Biomedical Nanotechnology - Neelina H. Malsch

SARS is an infection caused by a coronavirus, a type of RNA virus. The virus can be spread by droplets and causes infection of the lungs. Experts believe SARS is a recombinant animal virus that has changed itself so that it is now infectious and even deadly to humans. The severe acute respiratory syndrome (SARS) epidemic in 2003 and the threats of bioterrorism and biological warfare clearly show the continuing needs for new or improved antibiotics, vaccines, and rapid diagnostic tests for identifying dangerous viruses and bacteria.

Bioterrorists and even certain countries are believed to be able and willing to use biological weapons of mass destruction such as anthrax, smallpox, botulinum toxin, and Ebola virus. The U.S. and more recently governments of other countries5 are funding biodefense research to develop sensors to identify and vaccines to defend against such biological weapons. They are also developing sensors for detecting nuclear and chemical agents.

a. Types of Infectious Diseases and Treatments

We must distinguish viral and bacterial diseases. Bacteria are living microorganisms. They are complete cells that can replicate as long as they have suitable and sufficient food supplies. The two types of drugs able to fight bacterial infections are specific antibiotics and broad antibiotics that are effective against several different infections. The need for new antibacterial drugs continues because bacteria tend to become immune to antibiotics. A virus consists of a strand of DNA or RNA that requires a host cell to be able to replicate. Antiviral drugs developed to date are protease inhibitors that reduce the activities of the enzymes that replicate the virus strands. A protease inhibitor can be developed only in the presence of a specific viral protease — development of a protease takes about 10 years before the product can enter the market. Therefore it is not possible to quickly develop antiviral drugs against unknown emerging diseases such as SARS. The need for broad antiviral drugs that are effective against multiple viruses is especially pressing, based on an interview with Willy Spaan of Chemical 2 Weekly, a Dutch magazine for Chemists in the April 2003 issue. As noted earlier, nanotechnology can contribute to filling these needs by incorporation of advanced genomics, proteomics, and drug discovery techniques in laboratory instruments and developing better and more economical diagnostic methods.

2. Cancer

In 2000, 10 million people developed new cancers and 6.2 million people died of the disease. The WHO fears that by 2020, 15 million people will develop new cancers annually. However, preventive actions related to smoking, diet, and control of infections can prevent a third of new cases. Another third may be curable by then. The U.S., Italy, Australia, Germany, The Netherlands, Canada, and France had the highest overall cancer rates in 2000. Technical solutions include “early detection through screening, using methods such as mammography, magnetic resonance, or computed tomography …. Molecular genome research will reveal a tremendous amount of information, but it is not clear how easily these discoveries will translate into actual lives saved and may well be restricted to rare cancers…. The medical

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The brain is vulnerable to genetic disorders such as Parkinson’s, Alzheimer’s, and Huntington’s disease and also to brain damage caused by accidents or cancers. As the average life expectancy in Western countries increases, more people suffer from chronic age-related diseases that are not lethal but cause losses of quality of life. Parkinson’s and Alzheimer’s are among the better known diseases that emerge as people live longer. Nanotechnology can be used to develop drug delivery mechanisms across the blood–brain barrier and for gene therapy; single animal cells can be transplanted into a patient to enhance the production of serotonin against Parkinson’s disease. One way to avoid the risk of zoonoses from cell xenotransplantation is microencapsulation of a single cell or a cluster of cells in an artificial shell. In this way, the animal cells are not in direct contact with human tissue but can still perform the functions for which they were implanted in the body. This technique may be suitable for transplanting single cells but is not so relevant to implantations of entire organs.

Orphan diseases are chronic or lethal disorders affecting only a small part of the population — fewer than 1 person in 2000.7 These diseases are often genetically determined. Experimental drugs and therapies are under development in research laboratories and start-up companies because the drugs or treatments will be relatively expensive and the developers must find a niche where their products will not have to compete with existing drugs. Research is funded by special government or private funds. For several orphan diseases, gene therapy is a potential cure. Nanotechnology can contribute by developing drug delivery vectors or by contributing to diagnostic lab-on-a-chip techniques and high throughput screening for drug discovery.

