Jason Alderson; 21^st Century Legal Issues

I. Regulatory Challenges Presented By Nanotechnology

A. What is Nanotechnology?

Nanotechnology, less popularly known as molecular manufacturing, has within the last several years literally exploded onto the scene—both in media hype and government funding. Nanotechnology has the potential to impact areas as diverse as “materials and manufacturing; electronics, computation, and information technology; aeronautics and transportation; chemical and pharmaceutical development and production; and national security.”[1] The breadth of the technology has even caught the attention of the world’s leading governments, as exemplified by the United States passing in late 2003 the 21^st Century Nanotechnology Research and Development Act.[2] The specifics of the bill give an inkling of nanotechnologies perceived importance to the American economy in the coming century: an appropriation of $3.7 billion spread over four years.[3] The American initiative authorizes the President to create a permanent National nanotechnology Research Program, which in turn is designed to encourage the cooperation of various prominent research universities across the United States.[4]

Given its potential in so many varied areas, it is helpful to nail down what precisely nanotechnology is. Quite simply, molecular manufacturing involves manipulating matter on an atom-by-atom or molecule-by-molecule basis to attain desired configurations—seemingly only limited by ones imagination.[5] Most contemporary industrial manufacturing processes are based on top-down technologies—i.e., they take larger objects and make them smaller. Conversely, nanotechnology imitates the products of living organisms: tiny molecular machines, such as cells and organelles, work from the bottom up.[6] By organizing individual atoms and molecules into particular configurations, these molecular machines are able to create works of astonishing complexity and size, such as the human brain, a coral reef, or a redwood tree.[7] Nanotechnology has the potential to work in a similar fashion; atoms will be specifically placed and connected, at very rapid rates. Unlike living organisms, however, nanodevices would not be limited by their constraints—i.e., they would not have to be made of protein, or other substances readily extractable from the natural environment, nor would they have to be capable of reproducing themselves.[8] Instead, they could be constructed from whatever material, and in whatever fashion, is most suited to their task. Known as assemblers, these tiny devices would be capable of manipulating individual molecules very rapidly and precisely.[9]

At this point, its interesting to put the nanoscale in perspective; “nano” is the prefix for a billionth, so the application of nanotechnology is interested in processes that are taking place on the scale of roughly 1 to 100 nanometers, or a billionth of a meter up to one-hundred billionths of a meter.[10] By comparison the human hair, at 80,000 nanometers, is gigantic.[11] Even the human red blood cell, at 1000 nanometers or one micrometer, is a relative heavy weight and by most estimations large on the nanoscale.[12]

That man now possesses the ability to manufacture precise materials at the nano-scale is truly astonishing. In fact, the poster-child of nanotechnology and nanoscience is the carbon nanotube, coming in at a whopping one to two nanometers in diameter.[13] Once commercially feasible, a spectrum of applications becomes accessible. These include conductive plastics, advanced composites, and as delivery systems for pharmaceutical agents.[14] Similar particles are already in play commercially in nanomedince—one of the areas of nanotechnology to break out of the lab. Take, for example, nanosilver, which is 22 nanometers in diameter and manufactured as a superior form of anti-microbial agent—with possible uses on burn wounds.[15] . Another example is titanium dioxide as used in sunscreen protection. As a pigment of white paint, titanium dioxide is not a desirable substance to spread on human skin, despite its qualities as an excellent diffuser of UV radiation. But using nanotechnology, a company in the US figured out to make nanoscale titanium dioxide—which is invisible, unlike its non-nano ancestor. [16]

B. Nanotechnology as a Regulatory Challenge

As mentioned above, one of the few areas to see nanotechnology applied outside of a laboratory environment is that of nanomedicine. Exposing the problems encountered by nanotechnology is this area is likely to shed some light on a larger problem presented by nanotechnology: how once tidy regulatory distinctions are likely to be broken down in countless other fields.[17] By exposing the need to deal with antiquated legislation, part C of the paper discusses the larger question of how much regulation is desired, and suggests the model adopted with resounding success by the biotechnology industry: once focused based on professional ethics.

