Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
Twitter: Dereklowe
Ah, Remember Those Days? How Will We Remember These?
Posted by Derek
If you want to know what it was like during the height of the genomics frenzy, here's a quote for you, from an old Adam Feuerstein post. Return with me to the year 2000:
During his presentation Wednesday, Mark Levin, the very enthusiastic CEO of Millennium Pharmaceuticals (MLNM), remarked that his company's gene-to-patient technology would turbo-charge drug-development productivity to levels never before seen in the industry. Just how productive? Well, he predicted that by 2005, Millennium would be pushing one or two new drugs every year onto the market, while keeping the pipeline brimming with at least five experimental drugs entering human clinical trials every year.
Note that I'm not trying to make fun of Millennium, or of Mark Levin (still helping to found new companies at Third Rock Ventures). A lot of people were talking the same way back then - although, to be sure, Feuerstein notes that many people in the audience had trouble believing this one, too. But there's no doubt that a wild kind of optimism was in the air then. (Here's another Levin interview from that era).
That's as opposed to the wild kind of pessimism that's in the air these days. Here's hoping that it turns out to be as strange, in retrospect, as this earlier craziness. And yes, I know that the current reasons for pessimism are, in fact, rather bonier and more resilient than the glowing clouds of the genomics era were. But it's still possible to overdo it. Right?
I remember Robert X. Cringley, if I recall correctly, saying that technologies are overestimated in their short-term impact and underestimated in their long-term impact. One thing I will say is that we're just at the point where Genomics technology is ready for prime-time. I recall seeing that 30,000 genomes will be sequenced THIS YEAR. Also, we're at the point where genome-wide association studies are going to be a regular part of clinical trials. Being around the genomics revolution on various levels throughout the years, I think the technology is just about ready for prime-time. Proof of that is the new genomics industry effort to standardize data formats among the companies to better compare genomes from one machine versus another.
Also, clinical trials are still clinical trials, and they're still going to take a certain amount of time to run. 10-15 years from discovery to market is going to be here to stay for a long, long time. I think the fruits of the genomic revolution are starting to finally come out of the pipeline, and that's where the real fun will begin.
2. processchemist on September 29, 2011 9:51 AM writes...
The omics hangover is still here... I routinely hear academic scientists explaining their discoveries to the media: "we found the gene X involved in disease Y, now in 5 years we'll have a cure"...
4. johnnyboy on September 29, 2011 10:14 AM writes...
It is usually wisest to be as skeptical of the prophets of a new golden era as of the harbingers of the coming apocalypse. The recent developments in genomics are truly a remarkable feat in the advancement of science, but as with everything in biology, each new major advance serves mainly to reveal more of what we don't know. As Todd says, the more practical applications of this new genomics knowledge are more likely to be realized 20 or 50 years from now, when the findings are better understood. This said, it probably should have been stressed a bit more during those frenzy years that it's not the DNA in itself that can cause diseases, but rather the proteins that it encodes. Between knowing a DNA sequence and elaborating a drug that can have a reliable effect on the encoded protein, there is a rather large chasm.
6. You're Pfizered on September 29, 2011 10:58 AM writes...
I doubt that anyone truly believed most of the things that were being touted back then, but it did bring an awful lot of VC and investor money to the party.
8. johnnyboy on September 29, 2011 11:51 AM writes...
If by drug you mean a marketed product, Millenium has one, Velcade, which was developed up to phase 1 by another biotech and later bought by Millenium. So yes, not quite the results hyped in 2000.
9. cynical1 on September 29, 2011 11:56 AM writes...
"And yes, I know that the current reasons for pessimism are, in fact, rather bonier and more resilient than the glowing clouds of the genomics era were. But it's still possible to overdo it. Right?"
An optomist is someone who tells you to cheer up when things are going their way.
13. CMCguy on September 29, 2011 1:52 PM writes...
Has any other industry endured as much periodic over-touted technical revolutions or paradigm shifts as Pharma seems to go through. With so many changes of horses in midstream (especially since a marathon) for drug discovery its no wonder innovation lags. Analogies between Pharma/Biotech have been made with Movies, Auto and Software industries where each of those appear to follow occasion encompassing major trends however seems to be less inhibitory impact than what happens with Drug R&D. At the same time those industries seem adept at recycling old ideas in to new, some times with good outcomes and sometimes not so hot. What might happen if Phramas were to focus more effort in to practice of "old fashioned MedChem"?
16. Innovorich on September 29, 2011 2:37 PM writes...
Human genomics has had and will have the power to increase the cost of drug development like nothing else! It has and will produce an enormous array of invalid targets to suck away drug discovery research and increase the ratio of failed to successful drug discovery projects! (I believe there were reports around by at least 2003 that were saying this). Maybe the situation is not quite as bad as this since, at least in the short term, genomics has produced very little of anything either wasteful or useful!
