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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

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

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July 13, 2011

Book Review: The Quest for the Cure

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Posted by Derek

I wanted to mention that I have a review up at Cell for a new book by Brent Stockwell (at Columbia): The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines. I found it a good summary of recent drug discovery, and a look at the attempts to attack "undruggable" targets like protein-protein interaction, transcription factors, and so on. It's written for an educated general readership, and one of the things I wondered about was how books like this find an audience.

Comments (45) + TrackBacks (0) | Category: Book Recommendations


COMMENTS

1. Vader on July 13, 2011 11:00 AM writes...

Speaking as a non-biologist, I tend to pick up books like this when they pop up in my Amazon book recommendations.

Though these are not flawless, as when I entered the information that I had enjoyed a book on the life of Hirohito, and the recommendation engine came back with a recommendation for a book on breast reduction surgery. Go figure.

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2. Celia on July 13, 2011 11:53 AM writes...

One way to find out about books from university presses is in New York Review of Books. The ads can be quite informative. I learn of books I would never have heard of otherwise.

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3. Terry Liu on July 13, 2011 12:16 PM writes...

it is good for Americans have the habit of reading
in modern time, especially noways the whole world is popular with internet and free media.

It is one of the reasons of American's success, ppl hold on enough time to prove a habit is good to keep and to follow.

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4. Anonymous on July 13, 2011 12:39 PM writes...

@3 Terry Liu

Your comments are annoying and idiotic! The sheer disregard for English grammar discredits everything you mention. You should have someone proof-read your statements before commenting in the future; this includes your attempts in the Sames/Sezen post too.

Thanks

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5. Boghog on July 13, 2011 12:39 PM writes...

Just curious, did Brent describe any successes targeting "undruggable" targets? If there is a success then by definition the target is no longer undruggable. Presumably he reported "progress".

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6. Anonymous on July 13, 2011 12:40 PM writes...

@3 Terry Liu

Your comments are annoying and idiotic! The sheer disregard for English grammar discredits everything you mention. You should have someone proof-read your statements before commenting in the future; this includes your attempts in the Sames/Sezen post too.

Thanks

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7. Boghog on July 13, 2011 12:42 PM writes...

Opps, never mind, you described them as "attempts". I should read your post more carefully. Sorry.

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8. johnnyboy on July 13, 2011 1:13 PM writes...

@4-6: how's your mandarin ? just curious.

Thanks

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9. Not_A_Scientist on July 13, 2011 4:02 PM writes...

Derek - thanks for bringing the book to our notice. While I do not work as a scientist (though a science undergrad), I always enjoy reading books on scientific topics.

I was also very interested by your topic on Phenotypic Screening vs. target based discovery. I was wondering whether you, or the many scientists who frequent your blog, could provide me references to other books that give a semi-technical (doesn't need to be completely dumbed down!) overview of how drug discovery is done. I am looking for something that describes the whole process from target identification / validation to IND filing. Any suggestions of a good read that I could grab off Amazon?

Thanks!

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10. g on July 13, 2011 5:20 PM writes...

@Not_A_Scientist: "Science Business" by Gary P. Pisano and "From Alchemy to IPO" by Cynthia Robbins-Roth.

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11. Anonymous on July 13, 2011 5:34 PM writes...

To 4
Well, as a foreigner, I am only be responsible for the contents, and I encourage every Chinese students to speak bravely and publicly regardless someone complain of language issue.

The time, rely on complain of language issues to suppress other ppl's opinion, is passed away. Now China is the second biggest economic country in this world, and will be the number 1 in the near future.

one of the most important things for American chemists is to learn Chinese, if they still want to keep their jobs.

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12. Anonymous on July 13, 2011 5:40 PM writes...

To 8
我的普通话非常好,比奥巴马还能雄辩
To fulfill your curiosity--My Mandarin is one of my best skills, just a little bit below the level of president Obama's English skills.

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13. road on July 13, 2011 7:53 PM writes...

@Not_a_scientist: "The Billion Dollar Molecule" is one of my favorites. It's a true story, but has a great narrative and reads like fiction.

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14. Not_A_Scientist on July 13, 2011 9:52 PM writes...

g & road: thank you for the suggestions! I have actually read The Billion Dollar Molecule as well as From Alchemy To IPO. I am looking for something more hardcore :-).

Maybe a book that helps me understand how all the various groups in discovery fit into the jigsaw: HTS/Lead Discovery, Med Chem, Pharmacology, Structural Biology, Non Clinical Development, etc etc? Maybe such a book doesn't exist? Or exists as a highly technical textbook that's going to go over my head? Also would love to understand concepts like multiplexing, when / how x-ray crystallography is used in discovery, what decides which species (rats dogs, primates) to do preclinical tox studies in, are these studies 14 days or longer, etc etc.

The above is just an incoherent rambling of topics that I have run across so pardon me if they completely don't relate to each other.

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15. anon on July 13, 2011 10:11 PM writes...

@14 Not_A_Scientist

For the types of books you're looking for, search "Drug Development" on Amazaon. There will be several options that will be good overviews, but because of the topic and specialization, the "hardcore" ones will generally be over $150 new. If you see something you like, check your university library to see if they have it on the shelf. I can't confess to reading any of them, as I learned drug development on the job. And I continue to learn, as each program has it's unique challenges, and drug development is not one size fits all and widely varies depending on the type of molecule, clinical indication, biology, toxicity, ever changing regulatory environment, etc.

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16. johnnyboy on July 14, 2011 8:53 AM writes...

@12: It is truly a wonder that someone with your immense skills and knowledge chooses to remain 'anonymous' !

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17. partial agonist on July 14, 2011 8:57 AM writes...

20 years ago, kinases were considered by most to be undruggable targets, so it's a moving definition.

I think calling protein-protein interactions undruggable is fair at this point, but maybe the recent successes in cancer at Abbott and elsewhere are suggestive that this may change over time.

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18. spoons on July 14, 2011 9:00 AM writes...

These books find an audience by being available on kindle for $10. Bought.

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19. johnnyboy on July 14, 2011 9:05 AM writes...

@14 Not_A_Scientist:
Your enthusiasm is commendable, but I doubt you will find a book that covers in detail such a huge field. Preclinical development is not one thing, more like a very broad collection of quite different sciences, with a knowledge base (and regulatory requirements) that are constantly evolving. I myself am involved in the preclin toxicology/safety aspect, and I can't point to one book that would cover adequately this one field. I think that like #15 said, most of us learn on the job, and while we can use some textbooks for specific bits of the work, most of what we do is not really written down anywhere. Drug development would have to be a lot easier for someone to be able to write one 'how-to' manual for it ! Since you're a student, I would suggest you look at specific university courses, since some universities are developing undergrad programs or courses geared toward pharma R&D, and sometimes the course notes may be available online. Good luck !

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20. Barry Levine on July 14, 2011 11:00 AM writes...

until recently, such book found its audience when the interested party asked a librarian. As those positions vanish, that strategem becomes obsolete. In 2011, the interested party would ask for a recommendation from a reader/contributer on this 'blog.

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21. Anonymous on July 14, 2011 12:04 PM writes...

#4-6

I guess we won't be seeing you in a future ambassadorial position. At least not to anywhere in Asia.

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22. newnickname on July 14, 2011 4:07 PM writes...

I haven't read this yet, but it just popped up as a freebie (for those of you without paid access) at Nature: "How were new medicines discovered?" by David C. Swinney and Jason Anthony. Nature Reviews Drug Discovery 10, 507-519, (July 2011) doi:10.1038/nrd3480

Links aren't allowed to be posted, but I think the doi should help. Or maybe: append /nrd/journal/v10/n7/full/nrd3480.html to nature.com

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23. Not_A_Scientist on July 14, 2011 11:46 PM writes...

Thanks all for the suggestions! I trolled on Amazon extensively and looks like I might have found something that comes reasonably close to what I am looking for:

Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research

Robert M. Rydzewski

I think links are not allowed here? But you can find it on Amazon in a couple of clicks.

Does it look good? I am excited looking at its TOC and have an itch to pull the trigger before the weekend.

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24. milkshake on July 15, 2011 2:21 AM writes...

@23: You will be depressed to learn that Robert M. Rydzewski, the author of the book, is currently looking for employment. (It just so happens - I am sitting in the office/working in the same hood right next to his former boss)

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25. anon on July 15, 2011 11:32 AM writes...

I'll buy the book-on-tape version if it's read, or better yet, sung by Robert Smith.

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26. Ellen Clark, Clark Executive Search on July 15, 2011 1:38 PM writes...

@14 Not_A_Scientist: I have 3 suggestions:1. "Understanding Pharma; A Primer on How Pharmaceutical Companies really Work"By John Campbell 2."Drug Discovery from Bedside to Wall Street" by Tamas Bartfai & Graham Lees 3. " Drugs From Discovery to Approval" by Rick NG
And thanks for review Derek

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27. Not_A_Scientist on July 15, 2011 11:42 PM writes...

Tank you Ellen. I have read Rick NG's book. I will look into the other two.

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28. Just facts on July 17, 2011 9:25 AM writes...

To No. 11

At least scientists should be capable of making meaningful comparisons, one would have thought.

