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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