C. Disabilities

Many people suffer disabilities arising from birth, determined genetically, or resulting from accidents. Prostheses and implants can help these patients lead lives that are as normal as possible. Medical technology that is integrated into the human body is not the only solution available. Patients can also use other technologies and skills, such as wheelchairs for those with ambulation problems, Braille for the blind, and lip reading and sign language for the deaf people as alternatives.

1. Blindness and Visual Impairments

Worldwide, there are 180 million visually impaired people including about 40 to 45 million blind people. The WHO estimates that nine out of ten blind people live in developing countries. Blindness can be attributed to cataracts (clouding of the lenses, 46%), trachomas (eyelid infections, 12.5%), childhood onset (3.3%), onchocerciasis (river blindness, 0.6%), and other causes. Based on a number of factors including the aging of populations, the WHO expects the number of blind people to total 100 million worldwide by 2020.

To reverse this trend, WHO implemented Vision 2020, a global program that aims to eliminate avoidable blindness (about 80% of the total) by 2020. This program is more concerned with building health care facilities to treat patients in developing countries and with dissemination of existing technologies than with futuristic devices

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the pharmaceutical industry. Many people suffer from handicaps and nonlife-threat- ening diseases. Applications of biomedical nanotechnology in prostheses and active and passive implants may allow these patients a better quality of life.

III. HEALTH CARE SYSTEMS: TRENDS AND ECONOMICS

This section will sketch general trends in health care systems around the world as background to developments in biomedical nanotechnology. The populations of Western countries and more advanced developing countries are aging because of higher per capita income and better quality of life. Older people tend to suffer more age-related diseases, as a result of which they become more fragile and need more care. This leads to increased costs of health care systems. Another cost-increasing trend arises from the success of pharmaceutical and medical technology developments. In particular, the rapid progress in biotechnology, genomics, and proteomicsbased drug compound screening and development is leading to the availability of treatments for formerly untreatable diseases. This increases the direct cost of health care because medications must be paid for and are expensive during their 20 years on the market while they are still protected by patents. The emerging questions are whether we are willing to pay for all that is technically possible and, if not, what are our priorities for 21st century health care systems?

A. Health Care Market

Health care includes pharmaceuticals and medical technologies. The main actors in the health care market are governments, public and private health care insurance companies, suppliers of pharmaceuticals and medical technologies, medical professionals, patients and consumers, and outsiders (Table 6.2). Governments are responsible for organizing national health care systems; for financing the infrastructure and care; and for regulation. The governments and the health care insurance companies decide which care they will reimburse. The suppliers determine new drugs and technologies to develop and produce. Medical professionals, especially doctors, decide which drugs or technologies to prescribe to patients; patients and consumers are more decisive because they are better informed about alternative medications. Outsiders are uninsured people in developed countries and people in least developed countries who have no access to health care markets.

At this early stage of nanotechnology development, the market for health care is not directly relevant. However, if such development is to be demand-driven, nanotechnology researchers should take into account the general trends in this market. This means that cost–benefit analyses and the views of stakeholders must be considered at early stages of decision making that determines R&D priorities. Ascertaining which technological developments can potentially deliver the most benefits to world health for the least investment is the key question that should guide the decisions of policy makers.

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In Europe, health care policies are mainly organized on a national government basis, even by members of the European Union (EU). The EU is responsible for harmonization of legislation, primarily by imposing directives and other types of legislation. Directives are subsequently implemented in the national laws of the EU member states. The pharmaceutical and medical devices industries are regulated separately. The cost and organization of the health care sectors have been debated for over a decade in many countries.

