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Discussion Transcript

EurekAlert! Nanotechnology Portal

Past Transcripts:

Environmental Impact of Nanotechnology

Nanotechnology and Medicine

The Science of Nanofabrication


Dr. Phil Szuromi (moderator):

Good morning, and welcome to EurekAlert!'s online chat on the health and medical impacts of nanotechnology. I'm Phil Szuromi of Science Magazine, and I will be moderating our discussion with our expert panel, which includes Richard Siegel, James Baker and Jeffery Schloss. Richard Siegel is the Director of the Rensselaer Nanotechnology Center at Rensselaer Polytechnic Institute, and also serves on the President's Council of Advisors on Science and Technology (PCAST). James Baker, Jr. also serves on PCAST, and also founded the Center for Biologic Nanotechnology at the University of Michigan. Jeffery Schloss coordinates the development of nanotechnology strategy for the National Institutes of Health through his work with the National Human Genome Research Institute. Welcome Richard, James and Jeffery.



Dr. Phil Szuromi (moderator):

Before we start, I'd like to give each of you the chance to tell us a bit more about your research interests.



Dr. James Baker:

For background, I should say I am a physician by training. Our focus has been adapting nanotechnology for use in biological systems and medicine. We've examined a number of nanostructures for simplistic things like drug delivery, gene delivery, and more complex applications like the replacement of biological structures such as proteins or other types of materials. Our major focus is adapting synthetic nanostructures to be integral systems for biology and medicine. Our current work involves developing therapeutics from drug delivery systems to vaccines based on nanomaterials and also developing diagnostics and imaging agents based on nanoparticles.



Dr. Richard Siegel:

The main focus of our research efforts in the nanotechnology area at Rensselaer Polytechnic Institute is in creating new materials and devices based on nanoscale building blocks to enable new opportunities to help society. The effort is primarily on the directed assembly of these nanoscale building blocks to make new materials and devices. One of the most exciting current areas is in using biological molecules to help build these new materials whether they be biologically active or not. This has allowed us to create new materials with novel properties that have not been available before for a wide range of applications.



Dr. Jeffery Schloss:

At NIH, we have a number of programs that allow people to incorporate nanotechnology research into biomedical research in a number of different ways. Some of the research emphasizes the novel nanotechnology for applications to biology and medicine, and other research projects are attempting to solve basic biomedical problems for which nanotechnology promises an answer.



Carol Williams, University of Michigan in Ann Arbor:

For us novices, I hope someone will start with a basic explanation of nanotechnology...what it is, what's been done so far and perhaps an example or two of current applications.



rick weiss, washington post:

Dr. Siegel: What kinds of materials are you making, with what kinds of novel properties? Please give a couple of specific examples and why they would not be possible without nano.



Dr. Richard Siegel:

Nanotechnology really is a combination of nanoscience and a set of enabling technologies that utilize the fact that matter at very small length scales (less than 100 nanometers) have distinctly different properties than the same matter at larger length scales. Hence, the building blocks of matter below 100 nanometers can be used to create new materials and new devices for a wide range of applications that could not be created without nanotechnology. A couple examples of this which are in the marketplace today are high SPF sunscreens containing nanoparticles which allow excellent sun protection, transparency in the visible range and no apparent negative effects from skin reactions. Another example is the use of nanoparticle additions to plastics to increase their scratch resistance and strength while maintaining their low weight and visual characteristics important in the automobile industry. In both of these examples, fillers at larger sizes in either sunscreen formulations or in plastics would not work in the way that the nanostructured fillers do.



Salvatore Salamone, Bio-IT World:

How soon will we see nano-based products in the major medical areas including research devices (e.g., alternative or improved microarrays), clinical diagnostic devices, and drug delivery?



Dr. James Baker:

There are products that have been based on nanoscale materials that are already being used in clinical applications. One is a nanocrystal silver burn cream. The unique aspect of this material is that the small crystals have much more surface area than larger particles and are more effective in their antimicrobial action. In addition, in the next few years, many drugs that have been either stabilized or delivered with nanoparticles will start appearing in the clinics. A drug was recently approved that was stabilized by an albumin nanoparticle and other drugs will be delivered to specific cells using nanoparticle therapeutics.



Dr. Richard Siegel:

As a follow up, another example would be the use of nanosized anti-inflammatory drugs which have been utilized to increase the rise time in the blood of the patients to enable much more rapid release and relief than conventional delivery systems. The generic name of the drug is Naproxen.



Dr. Jeffery Schloss:

Regarding what nanotechnology offers that other approaches don't offer, the point is that by presenting the drug to the body in a different way, we may be able to use compounds that previously weren't therapeutically useful. We can change the way they are presented to the body because of the large surface-to-volume ratio.



