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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: Twitter: Dereklowe

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May 1, 2012

Chemists and Biologists, In Detail

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Posted by Derek

Let's file this one under "Cultural Differences Between Chemists and Biologists". Have any of my chemistry colleagues out there noticed the difference in presentation detail between the two disciplines?

It's struck me several times over the years. Biologists seem, on average, to go into much more granular detail about their experiments when presenting to a mixed audience than do most chemists. Buffers, buffers that worked a little better, buffers that worked a bit worse, the brand of the sizing column, western blot after western blot. The usual chemistry comment was always "Hey, I don't show pictures of my TLC plates", but eventually I suppose we'll need to come up with another line as LC/MS takes over the world.

Even presenting among their own tribe, most chemists don't (to me) seem to go to the level of detail that I often see from protein purification people or pharmacologists. My theory is that most forms of biology still have so many hidden variables in them (since it's an intrinsically more complex and less understood science) that all the details need to be specified. Organic chemistry, for all its troubles, still tends to be more reproducible, on average, than molecular biology, and at a less picky level of detail

That's why chemists don't often feel the need to go into details even in a room full of chemists: "We had the bromide, so we made these coupled products, and then we made these by reductive amination. . ." substitutes for "We had the aryl bromide, so we reacted it with a list of boronic acids under palladium-catalyzed coupling conditions to give these products, each of which still has the aldehyde in the 3-position, which we purified by chromatography in an ethyl acetate/hexane gradient over 8-gram ISCO silica gel cartridges. We then reacted them with a list of amines using sodium triacetoxyborohydride in dichloromethane at room temperature, followed by a chromatography in 1 to 5% methanol/dichloromethane. . . ". Each of those steps has plenty of other options - different reagent combinations, solvents, etc., and if some colleague needs to reproduce your work, they'll check your notebook or ask you "Hey, what did you guys use for those Suzukis? Dppf? Yuck."

We certainly won't go into that level of detail in a room half full of biologists - it's mostly "We made these, and these, and these", which spares everyone. No TLC plates, no LC/MS traces, no NMR spectra. But they're available if you want 'em.

Comments (61) + TrackBacks (0) | Category: Life in the Drug Labs


1. BIOchemER on May 1, 2012 7:39 AM writes...

As a card-carrying biochemist - biologist for the purpose of this post - I feel like the opposite is true. At least at Merck, my experience is that the chemists seem to take a certain amount of joy and pride (as they should) in showing lengthy syntheses in presentations, which to me is AS detailed as one could ever get. The thing that I always wanted to ask was whether chemists in the audience actually appreciate this as a bona fide scientific feat - or just "interesting", or, in fact completely useless. In other words, as a chemist, do you actually go "hey, that is something that I'm going to go back and use in my lab..." after seeing a talk like that. When I see a biology talk, I definitely don't need to hear super-fine detail, but I appreciate hearing about the process. To quote Rodney King: "Why can't we all just....get a....long?"

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2. Rick Wobbe on May 1, 2012 8:11 AM writes...

It all depends on context. As another biochemist interloping on this blog, as well as former researcher and former research director who led teams of biologists and chemists, my experience was that the "cultural" difference was more about perception than reality. One of my biggest responsibilities in cross-functional research team meetings involved watching out for the glazed eyes that are a sure signal of too much unnecessary info and asking the speaker to take the topic back to their department for further "fleshing out". I ended up saying that with equal frequency to, as you broadly bin them, chemists and biologists.

But your post also begs a question, "What do you suggest we 'do' about it?

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3. davesnyd on May 1, 2012 8:12 AM writes...

Is there a role for tools that provide more details, passively, during a presentation? A kind of movie that, while the presenter is speaking, cycles through each stage of the reaction on screen and displays a drill down of data (details of the reaction, spectra to prove completion)? Or are you merely commenting on the difference, as opposed to expressing a desire that chemistry presentations be more like biology?

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4. Anonymous on May 1, 2012 8:25 AM writes...

It's because Chemists are so used to presenting to rooms full of biologists that they develop a pared-down style. As someone who often has to sit through reams of detail about project biology I often wish it was the other way round!

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5. anchor on May 1, 2012 8:39 AM writes...

@ BIOchemER : As an ex-Merck colleague, who worked in the interface of biology and chemistry, I have a different take. We feel the same with biologist and watching those gel electrophoresis, southern blot, Western blot etc.. The fact of the matter is whoever is presenting (biologist or chemist) they take pride in what they do and at times can be a boring presentation.

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6. Stephen on May 1, 2012 9:33 AM writes...

It comes down to money in academic labs.

