NanoNews-Now Premium Report #36, June 2006

This issue of NanoNews-Now covers Nanomedicine. Editor Rocky Rawstern interviews J. Donald Payne of Nanospectra Biosciences, Sadik Esener (UCSD CCNE) and William Vine (NanoBioNexus), and Peter Searson of the Johns Hopkins Institute for NanoBioTechnology.

In our main article, Julian L. Zegelman, Director of Corporate Partnerships and Alliances at NanoBioNexus, writes an artice titled NanoBioNexus: a study in community building.

Next, the first of three interviews, this one with Sadik Esener (UCSD CCNE) and William Vine (NanoBioNexus) on the NanoTumor Center.

Following that are excerpts from several recent articles by the father of nanomedicine, Robert A. Freitas Jr.

Next up is Lynn Yoffee, of NanoBiotech News, with an article titled Nanomedicine and nano device pipeline surges 68%.

Contributing once again is Futurist Brian Wang, with his article titled On the way to Nanomedicine: Decisions and technology past and future.

Following Wang's article are two interviews, the first with J. Donald Payne of Nanospectra Biosciences, and the second with Peter Searson of the Johns Hopkins Institute for NanoBioTechnology.

In the 5th of 6 articles on Building The Winning Nano Venture Team, Bo Varga covers What investors and customers look for in start-up companies.

And last, two nanomedicine art pieces by Tim Fonseca.

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Table of contents:
Opening Statement
Julian L. Zegelman
Esener/Vine
Robert A. Freitas Jr.
Lynn Yoffee
Brian Wang
J. Donald Payne
Peter Searson
Bo Varga
Nanomedicine Gallery
Quotes
News
Useful Links
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While there is speculation surrounding the time-frame and extent to which nanomedicine will change our lives, there is no doubt about the level of seriousness that major research groups are giving to medically-oriented nanoscale technologies, nor the amount of dollars being spent in an effort to change one of today's greatest killers (1) into an easily diagnosed and treated illness.

Witness the Mission Statement of the National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer:

"To help meet the goal of eliminating suffering and death due to cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.

The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.

Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge."

And this, from the NIH Roadmap for Medical Research:

"What if doctors could search out and destroy the very first cancer cells that would otherwise have caused a tumor to develop in the body? What if a broken part of a cell could be removed and replaced with a miniature biological machine? What if pumps the size of molecules could be implanted to deliver life-saving medicines precisely when and where they are needed? These scenarios may sound unbelievable, but they are the long-term goals of the NIH Roadmap's Nanomedicine initiative that we anticipate will yield medical benefits as early as 10 years from now."

This isn't an Apollo Moon Mission, nor is it a Manhatten Project, yet. It is, however, a concerted effort to - as stated above - "meet the goal of eliminating suffering and death due to cancer" and is being funded to the tune of millions of dollars per year (2) by the NIH, and many more millions by groups spread around the world. Someone is taking nanomedicine seriously, and the upshot is potentially and end to one of humankind's greatest scourges, cancer.

As you will read below, efforts are underway to meet the challenge of diagnosing and treating many of the diseases that currently limit us to a scant seven or eight decades of life.

I, for one, look forward to however many extra (and extra quality) years that nanomedicine will offer.

(1) The CDC puts the total killed by cancer in the U.S. in 2003 at 557,271, second only to heart disease at 696,947.
(2) Centers of Cancer Nanotechnology Excellence (CCNEs): Eight hubs over 5 years - $26.3 million for the first year. Cancer Nanotechnology Platform Partnerships: 12, 5-year R01 awards - $7 million for the first year. From the CCNE Fact Sheet link

In the last thirty years, economic research has repeatedly demonstrated that successful development, growth and ultimate profitability of a new industry is intimately tied to the existence of active social networks serving to connect the otherwise autonomous players involved in the specific nascent industry.

While additional factors, such as high rate of technological innovation, timely commercialization of academic discoveries, and sufficient access to capital, are undoubtedly important to the success of a young industry, many of these aforementioned goals are readily accomplished through community building efforts designed to create sustainable interactive social networks within the industry.

Of particular interest is research done by Drs. Michael R. Darby (1) and Lynne G. Zucker (2), which emphasizes the fact that majority of biotechnology and nanotechnology innovation and commercialization takes place at a few locales within the United States (3). The narrow geographic distribution of nanotechnology activity can be explained in terms of existing local conditions fostering interaction between academia, investors, entrepreneurs, service providers, government, and the general public.

Although nanotechnology is not a single industry in itself but a collection of multidisciplinary technology platforms with broad applications across many fields, creation of localized community networks dedicated to identification, development, and commercialization of nanotechnology inventions remains important to overall success of any region attempting to benefit from the tremendous economic potential of nanotechnology.

Headquartered in Southern California's biotechnology powerhouse, NanoBioNexus (4) of San Diego, CA, is one such community network dedicated to increasing understanding of the issues surrounding nanotechnology and facilitating business opportunities for nanotechnology applications in the life sciences arena. NanoBioNexus is a non-profit, volunteer managed organization offering nanotechnology focused market research, consulting and business development services, in addition to monthly networking and educational programs delivered in the San Diego area. Through a series of monthly networking and educational forums combined with web-based outreaches, the organization connects with a broad target audience of business and legal professionals, venture capitalists, entrepreneurs, scientists, and members of the general public with an interest in nanobiotechnology.

NanoBioNexus was created in 2004 by Adriana Vela, a distinguished marketing executive with a keen interest in the life sciences, to fill an existing void in San Diego nanotechnology scene. Within two years from inception, we have attracted a devoted executive team, recruited committed industry supporters, produced monthly educational forums, launched a suite of professional consulting services for the benefit of our constituency, and were contracted to head the educational component at a regional Center of Cancer Nanotechnology Excellence.

NanoBioNexus's volunteer executive team unites accomplished professionals with such diverse yet highly complementary backgrounds as law, finance, marketing, science and medicine. Recent launch of consulting services enabled the organization to provide competent and competitively priced solutions to freshly minted nanotechnology entrepreneurs and established companies alike. NanoBioNexus consultants are often invited to provide expertise in the areas of technology due diligence, market research, executive recruiting, legal counseling, intellectual property management, business development, etc. As a non-profit organization looking to give back to the community it serves, NanoBioNexus is able to price its professional services below prevalent market rates.

Monthly forums produced by NanoBioNexus consist of both networking and educational components. At any given monthly forum, a networking reception taking place prior to the feature presentation gives attendees an opportunity to make new contacts in the area and meet other individuals active in the nanotechnology field. During the educational component, selected guest speakers deliver presentations on a particular topic of interest. Previously covered topics include nanotechnology applications to drug discovery and drug delivery, the future of nanotherapeutics, and commercialization of nanotechnology. Due to their increased popularity, the content of NanoBioNexus monthly forums is now available in the form of web-casts accessible through the organization's website.

NanoBioNexus's ability to educate and facilitate communication in the community for applications of nanotechnology in the life sciences was instrumental in its selection to head the educational component of the recently created Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer ("NanoTUMOR"), one of only seven such Centers of Cancer Nanotechnology Excellence nationwide (5). Funded by the National Cancer Institute and headed by the University of California San Diego, the Southern California based NanoTUMOR center is a research partnership bringing together the University of California San Diego, Moores UCSD Cancer Center, the Burnham Institute for Medical Research, NanoBioNexus, and University of California campuses at Irvine, Riverside, and Santa Barbara. The focus of the center is to develop multifunctional oncology nanoplatforms capable of selectively targeting tumors and delivering new generation of cancer therapeutics.

