People

Dr. Jeff Schloss is the NNI's NSET Committee representative for the NIH. His work at the NIH’s National Human Genome Research Institute centers on development of novel DNA sequencing technologies. He also is member of the NIH Bioengineering consortium, known here as BECON, and is one of the founding members.

Nanotech Briefs: How/why is the NIH involving nanotech in its research programs & goals?

Dr. Jeff Schloss: The NIH will explore what appears to be a scientifically valid technical approach in order to solve problems related to our mission of improving health. If there are medical or diagnostic treatment or disease prevention methods that come from any technological approach, we will try those out. We are not singling out nanotechnology as having necessarily more promise than other approaches, on the other hand there does appear that there could be some unique promise from nanotechnology so we want to pursue that.
We have some solicitations that call for nanotechnology approaches. However, there are lots of other solicitations where they may not call for a nanotechnology approach, but they are trying to solve a particular problem in medicine.

NB: Is it simply being able to work on the nano scale that appeals to the medical industry?

Dr. Schloss: These unique properties of materials exist because of our ability to manipulate them in the range of the molecular and atomic scales, which is why these materials or approaches hold appeal. New materials, new ways to sense things, new ways to make medical devices – I think that’s where the appeal lies. The other aspect, particularly for medicine, that is intriguing – and we don’t know if it will be useful although many of us think it might be – is the fact that at the fundamental level, biology operates at the nano scale; it’s molecular assemblies and so forth. If we could manipulate molecules at that level (as we try to do with genetics and molecular biology), nanotechnology simply gives us another way in to manipulate biology at this size scale.
Why do we want to manipulate biology? We want to understand it and if you want to do experiments you have to poke and prod and see what the effects are of your poking and prodding on the system. Simply put, to do an experiment, you change something and then see the result. Nano may gives us ways to change things at that level, and it may also give us ways to measure biology at the level. The hope then is that from this new knowledge of biology we can go in and using the same capabilities manipulate biology explicitly for medical purposes. Whether its measuring a pathological change in an individual’s biology or going in and changing something that’s going wrong and fixing it, again, we are trying to do this in the most precise ways that we can. We want to fix the thing that is wrong, without messing up something else nearby, which we ordinarily call side effects.

NB: It is said that nanotech is advancing or eventually will advance the following areas: detection, treatment, and prevention/cure. Can you comment on how nanotechnology research is being used to address these areas?

Dr. Schloss: I think people have all sorts of ideas for using nanomaterials as detectors. And so what’s nano here is 1) simply the way the surface might be prepared or 2) the sensor mechanism – a biological molecule that will look for another biological molecule to bind to the first one, with a little nanotechnology detector that will be able to identify that molecule two did indeed bind to molecule one. Our conventional technology requires the binding of many more molecules in order to detect that anything happen. Because the nanoscale detector is essentially more sensitive, you would be able to tell that it happened.

Another aspect is that a number of these sensors will simply be very small and you’ll be able to attach many of them – perhaps even hundreds – onto one very small device. This means that if you use the device in a doctor’s office or perhaps implanted in the body, you will be able to detect several different things with a small amount of sample.
In terms of body imaging, there are people coming up with ways to make little molecular switches. They are modifying the kinds of materials that would ordinarily be used in MRI to, instead of just being sensitive to anatomy, make them into switches that only turn on if they detect the presence of certain molecules in the body – only in the places in the body where those certain molecules exist, will the agent get turned on. This is called molecular imaging in contrast to anatomical imaging.

Assuming that you know that there is a problem and you want to give the person a drug, for example, or you want to do an implant - bone implant, nervous system damage you may want to fix – this is, again, new materials that will allow you to deliver a drug that was not deliverable before. A lot of drugs actually work quite well if you can get it to the site where the action is needed, but you can’t get it there because of the current ways of deliverability – particle size, insolubility, or you can’t get it absorbed out of the stomach into the bloodstream – it will just be better ways to deliver conventional medicines. There are some ideas about new ways to build new therapeutically relevant molecules. One example is a new kind of antibiotic that someone came up with that works by a different mechanism. So, it’s different delivery and different fundamental drugs in the first place.
With particle size, what some are doing with dendrimers is that you can precisely control the size of the particle and then put the drug either on the surface or pack the drug inside and then, because of the size of the particle, get it delivered.

One of the big powers of nanotechnology is it can be multifunctional. You can design particles that can do several things – to not only hold onto the drug, but also have a targeting entity on it. If you are talking about cancer, if you make the particle the right size, it will only leak out of the circulation where there is a tumor and then of just diffusing away, it will actually bind at the surface of the cancer cells – you may even be able to make it so its taken up by the cancer cells. We have ways of making things very small, but we don’t have ways of making things monodisperse where all of the particles are really the same size. Usually when we make stuff small by other methods, what you might end up with is the right average size, but you have many particles that are larger and many that are smaller. This is the idea of molecular control.

In some cases nano will enable new delivery methods, in some cases it will assist in the manufacturing of the drug, in some cases your nano-tools for biology research revealed something about biology that you didn’t know to give you a new strategy in which to use conventional pharmaceuticals, and in other cases it is the idea of these novel material properties, such as nanoshells where, if you get these little tiny particles to localize in a tumor, then shine the right wavelength of light on them, they heat up (University of Texas?) The point to make here is that there are new tools available that we didn’t have before. No one know if it’s gong to cure cancer, so let’s be clear. We have a new toolkit and new strategies that can be attempted.

The thing that we want to do here is combine surveillance with rapid action. One of the ideas is that with more sensitive detectors and with detectors for a large number of things that might be going wrong – assuming that we know what those physiological conditions are that need to be detected – new molecular signatures will be learned, in part because we have better tools through nanotechnology, that indicate a condition before you are clinically sick. If you can sense that earlier before you actually have a clinical disease, you could do something about it – this is the idea of prevention. The idea is not preventing a person from getting, for example, a bacterial infection in the first place, but detecting it earlier enough thereby preventing the person from getting clinically ill. For cancer signatures, the idea is to “nip it” before you actually have a tumor mass or preferably before the cells go all the through to full progression to being classified as cancer cells. If you could detect the number of changes that happen to cells before they actually became cancer cells, then maybe you could do something to those cells and you’d never get the full progression to cancer. There are all sorts of ideas about how we could intervene early on if we knew the right signatures to look for, and then had some way to go in and just kill those few cells.

NB: Is the research community moving to fast? Is enough being done to ensure that the technology is safe?

Dr. Schloss: We can’t ameliorate side effects or watch out for them until we have something to look for. We have to start doing some experiments. We have to start developing new materials. Then, once we have the new materials, we can start to try and use it. A lot of this is going to be done in research in laboratories on extracts on cells – not on people, which is how most medical research starts; that’s true whether we are doing nanotechnology or any other approach. When we are going to use nanotechnology to develop a treatment or a therapy, we are going to have to go through at least all of the same careful procedures for the protection of human subjects and regulatory approvals from FDA – all of those things that we have to do with anything else.

You can argue whether those things are effective anyway and people are arguing this point. But we do have lots of methods already in place. There are questions whether nano needs more and we are exploring that very carefully. On the one hand we are saying that these materials have novel properties that we might not be able to predict based on what we know about other properties that are similar except for the way its put together because of the unique property of the nanoscale material. People have to keep that in mind that it may not be the same as the bulk material.

This is where there is some question, whether the language of the regulations is adequate, but everyone is aware of that now because these discussions have taken place. So the regulatory agencies are tuned into this. It does not mean that all our regulations are exactly up to date, but it does mean that the regulatory agencies and their watchdogs are aware of these things. I would say we are not moving to fast. We are moving with deliberate speed because after all these are all risk-benefit equations and if you want to cure devastating diseases you are going to have to move forward and be careful of what you are doing as you move forward.

Dr. Schloss can be contacted at schlossj@exchange.nih.gov. Visit http://nihroadmap.nih.gov/nanomedicine