In organic chemistry, reagents are cheap, and productivity is proportional to the amount of time spent in front of your fume hood. Labor is the greatest expense, hence the emphasis on trying to run a certain number of experiments per day. An unintended consequence is the predilection for untenured faculty in organic chemistry to develop micromanaging behavior. In depicting one's work, due to the number of experiments run, it's better to focus on trends observed than the nuances in the details.

In molecular biology, reagents are very expensive, and can easily be much more than the cost of labor. Therefore, much more time goes into planning the experiment, and analyzing the results. Also as mentioned, coercing living systems is more complicated, and experiments can easily turn irreproducible. In presenting one's work, due to the limited number of experiments, the devil is in the details.

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7. Respisci on May 1, 2012 10:09 AM writes...

Weighing in from the biology perspective, what details are you seeing as TMI? I find it rare for a biologist to define the percent gel, buffers or antibody dulution when presenting a western blot in a lecture. For animal experiments especially knock outs and bone marrow transfers, yes the details can get quite hairy but they need to be there so as to follow the rationale and interpret the results. Although I agree that these types of experiments can be better reported.
As an immunologist, flow cytometry dot plots are only appreciated by other immunologists and I would never present them in a project meeting at the same level of detail I would within the team

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8. RD on May 1, 2012 10:24 AM writes...

Here's my experience at project team meetings:
1.) Biologists ALWAYS go first and present a lot of mind numbing detail on every conceivable parameter tweak. We stray quickly into My Eyes Glaze Over stage. There's no fricking straight answer on any of it. I'm not even sure most of the time that they have any idea how to interpret their data and I could swear that they use the same gel slide in every presentation but just relabel the lanes.
2.) Chemists get the last 20 minutes of a 3 hour meeting and all of the sudden, the biologists are restless. They're stomachs are grumbling, they're fidgety in their seats and it's all, "Can we please hurry this along? Our teleconference is only scheduled to go to 12 and no one ordered lunch in." The modelers have to rush through their complicated slides with the multiple colored surfaces and by then, the chemists are chomping at the bit at us for stealing their thunder and the last final seconds of their presentation time.
If you're lucky, you pick up a nugget or two of information to propel your project a millimeter forward.
And yes, biology seems to be like the elders sitting around the kiva dispensing folklore to the young. First we tried this but once upon a time, many moons ago, we increased the pH slightly and got something totally different. No one knows why. It is the gods.
The good news is that I went to a protein conference early last year and heard a bit more about design of experiments from the biologists so maybe they're catching on.
God, let's hope so.

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9. Chemjobber on May 1, 2012 10:44 AM writes...

It always seemed to me that medicinal chemistry isn't so much about the synthetic chemistry as opposed to the activity of the products; it seemed like the success of the chemistry presented was assumed (even as we all knew there was/may have been a struggle.) But the making in chemistry is sometimes The Main Thing, where in medchem, it's really not.

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10. entropyGain on May 1, 2012 10:56 AM writes...

The root of the difference between chemists and biologists is that chemists measure mass to a decimal and know they have what they want; biologists always have error bars.

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11. CanChem on May 1, 2012 10:58 AM writes...

To echo CJ, when I moved into medchem the first lesson I was taught was that there were two yields for reactions: enough, and not enough. If you got enough, shut up about synthesis, and get on with your talk.

The next lesson was that you only include as much info as the audience is going to find useful, and that it's always fine to make backup slides with more granularity of data if a technical question gets raised. That really helped to speed things up.

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12. ProteinChemist on May 1, 2012 11:07 AM writes...

As a biochemist who works in protein purification with a bit of signaling on the side, I think I should take offense to being lumped in with all those biologists. To address the main point, I am a chemistry island in a small biology-dominated biotech. From that perspective, I bet if you ask a biologist they will tell you that they glossed over their efforts quite a bit and you really should have summarized a bit more. It is all about your perspective and background.

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13. Former Biologist on May 1, 2012 11:40 AM writes...

I hesitate to weigh in here since I'm on foreign ground, but, let me share some of my experiences as a biology graduate student and post doc. Those little details that you don't seem to care about: they're essential. You chemists can go buy bulk solvents from any number of suppliers and get the same thing. I recall running three hand poured acrylamide gels side by side with the same samples. The only thing that varied between them was the Tris in the buffer. Two gels failed to resolve. One gel (with the most expensive Tris) ran nicely. Did I report the source of that Tris when I presented? Damn right I did. My results were irreproducible without that information.