The role of NanoBioNexus within the NanoTUMOR center is to coordinate education programs in nanotechnology and its applications to oncology, enhance interaction between the member institutions, and educate community healthcare providers and the general public about the nanotechnology applications to cancer treatment.

Two years later, NanoBioNexus begins to see some of its impact on the San Diego community. Long recognized for its vibrant biotechnology landscape, the city is now beginning to attract more nanotechnology start-ups interested in leveraging existing financial, personnel and scientific resources San Diego is able to provide. Not surprisingly, NanoBioNexus is repeatedly invited to serve as a conduit between incoming start-ups and the established local community.

As part of its commitment to global community building, NanoBioNexus is often called upon to share its lessons with communities outside of San Diego that become interested in starting local nanotechnology groups. In the past six months, members of the organization's executive team participated in dialogues with international colleagues from Sweden, Canada, Mexico, Israel and Russia. Some of the recent outreach efforts involved trips to Canada and Mexico by Adriana Vela, the founder and chair of NanoBioNexus. In the age of globalization and increased cooperation, NanoBioNexus stands ready to help other communities replicate its effort to jumpstart local nanotechnology initiatives.

1. Professor of Policy and Director of the John M. Olin Center for Policy at UCLA Anderson School of Management

2. Professor in the Departments of Sociology and Social Studies at UCLA

3. Intellectual Capital and the Birth of U.S. Biotechnology Enterprises. NBER Working Paper Series. Working Paper No: 4653, February 1994. Lynne G. Zucker, Michael R. Darby, and Marylinn B. Brewer. Grilichesian Breakthroughs: Inventions of Methods of Inventing and Firm Entry in Nanotechnology. NBER Working Paper Series. Working Paper No: 9825, July 2003. Michael R. Darby and Lynne G. Zucker.

4. www.nanobionexus.com

5. link

Julian L. Zegelman, Esq.

Zegelman is the Partnerships and Alliances Director at NanoBioNexus, a San Diego, CA based non-profit organization devoted to advancing applications of nanotechnology in the Life Sciences. He also practices Intellectual Property and Corporate Law at Catalyst Law Group, a boutique San Diego law firm serving the biotechnology and pharmaceutical industries. Julian is a graduate of the University of Minnesota Law School, where he served as a staff member of the Minnesota Intellectual Property Review, a publication devoted predominantly to intellectual property matters. Julian completed his undergraduate education at the University of California, San Diego (UCSD), where he was awarded a Bachelor of Science in biochemistry and chemistry with a minor in political science.

About NanoBioNexus

NanoBioNexus is a non-profit, volunteer-managed organization that showcases applications of nanotechnology in the Life Sciences. As an organization, its mission is to provide a community service by building awareness and understanding of nanotechnology and by fostering business opportunities in the application of nanotechnology in the life sciences. This is accomplished through market research as well as networking and partnering programs delivered in the San Diego area with outreach to all of Southern California and beyond.

Our vision is to be recognized as the leading group of economic observers and business arbiters for the nanobiotechnology field. The group's target audience is business and legal professionals, venture capitalists, entrepreneurs, academia, and members of the general public with an interest in nanobiotechnology.

NN: Please talk about the UCSD Center of Cancer Nanotechnology Excellence (AKA NanoTUMOR Center); how it came to be; its goals; and current status.

Esener: There was a considerable amount of ongoing work in various aspects of nanotechnology at different locations at the UCSD campus as well as our partner institutions. The NanoTUMORCenter has enabled us to bring researchers from various disciplines -such as chemists, physicists, engineers, biologist and oncologist - together with the aim of applying nanotechnology towards the understanding, treatment and monitoring of cancer. The center now supports more than 35 co-investigators. We now have a central laboratory dedicated to cancer nanotechnology at the Moores Cancer Center with satellite laboratories distributed at the UCSD campus including the CalIT2 building and at our partner institutions.

NN: The National Cancer Institute (NCI) awarded UCSD $3.9 million for the first year of a five-year, $20 million cancer-nanotechnology platform partnership. In general, how will the $3.9 million be allocated?

Esener: The $3.9 million per year funding is distributed among six projects and the related core facilities. Each project is developing a different aspect of cancer nanotechnology that will create platforms for more powerful and selective cancer therapy when integrated together. Each project will work to advance our tools for earlier detection of cancer, and our understanding of the progress of the disease.

NN: Which institutions are participating in the NTC? What expertise do they bring?

Esener: In addition to UCSD, our partner institutions include UCSB, which is well known for its capabilities in nanotechnology, and Burnham Institute, where different types of targeting peptides have been developed and tested. In addition, investigators from UC-Riverside and UC-Irvine bring certain specific expertise to the program while NanoBioNexus manages our educational activities.

NN: In general what types of research projects are planned over the five years of the program and what are their goals?

Esener: One focus of the UCSD effort will be to develop smart hierarchical delivery platforms about the size of a red blood cell. These "mother ships" would move through the body and target specific tumor cells or the blood vessels that feed them. After arriving at their destinations, the mother ships would release their payload nanoparticles, which could be designed to help image tumors, enter cells and perform measurements, and deliver therapies. Chemists at UCSD, together with materials scientists at the University of California, Santa Barbara nanofabrication facility, will synthesize nanoparticles that will be coated with "biolinkers," molecules developed at the Burnham Institute to make the particles attach to specific types of tumor cells.

NN: On April 4, 2006, NanoBioNexus announced that they will head the educational component of the NanoTUMOR Center. Why is an Educational Core needed?

Vine: The National Cancer Institute requested that each of the eight Centers of Cancer and Nanotechnology Excellence (CCNE) create community outreach and internal educational programs in nanotechnology and cancer. Nanotechnology is so new that scientists and physicians as well as the general public have a thirst to learn more. Certainly, they are curious about how nanotechnology can help people with cancer. Finally, we want to replace the misinformation that creates anxiety with the facts so that the full benefits of nanotechnology are realized. Thus, the job of the Educational Core is to plan and execute the corresponding programs

NN: Who are the intended "users" of the educational materials?

Vine: We want to target the general public because everyone, directly or indirectly, is affected by cancer. We also want to establish close ties to local health care providers and research professional so that they are aware of new discoveries and potential therapeutics. Finally, we shall catalyze education, communication and cooperation within the NTC by our efforts.

NN: Why was NanoBioNexus chosen by the NanoTUMOR Center to Implement the Educational Core?

Vine: NBN has an expertise in teaching the public, including scientists, about both nanotechnology and biotechnology. This combination of educational expertise in the nanotech/biotech space and in teaching both the general public as well as scientists is unusual.

NN: What are the goals of the educational efforts?

Vine: Our goals are tailored to audiences: For the general public, we want to provide realistic information about the emerging field of nanotechnology and its current and potential beneficial impacts upon cancer diagnosis and treatment. For the professionals of the community, we need to provide relevant and realistic technical information in an attractive format. For the members of the NTC, our goals are not only to provide technical information about nanotechnology and cancer but also to facilitate the research of the NTC through enhanced communication and networking.

NN: What types of projects will NanoBioNexus undertake?

