July 2003 Reporter Home

AAMC Panel releases Report on Bioterrorism Education

Lawsuit Filed Against Princeton Review

Containing SARS: University of Toronto Rises to the Challenge

Nanotechnology: The Science of the Very Small

Innovations in Medical Education: Doctor in the Court

A Word from the President: Clinical Investigators for a Global Future

Viewpoint: Summer School, NIH Style

Reporter Archive

AAMC Newsroom

Managing Editor Scott Harris sharris@aamc.org Staff Writer Elissa Fuchs efuchs@aamc.org

Nanotechnology: The Science of the Very Small

By Barbara A. Gabriel

The above prophetic words of Dr. Feynman came from a talk he gave at the 1959 annual meeting of the American Physical Society, at the California Institute of Technology. Titled "There's Plenty of Room at the Bottom," the talk invited scientists and biologists to explore the possibility of manufacturing tools at the molecular level.

Dr. Feynman's goal was to inspire his audience to push the frontiers of science and technology into the realm of the ultra-small, enabling novel engineering solutions to computing and, ultimately, disease. Although he did not coin the phrase, Dr. Feynman is now widely credited as being the first visionary in the field of nanotechnology and, more recently, nanomedicine.

At its core, the term "nano" has a dimensional connotation. A "nanometer" is a billionth of a meter. Mauro Ferrari, Ph.D., a professor of biomedical engineering, internal medicine, mechanical engineering, and materials science and engineering at Ohio State University, explains that the thickness of a strand of hair is about 100 micrometers, or microns. "It takes 1,000 nanometers to make one micron," he explains. "So when you are going across a human hair, you are crossing 100,000 nanometers. We are talking very small stuff here."

Dr. Ferrari, who is also president of the International Society for BioMEMS (bio-microelectromechanical systems) and Biomedical Nanotechnology, says that the field of "nanomedicine" holds much promise for diagnostics, targeted drug delivery, and therapeutics.

"Biology is organized like Russian dolls, where you start very small, and you build very large," he says. "The body is a large architecture comprised of smaller architectures. In terms of our current interventional abilities in medicine, we intervene at the large scale, at the systemic level. We do X-rays, CT scans, MRIs, and even though we are getting better and better resolution, we are still looking at big chunks of the body."

It is very difficult to intervene at the molecular or cellular level practicing this type of medicine, Dr. Ferrari says. Nanotechnology holds the promise of changing that.

Talking small

"Nanotechnology is giving us the opportunity to interface with biology at sub-molecular levels, enabling us to finally 'talk' to a biological entity from the molecular to the organism level with a single intervention," Dr. Ferrari explains. "I think it's a profound revolution that finally technology is catching up with the progress of the fundamental life sciences, allowing us to essentially be able to relate to the smallest building blocks of the human body on their own dimensional par."

One example Dr. Ferrari gives of nanomedicine in action is the preliminary success many scientists are having with the "targeted, timed, and smart delivery of therapeutic biological molecules so they reach the right targets at the right time. … I see the drugs of the future as targeted molecularly so they will reach, with great precision, the desired point of impact, avoiding all of the traps and the roadblocks of the body from the point of the needle to the point the drug needs to be." Such ability, he says, would greatly benefit cancer patients, whose healthy cells join cancer cells in equally bearing the brunt of chemotherapy drugs.

Dr. Ferrari himself is currently using nanomedical techniques to tackle diseases such as diabetes. He has manufactured tiny silicon capsules that can hold healthy cells to replace ones that are not functioning. For example, in diabetics, pancreatic cells fail to produce insulin. Newly implanted cells could restore this function. However, the body typically rejects any material foreign to it, and Dr. Ferrari admits that there is no "perfectly biocompatible material."

To get around this, Dr. Ferrari and his group have constructed what he terms a "nanotechnological membrane" in between the cells he is transplanting and the host organism. The membrane impedes molecules that trigger an immune response, rendering the synthetic cells essentially "rejection-free" in the animal models they have been injected into. "I don't mean to say that we have cured diabetes," says Dr. Ferrari with an enthusiasm he finds hard to contain, "but we have good animal results, and we are looking forward to further proof in clinical trials."

Thwarting immune response

Thinking small: James J. Baker Jr., M.D., works with a multidisciplinary team of researchers at the University of Michigan's Center for Biologic Nanotechnology. Photo courtesy of BMC Media

It was the same desire to circumvent the body's immune system that originally led James J. Baker, Jr., MD, the Ruth Dow Doan Professor of Biologic Nanotechnology and founding director of the Center for Biologic Nanotechnology at the University of Michigan Medical School, to his chosen field.

"I was involved in some of the early animal gene therapy trials where there were immune reactions to the viral vectors, and I started looking at synthetic alternatives," explains Dr. Baker. "That's when I came upon the idea that you need nanostructures to be able to get into cells and to do things within cells, so I began looking at nanotechnology as a way around some of the problems we had with biologic delivery systems."

Dr. Baker's current work is with synthetic molecules called "dendrimers" that can carry genes into cells without setting off the body's immune response system. They can also be used for drug delivery or as a means for carrying imaging or bioanalysis molecules into cells. "We finally have looked at them as a means for scaffolding multiple functions together," he says. "So you can have a therapeutic that includes an imaging component, a sensing component, and a drug component that can be delivered all at once to a particular cell."

The potential applications of dendrimers are almost limitless, at least theoretically. In reference to gene therapy, they can correct defects at a cellular level using materials that are the same size as the targeted cell's building blocks. Other possible uses that Dr. Baker's center is working on is targeting dendrimers to detect and characterize cancer cells and then destroy them by delivering a specific drug or gene therapy.

"The anti-cancer work has moved very rapidly," Dr. Baker says. "We've gone from concept to actual animal proof-of-concept in three years. And we're hoping to develop the ability within the next few years to enter clinical trials. So it's not like it's 10 to 20 years off."

Reorganizing, re-engineering

At the Institute of Nanoscience and Engineering at the University of Pittsburgh, William R. Wagner, Ph.D., deputy director of the McGowan Institute for Regenerative Medicine and associate professor of surgery and bioengineering, is applying nanotechnology to tissue engineering - the science of growing new tissue and even organs from a single cell. In order to "engineer" tissue from a stem cell, a plastic polymer "scaffolding" must be present on which to attach cells and instruct them how to grow and become the functional part of the body you want them to be.

"The question becomes: 'How do you take this scaffolding and shape it so the cells are presented with information on a scale that they recognize?' That's where the nanotechnology comes in," explains Dr. Wagner.

"We're working with a technique called 'electro-spinning' to generate fibers that are hundreds of nanometers thick for scaffolds for tissue engineering," he says. "We've generated 300- to 800-nanometer fiber diameters, we've shown that they have good mechanical properties, and we've shown that cells can grow on them." Dr. Wagner hopes to have his tissue engineering scaffolds ready for animal trials within a year.

The greatest impediment to his work, says Dr. Wagner, is want of knowledge about the biology that guides cell behavior. "What information do we give the cell to behave in a certain manner?" he asks. "We still have a lot to learn in that area. We have to rely on fundamental science and biology to guide us."

Pooling Talent

Even in 1959, Dr. Feynman understood the importance of the multidisciplinary aspect of the work he was proposing. Long before it was fashionable for different schools of study in a university to speak to one another about their work - much less combine their talents - Dr. Feynman knew that it was essential that they pool their intellectual resources to reach common goals.

Today, anyone who calls himself a nanotechnologist will tell you his work would be impossible without pooling the talents of physicists, chemists, biological engineers, computer scientists, basic scientists, and medical doctors. Dr. Baker's Center for Biologic Nanotechnology has made this principle the cornerstone of its philosophy.

True scientific exchanges among otherwise disparate laboratories from multiple schools take place in Dr. Baker's lab. As an MD nanotechnologist, Dr. Baker is somewhat of an anomaly in a field dominated by chemists, physicists, and engineers. He is trying to change that by approaching nanotechnology from the biologic perspective and working from there toward the materials sciences rather than the other way around.

This way, says Dr. Baker, issues like toxicology are addressed first, before a large amount of energy is put into engineering "nanomachines" that are not biologically compatible. "Our researchers really need to understand biologic systems before they can apply any of the engineering solutions that they develop," he says.

"At the center, we have a large contingent from the medical school involved with medical applications, toxicology, and biological evaluation; we have a large group from the engineering schools that works on materials development, the use of ultra-fast optics, or interfacing devices with magnetic applications," explains Dr. Baker. "And then we also have a large group from our literature, science, and arts college that is involved in materials science, analytical science, and bioinformatics; they do a lot of our molecular modeling. That broad background of expertise is necessary to make the technology work."

No formal program

Calling nanotechnology "the ultimate multidisciplinary field," Dr. Ferrari points out that there is no formal training program in nanotechnology anywhere in the world.

"Essentially, everyone who works in this field has been trained differently," he notes. "Thus, there is not going to be any breakthrough in medicine through nanotechnology unless we embrace this notion of the multidisciplinary work of individuals and of teams on a level that has never been seen before."

A consultant to the National Cancer Institute (NCI) and the National Heart, Lung, and Blood Institute on developing programs in nanotechnology, Dr. Ferrari hopes to use these powerful institutions as "matchmakers," bringing together experts in the material and biological sciences.

"We are looking at recommending that the NCI develop an internal facility or laboratory that brings together nano-technology researchers, who are essentially people with physics or chemistry backgrounds, and 'matches' them with experts in medicine, coupling the right technology with the right disease," he adds.

Dr. Ferrari is optimistic about the potential of nanotechnology to solve intractable medical problems. "I truly believe that nanotechnology is completely going to revolutionize medicine," he says enthusiastically. "The tools are here. But we need the guts to be truly visionary and think outside of the box, which is something we have not been as good at doing. Nevertheless, the changes coming in medicine are absolutely breathtaking."

Contact Us    © 1995-2008 AAMC    Terms and Conditions    Privacy Statement