I can strongly recommend this Bruce Booth post at LifeSciVC on computational models in drug discovery. He's referencing Marc Andreessen's famous "Why Software Is Eating the World" essay when he titles his "Four Decades of Hacking Biotech and Yet Biology Still Consumes Everything". To tell you about where Bruce is coming from, I can do no better than to quote an article just as he does. Here we go:
Drug companies know they simply cannot be without these computer techniques. They make drug design more rational. How? By helping scientists learn what is necessary, on the molecular level, to cure the body, then enabling them to tailor-make a drug to do the job This whole approach is helping us avoid the blind alleys before we even step into the lab Pharmaceutical firms are familiar with those alleys. Out of every 8,000 compounds the companies screen for medicinal use, only one reaches the market. The computer should help lower those odds This means that chemists will not be tied up for weeks, sometimes months, painstakingly assembling test drugs that a computer could show to have little chance of working. The potential saving to the pharmaceutical industry: millions of dollars and thousands of man-hours.
This quote is from a Discover magazine article from 1981. And there you have it. Over thirty-five years later, and this promise still hasn't really been fulfilled. As pointed out in his post, Bruce is no stick-in-the-mud about new technology, and I'm sure that he would absolutely love to realize the savings in time and money that robust computational modeling would provide. But it isn't there yet. We have useful techniques, we have techniques that can help, but we're never sure which projects are going to benefit and which techniques might be best to use. I have had the same experience that he mentions - virtually every project I've been on in my career has had a computational contribution. But it's the biology that comes along and overrules everything.
It's worth highlighting a few examples about biology defeating or obstructing CADD-inspired discovery, though the list of programs could be very very long. T-cell kinase ZAP70 has been attacked by CADD since mid 1990s (here), and yet there are no approved drugs against it. MAPK/p38 is another well-trodden CADD target: dozens of publications out there about CADD success stories against p38 with new and improved binders and the like; yet, clinical development is a veritable graveyard for these programs, as figuring out the safe and effective biology of these projects remains a challenge. Or take renin inhibition - after years of great CADD-enabled discovery, the first program got approved but only to find out in subsequent Phase III that drug development wasn't kind (see #16 in the FDA's recent roster of failures).
I also agree very heartily with the recommendations he makes at the end of the post. It's crucial that the computational folks be integrated as much as possible with the chemists and biologists. This is a terrible place for the "throw it over the wall" procedure; the modelers need to be speaking with the drug discovery team at all times. As tempting as it might be, they also need to be very careful about ruling things out, as opposed to recommending ideas that might work better. We don't have the horsepower we need, in most cases, to step in and say with confidence that "You shouldn't work on these compounds at all - our model says that they won't work". (And when there is that level of confidence, it's often something that you didn't need computation to know, frankly). Always check, if it's at all possible. Make some compounds - if they really don't work, it'll give you more confidence in the model, if nothing else, and if they do, you've learned something valuable and interesting.
Read the whole thing; there's a lot more than I've mentioned here. As Bruce takes pains to do, I want to emphasize that I'm not bashing the modelers, either. I've worked with a lot of good ones, and the ones who have been best at their job have also, without fail, been the best at not overpromising and realizing what they have the best chance of delivering for the project. And it's important to remember that computational hardware, software, and techniques are getting better all the time. They're not getting better as quickly as people thought they would in the 1980s, and they're not yet where we want to them to be in an ideal world, but the field is advancing every year. Don't turn your back on it, but don't fall for the hype that some folks will want to sell you, either. The Silicon Valley types are particularly vulnerable, because they don't know what biology is like (or how little we understand), and they can be particularly eager to sell you things, too, so be especially wary from that direction.
