Chapter 9: Innovation at the Frontiers of Nanomedicine – NanoInnovation: What Every Manager Needs to Know

9
Innovation at the Frontiers of Nanomedicine

Interpreting, replicating and modulating our biology in a bid to make our lives healthier and happier is one of the aims of the modern nanoscientist.

– Alok Jha, The Guardian, September 5, 2011

Bionanotechnology is the place where bio meets nano. This is a space where we focus on the biological impact of nanoinnovations on plants, animals, and humans.

Whether you manage a small or a large organization in industry, government, or academia, you need to know what's happening in bionano – and especially, nanomedicine – because medical nanoinnovations could save or prolong your life, and the lives of family members, friends, and colleagues. Nanomedical innovations are not just game-changing innovations. They are life-changing innovations.

Bionanoinnovation can be defined as the controlled use of biological materials, organisms, by-products, and processes with nanoscale dimensions to achieve a desired result.

Nanomedicine is the application of nanotechnology to medicine and healthcare. Nanomedicine is the subset of bionanotechnology where nanoinnovation is creating new healthcare solutions. Bionanoimaging is used to view and manipulate biological processes that cause diseases. Nanofluidic chips are used in the emerging field of nanodiagnostics. Most labs-on-a-chip have nanoscale features and properties. Nanomaterials are used in stents, pacemakers, and other medical implants. Much of what we call “molecular medicine” involves nanoscale structures.

As humans, our lives are enabled and sustained by biological nanomachines. Most of the cells, proteins, bacteria, and viruses that comprise the human ecosystem are nanoscale in size or have nanoscale features. Being able to view, manipulate, and control these structures is critical to preventing and treating disease, keeping us healthy and helping us live longer.

In this chapter and the next, we'll explore the implications of bionanoinnovations for human healthcare and take a closer look at some of the most promising emerging technologies and discoveries that are driving the future of medicine.

9.1 Medical Miracles and the Nanomedicine Landscape

Many of the breakthroughs coming out of nanomedical research sound like medical miracles. Curing a potentially fatal disease with a nanosized drug is a miracle. Replacing a defective or missing gene to cure inherited blindness – restoring the victim's sight – is truly miraculous. Engineering nanoparticles to find and destroy a cancer cell, that's a miracle. How about putting a tiny computerized “brain” in a drug tablet that sends information to the Internet after you swallow the pill? Or nanosizing a cooking spice that fights the cellular processes that cause disease and aging?

Some people would say these things are just “clever science” but for the people who would die without these solutions, and who dodge a medical bullet that could kill or cripple them and live longer healthier lives, these are miracles. In this sense, the research teams that are working on these innovations are miracle workers.

Thanks to a legion of hardworking scientists, researchers, educators, and students – and research communities enabled by the Internet – the world's collective genius is slowly but diligently unlocking the nanoscale structures and processes that cause disease. They are finding ways to make drugs more effective by nanosizing them to make them soluble, more bioavailable, and safer.

Just as nanotechnology is enabling semiconductors, thin and flexible display screens, and smaller electronics overall, nanoinnovations are helping to create the next generation of medical devices. The entire concept of mobile medicine is being fueled by nanoinnovations in semiconductors, smartphones, robotics, and other technologies. Smartphones are rapidly morphing into mobile diagnostic platforms. For example, smartphones are being equipped with microscopes that can magnify and identify pathogens. Medical implants such as pacemakers and stents are becoming smaller, more efficient, and durable. Nanotechnology is providing scaffolds for growing stem cells into organs. Nanomaterials are improving stents used to repair heart vessels. Nanotechnology is reducing the processing time and cost of analyzing medical samples. Cancer cells are infused with nanoparticles, so they show up more vividly on MRI scanners. Nanoparticles can also be heated to kill tumor cells without damaging healthy cells. Nanofluidic biochips are analyzing DNA molecules. Research teams have engineered biodegradable nanoparticles that can actually punch holes in harmful bacteria. And for the first time in medical history, scientists are getting close to an antiviral therapy that can treat a broad spectrum of nanosized viruses that cause everything from the common flu to AIDS and tuberculosis.

Mapping Bionanotechnology

The accompanying bionanotechnology map (Figure 9.1) shows some of the key areas where bionanotechnology is impacting human healthcare. This map is not intended to be comprehensive but rather representative of the functions, applications, and innovations encompassed by bionanotechnology. This dynamic map, which is constantly changing, offers a starting point to help understand the broad scope and potential of bionanotechnology.