Vine: Our projects are tailored to the specific audience and critical for success. For the general public we will create a website full of useful information on nanotechnology and cancer, provide a calendar of local events on these important subjects and encourage local media to produce timely and factual content. Our website will also contain more technical information for health care providers and professionals in the nanotech/biotech space. NanoBioNexus also seeks to establish personal ties to all professionals. We plan to visit local hospitals to lecture on cancer and nanotechnology in a way that is relevant for health care providers. Likewise, many of our seminars, which focus on research in nanotechnology and cancer, will be open to interested professionals.

We have an extensive list of projects specifically for the NTC. We shall plan and host multiple seminars, the staple of communication in the scientific community. We will add occasional workshops, intensive daylong meetings designed for extensive discussion, development and coordination. Then there is the private website of the NTC, which will have multiple tools for education and communication. The tools include recordings of seminars for later reference, FAQ's, calendar of events, a moderated forum, an annotated bibliography, etc.

We look forward to the full implementation of these and other projects, which will occur over the next few years. We are very excited about the opportunity to expose all to this exciting research and its vast potential to treat cancer.

NN: To date, what are the most promising nanoplatforms for cancer diagnostics and treatment? How do they work?

Esener: It is far too early to even attempt to answer this question. However, it is well accepted today that drug delivery via nanotechnology offers great potential and has significant advantages over more conventional techniques. The advantages include:

NN: Looking out 10 years, what are your hopes regarding medical diagnostics and treatments stemming from our understanding of the nanoscale?

Esener: Our hope in general is to be able to reduce suffering and death caused by cancer and to significantly improve the quality of life for cancer patients and their families. More specifically, we hope to develop platforms that can detect cancer at its earliest stage. We hope to be able to monitor and treat residual cancerous cells after treatment and be able to provide treatment with high specificity and efficiency eliminating side effects and the need to perform open surgery to remove tumors.

Sadik Esener, Ph.D.

Professor Esener is an internationally known expert in photonics and opto-electronics, and he has been closely involved with five startup companies based on technology developed in his laboratories. Professor Esener co-founded San Diego-based Nanogen, Optical Micro-Machines, Parallel Solutions, Genoptix, and Call/Recall Inc.

His research interests include light modulation, detection, and amplification, heterogeneous integration of optoelectronic components, optical data storage, optical interconnects and related computing architectures, and biophotonics as applied to gene chips. Esener is a pioneer in the fields of free-space optical interconnects, parallel access volumetric optical data storage, DNA-assisted heterogeneous integration and optical cell sorting, and holds many patents inthese areas. Esener's research team is working on diverse projects pushing the limits of the state of the art. They include active and passive photonic device processing and hybrid integration techniques; photonics sub-systems assembly such as optically interconnected Fast Fourier Transform accelerator boards; and parallel light tweezer systems for handling and characterization of biological entities.

Esener joined the UCSD faculty in 1987, after receiving his Ph.D. in Applied Physics and Electrical Engineering from UCSD the same year. He leads UCSD's OptoElectronic Computing Group, and is the director of: the DARPA-funded multi-university Center for Chips with Heterogenously Integrated Photonics (CHIPS); the 3D-Opto-Electronic Stacked Processors industry/university consortium; and the Fast Read-out Optical Storage (FROST) Industry consortium. He has authored more than 100 journal publications and 200 conference abstracts. Esener is a member of IEEE, OSA, and SPIE.

Dr. William Vine

Vine is Director of Strategic Programs at NanoBioNexus and PI of the Educational Core of the NanoTUMOR Center. He has been a Senior Scientist at Arena Pharmaceuticals, where he implemented SMART (Sensitive Mass Assisted Receptor Technology), which he had previously invented. SMART integrates high sensitivity mass spectrometry with endocrinology to discover new hormones. Previously, he was Associate Director of Physiology at Amylin Pharmaceuticals, where he made critical contributions to their drug pipeline, including Symlin and BYetta. He has been a member of the Faculty at Yale University, the University of Minnesota, and the University of Cincinnati, where he directed the Clinical Chemistry Laboratory as an Associate Professor. He earned his MD, PhD and AB from Washington University; has clinical expertise in Chemical Pathology, having completed a residency in Laboratory Medicine at Yale, New Haven Hospital; and completed an Internship in Pediatrics at Cardinal Glennon Hospital. He has one patent and over 40 peer-reviewed publications to his credit.

Additional Links:
CCNE Fact Sheet
Biographies - CCNEs
Questions and Answers: CCNE

(Ed.'s note: Special thanks to Sandra Kay Helsel and the team at NanoBioNexus for all their help putting this interview together.)

The following are excerpts from Dr. Freitas' most-recently published articles, reprinted here with his permission.

An exciting revolution in health care and medical technology looms large on the horizon. Yet the agents of change will be microscopically small, future products of a new discipline known as nanotechnology. Nanotechnology is the engineering of molecularly precise structures - typically 0.1 μm or smaller - and, ultimately, molecular machines.

Nanomedicine is the application of nanotechnology to medicine. It is the preservation and improvement of human health, using molecular tools and molecular knowledge of the human tools and molecular knowledge of the human structured nanoparticles such as dendrimers, carbon fullerenes (buckyballs) and nanoshells to target specific tissues and organs. These nanoparticles may serve as diagnostic and therapeutic antiviral, antitumor or anticancer agents. But as this technology matures in the years ahead, complex nanodevices and even nanorobots will be fabricated, first of biological materials but later using more durable materials such as diamond to achieve the most powerful results.

The greatest power of nanomedicine will emerge, perhaps in the 2020s, when we can design and construct complete artificial nanorobots using rigid diamondoid nanometer-scale parts like molecular gears and bearings. These nanorobots will possess a full panoply of autonomous subsystems including onboard sensors, motors, manipulators, power supplies, and molecular computers.

The ability to build complex diamondoid medical nanorobots to molecular precision, and then to build them cheaply enough in sufficiently large numbers to be useful therapeutically, will revolutionize the practice of medicine and surgery.

From "Nanotechnology, Nanomedicine and Nanosurgery (Invited Editorial)," Intl. J. Surgery 3(December 2005):1-4. (PDF)

Massively parallel assembly is the key to the economic viability of molecular manufacturing.Biology provides perhaps the best example of the power of massive parallelism in assembly, such as polysomes in living cells (multiple ribosomes translating a single mRNA strand simultaneously).The difference between serial and parallel processing is similarly crucial in molecular manufacturing, where the basic parts are very small. If a typical molecularly precise simple component is 1 nm³ in volume, then to manufacture a 1 cm³ volume of molecularly precise product requires the assembly of 1000 billion billion (10²¹) individual simple molecular components - even at a 1 GHz operating frequency, serial atom-by-atom manufacturing of a single object would take many thousands of years, clearly not economically viable.But with parallel manufacturing, vast numbers of molecular components can be processed simultaneously, reducing batch processing times to days, hours, or even less.At least two such techniques for performing massively parallel positional assembly have been identi.ed: (1) massively parallel manipulator arrays and (2) self-replicating systems.

From "Current Status of Nanomedicine and Medical Nanorobotics (Invited Survey)," J. Comput. Theor. Nanosci. 2(March 2005):1-25 (PDF)

Our near-term ability to structure materials and devices at the molecular scale brings enormous immediate benefits and will revolutionize the research and practice of medicine. Early theoretical and experimental studies of the biocompatibility of nanomaterials and advanced nanodevices have begun . Taking Feynman’s long-term vision of medical nanorobots to heart, our present knowledge tells us that these things violate no known laws of physics, chemistry, biology, or engineering. Complex issues relating to future US Food and Drug Administration approval of nanomedical materials, devices, and even the possibility of medical nanorobots are already being addressed in mainstream legal journals [82,83]. One hopes that our society will be able to muster the collective financial and moral courage to allow such extraordinarily powerful medicine to be deployed for human betterment, with due regard to essential ethical considerations.