We purified transcription factors from HeLa cells and reconstituted transcription reactions. Certain factors could only be purified from cells undergoing log phase growth. Moreover, only from cells beneath a certain passage number. For you chemists, that means that if we grew the same cells too long and too thick, they stopped producing what we needed. Chemists don't understand that as cell cultures undergo more and more passages, they change. They stop being what they were and they evolve into something new with additional confounding behavior. When I stood up and presented my results, did I name the cell line, the source and the passage number? Damn right I did. Without that information my results weren't reproducible. As lest you think that's all there was, we recorded freeze/thaw cycles on the protein samples (because it mattered), months that the samples were stored in LN2 (because it mattered), number of times the column resin had been used (because it mattered), flow rate of the column (that really mattered) and a host of other details that, 20 years later, I have blissfully forgotten. And in one particularly bad stretch, even the color of the pipette tips mattered (certain colors from certain makers were binding certain rare proteins in thin protein solutions and reducing their effective concentration to about zero). The chemists were incredulous.

This kind of nit picky detail? It's the hallmark of good biologist. Chemists (and I'm sorry to be blunt here) cannot comprehend the number of things that can go wrong in a biological reaction. Sadly, many biologists can't either.

These days, I work with computers. They're less frustrating.

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14. JC on May 1, 2012 11:41 AM writes...

Chemists wear safety glasses. Biologists do not.

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15. alf on May 1, 2012 11:57 AM writes...

There is a huge cultural difference between chemists and biologists. In my experience,

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16. johnnyboy on May 1, 2012 12:02 PM writes...

What #13 said, nicely summed up by "This kind of nit picky detail? It's the hallmark of good biologist."
Experimental techniques are often so finicky that you want to know EXACTLY what went into the recipe. Nothing more maddening than a paper showing a photo of cells reacting positively to a marker, but not bothering to even mention the source (company, clone, concentration, etc...) of the antibody used.
This said, however, common decency and empathy would dictate to keep the technical details to a minimum if presenting to a crowd of chemists or others who are not that into the biology. If you're not tailoring your presentation to your audience, you're an idiot, whether you're a biologist or a chemist.

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17. watcher on May 1, 2012 12:03 PM writes...

As mentioned by a colleague: "biology is messy, something that many chemists don't seem able to comprehend".

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18. Derek Lowe on May 1, 2012 12:04 PM writes...

Former (#13), I can very easily believe that all those matter - I've seen several of them matter, myself. But you may have missed the part at the beginning of the post where I said "to a mixed audience". These details are very appropriate (and vital) inside a group or department. But when you're presented across several, it's probably better to, for example, say that these variables are important without getting into the details of every single one. They can be on the slide, too, that's fine, as long as the whole slide doesn't get read off.

Just as the biologists mostly care that the chemists made compounds, and that the compounds are there in enough quantity and are what they say they are on the label, the chemists mostly care that the protein is there, it works, and the assay numbers are pretty much what they say they are. Details on request. . .

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19. InfMP on May 1, 2012 12:08 PM writes...

its so irritating when biologists spend more than half the meeting wasting everyones time with detail and then as soon as you put up your slides with pictures of molecules they either leave the meeting or open up their laptops.

I do appreciate the biologists who actually show the structure of the molecule they are talking about though. Its so troublesome when every chemist in the room has to go look up the serial code to find out what exactly which molecule they are talking about.

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20. Former Biologist on May 1, 2012 12:24 PM writes...

Derek, point well taken. But humor me for a moment. You're more than happy to take apart the occasional publication that raises an eyebrow, imagine (even in a mixed setting) a biologist watching another biologist present data. I can't tell you the number of times I watched fellow biologists present data that I wasn't certain they fully understood precisely because of the lack of details in the presentation. My internal monologue was saying, "Really, you think that? Did you check this, control for that and allow for this other thing? If so, why don't you say so?"

Is it boring to hear for biologists and non biologists alike? Yes. Does it validate that the speaker took the time to sweat the details? Yes.

@14. JC In a similar vein: Chemists understand that their experiments can have a negative effect on them. Biologists understand that they can have a negative effect on their experiments.

Imagine a world where everything in the tube was catalyst driven and that each tube had hundreds (even thousands perhaps) of uncharacterized catalysts. That's protein biology in a nutshell.

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21. To #19 on May 1, 2012 12:27 PM writes...


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22. cynical1 on May 1, 2012 12:35 PM writes...

You ever notice that the folks who spend the most time talking at meetings are usually the ones that did the least amount of lab work? For them, it validates their existence. Nothing worse than a desk jockey with some time to kill.........

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23. jasonP on May 1, 2012 12:42 PM writes...

As many have already said: chemistry is the art of redoing what has been done many times before. Going into detail about it does not add anything to the presentation since your reactions for the most part have been done a million times before across the world for a century or more.

