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Letters to Us

WorldView 2012

Asian Advances

Peter Gwynne’s “Biotech Without Borders” (2012, Scientific American Worldview) offered a fine introduction to biotechnology investment as an issue of increasing global interest. As cultural and economic shifts continue to drive renewed awareness in biotech around the world, attention is shifting to Asia—particularly towards Northeast Asian countries, including Japan, Taiwan, Korea, Hong Kong and Singapore, among others—as a region primed for investment and meaningful growth in R&D innovation. In addition, the region still has large unmet medical needs, especially in diseases particularly prevalent in Asia, such as gastric cancer and hepatocellular carcinoma.

Over the past ten years, Asia has moved toward a wider acceptance of foreign clinical data, increased promotion of drug development and structural and regulatory improvements. Countries like Japan and Singapore, for example, are making continued progress toward established regulatory practices. Over the last few years, Japan’s Ministry of Health, Labour and Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA) have made significant progress in driving innovation and evolving towards improved, stable processes with decreasing drug and device lag. Specifically, in 2007 the PMDA set a five-year plan to improve their performance, which has yielded impressive results over the past few years in achieving both of these targets.

Additionally, countries such as Singapore are enjoying significant government resources made available to strengthen R&D and are providing the structures and processes necessary for foreign companies to be successful. One example of this renewed R&D focus is Singapore’s internationally recognized Singapore Gastric Cancer Consortium.

As Northeast Asia’s biopharmaceutical growth continues, it is imperative to harmonize and streamline regulatory policy amongst these Asian countries, and countries around the world, so that patients receive access to new treatments in the most efficient and effective manner. Such coordination also allows for a balance between inward industry growth and successful outward collaboration. As a global biopharmaceutical leader, we at Merck Serono —a division of Merck, Darmstadt, Germany—are committed to making ongoing investments at our Northeast Asia Hub in Tokyo, expanding operations in countries including Thailand and Indonesia, and taking a lead role in developing drugs for Asia.

This year, we will increase R&D spending in the Asia Pacific region by 45 percent over 2012. Moving forward, we intend to build global research collaborations and development plans that are specifically tailored to the healthcare needs of all nations.

I invite others in biopharma to join us on this journey.

» Annalisa Jenkins
Executive Vice President and Head of Global Development and Medical
Merck Serono
Darmstadt, Germany

Seeking Solutions

Breaking the linkage between fossil-fuel consumption and GDP growth is a global imperative, and Ted Agres highlighted some emerging options (2012, Scientific American Worldview, “White Lightning”). But whilst the way forward in technological and financial terms seems relatively clear, for biosciences to become an engine for growth, two primary needs must first be addressed:

Mechanisms for accelerating collaboration. Since much of the demand for the products of a bio-economy will be from emerging and developing economies, the capacity to develop and deploy biotechnologies in these regions is essential. The global flow of technologies and knowledge on the scale required cannot happen without harmonization of regulations governing their development, diffusion and deployment. Mechanisms must also be found to enable policymakers to keep track of scientific innovation and to be free of ideological constraints. Objective, science-based decision-making is a must.

Creating the will to succeed. Science and society have become strangers and many technologies that would be the feedstock of a bio-economy have become the center of a polarized and fractious debate. The biotechnology industry and the scientific community need to find ways to articulate the merits of a bio-economy as a vehicle for ensuring the provision of the global commons—water, air and land—and the protection of natural resource boundaries. Alliances between civil society, industry and the scientific community must be established, since we can no longer afford to continue the dialogues structured around vested interests and must focus instead on finding working solutions.

There are grounds for optimism. The social competence and understanding that enable the transition to a bio-economy can be generated; in particular, the next phase of global development emerging in the United Nations’s Post-2015 Development Agenda could provide the necessary high-level focus. But within this, and for new opinion leadership to emerge and find acceptance, there is a need for the creation of a space in which tensions can be defused around biotechnology and for a new collective understanding of the role of science in society to find life.

» Mike May
(no relation to the editorial director) VP Public Affairs
São Paulo, Brazil

+ Ted Agres’s “White Lightning” piece (2012, Scientific American Worldview) addressed one of the most exciting revolutions in manufacturing, industrial biotechnology. It will indeed explode in size over the next few years, driven in large part by advances being made in biology-based manufacturing technologies, such as gene synthesis.

Innovations in high-accuracy, low-cost synthetic DNA fabrication technologies can finally offer any number of industries a source of biologically derived building blocks in a manner that enables them to perform the high-throughput screening needed to determine which genetic code makes for the most efficient enzyme, the most robust crop strain or anything else they might imagine.

