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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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November 4, 2011

What's the Hardest Thing?

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Posted by Derek

Here's a quick question for the crowd: when you're talking with people outside your field, or outside of science completely, what's the hardest thing in your area to explain? I end up doing a lot of explaining myself, and I find that a lot of key drug discovery concepts can be communicated pretty quickly.

But not all of them, and perhaps not all at the same time. I can talk about PK and absorption, metabolism, etc., and I can talk about molecular properties and selectivity, and toxicology. Keeping all of those in mind at the same time, though, seems to be difficult if you're not used to doing it, thus the trouble with explaining Paracelsus' remark that "the dose makes the poison". Selenium is a good place to experience that: try getting across to someone that there's an essential nutritional element that's also poisonous. It's like trying to say that cyanide is a vitamin - but then again, if carbon monoxide is a neurotransmitter, maybe it is.

I think that the other broad issue that's hard to communicate is the amount that we don't know. That specifically comes up in discussions of toxicology - people want to know if this drug, this compound, is toxic or not. And if it is, how do we know that the next one isn't like that? Those are all questions that do a sort of reverse origami trick: they start off in a neat, comprehensible shape, but unfold to heaps of crumpled paper as soon as you really start pulling on them. How can we know so much, yet know so little? Why have we been studying some of these systems for decades and still not understand them? That probably gets back to the repeated point that living biological systems are simply more complex - much more complex - than anything that anyone has ever dealt with in everyday life. And what's more, they're complex in different ways than we're ever used to dealing with; it's not just differences in degree (although those certainly apply) but differences in kind.

But don't confine yourself to the big meta-issues. There are plenty of smaller concepts and ideas that don't lend themselves to fast explanations. A meaningful one-paragraph (or one-sentence!) explanation of NMR imaging for someone with no background, for example, is no small undertaking. (My attempt: "We're all full of water molecules, in all sorts of environments in the body. And they behave differently when you put them in a strong magnetic field, which lets us pick up different signals from them and turn them into images.") How about hydrogen bonding? Or chirality? What are your sticking points when you try to explain what you do?

Comments (66) + TrackBacks (0) | Category: General Scientific News


COMMENTS

1. bbooooooya on November 4, 2011 9:34 AM writes...

Stereochemistry

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2. simpl on November 4, 2011 9:43 AM writes...

Computer models: only a minority, perhaps 25% of graduates, can abstract from a multi-level logical model in their head.

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3. Dickweed Jones on November 4, 2011 9:46 AM writes...

Stereochemistry for sure. Trying to explain an enantiomer vs. a racemate is just plain impossible. Might as well be talking in hieroglyphics.

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4. elperrogrande on November 4, 2011 9:46 AM writes...

As a concept, stereochemistry. Otherwise, explaining what I do on a day to day basis. I usually end up saying it's kind of like being a chef. If you think about it, it's not a bad analogy. Ingredients, recipe books, a bit of creativity, all in a days work for synthetic chemists.

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5. CMCguy on November 4, 2011 9:52 AM writes...

As discussed in a recent post for Process Chemistry it how one typically can't just keep increasing flask and reaction sizes as doing true scale-up is more complicated. It's particularly frustrating with Clinical/MDs and Marketing types who complain when tell them their timelines (theoretical which never hold) are problematic to keep up drug supply.

#1 bbooooya the concept of stereochemistry is easy to express by literal hand waving. Certainly the impact on chemistry and biology do get difficult to translate well

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6. SP on November 4, 2011 9:54 AM writes...

I don't see why stereochemistry is hard- everyone is familiar with the concept of non-superimposable hands. They look the same and can do all the same things until you run into something else that is also handed (shaking hands with someone else, only one pairing works.)

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7. See Arr Oh on November 4, 2011 9:56 AM writes...

Name Reactions sometimes trip me up in conversation, since I forget they're a form of reductio ad absurdum for us o-chemists that just don't translate outside the field.

Also, communicating the fact that just having a terminal degree does not mean you have an all-encompassing knowledge of the field.

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8. Curious Wavefunction on November 4, 2011 10:08 AM writes...

Conformational complexity.

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9. Student on November 4, 2011 10:15 AM writes...

Why my hypothesis is so hard to prove.
You can't explain context.