Biology on the other hand is always expanding and always unique. It's more complicated frankly. You HAVE to explain the minute details to deliver the fact that you have considered all possibilities and have created as accurate a picture of an imperfect process.

The mind of the chemist is in the world of absolutes and percentage yields which rarely change. They want to boil down their molecular entity to a single EC50 when the biologist can gleen so much more information from a concentration response curve than that.

Try telling a chemist that the receptor EC50 value you generated is not absolute, and could change depending on the linage of the cell, the cell type, the genetic form per individual, the presence of cofactors at a given time, the state of the cell membrane... they'll just look at you like you can't do your job. It's because they cannot understand.

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24. In Vivo Veritas on May 1, 2012 1:10 PM writes...

As a biologist, I think it's because of the Harvard Law:

"You can have the most beautifully designed experiment with the most carefully controlled variables, and the animal will do what it damn well pleases."

Basically, in vivo biology is the most variable read most programs have, so I want to be damn sure that my chemists don't need to ask me what brand of feed I use, what the room temp is, etc. It's all there in my slides, if only to show that it's the same as last time and I can't account for a between-study 5% difference in a behavioral variable, no matter how many times a chemists asks why it exists.

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25. Derek Lowe on May 1, 2012 1:14 PM writes...

JasonP (#23): you must work around some chemists who should be performing at a higher level. Any medicinal chemist who's not aware of the factors in that last paragraph of your comment needs to learn more about what their job is really like.

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26. Mike on May 1, 2012 1:42 PM writes...

@Biologists, and especially @13, 20, and 23:

Research is research. If we knew the answers, it wouldn't be research. Even us chemists get that. There are details to the ways that you set up your experiment that are absolutely critical to the results of the experiment, a knowledge of which is critically important to the interpretation of the experiment. We get that too. We have the same types of details in our own experiments - "this reaction was tried at temperatures ranging from 30C to 150C with the following 6 bases, using the following 15 solvents, and three different lots of catalyst, only one of which gave any product. The product was identified as the (S) conformation using 2D NMR spetroscopy with a lanthanide shift reagent, which gave us this tiny peak here... (pointing to NMR trace) consistent with the interacton of proton 1 with proton 2..." And many of us chemists are very interested in such details even if we didn't do the work, because they may impact the next project we do. For you, all you want to know is whether the compound in the bottle is what we say it is.

There comes a point when your listener passes the threshold from "How did you get that?" to "I'll take your word for it" and that's when their eyes glaze over. It may be really important to you that only a single lot of the most expensive Tris buffer actually worked in your assay, and you may have lots of nice Western blots and fluorescence assays and pretty photographs to prove it, but all I'm interested in is whether compound A was better than compound B and whether that data will have any relevance at all to a disease state. Anything else, I'll take your word for it.

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27. tevetorbes on May 1, 2012 1:49 PM writes...

"As many have already said: chemistry is the art of redoing what has been done many times before."

Huh? Who said that? They apparently aren't very intelligent.

At any rate, I think the point of the article is about presenting to a *mixed audience.* Where I work, I do not interact with biologists much. However, I work with a number of engineers and chemists of other disciplines (card-carrying organometallic chemist here.)

That said, I don't care to bore the engineers with the synthetic details of my reaction and they don't care to hear them. Did it work? Did you make my molecule? Awesome, next slide. Sometimes I get accosted after one of our (many many many) meetings and get asked to explain details, but it's most often because of genuine interest about how something works. I often do the same with the process engineers: scaling a reaction up in a stainless steel pipe is an amazing feat for a guy who does reactions on a milligram scale in a largely overpriced piece of glassware.

That all said, hell, I don't even like to hear details from people in other chemical disciplines most times. Oh yeah, you couldn't get the GC/MS to work properly? Cool- did you bang on the side of it with a wrench? Did that help? Awesome, next slide.

Finally, based on some of the comments here, perhaps it's better that I don't work with a number of biologists- I didn't know that they had such a narrow view of what chemistry is and why it's important.

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28. patentgeek on May 1, 2012 1:52 PM writes...

On the first day of my first job out of school, my boss the (old school) Med. Chem. Director explained it thusly: "Pharmacologists chase women, and chemists drink."

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29. Teddy Z on May 1, 2012 1:53 PM writes...

@#13...You describe tremendous effort on figuring out that one particular source of Tris is better than all others. That should be a single bullet point in a team meeting (Bullet Point #1). You also figured out that phase of growth and passage number are important to obtaining your transcription factors (Bullet Point #2 and #3). I understand you want the scope of the effort you put in to be recognized, but it is extraneous detail. As Derek says in #18, its a team meeting, with a mixed group. Get the summary out and leave the details for a paper or biology-specific meeting.