Figure 9.1 Bionanotechnology map (copyright 2012, Michael Tomczyk).

Typically, a nanomedical innovation gets its start at a university science center where a discovery is made by a research group, usually with government grants and corporate funding. If the innovation is successful, it may be spun out into a business venture or licensed to a biopharmaceutical company. In this sense, the business of nanomedicine follows the model of biotechnology boutiques that have helped maintain the drug pipelines of big pharma companies during the past three decades.

Nanomedical ventures and projects have to negotiate the same maze of challenges as any innovation, as well as some daunting obstacles that are unique to health-related technologies. Bionanoinnovations have long development cycles. Solutions that work in the laboratory need to be converted to commercial products. A nanomedical drug that works ex vivo – outside the body – may not work in vivo – inside the body. Most medical products need to survive expensive animal studies and human clinical trials before they are approved. Novel therapies, no matter how effective, still need to prove that they are substantially better than existing technologies that are familiar to the medical community. And with nanoparticles especially, there are safety concerns that need to be addressed.

Funding for nanomedical research is provided by government grants, corporate partners, venture capitalists, and angel investors, although funding has been tight in recent years. Overinvestment in gene therapy, early nanotechnology ventures, and ecommerce ventures led to “bubbles” that burst in the late 1990s and early 2000s. These notorious investment bubbles, combined with the economic crisis triggered by the subprime mortgage meltdown in 2008–2009, have tended to make venture capitalists and corporate R&D centers more risk-averse and cautious when it comes to bionanotechnology.

Fortunately, a solid core of nanomedical ventures survived the venture capital drought and this sector has been growing steadily.

The Business of Nanomedicine

Like any medical innovation, bionanotechnology needs to justify its existence, by saving and extending the lives of human patients, generating reasonable profits for its providers, and ideally reducing healthcare costs.

As a business sector, nanomedicine is tricky to analyze because the metrics are not yet well defined. However, there are ways to quantify nanomedicine. In the United States, we can count how many nanomedicine drugs and therapies are in clinical trials at the FDA. We can also quantify the value of the sector by calculating revenues, research grants, and milestone payments. One way to measure the progress of any medical technology is to track the number of projects that are in clinical trials. Currently, there are >250 nanomedicine projects in clinical trials at the FDA. Those nanomedical innovations that survive the rigorous clinical trial process will have an opportunity to generate value in both human and economic terms.

As a manager, you understand the critical need for better, cost-effective medical and healthcare solutions, especially in an era of spiraling healthcare costs. Economically, healthcare represents more than 17% of the US economy and is increasing as a percent of GDP in most countries in the world. Nanomedicine (and nanotechnology in general) has a unique opportunity to contribute innovations that reduce costs, replace expensive biological compounds with less expensive substitutes, and prevent/treat/cure medical conditions that keep inflating healthcare costs in all countries.

We can also think about nanomedicine as a sector of innovation that creates value in the form of entrepreneurial ventures, corporate and government research projects, educational programs, and jobs associated with these activities. The most important value proposition of bionanotechnology is that it is opening a portal to an entirely new set of medical solutions that were previously unavailable.

The Nanomedicine Market

Nanomedicine can be grouped in four basic categories: (1) novel platforms for improving medical treatment and delivery of secondary products (e.g., finding new and better ways to deliver chemotherapy molecules to tumors or coating stents with nanoparticles); (2) nanomaterials used in medical applications (e.g., antibacterial nanocoatings used to sterilize work surfaces in hospitals and scaffolds to grow human tissue); (3) pharmaceutical products (e.g., nanosized drugs and biomarkers); and (4) nano-enabled medical devices (biochips, DNA analyzers, and portable diagnostic devices).

A report from the Business Communications Company (BCC) projects that the market value of the global nanomedicine industry will grow from $63.8 billion in 2010 to $130.9 billion by 2016, with most of the current value concentrated in six therapeutic categories: cancer, infection, inflammation, cardiovascular problems, nervous system disorders, and other medical conditions [1].

During my research for this book, I came across an insightful article in The Journal of Drug Delivery [2]. Valentina Morigi and her colleagues calculated the economic value of the nanomedicine market by measuring sales revenues, licensing fees, and milestone payments. The authors determined that the US nanomedicine market has been growing steadily despite the impact of the 2008–2009 recession and the global nanomedicine market is growing at a compound annual growth rate (CAGR) of 13.5%, increasing from $53 billion in 2009 to a projected figure of $100 billion in 2014.