Hickey Burr, Ann Arbor, U-M:

Because of their size, what is the potential for nanoscopic particles used in targeted drug delivery to be absorbed by cells other then those targeted? What is the potential for damage to normal tissue?



Dr. James Baker:

One of the real hopes for this technology is the ability to target special cells so the biological effect of a drug is made specific for any particular type of cell you are trying to affect. In that way, we would actually improve the efficacy of the therapy while decreasing the toxicity. This is certainly an improvement over regular drug therapy where the drug can be taken up by almost any cell. There is always potential that therapeutics or drug delivery systems could damage normal tissue, but the whole premise of targeted therapy is to reduce that likelihood.



Miguel Castillo, Journalist in Diario Medico. Spain.:

Will nanotechnology improve gene therapy? Will we see in the long term the use of nanodevices to delivery genes to the correct cells in order to treat genetic diseases?



Dr. James Baker:

A major problem with gene therapy has been the ability to deliver the genetic material to specific cells. People have attempted to use viruses for this application but that has resulted in problems due to immune responses to the virus. Nanoparticle delivery systems have the potential to improve delivery of genetic materials to cells and thus, facilitate gene therapeutics. Early data suggests that using very small particles with a large surface area could deliver enough genetic material to actually have biological effects in cells. This is one of the ways that nanotechnology may facilitate gene therapy.



Dr. Jeffery Schloss:

While delivery is certainly an important issue, aren't there other steps in the process of incorporating and expressing introduced DNA that require attention?



Dr. James Baker:

Certainly, there are technical issues related to the activity of the genetic material once it gets into the cell and its ability to produce the desired biological effect. However, the limiting step in most gene therapy applications has been just getting the material to the cell.



Rocky Rawstern, Oregon, USA. Nanotechnology Now:

Given the recent advances in nanoparticle research as it applies to medicine, what practical applications do you see coming to market within the next five years?



Dr. Jeffery Schloss:

We've already heard about some examples of pharmaceuticals, and there are several more that are in clinical trials. To the extent that some of those succeed and are approved, we'll likely see new medicines such as cancer therapeutics. There may also be some new products for molecular and medical imaging to improve, for example, MRI exams.



Dr. James Baker:

Nanotechnology is a very young science and most of the breakthrough advances are in early stage development. Because it takes up to eight to ten years to get approval for new therapeutics, there will be a significant delay with many of the more remarkable applications for nanotechnology. Thus, the five-year window is less likely to bring unique change, whereas the ten to twenty year window is probably when the more remarkable applications will be seen.



J. Ross, University of Michigan, Medical School:

How are these nanostructures metabolized, or rather excreted from the body? Also, can these devices be utilized in any region of the body, including the neuro area?



Dr. James Baker:

Different types of nanostructures are metabolized by different means. Some nanoparticles are small enough that they can actually be excreted unchanged into the urine. Others are broken down into component parts by the liver in a manner similar to proteins. Still other metallic nanoparticles are broken down into metal atoms that are then be recycled by the body. Therefore, the metabolism is unique to the type of particle that's being used. These devices have the potential to be utilized in almost any region of the body. The reason for this is they are small enough that they can escape the vasculature and enter cells directly. Many of the nanoparticles used for drug delivery or imaging applications are only slightly larger in size than proteins. Therefore, one might expect that they would be broadly dispersed throughout the body including the potential for entering the central nervous system.



Robert Bradbury, Seattle, Aeiveos Corporation:

Given the fact that all drugs meet the 100nm cutoff for "nanotechnology" and the fact that many drugs are designed to bind to and inhibit or activate specific receptors what makes any of the work being done under the "nanotechnology" banner different from computer-aided drug design or the selection of antibodies with specific binding properties (both of which have been around for a decade or more)?



Dr. James Baker:

The difference between traditional drugs and nanotechnology (as currently defined) is that the drugs are really based on small molecule chemistry. Nanotechnology is more related to the design and structuring of complex arrays of molecules in the less than 100 nanometer size range. So, whereas, a drug itself would not be considered nanotechnology, structuring that drug as part of the delivery system using other molecules that are specifically engineered and designed for an application would be considered nanotechnology.



Dr. Jeffery Schloss:

To expand on Jim's comment, in nanotechnology, we're talking about not only the therapeutic agents themselves, but combining the abilities to deliver those agents to specific regions or tissues in the body, to specific cells, perhaps to a specific location within a cell, and also to make release of the therapeutic responsive to a physiological condition -- all in the same particle.



Johnson Jayakar Joseph, Johnsons Medicom Ltd, India; Affl: Consultancy Development Centre:

Can you comment of the role of the antibody-antigen reaction--is the bottleneck for the hyper-synthetic nanobotic applications.