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30. anon on May 1, 2012 1:53 PM writes...

23 -- jason p. its arogant biologists like yourself that are the problem...noone, other than fellow biologists, is interested in how awesome you are at solving finicky biology parameters. if you're good at your job, you solve problems behind the scenes and present data...exactly what chemists do.

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31. Anonymous on May 1, 2012 2:00 PM writes...

"...since your reactions for the most part have been done a million times before across the world for a century or more."

Wow... That's hostile. I think Mr Grumbly-pants needs some sensitivity training.

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32. jasonP on May 1, 2012 2:06 PM writes...

Oh relax people. I exaggerate a little, but you know there is truth to what I say.

Chemistry...they were even doing it in the middle ages. Alchemists you know. Lead to gold and all that. Has that much really changed? Same expectations and promises… 

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33. jasonP on May 1, 2012 2:11 PM writes...

I should also note that a part of my snide take on things is actually from the arrogance of chemists, not the other way around. I remember from late 90s to mid 2000's, it was the chemists calling the shots, earning the wages, working wherever they wanted and throwing their weight around in the biotechs I worked at.

Now look where we are: the truth all along is that the biological feedback is most sacred. The chemistry emperor wore no clothes after all.

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34. Anonymous on May 1, 2012 2:15 PM writes...

Biologists were using leeches in the middle ages. Come to think of it, they still are.

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35. RD on May 1, 2012 2:29 PM writes...

JasonP: Hardly. I've worked with biologists and you guys need us to tell you what the heck you're looking at. Ever been with a biologist while going through HTS screening hits? Ugly. And alarming. They sure know how to spot detergents.
Let's not get all up in each other's grill. It's true that biologists got the shaft in the 90s and chemists are getting it now. One thing I know for sure, we need each other. I wish I knew how to quit you biologists but there you go.
I just wish you guys would edit your presentations and make a conclusion once in awhile.

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36. See Arr Oh on May 1, 2012 2:30 PM writes...

"Can't we all just get along?" - Rodney King, 20 years ago

Biologists - Your field is complicated, and there are many variables and intricacies.

Chemists - Your field is complicated, and there are many variables and intricacies.

I think we all just want leaner, more efficient meetings, meetings that drive projects forward and present data in "chunks" understandable by both sides of the table.

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37. Jim on May 1, 2012 2:33 PM writes...

As an in vivo biologist, I see the distinction as being the difference between absolutes and caveats. Chemists are tasked with making specific compounds and have analytical tools to verify their success or failure. Biolgists have to test a hypothesis with a number of variables - the hypothesis may be proven true or false depending on how variables are tweaked. If the results from 2 different experiments with different conditions provide meaningfully different results, this is valuable information and should be communicated. The problem is, once you've seen the importance of such differences in conditions, you're much more likely to put that out in front of people so that someone can replicate your work and not call you a fraud or a liar.

Essentially, we're asking chemists "can you make this?" and we're asking biologists "does this work?" Biologists are just being skittish and hedging their bets and answering " depends." A biologist who is a good communicator and is working in an environment that actually promotes and fosters quality science (unfortunatly both circumstances are rare) will be able to express the robustness of the efficacy of the compound without pointing out that the amount of Tris is important.

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38. anon on May 1, 2012 3:01 PM writes...

ha! i was the first anon comment back to jasonP and i was just being provocative to stir it up! my real take is that they are both difficult, evolving fields...comparing the difficult of the trade is non-sense, plenty of challenges in each. the chemistry output tends to be more black and white (can usually confirm or deny final result), the biology output can be interpreted a hundred ways...perhaps why biologists spend a little more time in the dirt. also, chemistry is a different language altogether...its using words to describe cartoons of material that you can even see. it makes it boring for biologist as it takes years to learn how to speak this language. lastly, its about knowing the audience: as a chemist, i would not describe reaction conditions in a project team meeting, i would do it in a medchem or process meeting where someone could help should i need it or if it would help others. biologists should probably do the same: save 'buffer conversation' to the biology team, report in critical findings to project team. regardless, we all enjoy really fun careers in my opinion.

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39. Ginsberg on May 1, 2012 3:02 PM writes...

When I hear #13 talk about presenting the manufacturer of his Tris in a meeting I wince. Thank you for switching careers to the computer world.

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40. Rick Wobbe on May 1, 2012 3:21 PM writes...

Reading through the comments here reminds me of some of my unhappiest conference room memories, as a presenter and as a moderator. Few things drained the spirit out of a meeting faster or more completely than someone nastily asking why they should care about the "details" the speaker was presenting. I hear echoes of that tone here.