Dr. Morigi and her colleagues explored strategic and funding issues involved in nanomedicine projects, and conducted a detailed analysis of the relationship of nanomedicine markets, competitors, and investors. They found that the United States accounts for 53% of nanomedicine patent applications followed by Europe (25%) and Asia (12%). Drug delivery is the largest segment in nanomedicine, accounting for 76% of publications and 59% of nanomedicine patents. The second largest segment is in vitro diagnostics (11% publications and 14% of patent filings).

They analyzed the growth of nanotechnology investments from 2007 to 2009, which showed that the largest increase was in the healthcare sector (Figure 9.2a). They also found that the growth of the global nanomedicine market has been comparable to the growth of the anticancer products market (from 2006 to 2014 projections) (Figure 9.2b).

Figure 9.2 (a) Global nanomedicine: market size. (b) Market size for anticancer products (Source: BCC Research, Nanotechnology in Medical Applications: The Global Market, and “Nanotechnology in Medicine from Inception to Market Domination” [3]).

Based on their research, they observed what they call an “asymmetry” between investors and scientists involved in nanomedicine: “While most members of the investment community are able to grasp the meaning of nanotechnology and can expertly launch and manage a viable product into the market, they are limited in their conceptual understanding of this scientific discipline and the intricate inner workings behind the product's functionality. On the contrary, those involved in the scientific research recognize that nanomedicine is an expansion of nanotechnology but they have very little understanding of the business expertise required to develop their technologies into a commercial product” [4].

This asymmetry in mind-set between investors and scientists was mentioned by many of the nano-insiders interviewed for this book. It is essential for the investors in a nanomedicine project to understand that there are inevitably long lead times involved, high costs associated with animal studies and human clinical trials, and high uncertainties and risks.

Funding Issues for Bionano R&D

The high levels of risk, long-term commitments, and uncertainties in nanomedicine (and biotechnology in general) have made it difficult for large traditional investors to support bionano research. Consequently, most start-up ventures and pioneer technologies are started with the inventors' own money and funding from angel investors, government grants, and corporate partners.

The biopharmaceutical industry, which you would think would be the major player in this sector, has been unusually reluctant to invest in bionanotechnology. This bias was discussed in a 2006 Lux Research report entitled “Why Big Pharma Is Missing the Nanotech Opportunity” [5]. The research firm based its opinion on interviews with 33 global corporations that yielded some fascinating findings:

  • No life sciences interviewee rated nanotech as a high corporate priority, as opposed to 78% of interviewees in electronics and materials.
  • Only one out of six life sciences respondents claimed to have an explicit strategy for nanotechnology, compared with two-thirds of those in other electronics and materials.
  • Big pharma companies on average committed 16 people and less than half of 1% of R&D spending to nanotechnology research, whereas like-sized electronics and materials firms committed more than 100 people and more than 8% of R&D.

The Lux Research report went on to suggest that large drug manufacturers were paying little attention to nanotechnology for three reasons: organization, history, and hubris. The analysts observed that a big pharma focuses on drug discovery, whereas nanotechnology focuses on drug delivery. Many pharmaceutical firms felt they had nanotechnology experience because they developed small-molecule drugs, but this does not necessarily translate into bionanotechnology expertise.

The report concluded that big pharma's laissez-faire attitude toward nanotechnology could have serious consequences as generic drug makers create nanosized versions of branded drugs. The Lux Report recommended that big pharmaceutical firms should consider adding “nanoscale reformulation specialists” to their technology teams.

Anecdotally, I have spoken with executives at large corporations and pharmaceutical firms who confirm that they argued against or abolished in-house nanotechnology R&D projects, citing the high costs and risks and long development cycles. One former VP at a large multinational corporation recalls that he killed a billion dollar nanotechnology research commitment based on his belief that nanotech projects would be too expensive, the lead times were too long, and the therapies that would result did not seem to synch with the company's drug-oriented research focus. This confirms the notion that biopharmaceutical firms favor drug discovery over drug delivery and seem to have a bias against therapies that do not involve drugs. This bias exposes the industry to risks from disruptive technologies that cure diseases using nondrug therapies.

Nondrug Therapies: A Paradigm Shift?

Many of the most exciting innovations in nanomedicine involve therapies, not drugs. The question is: Will large pharmaceutical firms embrace a portfolio of therapies that are not necessarily drugs or will device companies such as Medtronic, AbbVie, or smaller biotechs provide nondrug therapies enabled by nanotechnology?