Japan has a system of compulsory health insurance for all and enjoys the highest life expectancy worldwide and a relatively inexpensive health care system. The high life expectancy may be related to healthy diets. Trends in new technology and drug development do not play a role in discussions about changes in health care economics in Japan.17

Especially in least developed countries, preventable diseases and disabilities cause considerable damage to national economies. The most pressing examples are HIV/AIDS, malaria, tuberculosis, and other tropical diseases that have produced catastrophic impacts on the economies and societies of sub-Saharan Africa. In the poorest countries, the issue is how to escape the poverty trap that prevents their populations from having ample food, clean water, sanitation, and housing to stay healthy enough to earn decent incomes that would enable them to pay for medical care and the basics required for leading healthy lives. These countries lack both national health care systems and provisions for health insurance. In September 2003, the international community reached an agreement in the course of World Trade Organization negotiations that will allow imports of inexpensive generic alternatives to expensive patented drugs in developing countries that do not produce the drugs in question.

C. Discussion

Developed countries offer still the most obvious market opportunities for innovative health care products, particularly because the aging populations of critical and insured health care consumers may lead to more demand for pharmaceuticals and medical devices that utilize nanotechnology. The increased use of nanotechnology and other innovations in health care may be hampered if it leads to rising costs. Politicians and insurance companies are already confronted with difficult choices in health care priorities. Nanotechnology will have to compete with other technical and nontechnical options.

The most pressing global needs for health care exist in countries that lack basic levels of national health care systems. Possible solutions in those countries do not concern new nano or other technologies; they require investments in health care workers, hospitals, local availability of sufficient supplies of essential drugs, and basic sanitation measures. Exceptions in which biomedical nanotechnology may be useful include high throughput screening technologies used to develop drugs to combat major infectious diseases and rapid and economical diagnostics. Water purification or desalination may also benefit from the use of nanomaterials, for example, for ultrafiltration membranes that can ensure safe water supplies and ultimately healthier populations. However, a discussion of these applications of nanotechnology is beyond the scope of this book.

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b.Global Competition

The pharmaceutical industry plays an important role in the global competition among Europe, the U.S., and Japan. The EU is developing new legislation to foster “a stronger European-based pharmaceutical industry for the benefit of the patient.”20 One of the main elements of EU policies affecting the pharmaceutical sector is “the need to strengthen the competitiveness of the European pharmaceutical industry, with particular regard to encouraging research and development.”21 The U.S. is clearly the world leader in venture capital investment in health care and biotechnology. The amount of investment has varied between two and five times the investment in the entire EU from 1995 to 2000 (see Table 6.3).

Government funding for health R&D shows the same pattern. “Most European governments invest less than 0.1% of GDP in health R&D; this compares to the U.S. figure of 0.19%. In 2000, the U.S. government invested nearly five times more in health R&D than the fourteen EU countries for which figures are available. This is almost $21 billion. The EU budget for life sciences, genomics, and biotechnology for health in the Sixth Research Framework Program amounts to $2,255 million for the period 2003–2006, i.e., $564 million per year on average.”20 U.S.-based pharmaceutical companies overtook European companies in R&D expenditures during the 1990s. In 1990 through 1992, European pharmaceutical companies invested more than their U.S.-based competitors. Between 1993 and 1996, their budgets were more or less the same, but from 1997 until 2000, the annual growth rate of R&D investment of U.S.-based companies was faster than the rates of European companies. Most European companies are headquartered in the United Kingdom, Germany, and France. Japanese companies invested considerably less in R&D.20 Europe leads only in employment levels. Between 1990 and 2000, the pharmaceutical industry in the EU employed almost 500,000 people (each year), compared to around 200,000 people in the U.S. and Japan.20 The pharmaceutical industry is the EU’s fifth largest industrial sector.

The European Commission intends to foster competitiveness of this important sector by a number of policy measures, including improving access to innovative medicines and a more transparent approach to the assessment of new medicines by improving dialogues during development. The commission intends to fund the development of innovative medicines through the Sixth Framework thematic program on “life sciences, genomics, and biotechnology for health.” The commission also intends to strengthen the European science base by stimulating networking in the form of “virtual institutes of health” and by setting up a European Center for Disease Prevention and Control. One area of particular concern is targeting communicable diseases prevalent in developing countries via the European Developing Countries Clinical Trial Partnership (EDCTP). The commission also intends to put into practice its “Life Science and Biotechnology Action Plan” that aims to foster a European biotechnology industry and stimulate dialogues between the public and the life sciences sectors. The European Commission has also developed an action plan focused on science and society.

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