People come to drug discovery research from a variety of disciplines with a variety of ideas of what are "important details" and perhaps in their earlier training or experience those details were important for success. The toughest challenge I've faced managing cross-functional teams has been getting scientists from different backgrounds to communicate effectively with each other across disciplines. The biggest barrier to achieving that kind of communication was having one group decide its definition of "most important details" should apply to all.

Rather than preemptively dismissing western blots or NMR spectra (or whatever your favorite bugaboo is) as boring, unnecessary detail, it would be better if presenters and listeners alike seriously considered why that bit of info could be important for the project. Sometimes the answer is a delightful surprise.

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41. RespiSci on May 1, 2012 4:34 PM writes...

"you may have lots of nice Western blots and fluorescence assays and pretty photographs to prove it, but all I'm interested in is whether compound A was better than compound B and whether that data will have any relevance at all to a disease state. Anything else, I'll take your word for it."

....but that is exactly the purpose of those Western blots and fluorescence assays, histopathology photos and survival curves.

For a mixed audience project meeting, I agree you don't need to go into details of the methodology but as a biologist I would think that the data described above is fundamental to understanding whether the compound works or not. There appears to be a disconnect between the complaints of the chemists here and what I as a biologist would want to demonstrate as a result. To me, depending on your target and MOA, you may want to show changes in RNA and in protein, then phenotype and functional assays in vitro, then efficacy in animal models (of which there may be more than one).

Which of those items as chemists do you deem to be irrelevant?

Or is it the manner and way that information is being presented which frustrates you?

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42. Old tTmer on May 1, 2012 5:03 PM writes...

In my experience, all the other disciplines present their segments of data and it's the chemists who conceived the compounds in the first place who pull together all the disparate data from birth onwards and recommend which compounds to progress. Not that chemists get much acknowledgement these days in a company that once rejoiced in "Chemical" in its name and is now run by biologists for biologists and shareholders...

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43. A. R. on May 1, 2012 6:46 PM writes...

Speaking as a biologist who presents, I can assure you that there's usually a whole filing cabinet of stuff we could include (I know of at least one at my institution that is full of just Westerns). It's all down to time limits and the amount of stuff you can fit on one slide!

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44. weirdo on May 1, 2012 6:50 PM writes...

I think the comments on this blog post speak more clearly to many of the problems with modern drug discovery than rants about ignorant MBAs and stupid managers.

Pretty depressing, really.

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45. alf on May 1, 2012 7:03 PM writes...

chemists: synthetic training/thinking with straightforward clear endpoints

biologists: trained to deconstruct complex systems with open-ended model endpoints

90% of each don't understand the details of the other

Both are required to make a drug. Based on my details am I a chemist or biologist?

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46. Cellbio on May 1, 2012 8:47 PM writes...

As a molecular biologist turned cell biologist supporting chemist, I have applied myself to understanding the differences and come to the conclusion that the main difference is that chemistry is, as was molecular biology, a physical science, where most biology is paradigm driven. The molecule is the molecule. The biological assay data are most often an indirect measurement of a biological process in a system that is a hopeful representation of the process as it occurs in vivo.

To illustrate, MTT, Tritiated thymidine incorporation or ATP titer-glo are not measures of proliferation. They are most often reflective of proliferation, but assay values and comparisons to controls depend on a lot of variables, like time of pulse, time of incubation prior to measure, wether cells were starved or synchronized, whether conditions are so severe in some settings that survival is dominant in generating a signal over actual proliferation.

All this demands proper explanation of variables to truly understand the data, whereas a gene sequence is a gene sequence regardless of how it was generated, and a molecule is a molecule regardless of synthetic route. The problem I see is too few biologists are actually aware of the limits of their measures, nor do they explore the manner in which their systems are sensitive to perturbation. This is not much of a problem if you are an immunologist working in a defined and useful system in academia, but quite a problem if you use a library of molecules to attempt to interrogate biology and instead interrogate the vagaries of a model system instead.

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47. Secondaire on May 1, 2012 10:33 PM writes...

Oh man! It's scientific platform wars. Why haven't any physicists showed up yet?

I'm a chemist, but came out of molecular biology. Basically, each field becomes mutually lost in the others' esoterica. As long as everyone is respectful along the boundaries, all is well.

Nonetheless, my biology colleagues don't want to see endless schematics of pentagons and hexagons, and I don't want to hear what amounts to 50 minutes of Lots O' Blots. C'est la vie. :)

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48. Dave on May 2, 2012 1:15 AM writes...