The current limitations that have hobbled the growth of synthetic DNA as an engineering tool for many industrial applications are finally being overcome. Using next-generation bio-fabrication platforms, R&D teams are now better able to predict what DNA sequences might work and test their functions faster and more reliably than ever before. That testing will support the development of new materials, optimized enzymes, higher-efficiency biofuels and much more.

Companies striving to design biofuels, for example, are already using DNA constructs to screen for pathways that optimize energy production and other components. Their success hinges on access to low-cost, high-throughput synthetic DNA. With better, more cost-effective and scalable DNA synthesis, industries ranging from agbio and enzyme manufacturing to biofuels and specialty chemicals stand to make rapid and significant gains. Next-generation gene synthesis could prove to be as transformative for these and other multibillion-dollar industries as the semiconductor has been.

» Kevin Munnelly
Chief Executive Officer
Cambridge, Massachusetts

The Double Bottom Line Dance

As a biotechnology start-up employing a creative mix of funding strategies, we read with interest “Navigating The New Normal: Framing the critical strategic choices for life science firms today” (2012, Scientific American Worldview). Undoubtedly, the recent economic climate has produced challenges for even the most innovative companies to raise the necessary funding, through traditional means, and launch a successful biotech, which can run into tens to hundreds of millions of dollars. However, for companies with a double bottom line—focusing on financial and social results—alternative sources of capital are available to augment traditional approaches.

PaxVax is such a double- bottom line company, developing an oral platform that delivers innovative vaccines against infectious diseases in a socially responsible manner. We have raised more than $30 million in investment—$20 million in government R&D revenue and $16 million in foundation debt financing plus a small amount of philanthropy. All of our investors have an interest in both financial and social returns, but to varying degrees. Even charitable foundations want to ensure there is a sustainable company that can deliver results just as financial investors want to see some positive social returns.

As a further novel funding mechanism, we are also pursuing the award and subsequent sale of a Priority Review Voucher (PRV). This government incentive, given for FDA approval of a therapy or vaccine against neglected tropical disease, grants the recipient priority review for another product that would not otherwise receive it and is worth potentially $50–300 million. PaxVax can develop vaccines that qualify and then sell the subsequent vouchers to large pharmaceutical companies for cash to fund more vaccine development.

We believe that in today’s economic climate it is prudent to examine all avenues to funding and capital efficiency, especially when it comes to public health.    

» Kenneth Kelley
Chief Executive Officer
Menlo Park, California

Talk about Tweets

In “Tweeting For Technology” (2012, Scientific American Worldview), Mike May took a good look at how biotech and pharma companies are trying to embrace mobile marketing and social networking tools to get their messages into the marketplace. One of the most significant barriers to adoption that he cited was the absence of clear government guidelines to enable industry to know precisely what they can and cannot do via the web.

As pharma, biologic and medical device marketers look to social media as a means to create communities of patients and physicians with whom they can interact, their actions may raise the concern of regulators. However, the FDA has provided only limited guidance on the proper use of social media despite citing social media guidance among the agency’s top priorities.

Despite public hearings and surveys, the FDA has only issued a single draft guidance to date that addresses social media. That guidance really focused on off-label marketing and barely addressed the subject of social media. However, the guidance does cite the FDA’s examples of what it believes might be off-label violations through social media, including creating web addresses that would suggest off-label use, actively encouraging bloggers to write about off-label use and more.

The previous guidance sheds some light on the ways in which the FDA may eventually regulate social media use by pharma, biotech and medical device manufacturers. The FDA will hold manufacturers responsible for their direct actions, as well as those of third parties. The FDA will monitor the implied meaning of content, as well as the direct meaning. Finally, the FDA will hold companies responsible for third party content even if it was unsolicited by the manufacturer.

Companies must carefully and cautiously continue marketing their products with an informed social media strategy. To do nothing and wait for regulators to define the way on their own will only set a standard far too conservative to be practical.

In his article, Mike May also suggested (very appropriately, I might add) that those individuals in biotech and pharma who are not currently using social media in their research and business activities should embrace a fundamental principle of Darwinism: adapt or face extinction. The same sage advice should be given to government regulators who remain slow to recognize that people communicate differently in the 21st century.  

» Erik Clausen
Managing Partner
Chempetitive Group
San Diego, California

+ In Mike May’s “Tweeting for Technology” (2012, Scientific American Worldview), he writes, “The way we communicate today is vastly different from just a few decades ago.” I suspect this comment seems obvious to most, but it is a good starting point when discussing social media, and specifically the reasons my company, a custom oligo- nucleotide and assay manufacturer supporting biotech researchers, has for being active on social networks.