From "What is Nanomedicine?” Nanomedicine: Nanotech. Biol. Med. 1(March 2005):2-9 (PDF)

Is the advent of, and mass availability of, desktop personal nanofactories (PNs) likely to cause deflation (a persistent decline in the general prices of goods and services), inflation (a persistent general price increase), or neither?

A definitive analysis would have to address: (1) the technical assumptions that are made, including as yet imprecisely defined future technological advances and the pace and order of their introduction; (2) the feedback-mediated dynamic responses of the macroeconomy in situations where we don’t have a lot of historical data to guide us; (3) the counter-leaning responses of existing power centers (corporate entities, wealthy owners/investors, influential political actors, antitechnology-driven activists, etc.) to the potential dilution of their power, influence, or interests, including their likely efforts to actively oppose or at least delay this potential dilution; (4) legal restrictions that may be placed on the widespread use of certain technological options, for reasons ranging from legitimate public safety and environmental concerns to crass political or commercial opportunism; (5) the possibility (having an as yet illdefined probability) that nanotechnology might actually “break the system” and render conventional capitalism obsolete (much as solid state electronics obsoleted vacuum tubes), in which case it is not clear what new economic system might replace capitalism; and (6) the changes in human economic behavior that may result when human nature itself may have changed.

Conclusions
Deflationary forces driven by advances in molecular manufacturing (MM) can be opposed by inflationary forces competently initiated by governmental monetary authorities. This allows the two forces to remain roughly in balance, with the incremental inflation at the general price level remaining close to zero as PNs are introduced. Since an MM-rich economy will be dominated by services and information, not goods, our expectation is that the prices of services and information might rise very slightly as the prices of PN-manufactured goods falls significantly. For example, if services and information comprise 95% of the economy and goods are only 5% of all sales, then a deflationary –20% decline in the prices of goods can be largely offset by an inflationary rise of just +1% in the prices of services and information.

From Economic Impact of the Personal Nanofactory (PDF)

Readers who would like to learn more are encouraged to read the following articles:

Microbivores: Artificial Mechanical Phagocytes using Digest and Discharge Protocol

This paper presents a theoretical nanorobot scaling study for artificial mechanical phagocytes of microscopic size, called "microbivores," whose primary function is to destroy microbiological pathogens found in the human bloodstream using a digest and discharge protocol.

Theoretical Analysis of Diamond Mechanosynthesis. Part III. Positional C2 Deposition on Diamond C(110) Surface Using Si/Ge/Sn-Based Dimer Placement Tools (PDF)

This paper reports that the most-studied mechanosynthesis tooltip motif (DCB6Ge) successfully places a C2 carbon dimer on a C(110) diamond surface at both 300K (room temperature) and 80K (liquid nitrogen temperature), and that the silicon variant (DCB6Si) also works at 80K but not at 300K. Maximum acceptable limits for tooltip translational and rotational misplacement errors are reported in the paper. Over 100,000 CPU hours were invested in this study. The DCB6 tooltip motif, initially described at a Foresight Conference in 2002, was the first complete tooltip ever proposed for diamond mechanosynthesis and remains today the only tooltip motif that has been successfully simulated for its intended function on a full 200-atom diamond surface.

According to data compiled in the NanoBiotech News 2006 Nanomedicine, Device & Diagnostic Report, 130 nanotech-based drugs and delivery systems and 125 devices or diagnostic tests have entered preclinical, clinical, or commercial development, meaning the clinical pipeline has grown 68% since 2005.

"What we're seeing is a growing community of nanobiotech drug and device developers who are digging in their heels -- and surviving," says Lynn Yoffee, associate publisher of NanoBiotech News, which produced the 2006 Nanomedicine, Device & Diagnostic Report. "Along with that comes the advance of numerous product candidates marching beyond concept well into trials, ever closer to market. The industry is experiencing an evolution similar to what we saw in biotechnology, but the nanobiotech developers are putting together therapies and diagnostics with an even more astonishing 'wow' factor." Some of those promising products include:

"Although we keep a very close eye on the progress of drug candidates, we know the most immediate impact of nanotechnology in health care will be seen in earnest within the next couple of years in the form of medical devices. It's less complicated to get them developed and through the regulatory process," says Yoffee.

Big pharmas sit on the sidelines

Even with big pharma companies largely sitting on the sidelines, start-up companies are surviving and even thriving and new start-ups are emerging nearly every month. And the U.S. government added financial muscle to nanobiotech development in 2005, with major capital infusions through the National Cancer Institute's Alliance for Nanotechnology in Cancer and the National Institutes of Health's Program of Excellence in Nanotechnology.

The U.S. remains the leader in terms of the shear number (75%) of nano-based medical products in development, and of the 25% of drug and device candidates being developed outside of the U.S., Canada, Australia and Israel are working on 43% of the total 63 drugs and devices in the works around the world.

A plethora of new deals brewed in 2005. Nearly a third (30%) of all products are under development as part of collaborations or licensing deals, a trend similar to the biotechnology industry evolution.

A weed-out of start-ups

But during tough markets, only the top deals attract capital, says Douglas W. Jamison, president of New York venture capital firm Harris & Harris Group, Inc. (NASDAQ:TINY). When the market opens up, marginal companies also receive funding -- not necessarily a positive event for the market but certainly good news for start-up companies. From a capitalization standpoint, the biggest news during 2005 was the introduction of $20 million series A financings, which allowed companies to move their technologies into phase II clinical trials, Jamison says. But without new players coming into the nanobiotech market, the same investors are putting money into these deals.

Consequently, he expects to see fewer early stage deals in 2006 and a corresponding weed-out of nanobiotech start-ups.

"This could be the winnowing year for nanobiotech," Jamison says. "The cream will rise, and others will fail to receive second and third rounds of funding. In fact, that's already starting to occur."

Lynn Yoffee

Yoffee is associate publisher of National Health Information LLC (NHI) and NanoBiotech News, a weekly intelligence service covering the development of nanomedicines and nanomedical devices. She is the former senior managing editor of BioWorld Today, the newspaper of record for the biotechnology industry (www.bioworld.com). She can be reached at lyoffee@nhionline.net or (404) 607-9500.

NHI publishes a variety of monthly newsletters and special reports offering practical advice and detailed information on how to succeed under managed care. Each one of our publications is written to help you meet the challenges you face today -- from negotiating profitable contracts, to reducing utilization and cutting costs, to implementing demand and disease management programs.

By Brian Wang, June 2006

Nanomedicine is the preservation and improvement of human health using molecular tools and molecular knowledge of the human body (1). The full realization of nanomedicine would require a robust form of molecular manufacturing. Molecular manufacturing is programmable control of precise molecular assembly that is highly scalable, but years - some say decades - in coming. However, a great deal could also be accomplished with advanced MEMS (2) (Micro-Electro-Mechanical Systems), genetics, bioengineering and synthetic biology. Nanomedicine will eliminate virtually all common diseases of the 20th century, virtually all medical pain and suffering, and allow the extension of human capabilities, most especially our mental abilities.

This paper will show that nanomedicine is a perfectly reasonable technological expectation. It will review some other powerful and nearer technologies for accomplishing some of the goals of nanomedicine. It will also review some of the arguments against medical technologies that could radically lengthen human lifespans. The case will be made that society should pursue better medical technologies and that we will be able to successfully adapt to increased lifespan and better health.

