Why study a drug in distilled water when urine is cheaper?

Or is it? This is the title I used at an American ChemicalSociety symposium on clinical chemistry in the late 1970s. Even in my youth, Iwas complaining about analytical chemistry faculty doing things that had verylittle biological relevance, when it was not that hard to do the opposite.Thirty years later, I've had to modify my opinion because urine, blood, rats,tissue, saliva and all the rest have recently become very expensive, andproperly so.

We talk about the valley of death from bench to bedside.This is not often right. There can be a series of valleys, all replete withpoisonous snakes and highway robbers allowing you to cross only if you give upmoney.

Today, my complaint is that many of us believe that ourtechnology, or our research area, is extremely valuable, while those in theneighboring spaces are, of course, much less valuable. To do translationalresearch, we must receive a baton from others and then hand it off to the nextin line. Let me give some examples, starting with urine.

Analytical Chemist: "I've developed a neat way to determine 500 compounds in urine that may be interesting to explore with patients having cardiovascular disease. Can you send me urine from 250 patients and 250 matching controls documented as to diet, medications and exercise habits? That shouldn't cost too much."
Clinician: "Do you have $300,000?"

Clinician: "I understand you can develop an assay for XYZ protein in blood plasma. I have 1,000 samples in my freezer. Can I send them to you to try with your marvelous new instrument? That shouldn't cost too much."
Bioanalytical Chemist: "Do you have $300,000?"

Organic Chemist: "I've made a small library of 500 compounds to test in vivo. What would it cost to test them in rats? That shouldn't cost too much."
Pharmacologist: "Do you have $25,000 for each compound to test? That's $12.5 million."

Pharmacologist: "I have an interesting drug candidate I found in eye of newt. I need an organic chemist to make 10 analogs to test in rats. That shouldn't cost too much."
Organic Chemist: "Do you have $500,000?"

We in academia follow our passions, and our passions don'toften line up with others outside of our own discipline. I'm a bioanalyticalchemist with passions about mass spectrometry, chromatography, in vivo sampling and electrochemistry. Over 35 years (ittook nearly that long), I've gained an appreciation for the fact that it isunrealistic for a surgeon, biochemist or pharmacologist to care more for a toolthan for the result. To make translational research work better, the hand-offsfrom discipline to discipline deserve more attention and they must be funded.If not, the translation comes to an abyss.

The National Institutes of Health (NIH) are aware of theproblem, and in some cases (the National Cancer Institute, for example) haveselected contractors to help their investigators with such hand-offs. I do nothave personal experience to know how well this is really working. I suspect itis pretty slow compared to many expectations. Drug development is a process ofhurry-up-and-stop.

Academia rewards individual accomplishment and creativity.We became academics because we didn't want to work on a problem defined bysomeone else. We are motivated to produce publications, lectures and Ph.D.dissertations. Much of translational research requires following rules andtesting rather than inventing. It can be very labor- and paperwork-intensive tocollect human urine or test a library of potential drugs in rodents or swine.To achieve these activities well, we must rely on technical people who are notscientists, but who pay close attention to details such as informed consent,sample labeling, animal husbandry, survival surgery and methodology shown to bevalidated for the purpose.

How can we get this paid for today? Any ideas?

The NIH StudySection model is not conducive to this. The experts around the table are notexperts in everything and very few, for example, have preclinical or clinicalpharmacology experience with intact mammals. Why not? Molecular biologydistracted us for the last 30 years.

Peter Kissinger is chairman emeritus of BASi, CEO ofProsolia in Indianapolis and a professor of chemistry at Purdue University.