First, we want to be good listeners. If a post doc at Northwestern University has success with quantitative PCR using our assays, and makes that known on Twitter, we want to be there to congratulate him or her. If a researcher expresses frustration with designing oligonucleotide primers, we want to reach out and offer advice. If a scientist at Yale is frustrated with our online ordering process, we want to be able to walk him or her through it.

Second, we want to be interesting. Not interesting to everybody on the planet, but interesting to those that have a passion for biology or science in general. We aim to do this by sharing and curating information that we hope is enlightening, educational, relevant, amusing, thoughtful, engaging.

Third, we want to enable. Specifically, we want to enable life science researchers to perform the multitude of laboratory techniques and applications where our products could be used, such as PCR, qPCR, synthetic biology, mutagenesis and DNA sequencing. We accomplish this by sharing our own educational content, sharing educational material of others, and responding to technical questions posed directly to us on social networks.

While we aim to do these three things, we remember some basic rules your mother probably taught you: Don’t dominate the conversation; know when to be quiet; know when to speak up; know when to offer advice; and be respectful and helpful.

»  Sean P. McCall
Web Content & Social Media Coordinator
Integrated DNA Technologies
Coralville, Iowa

Pushing Prenatal Testing

The infusion of advanced technologies into medicine has provoked a number of changes in the care paradigm, as Robert Goldberg thoughtfully addressed in “Moore’s Law is Remaking Medicine” (2012, Scientific American Worldview). Companies built upon rigorous scientific premises are introducing concepts in diagnosis and treatment of diseases that were altogether unachievable just a decade ago.

As these technologies are introduced, the community has been challenged to clearly articulate their value proposition and—to Goldberg’s point—define their cost relative to their value. A prime example of this can be found in the emergence of non-invasive prenatal testing (NIPT), in which genomic sequencing technology is used to detect fetal abnormalities very early in a pregnancy (well before current methods) through a simple test of the mother’s blood. In this case, the benefits of the technology offer vastly greater value for patients, who gain reliable information while avoiding the risks associated with current invasive tests.

A critical barrier to the introduction of technologies, like genomic sequencing, has been recognition of the role the technology plays in the ever-improving quality of healthcare. Like other innovations, the NIPT space has been subject to the struggle between the community and payers to adopt the technology in coverage programs. In terms of relative “cost” to current methods, the advantage of providing highly accurate information, much faster, and without risk is undoubtedly a more efficient and patient-friendly offering that has created significant value for the maternal-fetal community.

An important consideration within this paradigm is the power of the patient voice. In the NIPT community, both patients and physicians have been quick to adopt the technology, and have taken a leading role in advocating for their care in the interest of knowledge and convenience. As we see Moore’s law in motion, who knows where diagnostic technologies could lead us in just a few years.

» Harry F. Hixson, Jr.
Chairman and CEO
San Diego, California

Eating and the Epigenome

As Mike May pointed out in “Calculating E. Coli Contamination” (2012, Scientific American Worldview) and increasing media headlines suggest, more must be done to address food safety issues. Fortunately, recent advances in biotechnology are opening new doors to managing outbreaks, which can cause loss of lives, serious health problems and significant financial burden to the food industry.

Specifically, advances in new DNA sequencing technologies are providing exciting breakthroughs, as evidenced by the role of real-time sequencing to characterize the unusual strain that caused the deadly German E. coli outbreak.
The gold standard for pathogen detection is a complete genome assembly. It is now possible to produce a finished genome in a matter of hours of lab time and a few days or less of computational analysis. The availability of long-read sequencing technology allows the identification of full genes, genetic variants, structural variations and other virulence factors that could be missed with older techniques that required assembling the DNA fragments like a puzzle. As a result, the scientific community can welcome a new kind of molecular epidemiology made possible with whole genome sequencing.

Further, in the case of the German E. coli outbreak, it was demonstrated that the “epigenome” (e.g., genomic methylation patterns) of this bacterium was important to its virulence. These base modifications cannot be directly detected in methods that use PCR amplification, but can with one of the newest sequencing technologies—single molecule, real-time sequencing. Quickly generating high-quality reference genomes of outbreak strains can then facilitate the development of highly specific, cost-effective assays for testing purposes.

Thus, while PCR-based methods can assist in response to food-contamination outbreaks, we are concerned that any efforts that do not examine the whole genome and epigenome of a microorganism are missing an opportunity to reveal the full picture of information that may be critical to containing the outbreak.

» Jonas Korlach
Chief Scientific Officer
Pacific Biosciences
Menlo Park, California