17. milkshake on September 29, 2011 3:56 PM writes...
@ CMS: "Ideology is a specious way of relating to the world. It offers human beings the illusion of an identity, of dignity, and of morality while making it easier for them to part with them. As the repository of something supra-personal and objective, it enables people to deceive their conscience and conceal their true position and their inglorious modus vivendi, both from the world and from themselves. It is a very pragmatic but, at the same time, a seemingly dignified way of legitimizing what is above, below, and on either side... As the interpretation of reality by the power structure, ideology is always subordinated ultimately to the interests of the structure - therefore, it has a natural tendency to disengage itself from reality, to create a world of appearances, to become ritual... Increasingly, the virtuosity of the ritual becomes more important than the reality hidden behind it; the significance of phenomena no longer derives from the phenomena themselves but from their ideological context ...On all levels of the power hierarchy, individuals are being pushed aside by faceless puppets, those uniformed flunkeys of the rituals and routines of power ...Individuals need not believe all these mystifications, but they must behave as though they did, or they must at least tolerate them in silence and get along well with those who work with them. "
18. DrSnowboard on September 29, 2011 3:57 PM writes...
Genomics, at least the personalised medicine part is making a difference - see IL28 for predicting response to IFN/ribavirin in HCV. Problem is, it means the old days of shotgunning every patient who could take your drug might be over. Showing that the drug will work before dosing (or at least has some chance) will really restrict the size of the fag packet commercial are going to be writing their predictions on...
There's little doubt genomics will EVENTUALLY lead to plenty of new, exciting drug targets. Whether there will still be any med chemists left by then is an open question.
21. Jonathan on September 30, 2011 10:52 AM writes...
On the other hand, the recent papers from Atul Butte's group using gene expression profiles to repurpose drugs for new targets shows that actually, genomic approaches can be quite useful. Especially if the cimetidine/lung cancer thing pans out.
1. Todd on September 29, 2011 9:30 AM writes...
I remember Robert X. Cringley, if I recall correctly, saying that technologies are overestimated in their short-term impact and underestimated in their long-term impact. One thing I will say is that we're just at the point where Genomics technology is ready for prime-time. I recall seeing that 30,000 genomes will be sequenced THIS YEAR. Also, we're at the point where genome-wide association studies are going to be a regular part of clinical trials. Being around the genomics revolution on various levels throughout the years, I think the technology is just about ready for prime-time. Proof of that is the new genomics industry effort to standardize data formats among the companies to better compare genomes from one machine versus another.
Also, clinical trials are still clinical trials, and they're still going to take a certain amount of time to run. 10-15 years from discovery to market is going to be here to stay for a long, long time. I think the fruits of the genomic revolution are starting to finally come out of the pipeline, and that's where the real fun will begin.
Permalink to Comment2. processchemist on September 29, 2011 9:51 AM writes...
The omics hangover is still here... I routinely hear academic scientists explaining their discoveries to the media: "we found the gene X involved in disease Y, now in 5 years we'll have a cure"...
Permalink to Comment3. David Formerly Known as a Chemist on September 29, 2011 10:12 AM writes...
The most prominent "memory lane moment" in that link was seeing the name "H&Q Conference".
Permalink to Comment4. johnnyboy on September 29, 2011 10:14 AM writes...
It is usually wisest to be as skeptical of the prophets of a new golden era as of the harbingers of the coming apocalypse. The recent developments in genomics are truly a remarkable feat in the advancement of science, but as with everything in biology, each new major advance serves mainly to reveal more of what we don't know. As Todd says, the more practical applications of this new genomics knowledge are more likely to be realized 20 or 50 years from now, when the findings are better understood. This said, it probably should have been stressed a bit more during those frenzy years that it's not the DNA in itself that can cause diseases, but rather the proteins that it encodes. Between knowing a DNA sequence and elaborating a drug that can have a reliable effect on the encoded protein, there is a rather large chasm.
Permalink to Comment5. Student on September 29, 2011 10:20 AM writes...
Sorry to get off topic, but if investors dropped off of pharm/biotech in such a short span, when will they do this with social media companies?
Permalink to Comment6. You're Pfizered on September 29, 2011 10:58 AM writes...
I doubt that anyone truly believed most of the things that were being touted back then, but it did bring an awful lot of VC and investor money to the party.
Permalink to Comment7. Aspirin on September 29, 2011 11:13 AM writes...
So what's been Millennium's scorecard? Two drugs since 2000?
Permalink to Comment8. johnnyboy on September 29, 2011 11:51 AM writes...
If by drug you mean a marketed product, Millenium has one, Velcade, which was developed up to phase 1 by another biotech and later bought by Millenium. So yes, not quite the results hyped in 2000.
Permalink to Comment9. cynical1 on September 29, 2011 11:56 AM writes...