Nanomedicine and life extension are not crazy or impossible technologies

An example of a prospective nanomedicine system is the respirocyte, an artificial red blood cell. As envisioned, a respirocyte could transport oxygen 236 times more efficiently than red blood cells.

Nanomedicine capabilities are not far fetchedm and many goals could be achieved with other technical approaches. There are a lot of currently available blood substitutes (3). Red blood cells were modified in 2005 with magnetic beads that created an artificial tail. The artificial tail provided motion at one tenth the speed of sperm (4).

A group of NASA-funded bioengineers at the Universities of Pennsylvania and Minnesota have created double-walled artificial cells, called Polymersomes, that can potentially float through the bloodstream loaded with cargo, such as cancer-zapping drugs, imaging agents, and yes, extra oxygen (5).

The development of cell modification and small (less than 100nm) polymer spheres shows that creating a more complex device like a respirocyte is a difficult but achievable objective.

Aubrey De Grey has created a plan called SENS (6) (Strategies for Engineered Negligible Senescence) which has targeted seven factors that seem to be major components of aging. His basic argument is that "the SENS strategy is not to interfere with metabolism per se, but to repair or obviate the accumulating damage and thereby indefinitely postpone the age at which it reaches pathogenic levels." Nanomedicine seems likely to be able to help complete the aspects of SENS that are unsolved when nanomedicine arrives. If the seven factors of SENS are resolved, what will that mean for human lifespan? We do not know for sure, but it seems reasonable that it would be helpful.

Why make hasty assumptions about limits to health and lifespan?

Many people make hasty assumptions that there is a fixed maximum human lifespan.

According to a longevity study conducted by John Wilmoth ([S. J. Olshansky, B. A. Carnes, and A. Désesquelles, Science 292, 1654 (2001)] (7)) , a UC Berkeley associate, the "oldest age at death for humans has been rising for more than a century and shows no signs of leveling off." Wilmoth and fellow colleges from the United States and Sweden researched the national death records in Sweden and found an increase in the average maximum lifespan each year since 1861. This finding calls into question the 120-year lifespan limit (8).

People take the longest recorded human lifespan - that of Jeanne Calment, 122 years and 164 days - and then equate that as a fixed maximum. Before Jeanne Calment, the number was lower, at 110 or 120. Should Jeanne Calment have been euthanized at 115 years of age, before her longevity broke one of the prior records? Did her extra years take away from the dignity of other people who lived shorter lives?

Rational planning and control of medical research has flawed foundations

Rational planning and control of research is difficult, because we do not really have a good handle on what works with procedures that are already commonly used, and we have less of an idea about how well proposed research will succeed.

As shown in a recent Businessweek magazine article (9), the actual state of affairs in medicine is that we do not really know how well today's medical treatments work. This lack of certainty speaks against using some form of centralized planning to fund only what people think will work now. This method would prevent the funding of research, which could be surprisingly successful.

Many advanced medical technology are being opposed for non-technical reasons

Leon Kass, Chairman of the President's Council on Bioethics, and others argue for death by denying better technology. Arguing for death by enforced age limits or slaughtering the elderly are clearly moral non-starters. However, going at the issue of encouraging death indirectly is still extremely wrong. (Leon Kass, L'Chaim and Its Limits: Why Not Immortality? (10))

I will summarize Kass's argument for limited lifespans and my own rebuttals.

Kass asks "how might our finitude be good for us?" He offers four benefits.

First among which is interest and engagement. Kass asks: If the human life span were increased even by only twenty years, would the pleasures of life increase proportionately?

My answer: This is not a requirement. What we enjoy we will continue to enjoy. I do not affix a percentage to my enjoyment in life. The question is useless.

Second, seriousness and aspiration. Kass asks: Could life be serious or meaningful without the limit of mortality?

My answer: Day to day life would be the same for the first 40 years. The years from 50 to120 would be changed, to be similar to the condition from when the person was 30-40. It would not be a repeat of those years, but a rich and useful prolongation of that period. There are serious people who are 30-40 and even younger. The range of seriousness does not change with age. They have as many aspirations as those who are declining with age. Statistically, people will still die, but would no longer have the certainty of the decline in capacity and death from aging.

Most people do not spend more than a fraction of 1% of their time contemplating death from aging or factoring it into decisions and feelings. Most people do not consider death in any form more than 1% of the time. Most people do not plan for retirement, a widely expected phase of life before death. Why should one expect the loss of a consideration that is such a small percentage to have such an overweight impact? I say that it would not.

A third matter, beauty and love. Kass asserts: Someone who is immortal would not be able to love another as much because they would not have the fear of death to enhance their love and appreciation.

My answer: It is a warped individual who needs the fear of death to enhance his appreciation and love of another. I would assert that such a relationship is not healthy.

How does Kass believe this fear of death enhances love and appreciation?

Perhaps as follows: I was pretty sure I was going to die in 40 years of old age, but now I have been given a treatment which has extended my life indefinitely. Do I love my children less? How about my spouse? How about parents? How about granny? How about friends? Apparently the answer for Kass is yes, he would love and appreciate others less. For me the answer is no. Maybe Kass would only be motivated to be with friends and family more if he knew there was limited time to do so, otherwise he would blow them off. I think that the quality of relationships is relatively independent of lifespan.

Fourth, there is the peculiarly human beauty of character, virtue and moral excellence. Kass argues: if you cannot sacrifice your life then you are less virtuous and moral.

My answer: one who lives a lot longer could sacrifice multiple 120 year segments of life. Using Kass's point of view this person would be more moral and virtuous. My view is that there is no reduction in virtuousness or morality based on longer lifespan.

Kass's claims that these things will be diminished if we live longer are without evidence. If we reverse his assumptions and dial things back 60 years to when people had shorter lifespans, or if we go from the first world to the third world, do any of these arguments hold true? Is someone in North America or Japan less serious, aspiring, virtuous, moral or loving than someone with a shorter lifespan in Africa?

Bill McKibben, who wrote the book Enough, claims that human lives would no longer seem meaningful (11) in a world where such limitations (aging, constraints on physical and cognitive ability) could be overcome technologically.

A lot of McKibben and Kass's arguments seems to be that humanity should continue to battle death, but fail in this endeavor. They conclude that so long as we fail then our spirit will be good. I think this is crazy and wrong. Encouraging everyone to be a failure and a loser is wrong and immoral. It is still wrong even if McKibben and Kass have personal worldviews where they are mentally uncomfortable with less death and suffering. By their logic millions should die every year so that they might not have to re-examine whether some of their personal beliefs are wrong. Those who promote the continuation of death, suffering and failure are at best misguided, and at worst evil.

Accusations of religious motivation for those in favor of life extension

Some accuse those who are in favor of life extension and nanomedicine of having quasi-religious motivations. They label all those in favor of it to be Transhumanists, which they call a religion. (Transhumanism [sometimes abbreviated >H or H+] is an international intellectual and cultural movement supporting the use of new sciences and technologies to enhance human physical and cognitive abilities and ameliorate what it regards as harsh and unnecessary aspects of the human condition, such as disease and aging.)

I think this is a pointless argument. Let us assume the accusation was true, which I do not believe. Most of those who are opposed are usually staunchly religious. If being religious is not a flaw in them, then why is it a flaw for those with differing beliefs?

The range of new and prospective medical technology

Here is an additional summary of some controversial existing and potential medical technologies.