Dr. James Baker:

One of the major reasons for going to synthetic nanomaterials is to avoid the immune responses that have been observed to biological systems such as viruses. The hope is to create synthetic materials that have the same size as biological components but avoid the induction of immunity that has caused problems with gene therapy vectors or with other drug delivery systems. Many of the metal nanoparticles and polymers that have been used in nanosystems do not induce antibody responses and therefore are a major advance over viral systems. We will still need to be diligent, however, and monitor nanomaterials closely as they're used in larger numbers of people to assure that they are non-immunogenic and appropriate for use in medical and biological applications.



Matthew Levine, Research to Prevent Blindness, NYC:

Are there applications for nanotech in the area of vision repair / restoration / treatment (implantable drug delivery devices, sensors, etc.)?



Dr. James Baker:

There are specific research programs directed towards the area of vision restoration using nanotechnology. Artificial vision systems are under development at the University of Southern California, led by Dr. Mark Humayun, that offer the potential to replace the retina with artificial photo receptors. This work requires nanoscaled electrodes to specifically correlate with different cells in the brain to produce visual images.



Dr. Jeffery Schloss:

We should probably add that it's been tried in a few people. It's very early work with a reasonable amount of success--in other words, it's not just a lab device.



Dr. Richard Siegel:

In addition, nanostructured materials are being used to create precision cutting tools, such as scalpels for eye surgery, which are being used clinically in Europe today for difficult eye repair operations. These tools have the advantage of much greater sharpness and durability than previously available tools.



Elizabeth Tolchin, New Jersey, Genomics & Proteomics Magazine:

Good morning. My question is for Dr. Jeffery Schloss. Are there any specific research areas within the Institutes where nanotechnology is being implemented, and if not yet then where would you see it being applied in the future?



Dr. Jeffery Schloss:

We're trying to use nanotechnology in combination with a number of technological approaches to develop better technology for genomics and proteomics. A very promising, though certainly very speculative, applications of nanotechnology is for sequencing DNA. This is an exciting area because it would be a completely revolutionary technology approach while at the same time requiring substantive advances in physics and chemistry. The results could ultimately change the way we do experimental biology as well as changing the way we deliver healthcare. That is, if we could really sequence the DNA of individuals or extract the majority of relevant genomic information from individuals, our understanding of disease and health would be advanced and our ability to tune therapies to the individual would be enabled.



Elizabeth Tolchin, Genomics & Proteomics Magazine:

This is a follow up to my question to Dr. Schloss. Can you provide an example of how nanotechnology would be applied to the sequencing of DNA?



Dr. Jeffery Schloss:

One concept being pursued for using nanotechnology for DNA sequencing is to thread DNA molecules through pores that are essentially the same diameter as the DNA. The idea is that if one can design an appropriate sensor to distinguish between the different DNA bases, then one could conceivably sequence very long DNA molecules. If this works, it should be very rapid and very inexpensive. Of course, we don't know yet whether it will work.



Mark Burgess, editor The Biochemist, UK:

How much damage has Michael Crichton's book (Prey) done?



Dr. Richard Siegel:

The book Prey has certainly increased the awareness by the public of nanotechnology and the forthcoming movie based on that book will undoubtedly further help in this regard. It is clear that most science literate people understand the science fiction nature of this treatment of nanotechnology and the related fields of applied mathematics and computer science, because the book certainly dealt with more than nanotechnology. It's important for the scientific community to use this heightened awareness of nanotechnology to help educate the public about the potential positive aspects of this field, as well as some of the potential negative aspects which, of course, every new technology, from the advent of mechanical engines to the automobile to television, have engendered.



Dr. James Baker:

I think people need to remember that Prey is truly science fiction. Many of the concepts on which the book is based violate the laws of physics. While there obviously are concerns for adverse problems that could occur from nanotechnology, these concerns should be directed towards rational problems. The idea that nanomachines would coalesce to attack and eat humans is not rational.



Rocky Rawstern, Editor, Nanotechnology Now, Oregon, USA:

How do you as scientists help the public to understand the potential of nanomedicine? How can we as a society help insure that a nano-divide does not occur when it comes to distributing the benefits of nanomedicine to all?