See the original post:
Software Eats The World, But Biology Eats It - Seeking Alpha
- Howard H. Seliger, Hopkins biology professor - January 1st, 2013 [January 1st, 2013]
- General Biology-Concepts and Investigations - Video - January 31st, 2013 [January 31st, 2013]
- Biology Reproduction part 13 (Sexual reproduction: Flower Structure) CBSE class 10 X - Video - January 9th, 2014 [January 9th, 2014]
- How far can a Buddhist approach to biology take us? - January 14th, 2014 [January 14th, 2014]
- Biology revision song on protein synthesis by Andrew Perkins - Video - January 30th, 2014 [January 30th, 2014]
- Scientific Evidence for Creation CSE BIBLE FORUM Origins 1212 Dr Seuss Biology - Video - February 9th, 2014 [February 9th, 2014]
- Synthetic biology lab backed by 2 million award - April 9th, 2014 [April 9th, 2014]
- Vanguard High teacher wins 2014 Shell Science Lab Challenge - April 9th, 2014 [April 9th, 2014]
- Biohacking and the problem of bioterrorism - April 9th, 2014 [April 9th, 2014]
- Synthetic genetic clock keeps accurate time across a range of temperatures - April 9th, 2014 [April 9th, 2014]
- Math modeling integral to synthetic biology research - April 9th, 2014 [April 9th, 2014]
- Vacancies in biology dept. impact course options - April 9th, 2014 [April 9th, 2014]
- Dr. Joshua Reece Earns Best Presentation Award At Conference - April 9th, 2014 [April 9th, 2014]
- Life Science Reference - Biology Online - April 9th, 2014 [April 9th, 2014]
- 9th Grade Biology: A Hectic Introduction to Mammals - Video - April 9th, 2014 [April 9th, 2014]
- Theism vs Evolution, Biology, and History - Video - April 9th, 2014 [April 9th, 2014]
- AP Biology Ch.49 Circulatory System Livestream - Video - April 9th, 2014 [April 9th, 2014]
- AP Biology Review Cards - Video - April 9th, 2014 [April 9th, 2014]
- AP Biology - Chapter 49 Circulatory System Part 1 - Video - April 9th, 2014 [April 9th, 2014]
- MSc Biology and PhD Boreal Ecology - Video - April 9th, 2014 [April 9th, 2014]
- Whale tales: Students set sail for biology class research - April 10th, 2014 [April 10th, 2014]
- Barnard biology professor honored with Emily Gregory award for teaching - April 10th, 2014 [April 10th, 2014]
- biology: Definition from Answers.com - Answers - The Most ... - April 10th, 2014 [April 10th, 2014]
- Biology - Wikipedia, the free encyclopedia - April 10th, 2014 [April 10th, 2014]
- Bridging the Brain Disease Knowledge Gap through Computational Modeling and Systems Biology: An O... - Video - April 10th, 2014 [April 10th, 2014]
- Sharpening microscope images: New technique takes cues from astronomy, ophthalmology - April 15th, 2014 [April 15th, 2014]
- COLLEGE NEWS: April 13 - April 15th, 2014 [April 15th, 2014]
- Eureka Once, Eureka Twice - April 15th, 2014 [April 15th, 2014]
- Biology - April 15th, 2014 [April 15th, 2014]
- The Art of Nutrients - Biology Song - 'Counting Stars' Remake - Video - April 15th, 2014 [April 15th, 2014]
- Biology - The Nervous System - Video - April 15th, 2014 [April 15th, 2014]
- OCR AS BIOLOGY: - Cell Structures - Video - April 15th, 2014 [April 15th, 2014]
- Evolutionary Biology Research / F. Robin O'Keefe and Julie Meachen / Page Museum - Video - April 15th, 2014 [April 15th, 2014]
- What Is a Thyroid In Biology? : Let's Get Medical - Video - April 15th, 2014 [April 15th, 2014]
- Red Ice Radio - Sofia Smallstorm - Hour 1 - Chemtrails to Pseudo-Life & Synthetic Biology - Video - April 15th, 2014 [April 15th, 2014]
- STARNES: Did professor advocate censorship of conservative student newspaper? - April 15th, 2014 [April 15th, 2014]
- German Research Foundation approves new priority program in the life sciences - April 15th, 2014 [April 15th, 2014]
- Announcing BioCoder issue 3 - April 15th, 2014 [April 15th, 2014]
- Poetry by Linda Bierds, Buddhism and biology - April 15th, 2014 [April 15th, 2014]