1.Genetic Manipulation
With the human genetic code now mapped, the race is on to find anti-aging genes.

Gene Therapy will probably be widely used to cure or treat muscular dystrophy. It seems likely to be more effective than steroids, and comes without the downsides. Millions will use it.

2. Stem Cells and Regeneration
While still a hot button issue, the potential of theraputic cloning and regenerative medicine using stem cells is enormous. Imagine growing a new heart from your own stem cells, creating a replacement organ without the dreaded problem of immune rejection from your body.

3. Small Biomechanical Devices and robotics
With smaller technology showing more and more promise, doctors are willing to take a look at MEMS and Nanotechnology for less invasive devices to monitor and repair aging cells and organs. In robotics, Bleex and other exoskeletons are working now and can be worn to boost the strength of the wearer. They will be used to help the elderly and for military purposes. Assuming Moore's law holds, there will be in about 30 years cheaply implantable petaflop computers.

4. Nanomedicine, which is discussed at the beginning of this article and at www.nanomedicine.com.

Let us look at a spectrum of treatments and enhancements to see how making something better does not transform it into something evil.

Why cut off better treatments? We should keep making things better

I will now pose a series of questions and situations, which I think illustrate the absurdity of not trying to make things better and how society has already made the choice that it is OK to augment human performance and to help save the dying and to improve the health of every person as much as possible.

In 20 years, Granny is wearing an exoskeleton and outperforming the ESPN4 world's strongest man without a suit. Why is this a problem? The world fastest man is slower than Granny when she is driving a car.

Super-granny with an exoskeleton. Maybe that's OK cause it is a tool on the outside. Hip replacement is under the skin. Well that's OK, it is just restoring some function. But if we combine some exoskeleton function with Hip replacement ? Is that banned ? Is it because granny is hiding enhancement under her skin ?

Oscar Pistorius, a South African who won bronze and gold in the 100 and 200 meter sprints respectively at the Athens Paralympics, and swept the events in last month's Visa Paralympic World Cup in Manchester, UK. Pistorius, 19, who is missing both legs below the knee, wears carbon fiber prosthetic devices. Those devices can be adjusted to enable a longer stride, an advantage in a running race. A likely development is for Pistorius to qualify for the able-bodied Olympics, a goal he is pursuing and one he might attain given his remarkable times (12). Advanced prosthetics are being attached to nerves, the brain and bone (13). They are being used to provide help to those who have lost limbs (like wounded U.S. soldiers) or who are deaf or blind.

Lasik eye surgery? Usually it is just restoring up to human level function. Well some get better than 20-20. what if they make it better. Everyone can have 20-5. 20-2. Have we crossed a line? Is it only OK to have inferior Lasik?

Some people say that we should not even think about curing ageing until people are assured of getting old in the first place. Then why give any treatment to anyone who is over the life expectancy of about 77 years of age? This is just giving an additional advantage to someone who has done better than the average expectation.

Should we research ways to help older stroke victims or heart disease patients? Maybe we should cut off that research and those treatments until we cure diseases and causes that hit earlier. This is tough luck for Granny and Granddad. They only thought they were lucky to live older. Maybe it is also tough for mom, dad and you and me too. By following that logic we should be concentrating money for diseases and problems at birth and childhood.

What seems like an argument for fairness to help those worse off first would result in trying to make everyone as sick as those who are the most unlucky. Not everything can or should be fair.

Stopping the development of better treatments hurts those who are more prone to die now. They are getting perpetual discrimination. The status quo is not always a safer or better choice.

Summarizing some "enhancement" questions society has already answered

Conclusion: Society will be able to successfully adapt to better health and lifespan increases

Past increases in lifespan and health have made for a richer and better society.

Those who oppose the development of better medicine when we could create it are in favor of continued suffering, deterioration, and unnecessary death. The arguments that society will suffer are without a firm basis. A false assumption is that society will not constructively adapt to improved health and longer lifespans.

We already have widespread internal and external devices that enhance our capabilities, both physical and mental. The cases that are made for the rejection of superior performance or finer grained modifications are inconsistent and harmful to individuals, individual rights, and the productivity of society.

Brian Wang is a long time futurist, who has been involved with nanotechnology associations since 1994. He is now a member of the Center for Responsible Nanotechnology (CRN) taskforce, and is moderating the technology sub-taskforce. He is also on the Nanoethics Group advisory board.

Wang has a degree in computer science and an MBA (from Canadian universities) and has worked in the information technology industry for 20 years. He created and ran his own professional services computer consulting company with offices in Canada and the United states and clients in the USA and Europe.

He won second place in the Honeywell University Futurist essay contest. He has been involved in nanotechnology as a Senior Associate of the Foresight Institute since 1997, and he helped write Foresight's 2003 relaunch plan.

Wang has a nanotech blog which we encourage you to visit at advancednano.blogspot.com

Nanospectra Biosciences has an exclusive license to a new class of materials developed at Rice University, AuroShell™ microparticles (originally called nanoshells). While there are numerous therapeutic, diagnostic and industrial commercial opportunities, Nanospectra is focused on the development of a therapy broadly applicable to virtually all solid tumors, AuroLase™ Cancer Therapy.

AuroShell™ microparticles were developed in the laboratories of Naomi Halas, PhD, at Rice University in the 1990s. In collaboration with Jennifer West, PhD, of Rice University, a series of life science applications were envisioned which led to the formation of Nanospectra. Formal operations commenced in 2002 to commercialize applications using AuroShell™ microparticles.

Nanospectra is focused on the development of AuroLase™ Therapy to selectively destroy solid tumors. We currently intend to seek FDA approval to commence a human trial for the treatment of head and neck cancers in 2006. Other cancer applications will be developed after these initial trials.

NN: When you talk to non-scientists, how do you describe your AuroShell™ technology and AuroLase™ Therapy?

Our AuroLase Therapy is a particle-based thermal destruction of cancer, enabled by a new class of materials developed at Rice University which we call AuroShell particles. You can penetrate tissue with light in the near infrared wavelengths, but there previously were no biocompatible materials that absorb this wavelength. We construct particles small enough to be delivered to a tumor from the blood stream, but uniquely designed to absorb near infrared. Thus, when we shine a laser on a tumor area, our AuroShell particles will absorb this light. Anyone who has placed their hand on a metal surface in the summer sun knows that metals convert absorbed light to heat. In this same way, our particles in the tumor convert the laser light to heat to thermally destroy a tumor. And, unlike drugs and radiation, there is no immunity to heat – it can kill all cells.

While you can burn tissue in other ways, our particle-based approach allows the treatment of irregular shaped tumors, inoperable cancers and areas of regional disease. This is all enabled by the special properties of this new class of materials.

AuroShell particles can be uniquely tunable to absorb or scatter different wavelengths of light. Consisting of a thin gold metal shell surrounding a glass, or silica, core, this structure appears hollow when it interacts with light, giving it special optical properties and creating, in essence, a new biocompatible material for medical applications.

NN: What is your vision for the AuroShell™ microparticles and AuroLase™ Therapy?

We believe AuroLase Therapy will have broad applications in cancer. We will initially focus on head and neck cancer to fill the significant unmet medical need in this serious cancer, and then expand to other cancers after FDA approval. We hope to start our first human trial later in 2006. While cancer is our focus, our AuroShell particles have broad uses in other areas, which will be pursued as time and resources allow.