Dr. James Baker:

Scientists need to take a lead role in educating the public about the potential for nanomedicine. By using the media to give real-life examples and visual representations of nanomaterials, we will be able to have people understand what is truly a real possibility and how it can benefit people's lives. The better educated the public are, the more supportive they will be of nanomedicine and the more rapidly we'll be able to develop nanomedicine applications. This relates to the second question. All healthcare is a societal issue that we need to deal with and the distribution of healthcare is one of the major issues our society will face as we move forward and our population ages. One of the hopes is that nanomedicines, nanobased health monitoring systems and nanodiagnostics can actually reduce the cost of healthcare to society. This will allow greater application of higher-quality healthcare to more individuals in our society, while at the same time, avoiding both the costs and pitfalls of current therapies. Let me give an example: To diagnose a tumor, we often have to use many different, expensive imaging studies, followed up by surgical procedures. If we can replace this with a nanomaterial, that could give a real-time diagnosis and allow earlier treatment of the disease before it becomes critical, we can save money in both the diagnostic and the therapeutic arena.



rick weiss, washington post:

Given the very different surface areas/reactivities of nanomaterials, do you think the FDA approach to testing and approving nano-based medicines and medical delivery systems (which, as far as I can tell, is not any different than for conventional products) has adequate precautions built in?



Dr. James Baker:

Clearly, nanomaterials provide a challenge to regulatory agencies. Current outlines for the review of nanomaterials are based on regulations developed for standard materials. The FDA is taking a number of steps to revise their process of evaluating nanomaterials and is having a national conference in Washington in March to address these issues. From these meetings, a broad consensus of additional analytical testing for nanomaterials should emerge.



rick weiss, washington post:

Dr. Baker, as a follow up: Does it seem backwards to you for the FDA to be approving nanodrugs and devices now and holding a conference to consider inadequacies later? Especially in this age of Vioxx/Celebrex, are you aware of any beefed up phase four/ post-marketing surveillance being asked of manufacturers of approved nanoproducts?



Dr. James Baker:

Most of the products that have been approved using nanoscaled materials are truly incremental advances over currently marketed products. The FDA is being proactive in early analysis of the more complex and unique nanomaterials that will develop the next generation of targeted drugs, genes, therapeutics and imaging agents. Conferences have been held already defining issues related to structure, function, and characteristics of nanomaterials and how they might interact with biological systems. The FDA is being very aggressive in obtaining data on this as soon as it becomes available.



Dale Litzenberg, Ann Arbor, University of Michigan:

Dr. Baker, would you please give an example of how nanomaterials may be used in real-time diagnosis of tumors?



Dr. James Baker:

In response to this question, a good example of how nanomaterials might aid in the real-time diagnosis of tumors would be a nanoparticle that could be detected through radiation or MRI studies that would be targeted to a tumor-specific receptor. Once injected into the body, these nanoparticles could identify tumors at a much earlier stage, when they could be readily treated. In addition, they might offer the potential for the induction of anti-tumor therapeutics in and of themselves through selective release of drugs or physical disruption of tumor cells.



Dr. Phil Szuromi (moderator):

But how good are such cell receptor profiles at this stage?



Dr. Jeffery Schloss:

This is an extremely important question and area of intensive research and it is where many NIH resources are being focused to explore basic biological mechanisms using nanotechnology and other methods. We understand very well that our knowledge of biological pathways and key nodes in those pathways is inadequate. At the present, we use this knowledge in the best ways we can, to improve diagnostics and therapeutics. NIH and other agencies are working aggressively to acquire deeper and more precise knowledge of these profiles.



Dr. Phil Szuromi (moderator):

We thank all of you for your participation today. Before we go, I'd like to let all of you have a chance to give us some final thoughts.



Dr. Richard Siegel:

It is clear even now in the very early stage of the development of nanoscience and nanotechnology that tremendous positive impacts on medicine and healthcare will result from nanotechnology in the future. Nevertheless, at this very early stage it is difficult to anticipate just how large this impact will be. However, clearly even today we see a number of examples of potential benefits that may result. Given sustained and increased funding by the federal and state governments and by industry these developments will go forward and greatly increase the future benefits to society.



Dr. James Baker:

One area that we haven't addressed is how tools developed in nanoscience will allow us to learn more about how biological systems function. Many of the structures in cells and organelles function in a nanoscale. We have been very effective in medicine, looking top-down at pathology to get an idea of disease processes, and bottom-up, using molecular biology to understand the building blocks. But there is a gap in our knowledge in understanding how biological structures function at nanoscale dimensions. Many of the tools we are developing in nanotechnology in a broad range of areas can be applied to understanding the structure and function of these systems to provide us better knowledge to understanding how biology actually works.



Dr. Jeffery Schloss:

Achieving these results offers the opportunity and indeed the imperative to change the scientific and educational enterprise in the United States. In the nanotechnology area, more than in most, we are seeing already and will see in the future many productive collaborations among scientists from different fields, clinicians and social scientists to achieve the scientific results and bring them to realization, both effectively and safely.



Dr. Phil Szuromi (moderator):

Thank you for joining us today. Please join us for our next chat in the Nanotechnology Talk series in February 2005. Visit www.eurekalert.org/nanotalk for details.