Just to be clear, when 13 reported positive results with 2 out of 3 not resolving. He did replicate the 3rd several times, right?
It is great that after a synthesis we are always left with a 100.000% pure compound with no tendency to degrade. Chemistry has come a long way. Too bad there isn't some way to get more information than what is on the wall. Maybe I'll invent something called a QR code, or a hashmark, or perhaps a way to somehow have my cell phone "communicate" with a db. Maybe I'll call it "wi-fi" or "internet".

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49. Dave on May 2, 2012 1:27 AM writes...

Oh, and I forgot to applaud all of those who have gone before so that all of the syntheses and activity studies we do publish have at least a 95% reproducibility rate. What do they say about academics' politics? Its visciousness is inversely proportional to the importance of the issue. Commercial Research community are, of course, steeped in academia. Halo effect.

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50. hn on May 2, 2012 4:15 AM writes...

This is why I prefer posters to talks at conferences. If I want to skip your blots or NMR spectra, I can. If I want to stare at them all day, I can. Too often, talks are focused on what the presenter has done - "I worked really hard on this!" Instead, talks should be focused on what the audience wants to learn.

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51. sfbaycellguy on May 2, 2012 9:51 AM writes...

I love this blog, but I don't like this needlessly divisive post. I'm an industry cell biologist that enjoys watching chemists present, and think what they do is amazing. In science the devil is usually in the details. Maybe we could all just lighten up a little and work on mutual appreciation and improving our attention spans.

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52. Ex-med chemist on May 2, 2012 10:04 AM writes...

In my experience the vast majority of both chemists and biologists suffer from the same crippling error in presentations, they fail to clearly get the key points across by diluting it/complicating it with too much information.
The vast majority of audiences want to know the top line results/conclusion with an explanation of why. Save the procedure details for off-line talks.
As I chemist I always wished the presenting biologist would walk me through the money slide be it western blot, assay results and not assume everyone is an expert enough to get it when it is flashed up after 20mins of details of how they got there.

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53. In Vitro on May 2, 2012 10:45 AM writes...

It all comes down to respect and focus. If the individuals representing each discipline in a meeting respect each other and their abilities you can have a highly collaborative team. If they don't.....

If they tailor their presentations to address the needs of the participants and their decision making process you have productive meetings. If they don't.....

It is easy to fall into the them vs. us mentality, one abuse can trigger a period of resentment. The ability to forgive transgressions probably plays a large part in establishing a truely collaborative discovery team.

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54. Doc Bushwell on May 2, 2012 2:20 PM writes...

Re: "No TLC plates, no LC/MS traces, no NMR spectra."

What? Seriously? I've seen such on any number of occasions from medicinal chemists. As a biochemist,* I was able to straddle both worlds and appreciated the need for certain details of either discipline. The finer points of biologically oriented experiments can be critical. By the same token, I have been subject to lousy presentations on the part of both biologists and medicinal chemists who have no clue as to how to convey a streamlined message to their audience.

But if you think medicinal chemists' eyes glaze over when confronted with the subtleties of buffers, salts and gels, then imagine the reaction of med. chemists and biologists both when presented with the equations describing steady-state kinetics or slow-binding/tight-binding inhibition, both of which are essential components to the understanding of inhibitor behavior. Cue Malibu Stacy: "Math is haaaaaaard!"

Such was my experience as a mechanistic enzymologist.

*As Mo Cleland said, "Biochemistry is three parts biology and nine parts chemistry."

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55. Ex-med chemist on May 3, 2012 10:01 AM writes...

# 54 Doc Bushwell

"But if you think medicinal chemists' eyes glaze over when confronted with the subtleties of buffers, salts and gels, then imagine the reaction of med. chemists and biologists both when presented with the equations describing steady-state kinetics or slow-binding/tight-binding inhibition, both of which are essential components to the understanding of inhibitor behavior."

This is exactly my point. Why does the audience need to see the equations. The key information to present is what type of binder it is and what the are the advantages/disadvantages/etc of this data. The equations are not important to the other disciplines.
It's the same as if you were presenting how an aerofoil works to non-experts. Presenting the equations is a bad idea. Surely it would be more effective to simple say, the design of the aerofoil is such that air flows faster over the top than the bottom creating lift (you could add it's due to pressure differences). Then, for example, if you'd made an improvement, you could say, we modified X in the design to give us Y advantage. If you want to know how in more detail I'd be happy to do that either offline or now if the audience would prefer.

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56. easong on May 5, 2012 11:17 PM writes...

I can watch a hundred bio presentations full of gels and qPCR plots, but if I show the biologists a chemical scheme and an NMR spectrum on the same day their heads will explode.

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57. WD on May 6, 2012 2:36 AM writes...