J. Donald Payne

Mr. Payne is the President and CEO of Nanospectra Biosciences, a Rice University spin-out developing medical therapeutic and diagnostic applications. As CEO, he has led NBI through preclinical development of its broad-based cancer therapy and plans to move this technology into clinical trials by the end of 2006. Mr. Payne has held progressively senior positions in the life science industry since 1992, holding executive positions with biopharmaceutical, tissue engineering and diagnostic companies. Prior to 1992, he held executive positions in the energy industry. He has an MBA from Rice University and a BBA from Texas A&M University.

Nanospectra Biosciences
8285 El Rio Street, Suite 150
Houston, Texas 77054
(713) 842-2720
Fax (713) 440-9349

NN: Please talk about the Institute for NanoBioTechnology; how it came to be; it's goals; and current status.

The Institute for NanoBioTechnology was launched on May 15, 2006. The Institute was conceived and created by a team of faculty from four divisions across the University: Peter Devreotes (Department of Cell Biology, School of Medicine), Michael Edidin (Department of Biology in the Krieger School of Arts and Sciences), Jon Links (Department of Environmental Health Sciences, in the Bloomberg School of Public Health), Marty Pomper (Department of Radiology, School of Medicine), Denis Wirtz (Department of Chemical and Biomolecular Engineering, Whiting School of Engineering), and myself (Department of Materials Science and Engineering, Whiting School of Engineering).

Over the last few years it has become recognized that nanotechnology has a critical role to play in health care and medicine. Hopkins is one of the few institutions with the faculty expertise, the research facilities, and the resources to undertake such as challenge. This was the motivation to create the Institute. The launch was the culmination of 18 months planning, discussions with faculty, and meetings with the university administration.

During the planning period we quickly realized that solving the complex scientific and engineering issues associated with the diagnosis and treatment of diseases and other medical conditions requires multidisciplinary teams. This provides a tremendous challenge in linking together faculty and students across the university. We believe that the key to solving this problem is to integrate research, education, corporate partnerships, and technology transfer across traditional departmental and divisional boundaries. Examples include, multidisciplinary graduate training programs, an undergraduate nano-bio minor, an industry affiliates program, and seed funding for research collaborations.

The goal is for Hopkins to become a leader in nano-biotechnology.

NN: What areas of expertise will the Institute be drawing on, and how do you see them collaborating?

The Institute will link faculty with expertise in molecular synthesis, device fabrication, surface science, molecular engineering, cell biology, diagnostics, therapeutics, and ultimately, clinical trials.

NN: How is the Institute being funded?

We have support from NASA to launch the Institute. We also have support for new graduate nano-biotechnology training programs from NSF and the Howard Hughes Medical Institute.

NN: Looking out ten years, what are your hopes regarding medical diagnostics and treatments stemming from our understanding of the nanoscale?

Very simply, we will develop new scientific tools and create new technologies for the diagnosis and treatment of diseases and medical conditions. We will develop new tools will allow us to develop a better understanding of how cells function, and misfunction, at the molecular level. Research will also focus on the development of new diagnostic and therapeutic strategies, for example, for the early detection and treatment of cancer.

Peter Searson

Searson is Director for the Johns Hopkins Institute for NanoBioTechnology. He is also a professor in Materials Science and Engineering in the Whiting School of Engineering and is Associate Director of the Materials Research Science and Engineering Center. He served as Chair of the Department of Materials Science and Engineering from 1997 - 2003. His research interests are in the synthesis and characterization of nanostructured materials and the applications for nanotechnology in biology and medicine, and he has more than 160 papers in scientific journals.

About the Johns Hopkins Institute for NanoBioTechnology

The Institute for Nanobiotechnology has been established at Hopkins to bring together expertise from the fields of nanotechnology, biotechnology, biology, medicine, and engineering to enable the creation of new knowledge and new technologies. In partnership with research facilities and universities throughout the country, the INBT will revolutionize health care and medicine by creating groundbreaking technologies based on nanotechnology.

The Institute's vision includes the development of innovative, interdisciplinary research programs focused in four interrelated thrust areas--therapeutics, diagnostics, cellular and molecular dynamics, and health and the environment. Interdisciplinary educational programs, public outreach programs, as well as industrial outreach programs at INBT are designed to foster the next generation of nanobiotechnology research and development.

Introduction: Bo Varga has helped start-up & early stage high technology companies close funding, customers, and people, including recruiting senior technical and executive talent. Bo is currently recruiting team members for a nano separations start-up with major price-performance benefits in metals recovery for environmental, industrial, and mining applications. He is also consulting with a project for a media portal in China.

Article 1: Why Hire an External Recruiter? (Click here for a quote, and to here to buy.)

Article 2: Building The Winning Start-Up Team: Performance Requirements

Entrepreneurs, start-up teams, investors, and recruiters often intersect to match a startup with the experienced business management required for success.

Click here to read (for free) the rest of this report in full.

Article 3: The Recruiting Process

This article addresses the actual recruiting process an entrepreneur or team can use and the knowledge, background and reference checking to establish baseline trust in a new team member.

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Article 4: Covered: Hiring, Motivating, Retaining Key Employees - the CEO example

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Article 5: What investors and customers look for in start-up companies

Introduction:

Often nanotechnology companies are started by scientists or engineers with limited or no business experience. We have worked with people who do not know what a "bill of materials" or a "whole product" is. These entrepreneurs often have a standard set of weak spots in their management skills - especially a lack of investor focus or customer focus. Even companies with the strongest product/market potential and IP can fail to close required funding or fail to close or keep key customers, if the team does not include people who can "talk the talk and walk the walk" with investors and customers.

Article 5: What investors and customers look for in start-up companies

Objectives: Upon completion of this article, you will understand the key elements in the team that a professional investor or a major corporate customer needs to see in order to work with the start-up or early stage nano company. We include joint ventures, strategic alliances, and OEM relationships - as well as direct sales - in the customer category.

Elements in common are covered in section 1, elements specific to investors are covered in section 2, and elements specific to customers are covered in section 3.

1) Investors and Customers:

Investors & customers know that working with a start-up or early stage nano venture is risky. More to the point, whether working with a venture capital fund or a large corporate strategic ally, someone on the other side of the table has to stand up and be your "champion" and risk their own credibility, reputation, and possibly career path by buying into your venture. Often "gate keepers" have to pass your venture as suitable for an investment or vendor status. And "decision makers" have to agree to funding your company, purchasing your product, or making other commitments to your company to move you into the fast growth development path.

How can these key people be moved to engage with your nano venture in the first place? And how can you move them to a positive decision and positive action.

It all depends on your team, how they position and present themselves, what they say and do and how they say and do it. It is all about building trust and reducing perceived risk and managing expectations. And about using all your stakeholders as part of your virtual team.

Positioning and presentation are usually handled by PPT/PDF presentations, executive summaries, product data sheets, company brochures, company web sites and the like. We focus on quality presentations, clean layout and graphics, relevant information - different presentations for different targets from a master set, and staged presentations.

That is, initially the person or team on the other side of the table wants to explain their interests and how you can help them meet their business goals. Your positioning and presentations should be focused on the space where your needs and business goals intersect theirs - so much information is available on line and through relationship networks that there is no excuse for not understanding the general positioning and interests of the other team.

As you build your relationship your positioning and presentation needs to adapt to the specifics of the situation - you need to meet the needs to gatekeepers, identify and close with a champion, and move decision makers to your desired goals.

Your relationships and those established via your stakeholders can get you in the door and help convince gatekeepers, champions, and decision makers to work with you. After that your success depends on your actions and behavior.