Nanomedicine is helping to create an entirely new portfolio of medical therapies to combat disease and allow people to live longer, healthier lives. Many of these innovations have the potential to replace drugs, surgery, and other traditional medical treatments. This could represent a major paradigm shift in the healthcare industry. Drugs and surgery have been the dominant medical treatments for more than a century. Nanomedicine not only scales down the treatment of medical conditions to individual cells and molecules but it also includes solutions that are already changing the concept of how we diagnose, prevent, treat, and cure disease.

For example, nanoparticles of gold or iron, or carbon nanotubes have been shown to deliver cancer-killing heat and radiation to tumor sites. Near-infrared radiation is a promising cancer-fighting innovation that involves injecting gold or iron nanoparticles at the site of a tumor and administering radiation to heat the cells, which kills the tumor cells but leaves the healthy cells undamaged. The heated nanoparticles are technically not a “drug.” They are a therapy.

Experimentally, nanoparticles are being used to focus and intensify heat at tumor sites. But heat is not a drug. It is not a surgical procedure. It is a treatment or a therapy. Heat has been shown to kill temperature-sensitive cancer cells. In Europe, cancer specialist Dr. Carlo Pastore has been designing “temperature therapy centers” in Italy, Spain, and other countries, where the primary cancer-fighting therapy is the administration of heat to destroy tumors, especially tumors that can't be treated with conventional drugs or surgery. In the United States, Dr. Lance Becker and his colleagues at the University of Pennsylvania pioneered the use of therapeutic hypothermia to stabilize critical care stroke and cardiac patient during treatment and recovery. Temperature therapy goes far beyond simply bringing down the temperature of a patient. Special cooling systems and instruments are needed to administer cooling evenly without damaging the body. For heat treatments, the opposite is often true, as heat needs to be directed and focused not only to small tissues but also, in the case of cancer, to tumor cells.

A more established medical technology that is benefiting from nanoinnovation is the cardiac stent, essentially a tube used to sustain blood flow through constricted or clogged blood vessels. Stents are typically smooth or mesh tubes implanted in blood vessels to increase blood flow. Drug-eluting stents are infused with drugs that prevent cells, platelets, and other cell fragments from proliferating on the stent surface. Magnetic nanoparticles are being used to extend or renew the drug coatings, and biodegradable nanoparticles are being developed for applications where the stents are intended to dissolve over time. Nanomaterials are also used to smooth the surface of metallic stents to improve blood flow.

Gene therapy is one of the best-publicized “new vistas” of medical research that involves nanotechnology if because the DNA molecules that carry genetic codes are only 2 nm wide. Gene therapy involves administering a single injection of genetic material to cure a protein deficiency with one shot. In some cases, a single treatment can last a decade or a lifetime. It has taken a decade and a half to achieve, but gene therapy is finally showing signs of success. Scientists are beginning to cure several rare diseases using gene therapy – including hemophilia B and genetic blindness. There are signs that gene therapy will also provide new methods for treating cancer, heart disease, and even the flu.

Nanomedicine includes preventive medicine as well as medical treatments and cures. This includes the development of nanosized versions of natural foods and chemicals that have disease-fighting and even age-extending properties. Natural compounds with cancer-fighting properties such as curcumin (turmeric) are being nanoengineered to make them more soluble, safer, and able to penetrate cell membranes. One day, your mother or wife may ask, “Would you like some nano-cumin in your soup?”

New Therapies, New Issues

These new therapies raise some interesting questions and issues. For example, a drug or medicine is prescribed and administered by a doctor, often in a hospital or clinic. However, if a therapy delivers heat or radiation or genes to a patient, does this have to be done in a hospital or clinic? Can it be done at a new type of facility, such as a nanotherapy or gene therapy center?

Another issue involves pricing. How do you price a therapy that is not a drug or a surgical procedure? It's relatively easy to price a pill but how do you price a treatment? How does a biotech or pharmaceutical company recover its R&D investment if the medical solution cures a disease with a single injection of genes? If it takes a billion dollars to develop that single shot therapy and the therapy works with a single treatment, does the company have to charge $1 million for each injection to recover its R&D costs?

If a worker gets sick because he or she was exposed to toxic nanoparticles, how does a hospital detect the nanoparticles? How does a diagnostician know if a symptom is caused by a toxic that is known, or a reaction to nanoparticles, which are not yet well understood? Will medical labs need to have atomic force microscopes?

These are a few of the critical issues involved in the emerging field of bionanomedicine.