- Digestion - Biology Music Video - Video - April 15th, 2014 [April 15th, 2014]
- AS Level Biology- Edexcel/SNAB- Unit 1 Revision Notes - Video - April 15th, 2014 [April 15th, 2014]
- The Anatomy Of The Heart - Video - April 15th, 2014 [April 15th, 2014]
- #OilerNation Biology Program Q & A Hangout - Video - April 15th, 2014 [April 15th, 2014]
- Northwestern University researchers on synthetic biology - Video - April 15th, 2014 [April 15th, 2014]
- Gregor Mendel Institute of Molecular Plant Biology (Vienna) - Video - April 16th, 2014 [April 16th, 2014]
- Biology 1B - 2014-04-14 - Video - April 16th, 2014 [April 16th, 2014]
- AP Biology Review 3/7: Cell Energy - Video - April 16th, 2014 [April 16th, 2014]
- MCB 410: Developmental Biology - Video - April 16th, 2014 [April 16th, 2014]
- Dyslexic Advantage - UCSF Symposium - Dr Fumiko Hoeft - Biology of Stealth Dyslexia - Video - April 16th, 2014 [April 16th, 2014]
- Life cycle of Silkworm- Insect Molecular Biology Lab, Dr.M.Krishnan, Bharathithasan University. - Video - April 16th, 2014 [April 16th, 2014]
- Tracking flu levels with Wikipedia - April 17th, 2014 [April 17th, 2014]
- Biology major Katharine Leigh '15 wins Udall scholarship - April 17th, 2014 [April 17th, 2014]
- First in the nation: UW-Madison establishes post-doc in feminist biology - April 17th, 2014 [April 17th, 2014]
- Biology Project: Predation - Video - April 17th, 2014 [April 17th, 2014]
- Report Focussing On Biology Underlining - Video - April 17th, 2014 [April 17th, 2014]
- edX | MITx: Quantitative Biology Workshop: 7QBWx About Video - Video - April 17th, 2014 [April 17th, 2014]
- Cell Mediated Response (Erdmann's 2B-3 AP Biology) - Video - April 17th, 2014 [April 17th, 2014]
- Biology Plantae part 13 (Mosses: structure, life cycle, mosses vs leafy liverwots) CBSE class 11 XI - Video - April 17th, 2014 [April 17th, 2014]
- Biology - Photosynthesis - Video - April 19th, 2014 [April 19th, 2014]
- The Genie in Your Genes: Epigenetics and Biology of Intention - Video - April 19th, 2014 [April 19th, 2014]
- Introduction to Synthetic Biology Andrew Hessel - Video - April 19th, 2014 [April 19th, 2014]
- Teacher of Biology - April 21st, 2014 [April 21st, 2014]
- Biology - Osmosis - Video - April 21st, 2014 [April 21st, 2014]
- UW to host first feminist biology post-doc program in nation - April 22nd, 2014 [April 22nd, 2014]
- The Biology Project: Cell Biology - University of Arizona - April 22nd, 2014 [April 22nd, 2014]
- The Biology Corner - April 22nd, 2014 [April 22nd, 2014]
- Rader's BIOLOGY 4 KIDS.COM - Biology basics for everyone! - April 22nd, 2014 [April 22nd, 2014]
- Stanford CF Education Day 2014 Understanding the Biology - Video - April 22nd, 2014 [April 22nd, 2014]
- 9th Grade Biology: Hectic Introduction to the Human Organ Systems pt.1 - Video - April 22nd, 2014 [April 22nd, 2014]
- Honors Biology and Biology Mrs. Ellis - Video - April 22nd, 2014 [April 22nd, 2014]
- Biology professor researches parasites - April 22nd, 2014 [April 22nd, 2014]
- TRANSCRIPTION-Biology - Video - April 22nd, 2014 [April 22nd, 2014]
- 2014 Interdisciplinary Innovation Forum: "Mathematical Biology" - Video - April 22nd, 2014 [April 22nd, 2014]
- This Week in Genome Biology - April 24th, 2014 [April 24th, 2014]
- Biology - Calvin Cycle - Video - April 24th, 2014 [April 24th, 2014]
- Systems biology course 2014 Uri Alon - lecture 3: FFL and more - Video - April 24th, 2014 [April 24th, 2014]
- Systems biology course 2014 Uri Alon - lecture 2: Auto regulation - Video - April 24th, 2014 [April 24th, 2014]
- Systems biology course 2014 Uri Alon - lecture 1: Basic concepts - Video - April 24th, 2014 [April 24th, 2014]
- 9th Grade Biology: Hectic Introduction to the Human Organ Systems pt.2 - Video - April 24th, 2014 [April 24th, 2014]
- Have Atheists Hijacked Biology? - Video - April 24th, 2014 [April 24th, 2014]