Your stakeholders include anyone in your business network who will work on your behalf because they are engaged with your team, stand to benefit from the success of your business, or have prior knowledge & experience working with your team. Besides your founders, employees, and consultants, your stakeholders include your accountants, lawyers, board of advisors & directors, consultants in marketing, technical, & other areas, customers & vendors (including your landlord), as well as the prior business network of founders, employees, and contractors usually thought of as the team.

Introduction to investors or customers by a trusted source who references your company or team is the fastest way to start building a relationship. Ongoing support by a trusted source can help build relationships and work through problems, including miscommunications that occur in every relationship.

You can cast a much wider net to establish relationships using trusted sources by setting up a formal process that includes:

(i) identifying stakeholders who can help you with targeted investor or customer networks - best done by profiling the kinds of investor or customers you are targeting including specific sources so you can both identify those you know and learn about those you do not.

(ii) working a process to discover who will help you - you will need to know the nature of the relationship and how much time and energy the individual can and will commit on your behalf as a reference and to get and keep their commitment to help as needed - including participating at "get acquainted meetings," phone conferences, emails, etc.

(iii) aggressively following up on relationship leads provided by stakeholders - this is a balancing act - especially at the beginning of a relationship too many phone calls, emails, etc. can position you as a nuisance while too few indicates a lack of interest. In general we recommend and use staged communications, that is new information should be provided in each communication "we just got our second patent issued" to help move the target towards your goal.

(iv) keeping your active references in the loop as you build relationships with the people they referenced - copying them on key emails, calling them or meeting them regularly for coffee, sending "thank you" notes, etc.

Is there an easy way to do this? Ideally there is someone on your team who has worked marketing, sales, or business development and for whom the above process is part of his professional repertoire and for whom planning & implementation of this process is second nature.

While this process may seem like a great deal of work, in our experience it is not because a very few contacts will lead to the desired result, at least in Silicon Valley. For example with a recent start-up company we contacted 10 investors and 10 consultants we know who work investment networks. The 10 consultants referenced another 10 investors. We checked web sites, on-line biographies, and other publicly available information on the 20 target investors, narrowed the list to 7, and got strong investment interest from 5. The company actually pitched only 5 investors, 3 offered to lead and 2 to participate in any syndication.

We work as consultants, either directly with the founding team as temporary members or with the founder, entrepreneur, or CEO to help with positioning, presentations, and networking to targeted investors and customers.

We work on a retainer and transaction fee basis and are paid in stock before funding and post funding with a combination of cash and stock.

There are many individuals and teams in Silicon Valley that provide business development and marketing services if the company team does not have an experienced individual on board.

Of course we recommend the earliest possible hiring of a qualified CEO for funds raising and of a VP Marketing, VP Marketing & Sales, VP Business Development or similar.

However the start-up often has to gain some traction with investors or customers before a qualified individual is willing to risk his or her career, credibility, or reputation to join a new venture, so consultants are used to provide the required help.

Finally action and behavior are key to building and maintaining strong positive relationships.

We recommend a team focus to stay "on message" regarding the current company positioning and presentation, to "under commit and over deliver" rather than to "over commit and under deliver," to always address any concerns or problems from the other party directly and immediately, and to build trust with the other party and a reputation for professionalism and strong concern for the requirements and needs of the other party. "On time, on spec, and on budget" is the best bottom line summary for any business relationship.

2) Investors:

Investors understand that a start-up or early-stage company has more vision than reality, more flexibility than stability, and that the most important factor for success is the energy, focus, and perseverance of the team. That is, a strong team with a weak idea is more likely to succeed than a weak team with a strong idea. And investors also understand that the team is fighting the odds against success and therefore needs to be opportunistic, to rapidly shift gears when a major new opportunity is created, to use a business plan as a roadmap and not as a straight jacket. Sometimes teams do not understand this and stick to a business plan longer than useful or productive, so investors can act as a "reality check" at monthly Board of Directors meetings.

Investors are most concerned with the ability of the entrepreneur, founder, or inventor to be able to clearly plan what the team will do with the money and how they plan to repay the investor, usually by selling the company or taking it public. The team is focused on building a company, the investors on making an extraordinary return within a fixed time period - usually no more than 5 years. Investors see and invest in many deals, the team has only one company. The investors want to be as helpful as possible - including using their experience to prevent problems - the team often sees the investor as interfering, controlling, or trying to dominate the company without knowing the technology, market, or product details required for success.

Clearly there are built in tensions in the relationship between investors and the nano venture and the team needs to have on-board or as a stakeholder people who understand and can work with these tensions in a productive manner. That is, someone who talks investor.

Investors prefer not to replace the CEO or other team members but they prefer even less losing their money.

3) Customers:

Customers have a much more specific technology, market, product focused that is often more in tune with a founding team. However, they also understand the time and costs of delivering a "whole product," that is, commercializing a technology so that it delivers the whole package - documentation, service, support, upgrades, drivers, interfaces, etc. And they also understand the time, costs, & difficulties of scaling up to the volume required to gain the market share that will earn the profit that justifies the investment.

A start-up or early-stage company is risky to do business with. For example major corporations often require such a company to put into escrow the IP, technology, BOM, source code, etc. - all the elements required to produce the target product in case the small company goes out of business.

Start-up or early stage teams often do not understand product market dynamics - existing supply chains and value chains will react to new, breakthrough technology with defensive measures - from the large company's point of view the issue is what the product market dynamic is when the new technology or product is in mass production, not the situation today.

And start-ups are on a different time schedule - they need to show results fast - both to keep the team motivated and to keep attracting capital or market share or the other factors required for success. Fast for a major corporation may mean 5 to 10 years and for the nano venture 5 to 10 months. A middle ground must be found to make the relationship a success.

A scientist, engineer, or similar founder without this knowledge or experience will have difficulty convincing a champion or decision maker to proceed with the commitment, investment, and opportunity cost to partner with, buy from, or work with the nano venture.

Once again, we recommend recruiting people who understand and can work with established players. "A start-up cannot rely on another start-up for market penetration."

Negotiation of the joint venture or strategic alliance can be successfully concluded working with investment bankers, business development consultants, and marketing consultants and we have worked in these roles. At times it may make sense to enter into long-term relationships with consultants who have the required connections, experience, and knowledge and who only work part time for the nano venture.

This can both reduce fixed costs for the team and bring on-board people who are too expensive to hire as full time employees. The last and final article in this series will address the tradeoffs between full time employees, part time but long-term consultants, and short-term contractors.

Article 6, the final article in this series, "Building the Winning Nano Team" will help you identify gaps in team capabilities and understand how to fill those gaps through employees, consultants, boards of directors, and boards of advisors. The article will cover relevant aspects of the Bell Mason Diagnostics and the Stage Gate Business Development Process and how these can help to shape the nano venture's planning & implementation of team building.

Please address all comments and inquiries to: Bo Varga, bvarga@USnano.biz, skype siliconvalleynano.

© Copyright 2006 Bo Varga

Technology Monitoring Service

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Nanomedicine and nano device pipeline surges 68%

On the way to Nanomedicine: Decisions and technology past and future

Figure 1. Source: sciencemag

Interview with J. Donald Payne of Nanospectra Biosciences

Interview with Peter Searson, Director, Johns Hopkins Institute for NanoBioTechnology

Building The Winning Start-Up Team: Part 5 of 6

Nanotechnology and Nanomedicine Artwork can be viewed at these locations: