New tools take time

It’s been a rough first half in 2011, but beneath the noise, much progress is being made, and the last five years have been a lot more productive than we take time to realize.

Peter Kissinger
I'm feeling better. It may just be that many of us are tiredof negativity. We are so fatigued from it that we are getting things back on a positivetrack. Our undergraduates have left town and the reduced traffic in WestLafayette calms the soul and our labs buzz with fresh new ideas. Life scienceventure funding is up a little bit. The federal budget has been kinder toscience than it might have been. On both ends of the political spectrum, weagree that spending must come down and tax revenues (I didn't say rates) mustgo up.
 
 
Happy days are here again. If not, it's up to us to make itso. I list here a few topics that I find interesting, where progress has beenquite good against early negative thinking.
 
Adaptive clinicaltrials: This one has been under consideration for some time, but seems tobe accelerating with better computational tools and the pressure to conservetime and money. Earlier, one wouldn't peek at the results from a classicaldouble blind trial until it was over, or something went drastically wrong alongthe way. This is satisfying only in its simplicity. Suppose the wrong dose waschosen? Suppose the inclusion criteria for patients were too broad where somewould benefit, some not respond and others would suffer? We'd like to knowsooner. While this is a subject for experts, I'm encouraged to see thismethodology being refined and gaining in popularity. 
 
ClinTrials.gov providestransparency with clinical trials intentions and results. It's helpful to knowwhat has not worked. Sharing the disappointing data is a very good thing. Whilethis got started only recently (September 2007), progress has been very good.It's easy to search on your favorite disease and see those studies that havebeen completed and others in process. You can learn about the endpoints,inclusion/exclusion criteria and much more. Take a look.
 
 
Molecular imagingof cells, organs, and mammals, based on a wide variety of principles, is makinga dramatic difference in discovery, preclinical and clinical development. Thishas moved from the esoteric to the routine. It's a validated approach. Thereare some amazing new variations, such as cell imaging on the fly with flowcytometry and imaging of biopsied tissue with mass spectrometry. It's going toget a lot better and more economical. While we all looked at pond watercreatures swimming about on a microscope slide in high school biology, for mostof my scientific life, when cells were to be seen, they were also to be dead,fixed, stained and everything but stuffed. Now they can be seen very much alivewith specific components labeled. The definition of a microscope has broadenedto an amazing array of high-performance devices. FRET and FRAP may sound likecartoon characters of old, but they are making biology history today.
 
 
Personalized medicine(at least patient segmentation into more narrowly defined classes) is gainingground with diagnostics that are prognostic of both pharmacology andtoxicology. While approved companion diagnostics remain few, markers duringclinical research phases support the mechanism of action, while demonstratingefficacy and safety. Early success presages further change. Five years ago, therewas much skepticism, but that is slowly abating. Related terms such as"targeted" or "tailored" therapeutics are frequent additions to the lexicon andlikewise are real. Genomic characterization of cancer biopsies is now anavailable tool for personalized medicine. Given the long-understood phrase thatchildren are not small adults, pediatrics remains a personalized medicinechallenge that is getting attention, but continues to suffer from both financialand ethical realities. Being aware of a problem is the first step to solvingit.
 
Dried blood/plasmaspots on cellulose have been featured in a number of recent bioanalyticalpublications, taking the idea from its origins for qualitatively detectinginborn errors of metabolism to a new tactic for sample collection and transportfor quantitative pharmacokinetics. This is made possible primarily by advancesin mass spectrometry. It's too early to say for sure what the acceptance of thetechnology will be, but no doubt some great minds are in the lab sorting outthe several challenges. Here we have another example of precompetitivetechnology where sharing among pharma and CROs is advancing the art. I amconfident that this will not replace liquid samples to the extent the earlyproponents have predicted.
 
 
Malaria, HIV and TB:Altruism is making progress here with open innovation among pharma, academicinstitutes and not-for-profit firms. For example, new approaches to aninfectious disease are being explored after a nearly 50-year hiatus in the caseof tuberculosis. It is very gratifying to see the altruism of pharma sharinglibraries for this effort. More rapid diagnostics for TB are also becomingavailable, potentially saving many weeks of time. The Global Alliance for TBDrug Development now includes the Global Health R&D Center of China.Imagine trying that in 1970.
 
 
Rare diseases: Some6,000 to 8,000 diseases have been too rare to attract investment inpharmacology. Thus, another consortium is assembling this year with theunsurprising name of International Rare Disease Research Consortium. A numberof national health organizations are signing on to participate, among them theEuropean Commission and the U.S. National Institutes of Health (NIH). Thechallenges are daunting when it comes to return on R&D investment andachieving statistical power in clinical trials when the entire disease cohortcan be in hundreds, not millions. It therefore makes sense to plan to useglobal resources wisely and to share thoughts and data for the common good. Isuspect that the biology of these unusual cases may well help sharpen solutionsfor more common diseases as well. Diseases thought to be common (such as cancerand influenza) are becoming much more rare as subclassifications are revealed.Along the same lines, the NIH Chemical Genomics Center (NCGC) has created adatabase of approved and currently investigational drugs. This approaches 3,000drugs approved in several countries. It promises to stimulate the repurposingof approved drugs for rare diseases, by providing sample compounds forscreening.
 
Every biopharma, big and small, must balance the cost of toomany projects versus the risk of too few. There is no way to get this rightexcept by luck. Planning cannot work! This is the problem with science! If we knew what was going to happen,it would not be science, but rather engineering! Sharing risk and bestpractices sure beats the "not invented here" closed environment of the 1980s. Allthe examples noted above are enhanced by sharing data and open debate. It'sbeen a rough first half in 2011, but beneath the noise, much progress is beingmade, and the last five years have been a lot more productive than we take timeto realize. The glass is not empty.
 
Peter Kissinger ischairman emeritus of BASi, CEO of Prosolia in Indianapolis and a professor ofchemistry at Purdue University.
 

Peter Kissinger

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