Briefly, nanomedicine has been defined “as the monitoring, repair, construction and control of human biological systems at the molecular level, using engineered nandevices and nanostructures.”[18] Nanomedicine has far outpaced other nano application partly on the collective resources of the world’s drug giants; almost every drug company in the world has begun to engage in nanotechnology research.[19] Current applications of nanomedicine range from research involving diagnostic devices and drug delivery vehicles to robot that can enter the body and perform specific task.[20] In the near future, applications of nanomedicine will involve engineered molecules to develop drugs, drug delivery techniques, diagnostics, medical devices and enhanced gene therapy and tissue engineering procedures.[21]

1. Classification as Drugs or Devices? Traps for the Unwary

Illustrative of the legal and regulatory landmine posed by nanotechnology is whether medical applications of nanotechnology would be regulated as drugs, devices or something else entirely. [22] The Federal Food, Drug and Cosmetic Act defines “drug” as:[23]

(A) articles recognized in the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, or official Nation Formulary, or nay supplement to any of them; and (B) articles intended for use in the diagnostics, cure, mitigation, treatment, or prevention of disease in mane or other animals; and (C) articles (other than food) intended to affect the structure of any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C) . . .[24]

A device is defined as:

an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part or accessory, which is-

(1) recognized n the official National Formulary, or the United State Pharmacopoeia, or any supplement to them,

(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease, in man or other animals, or

(3) intended to affect the structure or any function of the body of man other, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.[25]

In short, the statue provides that treatments that operate through mechanical means are to be treated as devices; those that rely on chemical means are considered drugs. A manufacturer can submit a request to have the product characterized as a drug or device, and a combination thereto.[26] A manufacture may prefer that the product be characterized in a particular fashion for a number of reasons, chief among them the differences between the approval process for devices and the approval process for drugs and biologicals.[27] There are statutory differences in approval times, and there may be a greater likelihood of securing approval for a product if it is designated as a device, as opposed to a drug.[28]

Throughout the 1990s the agency and manufactures were generally able to determine if a product was a device or a drug because the products coming out the research pipe clearly fell into a statutorily defined category.[29] But as nanomedicine enters the fold, classification will become increasingly difficult for two reasons. First, the ability to operate at the nano level will enable manufacturers to combine different types of components in producing a single therapy.[30] Second, in the long run, sophisticated nanomedical products will blur the distinction between “mechanical”, “chemical”, and “biological” and make it difficult to determine if a product is a drug or device.[31]

To help elucidate the blurring of these present-day distinctions, consider one proposed use of medical nanotechnology: the removal of atherosclerotic “plaque” from coronary arteries.[32] Otherwise known as the hardening of the arteries, plaque is composed mainly of cholesterol, calcium, and other substances exceedingly difficult to remove, and as such, a major precursor to heart disease.[33] Current removal techniques involve the use of devices commonly found at Home Depot: wires, drills, balloons, and lasers.[34] However, proponents suggest that nanotechnology is ideally suited for the task of continuously removing damaging plaque around the clock.[35] The size of bacteria, these pre-programmed nano-cleaners could be injected into the body in very large numbers.[36] Once the plaque deposits are found, the nano-cleaners could scrape the plaque away—molecule-by-molecule—and thereby prevent their damaging accumulation. [37]

The manner in which our nano-cleaner works, is the regulatory rubric: if the nanorobot effects the removal of plaque from an artery by mechanical force (e.g., if that force removes the plaque in tiny bits), then the nano-cleaner is a device; but if the nanorobot effects such removal by “chemical action” (e.g., a solvent or binder with the bloodstream), then the nanorobot is arguably a drug.[38] Further complicating matters is that nanotechnology will invariable blend the two—devices and drugs—into one unit, and distinguishing between the two at a micro scale is less clear.[39] If the tiny bits of plaque are individual cholesterol molecules or calcium action, it is unclear if the removal action is chemical or mechanical.[40] Researchers posit that it is easy to imagine a plaque destroying nanorobot that uses a chelating device, by means of a crawlike molecule that is chemically sticky to the plaque molecules.[41] The removal operation would entail the nano-cleaner reaching out to bond with the plaque molecules, retract, and pulling them free to be broken down in the bloodstream.[42]

As the above example makes clear, a major barrier to the use of current legislation to govern medical nanotechnology is linguistic—many nanoproducts will likely use forces not described or included in current legislation. Without revision of the current laws and regulations, accurate governance of a technology that employs entirely new mechanisms will be elusive—resulting in an increasing number of jurisdiction disputes. The danger, however, then becomes one of overregulation as overzealous lawmakers enact legislation that all too often encompasses not what is real, but irrational fears that could potentially cripple an industry. Are there any alternatives to willy-nilly overhauls? The answer, encouragingly for the burgeoning nanotechnology industry, is yes.

