at their tips – seem to trigger the inflammatory reaction.  The researchers mention asbestos fibers in their abstract as being analogous (though they are clearly physically different) in this important aspect.

Does this mean that carbon nanotubes will create the same health problems that asbestos created?  Not necessarily.  Some might consider asbestos-related illness to be one of the major scourges of the last quarter of the 20th Century and well beyond.  Asbestos has shaped the law in relation to workplace safety and mass tort litigation, and has transformed industry.  Asbestos is a naturally occurring substance, and its use has been limited since the 1970s.  Its health effects, however, are ongoing because symptoms of asbestos-related disease typically occur after a latency period that may be quite long.

Nanomaterials, however, are engineered and represent new technology in a new technological world.  A new response is warranted.  What can be done going forward?  Scientists may be able to engineer carbon nanotubes in a way that will eliminate this particular inflammatory response.  But more research needs to be done before that.  For example, these same researchers intend to study whether nanotubes with others types of tips create the same or similar cellular response.

For now, we may be heading in the direction of “intelligent tip modification,” as the researchers refer to it.  Let’s hope we aren’t headed down the asbestos road again.


The abstract of the article may be accessed at


For a report on the Brown University study, see the following piece in the BNA subscription service:

Greg Hellman, Researchers Show How Carbon Nanotubes Pierce Cells, Leading to Inflammation, 18 Daily Env’t Rep. (BNA) A-12 (Sept. 20, 2011).



In May 2009, the American Civil Liberties Union and the Association for Molecular Pathology filed suit, in the United States District Court for the Southern District of New York, against the United States Patent and Trademark Office and Myriad Genetics. The complaint pertained to patents that were granted on the BRCA1 and BRCA2 human genes that are mutations correlated to the increased risk of breast or ovarian cancer.  Myriad Genetics designed a procedure to test for these mutations to indicate the likelihood of a woman developing either or both of the diseases.  The complaint asserted that patents on genes should not be allowed because they are violative of § 101, patentable subject matter, of the Patent Act, namely all three of the judicially recognized exceptions to patentability:  natural phenomena, laws of nature, and abstract ideas. Subsequently, the American Civil Liberties Union and the Public Patent Foundation filed a motion for summary judgment, in August 2009.  On March 29, 2010, the District Court found that the isolated segments of DNA utilized for the diagnostic tests were “not markedly different from native DNA as it exists in nature” and held the patents granted to Myriad were not valid.  Ass’n. for Molecular Pathology v. U.S.P.T.O., 702 F. Supp. 2d 181 (S.D.N.Y. 2010).

On July 29, 2011, the United States Court of Appeals for the Federal Circuit reversed the decision of the district court stating “the molecules as claimed do not exist in nature.”  According to a report on, Bruce Wexler, a partner in the law firm Paul Hastings, commented “[t]he appeals court has now held that isolated DNA is patent eligible, and it recognized that isolated DNA has a different molecular structure than DNA as it exists in the body. That is a very significant result that is very important to the biotech industry.”

This decision is equally important to the future of the nanotech industry because the starting point for nearly all nanoparticle inventions is the same as biotech – nature.  While it is well established that those materials found in nature are not patentable, the Federal Circuit has signaled its acknowledgement of the intellectual investment inherent in the advancement of science.  There would have been seismic effects on the future of biotech and nanotech development had the district court’s decision been affirmed.  For now, it is full steam ahead for the scientists and investors.   

For further information, see an earlier post I wrote – Patents on Genes and the Future of Personal Nanomedicine.

Read the full Federal Circuit decision here: