Nanotech Poised To Fire Up Medicine's Next Revolution! From Polio to Cancer — Diagnosis and Delivery Tools Are Key
Fifty years ago, in 1955, Jonas Salk unlocked the secrets of the polio vaccine. Soon after, children could take a pill, rather than a needle, thanks to the work of Albert Sabin. Both were aided by new technologies of the time that provided better imaging, quicker diagnosis, and easier delivery. Today, 50 years later, cancer researchers say many areas of nanotechnology -- not simply bio-nano -- will provide the next wave of precision research and delivery tools, and in the bargain set the stage for the next Salk and Sabin.On April 12, 1955, Dr. Thomas Francis Jr. entered the University of Michigan's Rackham Auditorium to face a crowd of scientists, dignitaries and hundreds of reporters wielding TV cameras and radio microphones.
Francis then did something slightly unusual for a medical researcher. He used concise, simple language. “The vaccine works. It is safe, effective and potent.”
By Francis' side was his former student, Jonas Salk, who had just won a hotly contested race to be first with a polio vaccine. Salk was immediately propelled to rock-star status because he seemed to have performed a miracle by reversing death sentences for the thousands around the world who might have perished in further epidemics. It was a good time to be a medical researcher.
Since then, the inheritors of Salk's mantle have been greatly diminished in the eyes of the general public. Anti-vaccination movements have taken root in Great Britain and the United States, and some high-profile blunders in the pharmaceutical industry have taken modern medicine down another notch when it comes to the public's perception.
Part of this image problem can be traced to Salk, himself. He changed life expectancies, yes, but he also forever altered public expectations. The baby-boom generation growing up in a post-polio world was no longer grateful for innovations that targeted their specific ailments. They now expected it. The trouble was, medicine was not as tailored and fine-tuned as the public believed.
Nanotechnology is poised to change all that. A few nanotech-enabled medical products and pharmaceuticals are either on the market or in the pipeline, and right behind them is a vast new research and development infrastructure being funded generously and built quickly. Today, nanotechnology brings us closer to fulfillment of the Salk promise, cures for mankind's deadliest diseases. But before that could happen, science needed to go smaller – smaller than the murderous viruses, small enough to attack tumors and destroy them from within. Smaller because, in the words of buckyball co-discoverer and nobel laureate Richard Smalley, "that's really where the action is."
So, that brings us to just a little more than 50 years after Salk's moment of triumph. On April 22, 2005, the University of Michigan announced the creation of its new Nanotechnology Institute for Medicine and the Biological Sciences. Its leader will be Dr. James Baker, one of the world's top nanohealth researchers who just might be the Jonas Salk of our time. But, then, so could any number of other researchers working in the science of the small, like Naomi Halas of Rice University or Uri Sagman, formerly of C Sixty or Chad Mirkin of Northwestern University. But, unlike the polio pioneer who refused to patent his invention, the Salks of today are more likely to be hanging around venture capitalists' offices in search of funding than at the March of Dimes.
Today, with polio a distant memory, it is cancer that is very much on everybody's mind and the "race" is on for new technologies to detect, treat and cure them – a much larger task that will take teams of Salks working in different disciplines around the world. U.S. National Nanotechnology Initiative officials often talk about "converging technologies," that is, connecting all the sciences – physics, chemistry, biology, information technology – and making connections as all these disciplines converge at the nanoscale.
That's exactly what's happening at Salk's old University of Michigan stomping grounds, where the new nanotech "institute" is so cross-disciplinary that it's not asking any of its faculty or staff to leave their existing buildings.
The institute's strategy is important for a few reasons:
- Funding: There is a great deal of grant money coming to university research institutes that are prepared to take on the challenges of nanoscale science. So, U-M is making it easier for the various U.S. funding agencies giving out nanotech-related grants by having them deal with only one central academic unit.
- Spinout central: Baker says plans also are already in the works to spin out new companies to commercialize the technologies that are ready for prime time. Baker, himself a nano startup veteran, is an ideal coordinator for a central "spinout" headquarters.
- The art of collaboration: It's going to be a very much a learning experience for everybody, including faculty, who need to learn the art of collaboration. "This is a totally different model," Baker recently told the Ann Arbor News. "This is a faculty-based effort and reaches broadly across the university and is composed of faculty who are already here."
On the surface, these considerations might seem to be of interest only to those at U-M involved in the restructuring. But this is not "inside baseball." The University of Michigan is one of many key institutes across the country preparing themselves for prominence – and for funding – in the next technological wave. The universities that fail to prepare for centrally coordinated, cross-disciplinary research will be left behind.
To understand why this is so, we need to move up a link or two in the money chain and see what the National Cancer Institute is up to. The NCI understands not only that it needs to incorporate nanotech into its research programs and goals – indeed, the institute itself seems destined to become a nanotech funding center -- but also that cancer needs to be attacked through cross-disciplinary cooperation and streamlining.
With an aging population, and the baby-boomers' famous proclivity to reinvent every stage of life, you can bet that cancer detection and treatment will get top priority. It already has, through a few programs that are changing the way research centers like U-M's are to receive funding for cancer research.
- Centers for Cancer Nanotechnology Excellence (CCNE): The NCI plans to create up to five of these centers, with the goal of integrating basic and applied sciences with engineering to accelerate nanotech research. What they're after is nanotech-enabled cancer treatment at the clinic, and these centers will be the focal point of the effort. The NCI plans to spend $90.8 million in fiscal years 2005 to 2009 – with about $20 million spent in fiscal 2005 – to create these centers.
- Cancer Nanotechnology Platform Partnerships: The NCI plans to spend about $7 million in fiscal 2005 to fund 10 new grants that address issues that support nanotech cancer research, such as molecular imaging and early detection, reporting of therapeutic efficacy and other "research enablers."
- Alliance for Nanotechnology in Cancer: This entity, launched in September 2004, unites an array of cross-disciplinary programs that partner with other NCI efforts or the private sector. This alliance is probably the most significant development, and shows how seriously the NCI takes the idea of "convergence." One important initiative to come out of the alliance is a "teaming site," where cancer researchers can find collaborators who match their needs.
- Nanotechnology Characterization Laboratory: The NCI is establishing a lab in conjunction with National Institute of Standards and Technology and the U.S. Food and Drug Administration to accelerate development of technologies that can manipulate tiny particles and engineer them in specific ways. This will go a long way toward a long-sought-after goal for nanotech: standardization.
The NCI is requesting a $40 million budget increase in 2006 to build the Alliance and the centers. But if you look closely at all of the NCI's budget increase requests for 2006, you'll see that nanotech is not confined to its own category, but infuses just about all of them: An $18 million increase is being requested for development of advanced imaging technologies, including nanotechnology for contrast agents and nanoscale devices to address cancer cell diversity. A $50 million increase is being requested for a "proteomic technologies initiative."
The NCI's efforts will likely be a model for other medical specialties looking to coordinate their own efforts into nanoscale research. And since this is all multidisciplinary, it is possible that the NCI's alliance will become a de facto clearinghouse for all nanobiotech activity.
The immediate needs – and the areas in which there is a "breakthrough of the week" in your local newspaper – can be broken down into a few main categories:
Imaging
The first line of defense against cancer is to catch it early and catch it small, a natural for nanotech. The NCI's stated goals include funding for nanodevices that will pinpoint exactly where the cancer is in the body, deliver anti-cancer drugs only to malignant cells while leaving healthy ones alone and to keep tabs on a drug as it circulates through the body.
Serendipidously, the new field of bioinformatics is emerging just in time to meet up with clinicians who are using smaller and more sophisticated biomarkers to detect cancer and monitor its treatment. To crunch the numbers and make sense of the data coming in from biomarkers and high-throughput screening takes some incredible computing power. Imaging informatics is an industry that's growing alongside our increased knowledge of how cancers are formed and grow in the body. The NCI's priorities for fiscal 2006 include:
- Using nanotechnology to design "smart" injectable, targeted contrast agents that improve the resolution of cancer to the single cell level.
- Engineering nanoscale devices that can deal with the diverse types of cancer cells within a tumor.
Each one of these goals are being worked on by disparate research groups and companies, some of them involving other diseases. For example, the National Heart, Lung, and Blood Institute, recently awarded $11.5 million to the Georgia Institute of Technology and Emory University. Some of that cash will go toward developing magnetic particles that can be used as MRI contrast agents that target proteins on individual cells to detect plaque long before it builds up enough to cause a heart attack. This research is headed by Dr. Gang Bao, and helps move the National Institutes of Health farther along in its own nanotech roadmap. With streamlining and coordination, it's more likely that Bao's results would also be used by the NCI to meet its goal for single-cell contrast agents.
For a more direct connection to the NCI's goal, we go back to the University of Michigan's James Baker. One of the companies he's founded based on his research is NanoCure Corp., which is developing nanostructures for use in targeted cell imaging.
A similar effort can be found at the Washington University School of Medicine, where professors Gregory Lanza and Samuel Wickline have successfully demonstrated a nanoparticle contrast agent in mice.
In the private sector, Biophan Technologies Inc. has a unique application for its nanocoating – it helps doctors check out implanted devices by enhancing their ability to be detected by MRI. The company's slogan is a variation on a reoccurring theme throughout nanotech: "We don't make medical devices. We make them safe and imagable."
The second goal, to engineer devices that can address tumor cell diversity, is also on its way to being met by Rebekah Drezek and Jennifer West of Rice University. They're working on a kind of two-for-one deal – a nanoparticle contrast agent that can not only shine its light on a potential problem cell, but then can go directly to the next step – get rid of it before it spreads to nearby healthy cells. Their nanoweapon of choice is the gold nanoshell, invented by Naomi Halas, also of Rice University. The shells react to light and heat to sort out the good from the bad. The light is shined by the doc, and the shells produce the heat that cooks the bad guys.
Halas, Drezek and West might have some serious competition over in Singapore, where Dr Yi-Yan Yang has found a way to make smart drug delivery even smarter. His nanoshells respond not only to changes in temperature, but also in pH levels. Tumor tissues are more acidic, so a change in pH would raise alarms where Halas' shells would just cruise on by. That will get the drugs into deep tissues or cell compartments without the need to shine a light on them.
Diagnostics
Not all nanohealth applications involve introducing a foreign particle. Some involve sensitive detectors that will not invade your body. Instead, in a recent breakthrough at UCLA’s Jonsson Cancer Center, you send out your message in the form of spit. The UCLA team was used the spit test to successfully sort out head and neck cancer patients from a group healthy volunteers. The researchers used nature's own biomarkers to tell them the story. Researcher David Wong says his group will see if they can't prove the same concept for breast cancer patients.
It's not enough for nanoscale technology to simply be nanosized. The "tech" in nanotech comes from engineering tiny particles to perform specific functions, and we're already seeing some intense competition between companies going after one of the earliest markets created by this new ability: diagnosing diseases using nanosized semiconductor biomarkers known as nanocrystals or quantum dots. Like nanoshells, the size of the crystal determines its color. Engineer each color to attach to a different type of of cancer antibody, and you can get an early and accurage diagnosis. Since these tests are done outside the body, there is no cumbersome FDA approval process. So, the area is wide open to whomever can design the better dot first. Evident Technologies, Quantum Dot Corp. and Nanosys are the leaders in this area.
And new instruments are being devised to detect existing nanoparticles in the body that indicate certain dieseases or conditions. One, known as ADDL, is associated with Alzheimer's disease. Design a device to detect the presence of ADDL, and you have an early diagnosis. Northwestern University's William L. Klein made the discovery, while Chad Mirkin and Richard Van Duyne of Northwestern's Institute for Nanotechnology, are working on a diagnostic device that can find ADDLs.
Drug Delivery
While you might read a great deal about the possibilities for improved cancer treatment using nanoparticles, there are very few of them on the market. And it's not only because the technologies aren't quite ready. It's also a reflection of the cumbersome drug-approval process and an unwillingness of Big Pharma to take a look at some of these new technologies.
That situation is reflected in the long struggle of Patrick Soon-Shiong to get his nanotech-enabled drug, Abraxane, approved by the U.S. Food and Drug Administration. Marketed by American Pharmaceutical Partners, Abraxane is the anticancer drug paclitaxel (Taxol), reengineered into a nanoparticle that can be easily absorbed by the body. That saves breast cancer patients from having to take toxic Cremophor to help the body absorb Taxol. So, Abraxane is targeted drug delivery without negative side effects – fulfilling one of nanotech's big promises. The FDA approval should help open doors for Abraxane, where they had remained shut for a long time. He had approached five major pharmaceutical companies and was rejected five times. Nano is just too risky, he was told. In light of recent publicity for pharma involving unwanted side effects of older drugs, they're more willing to listen to new ideas that promise to treat only the disease.
Drug discovery and development
The first of nanotech's many opportunities is one that has the potential for some high-profile payoffs. And that payoff does not only take the form of cash. What nanotech can do is add a significant reformulation of an existing drug that's nearing the end of its patent lifecycle. If a nanotech startup can help Big Pharma squeeze more life out of old drugs, that right there will convince the right people that nanotech has truly arrived for their business.
There are many nanoscale approaches to drug discovery, but one that shows the most promise is to bring the already established tools of microfluidics down to the nanoscale. Researchers at Purdue University recently built prototype nanofluidic chip that contains vast numbers of "nanopores," each able to carry out their own little reactions. The arrival of nanofluidics promises to save inestimable time and money along the road to drug discovery.
Investigating life
And they're thinking across disciplines over at the University of Wisconsin-Madison, where a team of electrical and computer engineers and biologists were poking some quantum dots around a biological membrane and discovered one more thing these semiconductor nanocrystals can do: Zap them with a few volts and the dots press into the membrane, and form "rings" which then act as a kind of nanoscale doorway inside, enabling researchers to see how they tick. So far, this has been demonstrated on membranes, but more investigation is necessary before they try it on a living organism.