Speaking of details for mixed audiences, I get fairly annoyed with biologists who present the results of an assay (such as IC50 values) without giving the standard deviations and reproducibility. And worse, biologists who don't even apply simple reason to determine if the results are significant. I'm not even talking about complex statistics, just plain old common sense. Has anyone else encountered problems such as this:
1. A purported IC50 value for a compound, which upon examining the actual curve fit does not even reach 40% maximal inhibition.
2. Ditto for claims of an IC50 on a standard curve which is missing its plateau.
3. A reported "significant result" which is indistinguishable from background noise. And similarly, experiments where they didn't run controls.

I once had the misfortune to attend a talk where a chemist was boasting that they had a potent molluscicide. His evidence was there were only 5 snails crawling on his bait, versus 10 snails on the untreated control. And there were no replicates.

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58. RJH on May 6, 2012 10:43 AM writes...

OK, remember the original point from Derek: presentations in multi-disciplinary venues, where presumably the point is moving a program forward as a team. In the really important driver meetings, everyone needs to see summaries that include historical and recent update data as well as future plans--in other words, what did we learn and what are we going to do about it. You figure maybe 15 minutes or less from in vitro and in vivo biologists, CADD and medicinal chemists, DMPK and pharmacology folks--that is an action-packed 1.5-hour meeting *IF* everyone stays within their time frames and there has to be time to discuss all of this and agree on a path forward.

So the trick for all presenters is to be concise with your portion, and present what is really the point for your portion that affects the overall team's research goals. And sometimes that does demand a discussion of all of those minutia. Painful for others, yeah sure, but necessary. But it can feel like an unfair barrage on the captive audience when excruciating details are presented that aren't framed in a manner that shows its relevance to the program (not to mention cutting into other folks' time).

I'm a med chemist and am party to two-hour discovery team meetings where the chemists end up with only a small bit to speak. So we--like other disciplines presenting--have to be concise. What we find works well is to create slides that have structures, but are set up to be talking points. Details can be there, but we don't read them off, we give highlights--people can read over the words later, since everyone has a copy anyhow. What we're calling minute details in this discussion thread are sometimes there, but more often included as appendices to go through if there is interest, or time.

See the point here? It isn't that others don't appreciate your important details, it is just not always crucial to the mixed audience as a whole. If you want your team to go forward together, don't accidentally create animosity--the number one rule of speaking is KNOW YOUR AUDIENCE.

Of course, I am also mindful of the reality that knowing your audience includes awareness that your boss is sitting in the audience, and maybe she/he thrives on the excruciating details. But your duty is to the program, and not annoying everyone else is part of that contribution.

Why can't we all just get along? In my mind, it's because not everyone cares enough to try to. I've asked biologists if they get what they need from us chemists, and some really great biology collaborators have asked me the same thing. Unless the program leader is a social misfit (and I think that topic has been covered here enough), the whole mixed-group team meetings really are great sometimes.

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59. biochemist on May 7, 2012 1:08 PM writes...

As someone who was trained as a chemist but has always been migrating more and more into biology, I feel like it comes down to what people's interests are. The animosity from chemists toward biologists presenting the details of their data has its own reciprocal for biologists.

For a chemist, on whom biological nuance is lost simply because it's not your training or interest, you don't want to know the details of how an assay was optimized, you want to know whether it worked. Biologists worry about all the unpredictable factors that go with working with living things; chemists want to know the final result.

Likewise, when I see a synthetic chemist present his work, and I want to tear my eyeballs out as names of reactions and reagents are dropped left and right, names which are now only vaguely in my memory (as with anything, you use it or lose it), and when it finally gets to the end and I raise my hand and ask, "So, did they have the biological activity you thought they would?" and he says, "I don't know," I instantly stop caring. Chemists care how you make it. Biologists don't -- they just want to know if it works.

I don't see why both sides can't consider the interests of the other without slinging mud.

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60. ^hypnos on May 7, 2012 2:03 PM writes...

Well, maybe chemists don't go into that much detail with respect to their experimental conditions. However, they find it often difficult to cut down their SAR slides to those few example compounds that are actually needed to show the effect. In my experience, if 57 compounds have been made, they have to be on that slide ...

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61. Bachelor in Molecular Biologist- PhD in Med Chemistry on May 12, 2012 1:21 PM writes...

Why do you always try to point out the differences between chemists and biologists and you are not seeing reality! Cooperation!!
I am a molecular biologist with a PhD in Medicinal Chemistry. I am doing both synthesis and biol experiments and I understand both NMR...and PCR.... So as I have experience in both fields the only thing that matters is that both sides should work together in drug discovery and should not argue which field is better or not!

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