Nanomedicine Is a Solution, Not Just a “Product”

Thinking of nanomedicine as a “product” is an outdated concept. Nanomedical innovations are more appropriately categorized as solutions. To deal with these and other nanoinnovations, you need to adjust your concept of marketing.

If you studied marketing in college, you probably learned about the “five P's” of marketing – also called the “marketing mix.” This includes five market factors that decision-makers can control and incorporate into their business strategy. Traditionally, the 5 P's include Product, Price, Place, Promotion, and People. That's the traditional framework previously used to promote and sell products and services.

The new concept of marketing is more customer-centered, and thinks of innovations as solutions rather than mere products and services. In 2005, Chekitan Dev and Don Schulz presented an expanded next-gen marketing mix called SIVA [6] that stands for Solution, Information, Value, and Access – where Product becomes Solution, Price becomes Value, Place becomes Access, and Promotion becomes Information. You might notice that SIVA only replaces four of the “5 P's.” In a book chapter I wrote in 2011, I suggested adding a fifth element to SIVA, by replacing “People” in the traditional marketing mix with “Community,” so SIVA becomes SIVAC (Solution, Information, Value, Access, and Community) [7]. These five elements can be used to develop and analyze markets for almost any innovation. The SIVAC framework works especially well for entirely new innovations and markets that previously did not exist. This is a “nextgen” way of thinking about technologies, products, services, and markets. To paraphrase Tom Friedman, we live in a flat world, where solutions rule. We need to be constantly updating our frameworks for dealing with this fast-changing world.

Nanomedical Solutions Need to Be Affordable

It is becoming clear that most economies, even in the industrialized world, can't afford to keep increasing their healthcare costs. Either we have to learn to prevent a disease or detect and cure it earlier, or we need to develop a portfolio of affordable solutions that are effective and available in any country in the world.

In the near future, it will be necessary to have healthcare solutions that are more affordable. We can't keep developing increasingly expensive technologies and solutions that most countries and socioeconomic groups can't afford – creating a world of medical haves and have-nots (which exists to some extent, already). We can't allow the burgeoning healthcare budget to consume a disproportionate share of national economies. Fortunately, there are remedies looming on the near horizon and many of these involve nanotechnology and nanomedicine.

For example, instead of using customized drugs to treat hundreds of different viral diseases, nanomedicine may be able to deliver one therapy that can treat 80 or 90% of all viruses. Instead of waiting for an inherited genetic disease to manifest itself, we may analyze an individual's genome and see the disease coming before it strikes, allowing us to preempt and cure the disease. Scientists are already developing binding agents that identify, target, and deliver cancer killing drugs to tumor cells, and at some point we may be able to draw from a mix-and-match menu of cancer fighting systems that target specific types of cancers and target individual cells. Also, we are close to being able to “print” human organs using our own cells, to replace damaged or diseased organs, using scaffolds made with nanomaterials. This would not only provide organ transplants without worrying about rejection of donated organs but could also provide a means to replace failing organs in older people, to extend their lives and provide a better quality of life.

These are only a few examples. In the next chapter, we'll examine bionanoinnovations that have the potential to radically transform the practice of medicine and healthcare – with solutions that are both effective and affordable.

References

  1. 1. Chai, Cameron (2012) Global Nanomedicine Market to Reach $130.9 Billion by 2016, Azonano.com (accessed January 23, 2012).
  2. 2. Morigi, V., Tocchio, A., Pellegrini, C. B., Sakamoto, J.H., Arnone, M., and Tasciotti, E. (2012) Nanotechnology in medicine: from inception to market domination. Journal of Drug Delivery, 2012, http://dx.doi.org/10.1155/2012/389485.
  3. 3. Morigi, V. et. al. (2012) Nanotechnology in Medicine: From Inception to Market Domination, Journal of Drug Delivery, p. 3.
  4. 4. Flynn, T. and Wei, C. (2005) The pathway to commercialization for nanomedicine. Nanomedicine: Nanotechnology, Biology, and Medicine, 1 (1), 47–51.
  5. 5. PR Newswire (2006) Big Pharma Is Missing the Nanotechnology Opportunity, February 15.
  6. 6. Dev, C.S. and Schultz, D.E. (2005) A customer focused approach can bring the current marketing mix into the 21st century, Marketing Management, 14 (1), 18–24.
  7. 7. Tomczyk, M.S. (2011) Applying the Marketing Mix (5 Ps) to Bionanotechnology. Biomedical Nanotechnology. Humana Press, 393–411.