Here is the ranking of some countries based on nominal GDP per capita (IMF, 2010):

1. Luxembourg US$ 108,832
2. Norway 84,444
3. Qatar 76,168
4. Switzerland 67,246
7. Australia 55,590
9. USA 48,875
91. Angola 4,478
94. China 4,382

Need to say any more?

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29. huh on July 17, 2011 11:57 AM writes...

@28: Wow...on average the Aussies make more (+15%) than we do...how the hell is that possible?! There are more sheep than people in that country!

The figures for China don't bode well for those who hope that rising labor costs over there will encourage manufacturing and research jobs to return to the US. Even if doing business in the coastal cities becomes too expensive, there's a huge population in the Chinese hinterland waiting to be exploited. It's no wonder that industrial chemists are compelled to write foolproof SOPs whenever they can: easy translation into the native language of the outsource CRO.

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30. Just facts on July 17, 2011 1:13 PM writes...

A minor error spotted in the GDP data:


8. Sweden 48,875
9. USA 47,284

And never underestimate the Aussies, mate!

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31. Terry Liu on July 17, 2011 8:58 PM writes...

GDP per capita cant explain anything in China, it is such a big country, divided clearly by coast area and hinterland, city and village.
i know in shanghai the GDP is around 20k/capita,however, in Tibet, the gdp is about 800/capita.
Now the population of shanghai exceeded the population of Newyork, even more, the population lived in coast area, with GDP capita around 8000/capita exceed the population of US population!

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32. cancer_man on July 18, 2011 12:42 PM writes...

"At least scientists should be capable of making meaningful comparisons, one would have thought."

One would hope, but you didn't do it. You need to control for purchasing power.

China is around $11,000 per capita.Sweden isn't close to $48,000, either.

Come on scientists, learn a bit of economics in your spare time.

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33. Terry on July 18, 2011 3:33 PM writes...

A huge market in china-pharmaceutical industry

I hope i can met some experts here who intended to work in china to promote the generic drug industry there. It is challenging but it also provides a chance to be a millionaire. not in us, but in China. If you are ex-employee in the drug discovery and development department of the big phama in US, let me know! let's be our own boss instead being employed by others!


China's pharmaceutical market has experienced significant growth in recent years, fueled by increasing wealth among its own population[1] as well as accelerating global demand for cheap, effective medicines to treat ailments ranging from high cholesterol to HIV/AIDS.[2] Along with India, China supplies more than 40 percent of the active pharmaceutical ingredients (API) used to make U.S. pharmaceuticals. The current financial crisis, and the limited resources and tighter budgets it has engendered, may accelerate the trend.

China boasts the world's ninth largest pharmaceutical market--and one of the most rapidly growing. In 2007, total output was valued at RMB 667.9 billion (more than $86 billion); its growth rate has averaged around 17 percent over the last few decades, according to Chinese government figures.[3] Aid agencies aspiring to treat as many patients as possible and pharmaceutical companies in quest of the least expensive inputs--that is, labor, clinical trials, and API--have all looked to producers in or partnerships with China.[4] From 1998 to 2007, China's pharmaceutical export trade increased from $3.4 billion to $24.6 billion;[5] currently, more than 40 percent of API used by U.S. manufacturers is imported from India and China, a number that is expected to double within the next fifteen years.[6] China remains an important supplier of artemisinin, a vital component of the best antimalarial drugs, and its Academy of Military Medicine helped develop artemether-lumefantrine, considered the most effective antimalarial drug on the market.[7] Many Chinese producers operate in state-of-the-art production facilities and supply the U.S. market with high-quality products.

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34. Anonymous on July 18, 2011 4:33 PM writes...

@ 33. Terry

I see you are back…

I also noticed that you have 'cut and pasted' someone else’s article/writing with references without properly citing them. This is similar to the your “Great China” mentality of ripping-off Western patented ideas, exploiting your cheap labor, and selling your products at a minimum price. Your idea of making millions by stealing ideas and exploiting your people is frightening and unethical.

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35. anchor on July 19, 2011 5:55 AM writes...

# 34 anonymous....way to go with your observations! Indeed, Mr. Terri Liu has plagiarized the article. I missed out on that "cut and paste" antics. I mean where he "cut and pasted", the flow of English is mellifluous. Given his past postings I was surprised if it was him and this was until you pointed it out.

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36. Just facts on July 19, 2011 10:19 AM writes...

To cancer_man (No. 32):

And how do you adjust for purchasing power? Certainly not by using purchasing power parity (PPP) figures which are cooked up data based primarily on the habits of US-stereotypes reflecting the cost of services and goods such as a big Mac trio and the like.

PPP figures are meaningless for international comparisons (or even for comparing states state like Hawaii and Alaska for example).

Here is what Wikipedia says: "PPP figures are estimates rather than hard facts, and should be used with caution."

I was under the impression that scientists like hard facts, but it seems there are some exceptions...

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37. Terry Liu on July 19, 2011 1:22 PM writes...

To 34
Hey jealous man

Where did you get these ideas that Chinese don’t respect patents? After China signed the WTO regulation, China started its own intellectual property law in 1990, prior to that it is a communism country, obviously it is not necessary to obey the rule designed by western countries. However, that time, being threatened by western countries, Chinese government turned to sacrifice the pharmaceutical industry to offset the other requirements of the WTO regulation. It is a long story, lots of domestic phama suffered from these regulations that time, along with this lots of workers and researchers in the pharmaceutical industries have been laid off during the 1990s.

Same situation happened in India, after revolution India failed their first Ip law in 1960s when they declared the independence. In 1980s during the WTO negotiation, they signed an agreement with western countries to respect their Ip, but in the agreement they only agree to infringement IP after 2005! Also they declared lots of patents invalid after 2005, Since they are slaved by Britain kingdom for over one century, they clearly know how to negotiate with the big international phama which are trying to file as many as possible sophiscated drug patents to prevent the coming NADA application. Indeed, there are some reports indicated that last year India ranked Number 1 country to file NADA application to FDA, also India exceeded us to be the number 1 country to file the paragraph IV application to FDA with a patent challenge according to the FDA regulation.

As to your plagiarism accuse, I don’t think it is necessary to address an issue in a forum similar as to publish a peer reviewed paper!

Indeed, I studied intellectual property law class in law school, and I clearly know the laws and the regulations related with pharmaceutical industries both in US and China. During my study I even analyzed two law sue cases in China, which happened between the international pharma (Aventis, Merck) and domestic pharma (Hengrui, Tianfang) in China regard patent violation in China.

While on the other hand, I also noticed that in lots of cases, the new drug discovery and development rely on the traditional Chinese medicine; this trend has been reflected in recent drug discovery, for example: “Fingolimod” was approved by FDA last year, which is discovered and derived from a Chinese herb!

These days more and more Chinese students acquiring education in western system, and soon they realized that it is the time to persuade the Chinese government to take action to protect their own intellectual properties in medical area, especially in traditional Chinese medicines. Now they are persuading Chinese movement to approve the patent related to Chinese medicine and herb, which of course including the chemicals separated from Chinese medicines and herbs. Once there is a new drug patent application in China, regardless it is by international or domestic pharma, it must be a really new chemical entry, which means the first invented chemical instead being separated from a Chinese medicine. That may be fair for Chinese and their long history.

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38. Hap on July 19, 2011 1:56 PM writes...

"Terry Liu" isn't even up to Srikanth's level of trolldom.

Come on, dude. If you're going to rule the world, then trolling competently should be a piece of cake.

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39. MTK on July 19, 2011 3:12 PM writes...

Hap,

His level and tone of condescension is actually world-class.

I truly appreciate the praise he heaps upon Americans for our habit of reading. (my attempt at sarcasm)

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40. Anonymous on July 19, 2011 3:47 PM writes...

@37 Terry Liu

Part Duex

Wow your English has improved immensely and you're right! You make me want to be a better 'man'!

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41. processchemist on July 20, 2011 10:53 AM writes...

I wish I had a cent for every time some indian or chinese company offered to us bulk APIs before expiration of their patents.... sure, the highest respect for IP...

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42. Terry Liu on July 20, 2011 12:23 PM writes...

To 41
bulk API is chemical not medicine, it is usually protected in the form of processing patents, such patents are protected loosely compared to the chemical entry(new drug) protection in China. it means a company can produce such chemicals using their own unique process and synthetic route, which is different as described in the international pharma's patents

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43. processchemist on July 20, 2011 1:02 PM writes...

@42

Wonderful... Can I suggest to start a chinese based company that offers bulk sitagliptin and liraglutide, then to buy a stand at next Informex advertising your product list? Most important, you must attend Informex personally.

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44. Terry Liu on July 20, 2011 7:13 PM writes...


to 43

There are some concerns about this idea

1 These two API are proved as drugs in America and Europe, the patents in regulated market such US are not expired yet, that means only the original company can sale them in the form of dosage(Drug). These international pharma should have their own capacity for manufacturing these chemicals.

2 if you gonna to provide the API to Merck, the original company, of course it is legal. But at least merck should be interested to buy it. Also there are regulations for producing these chemicals as API, for example CGMP.

In china, nowdays we also respect the IP for new DRUG, due to this there could not be a real market, so the bulk API will be only meaningful after the expiration of the drug patent.

Now we can make conclusion, once there is a NADA application to FDA and it is approved by FDA, these chemicals could have their real market value.

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45. processchemist on July 21, 2011 12:47 AM writes...

OMG... I must recalibrate my sarcasm

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