Support : eNewsletters : Eye on Innovation : Issue 3, February 2010

Autophagy, a double-edged sword? — Innovation in biomedicine

The global recession is waning for most of the world, but the recovery reveals relatively meager R&D increases for most advanced economies—and strong gains for emerging economies. Research organizations need to position themselves to take full advantage of ideas generated from a myriad of sources worldwide. They must be able to not only advance technology themselves, but also integrate their innovations with those developed by others to stay competitive.

This issue of Eye on Innovation explores innovation in the multifaceted biomedical industry—prescription drugs, clinical trials, research on cures for disease, to name a few examples. We will:

• Review scientific research in authoritative biomedical databases to identify literature on autophagy, a hot topic in the medical field
• Scour the world to investigate geographically where the next players for autophagy research might arise
• Take a peek at patents to see what's in the future for this important area of research.

And, oh yes, we want to follow up by looking more globally at medical device innovation discussed in Eye on Innovation, Issue 2.

The "aha" moment
In the "Areas to Watch'section of the December, 2004, Science article, "Breakthroughs of the year—the runners-up,'one of the top areas to watch for 2005 was autophagy. Simply put, autophagy is a tightly regulated process of cellular self-eating, a sort of cellular recycling program. Autophagy is a serious area of research as defects in cell turnover have been linked to many disease states such as cancer, neurodegenerative disease and microbial infection. However, autophagy is also a healthy and necessary cellular process that prevents over-accumulation of cellular products – truly a double-edged sword.

Probe and learn
Searching three top biomedical databases on Dialog — MEDLINE^®, Embase^® and SciSearch^®: a Cited Science Reference Database — for several years prior to- and post-2005, we find the number of papers published concerning autophagy and humans. Figure 1 points out that the number of autophagy papers published between 2004 and 2008 has more than quadrupled, indicating the great interest in this field.

Although this process has been known for years, it wasn't until the end of 1998 that the gene Beclin was discovered to be one of the genes to regulate autophagy in humans. Knowledge of the proteins involved in the process has furthered research on the role of autophagy in health and its contribution to disease. Research into how autophagy is regulated may provide insights into preventing or treating autophagic dysfunction-related diseases such as Parkinson's and Lewy Body Disease.

Figure 2 shows the number of papers written about Beclin 1 and autophagy since 1999. In 1999 there were two papers published concerning autophagy and Beclin 1; by 2008 more than 100 papers were published on the subject.

The two papers written in 1999 were "Induction of autophagy and inhibition of tumorigenesis by beclin 1'by Liang XH et al and "Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21'by Aita VM et al.

Find the opportunity
To understand who the main players are for autophagy research, check the SciSearch database on Dialog. During the years 2004 through 2009, the top cited papers concerning autophagy were:

Digging deeper, we find the 1999 groundbreaking paper by Liang XH concerning the induction of autophagy by Beclin 1 has been cited 545 times since it was published. The second 1999 paper focusing on the genetics of Beclin 1 was also from the same laboratory—the laboratory of Beth Levine, former Director of Virology Research at Columbia University. In fact, three of the top five-cited autophagy papers are from the Levine laboratory. The other two leading cited papers are from the Howard Hughes Medical Center in New York and the National Institute of Basic Biology in Japan. It is in this way we can determine leaders in fields of research.

Identify world leaders
Not only is China breaking into the medical device market as we saw in Issue 2 of Eye on Innovation, but they are also gaining on Japan in the number of papers published related to autophagy during the timeframe 2007 to 2010. Searching in two authoritative medical databases — MEDLINE^® and Embase^® — we see the top six publishing countries in the field of autophagy. During this three-year span, China moves into the top 5 position ousting Japan. A similar search encompassing the years 2002-2010 shows Japan in position 5 and China in position 7 (data not shown).

Are we missing something here? Enter patents.
A summary of key patents is likely to give insight into notable activities, technology trends, and major participants involved in the development and application of a particular technology. Figure 3 shows the results of a search in Derwent World Patents Index^® identifying patent applications mentioning autophagy published from 2002 through 2009. Grouping by inventor location reveals where research ideas are being born.

While not all research can be patented, Table 2 gives an indication of the novelty of the research and of the discoveries yet to come.

Further emphasizing the novelty of autophagy research and the boom of investigation, the majority of patent applications were between 2007 and 2009. This patent analysis supports our medical research demonstrating that autophagy is a growing field of interest globally. Again, China is the number two inventor location.

Conclusions and next steps

The growing awareness of the potential impact of autophagy on certain aspects of human health and disease and the potential opportunity to develop novel therapies based on the manipulation of autophagy is drawing investigators to this field.

What's next?

• Increased insight into the developmental roles of autophagy is likely to point toward ways in which this process can be exploited for therapeutic purposes.
• As our appreciation of the roles of autophagy in cancer, neurodegeneration and other diseases grows, it will become increasingly important to understand the normal range of autophagic functions.

A challenge for the future will be to determine the circumstances under which autophagy plays a beneficial, not a detrimental, role in disease and to shed light on the variety of uses for this fascinating process that influences a wide spectrum of developmental events.

A combination of scientific and patent databases on Dialog enables you to identify any area of research—past, present and future—its status and whether it is where you want to spend your research dollars. Tracking research being conducted and where and how far the technology is from the market may indicate how this research is likely to affect current products and technologies. Reviewing patents shows where these technologies are heading and a fair indication about their road to commercialization. A strong, sound, forward-looking innovation strategy based on actionable biomedical intelligence may decide the place your company and others will have in the healthcare revolution.

Note: "The 12 different ways for companies to innovate, "Mohanbir Sawhney, Robert C. Wolcott and Inigo Arroniz, April 1, 2006
http://sloanreview.mit.edu/the-magazine/articles/2006/spring/47314/
the-different-ways-for-companies-to-innovate/

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