"And yes, I know that the current reasons for pessimism are, in fact, rather bonier and more resilient than the glowing clouds of the genomics era were. But it's still possible to overdo it. Right?"
An optomist is someone who tells you to cheer up when things are going their way.
Permalink to Comment10. LeeH on September 29, 2011 1:09 PM writes...
That was a fun time...
(Cue Lisa Lisa and Kool and the Gang)
Permalink to Comment11. Dan Spinato on September 29, 2011 1:16 PM writes...
Who could ever forget that? Fun times indeed.
Permalink to Comment12. Dan Spinato on September 29, 2011 1:17 PM writes...
Who could ever forget that? Fun times indeed.
Permalink to Comment13. CMCguy on September 29, 2011 1:52 PM writes...
Has any other industry endured as much periodic over-touted technical revolutions or paradigm shifts as Pharma seems to go through. With so many changes of horses in midstream (especially since a marathon) for drug discovery its no wonder innovation lags. Analogies between Pharma/Biotech have been made with Movies, Auto and Software industries where each of those appear to follow occasion encompassing major trends however seems to be less inhibitory impact than what happens with Drug R&D. At the same time those industries seem adept at recycling old ideas in to new, some times with good outcomes and sometimes not so hot. What might happen if Phramas were to focus more effort in to practice of "old fashioned MedChem"?
Permalink to Comment14. petros on September 29, 2011 1:53 PM writes...
And as you noted the other week our old employers threw shedloads of cash at Millennium for all those wonderful genomic targets.
Did any lead anywhere for Bayer?
Permalink to Comment15. coprolite on September 29, 2011 2:16 PM writes...
@CMCguy--Old fashioned medchem? I've been saying for years we should go back to experimenting on the Irish. Huzzah!
Permalink to Comment16. Innovorich on September 29, 2011 2:37 PM writes...
Human genomics has had and will have the power to increase the cost of drug development like nothing else! It has and will produce an enormous array of invalid targets to suck away drug discovery research and increase the ratio of failed to successful drug discovery projects! (I believe there were reports around by at least 2003 that were saying this). Maybe the situation is not quite as bad as this since, at least in the short term, genomics has produced very little of anything either wasteful or useful!
Permalink to Comment17. milkshake on September 29, 2011 3:56 PM writes...
@ CMS: "Ideology is a specious way of relating to the world. It offers human beings the illusion of an identity, of dignity, and of morality while making it easier for them to part with them. As the repository of something supra-personal and objective, it enables people to deceive their conscience and conceal their true position and their inglorious modus vivendi, both from the world and from themselves. It is a very pragmatic but, at the same time, a seemingly dignified way of legitimizing what is above, below, and on either side... As the interpretation of reality by the power structure, ideology is always subordinated ultimately to the interests of the structure - therefore, it has a natural tendency to disengage itself from reality, to create a world of appearances, to become ritual... Increasingly, the virtuosity of the ritual becomes more important than the reality hidden behind it; the significance of phenomena no longer derives from the phenomena themselves but from their ideological context ...On all levels of the power hierarchy, individuals are being pushed aside by faceless puppets, those uniformed flunkeys of the rituals and routines of power ...Individuals need not believe all these mystifications, but they must behave as though they did, or they must at least tolerate them in silence and get along well with those who work with them. "
Permalink to Comment18. DrSnowboard on September 29, 2011 3:57 PM writes...
Genomics, at least the personalised medicine part is making a difference - see IL28 for predicting response to IFN/ribavirin in HCV. Problem is, it means the old days of shotgunning every patient who could take your drug might be over. Showing that the drug will work before dosing (or at least has some chance) will really restrict the size of the fag packet commercial are going to be writing their predictions on...
Permalink to Comment19. Fred on September 29, 2011 6:30 PM writes...
There's little doubt genomics will EVENTUALLY lead to plenty of new, exciting drug targets. Whether there will still be any med chemists left by then is an open question.
Permalink to Comment20. Morten G on September 30, 2011 12:26 AM writes...
11 years ago we barely knew about miRNA. There could be more unknown unknowns.
Permalink to Comment21. Jonathan on September 30, 2011 10:52 AM writes...
On the other hand, the recent papers from Atul Butte's group using gene expression profiles to repurpose drugs for new targets shows that actually, genomic approaches can be quite useful. Especially if the cimetidine/lung cancer thing pans out.
Permalink to Comment22. MIMD on October 3, 2011 4:32 PM writes...
In the late 1990's the CEO of DuPont presented his strategy for moving DuPont into genomics-based drug discovery at a Wilmington, DE Rotary meeting.
During Q&A I asked if he really felt he could transform a primarily chemical company into a genomics-based drug company.
He said "yes" and remarked that success was assured because "he, himself was going to become an expert."
I knew right then and there not to invest my $.
Permalink to Comment