C. As the Foregoing Suggest, Regulatory Overhaul is Needed, but in Moderation.

In order not to throw wet-sand into the gears of what truly promises to be spectacular technology, the foregoing call for regulatory overhaul must be tempered in order to foster robust civilian research. Some scholars posit a regulatory scheme modeled after the biotechnology industries early days. In the early 1970s, when it became apparent that genetic modification was becoming feasible, some scientist became worried about potential dangers.[43] Over 100 scientists met and discussed those dangers at the Asilomar I Conference in 1973.[44] The result of the conference was that scientist agreed that research in certain potentially dangerous areas should not progress until the subject had been studied.[45] In 1975 the scientist met again at “Asilomar II” to develop more detailed guidelines, which later became the basis of governmental regulations covering biotechnology research funded by the National Institutes of Health.[46] The guidelines—though modified through the years and knowledge increased—still remain intact, and are generally followed on a voluntarily basis industry wide.[47]

Critics have generally labeled the biotechnology regulatory scheme a resounding success; the horrible scenarios first envision by early nay-sayers have neither materialized nor turned out to be a real threat.[48] Just as important, the biotechnology industry has exploded onto the scene—all within the confines of a modest regulatory regime.[49]

The central tenant of the biotechnology model—professional voluntariness coupled with strenuous study into the unknown before research commences—is readily adaptable to the emerging field of nanotechnology.[50]

1. Research Regulation

The real problem with nanotechnology is not abuse, but accidents. For nanotechnology, this chiefly means ensuring that research with self-replicating systems (replicators) is conduced under conditions that ensure none will escape the laboratory, and that if such escape did occur, the replicators would be unable to reproduce in the wild.[51] Possible regulatory measures include:

a. Access Limitation

Only allow licensed dependable professionals to work with nanotechnology, or at least those areas deemed inherently risky (e.g., general-purpose self replicating devices, which might be easier to reprogram in destructive ways).[52] Such an approach finds parallels in the regulation of explosives and toxic substances.

b. Export Controls

One might attempt to limit the spread of nanotechnology to hostile or irresponsible nation-states through export controls, an approach used for years in the defense industry with mixed degrees of success.[53] A good example is that of nuclear programs—where large conspicuous plants and significant quantities of rare fissionable materials are necessary. Whether nanotechnology requires the same outlays is questionable.

c. Professional Ethics

The single most successful example of technology control of the last century was the regulatory regime established for biotechnology.[54] In large measure, the regulatory success of the biotechnology arena is more the product of professional self-regulation, culture and expectations than of harsh regulatory systems.[55] Applying this approach to the nanotechnology community has a number of advantages: (1) “if the nanotechnology community in general can be imbued with positive values, this approach produces a large number of regulators who can identify and respond to improper conduct that governmental authorities would be unlikely to notice”[56]; (2) “if such an approach is regarded as morally binding by large numbers of people in the field, it is likely to be obeyed even under circumstances where formal legal controls would be unable to operate”[57]; and (3) “such attitudes are likely to be self-reinforcing, spreading from those initially adopting the attitude of to coworkers.”[58]

D. Nanotechnology’s Own Asilomar Conference? The Foresight Guidelines on Molecular Nanotechnology

Knowing that the government eventually adopted a version of the Asilomar scheme with respect to biotechnology, the Foresight Institute conducted a workshop in the spring of 1999 aimed at drafting a set of guidelines for the budding nanotechnology industry. The conference, which included individuals from the scientific, defense, environmental and legal communities, undertook considerable discussion of the proper approach for nanotechnology regulation before producing draft guidelines.[59] Since its adoption, the guidelines have undergone extensive revisions—much like the biotechnology Asilomar guidelines—in an effort to reflect current understanding and expunge flaws. In fact, the Foresight Guidelines resemble guidelines for regulatory drafters rather than regulations themselves, but it gives the reader where the government is headed as nanotechnology comes into its own:

(1): People who working in the MNT (molecular nanotechnology) filed should develop and utilize professional guidelines that are grounded in reliable technology, and knowledge of the environmental, security, ethical, and economic issues relevant to the development of MNT.

(2): Artificial replicators must not be capable of replication in a natural, uncontrolled environment

(3): Evolution within the context of a self-replicating manufacturing system is discouraged

(4): Any replicated information should be error free.

(5): MNT device designs should specifically limit proliferation and provide traceability of any replication systems.

(6): Developers should attempt to consider systematically the environmental consequences of the technology, and to limit these consequences to intended effects. This requires significant research on environmental models, risk management, as well as the theory, mechanisms, and experimental designs for built-in safeguard systems.

(7): Industry self-regulation should be designed in whenever possible. Economic incentives could be provided through discounts on insurance policies for MNT developmental organizations that certify Guideline compliance. Willingness to provide self-regulation should be one condition for access to advanced forms of the technology.

(8): Distribution of molecular manufacturing development capability should be restricted, whenever possible, to responsible actors that have agreed to use the Guidelines. No such restrictions need apply to end products of the development process that satisfy the Guidelines.[60]

E. Conclusion

As nanotechnology continues to develop, the debate over regulation will likely intensify—especially as antiquated regulations are exposed by nano-products hitting the marketplace. Besides creating costly traps for the unwary, overhauling regulations after the fact is dangerous, and often done in an injudicious knee-jerk manner. The danger then becomes one of overregulation, and the corresponding result that many emerging advancements are stillborn. For this reason, the Foresight Guidelines provides not only some insight as to what an overall regulatory might look like, it serves to avoid the danger that has befallen other industries when Congress suddenly discovers, in unflattering circumstances, a new technology. Congress usually reacts only to intense media attention, and then moves rapidly to regulate—usually to everyone’s subsequent detriment (consider the Patriot Act). The presence of the Foresight Guideline serves to mitigate this: it represent widespread forethought on the subject that will help ensure, should a spasm of regulatory interest hit the industry, the more thoughtful, constrained approach that has served the biotechnology industry so well.

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[1] Edward Etzkorn & Susan Hackwood,¸ Nanoscience and Nanotechnology: Opportunities and Challenges in California , California Council on Science and Technology 99, http://www.ccst.us/ccst/pubs/nano/nanohome.htm (last visited Apr. 04, 2004).

[2] R. Colin Johnson, Nanotech R&D Act Becomes Law, EETIMES, Dec 03, 2003 (last visited on April 6, 2004), http://www. Eetimes.com/article/showArticle.jhtml?articleId=18310442 (last visited Apr. 06, 2004).

[3] Id.

[4] Id.

[5] Glenn H. Reynolds, Nanotechnology and Regulatory Policy: Three Futures, 17 Harv. J.L. & Tech. 179, 181-183 (2003).

[6] Id.

[7] Id.

[8] Id.

[9] Id.

[10] Dr. Barry Newberger, Intellectual Property and Nanotechnology, 11 Tex. Intell. Prop. L.J. 649, 650 (2003).

[11] Id. at 650-653

[12] Id.

[13] Id.

[14] Id.

[15] Id.

[16] Id.

[17] Glenn H. Reynolds, Legal Problems of Nanotechnology, An Overview, 3 S. Cal. Interdisc. L.J. 593, 606 (1994).

[18] Robet Freitas, Nanomedicine 2, (1999), available at http://www.foresight.org/Nanomedicine.

[19] John Miller, Beyond Biotechnology: Fda Regulation of Nanomedicine, 4 Colum. Sci. & Tech. L. Rev. 5, 5-15 (2003).

[20] Id.

[21] Id.

[22] Id.

[23] See Reynolds, supra note 12, at 605.

[24] 21 U.S.C. § 321(g)(1) (2001).

[25] § 321(h).

[26] Food and Drug Modernization Act of 1997 § 123(d)(1), 21 U.S.C. § 301 (2003).

[27] See Miller, supra note 14, at 5-15.

[28] See Miller, supra note 14, at 5-15

[29] See Miller, supra note 14, at 5-15

[30] See Miller, supra note 14, at 5-15

[31] See Miller, supra note 14, at 5-15

[32] See Reynolds, supra note 12, at 610.

[33] See Reynolds, supra note 12, at 605.

[34] See Reynolds, supra note 12, at 605.

[35] See Reynolds, supra note 12, at 605.

[36] See Reynolds, supra note 12, at 605.

[37] See Reynolds, supra note 12, at 605.

[38] See Reynolds, supra note 12, at 605.

[39] See Reynolds, supra note 12, at 605.

[40] See Reynolds, supra note 12, at 605.

[41] See Reynolds, supra note 12, at 605.

[42] See Reynolds, supra note 12, at 605.

[43] Glenn H. Reynolds, Nanotechnology and Regulatory Policy: Three Futures, 17 Harv. J.L. & Tech. 179, 198 (2003).

[44] Id.

[45] Id.

[46] Id.

[47] Id.

[48] Id.

[49] Id. at 200.

[50] Id.

[51] Id. at 201.

[52] Id. at 202.

[53] Id. at 202.

[54] Id. at 203.

[55] Id. at 203.

[56] Id.

[57] Id.

[58] Id.

[59] See FORESIGHT INST., FORESIGHT GUIDELINES ON MOLECULAR NANOTECHNOLOGY (2000), at http://www.foresight.org/guidelines/current.html (last visited Apr. 1, 2004).

[60] Id.