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10. imarx on November 4, 2011 10:25 AM writes...

Everything? I think that's more my fault though - I have a hard time with concise explanations. Every time I try to explain something to my wife her eyes glaze over.

I do get tripped up when trying to explain the concept of a functional group to non-chemists. Even my most basic explanation (a group of atoms that has a particular reactivity) leads to a bunch of blank stares.

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11. LittleGreenPills on November 4, 2011 10:28 AM writes...

As a natural product chemist a big part of my job is structure elucidation of unknowns. Occasionally, while trying to explain that, I realize that the person I am talking to has little or no concept of atoms and bonding. The thought then occurs to me that I do not have the time to give them a quick lesson in general chemistry. So I usually just tell them it is a little like solving a Suduku. At that point they usually nod and the conversation is over.

A close second is that the little green pills that they buy are at best a waste of money. If they actually do something then they could be dangerous.

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12. DV Henkel-Wallace on November 4, 2011 10:34 AM writes...

I'm not sure that "the dose makes the poison" is so hard to explain. I use water to explain that -- I think people understand that.

The hardest thing is to explain how non-deterministic the body is and how many layers of approximation go into determining efficacy, mechanism et al. One of my closest friends is a great (electrical) engineer but nevertheless has a hard time believing that we need animal models and can't just do everything in vitro.

More generally, I think people have what I consider an "automotive" model of the body: when their car makes a funny noise they take it to the mechanic and it is fixed. They expect the same from their drugs: they have symptom X and thus a visit to the doctor should result in table Y which will definitively make X go away.

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13. barry on November 4, 2011 10:42 AM writes...

I haven't found Paracelsus hard to explain. Stereochemistry and conformational complexity block far more conversations. Also, the difference between Research and Development seems strangely arcane to many people.

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14. Nick K on November 4, 2011 10:57 AM writes...

It's a completely hopeless task trying to explain anything chemical or pharmaceutical to non-technical people. Even worse is arguing with proponents of homeopathy or alternative medicine. Their mental universe is disjoint from that of scientists - not even touching, let alone overlapping.

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15. Wile E. Coyote, Genius on November 4, 2011 11:03 AM writes...

I think the most difficult is explaining the "hit the post button only once" concept.

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16. Jeffrey Soreff on November 4, 2011 11:12 AM writes...

This isn't chemistry but, as an example of something that is hard to explain:
Independent random variables - particularly a
sequence of them. Getting across the notion of:
"No, if you've seen a coin come up heads a dozen
times in a row, it _doesn't_ mean that it is now
time for it to come up tails, even though the
long run odds are 50:50"
seems to be a _very_ hard notion for people to
grasp.

(By contrast, the idea of contagion seems to
be particularly easy for people to grasp.)

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17. Kay on November 4, 2011 11:17 AM writes...

The hardest thing for me to explain is that some molecules are more difficult to make than others. I think a lot of non-chemists think of molecules like the plastic models you see in class - you just take all the pieces and put them together like a puzzle. It's very hard to explain that you can put a chloride in spot X very easily but not in spot Y, or you can make functional group A but not B. Even scientists from other disciplines seem to find this hard to understand - if you can draw molecule X, why can't you make molecule X?

The idea that pharmaceutical companies get all their research from government funded labs is also a persistent myth that's hard to dispel.

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18. cynical1 on November 4, 2011 11:47 AM writes...

It's particularly hard to explain at your WalMart or Burger King interview how what you used to do for a living would make you uniquely qualified to be an outstanding shelving clerk or fast food chef. They get particularly frustrated when they can't understand or pronounce any of the titles of your publications and patents. Besides, nobody likes a smarty pants.

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19. Hap on November 4, 2011 11:57 AM writes...

15: Nah - Corante's servers suck sometimes and it's hard to tell when your post has been received so people sometimes post again. Sometimes even when you post only once Corante doubles them up.

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20. neo on November 4, 2011 12:02 PM writes...

Statistics. If my compound is 96% pure (p=0.04) then it is right. If it is 94% pure (p=0.06) then it is wrong. Oh wait. That was my biology colleague.

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21. CR on November 4, 2011 12:10 PM writes...

@10, imarx...

No offense, but when in the world would the concept of functional groups come up in normal conversation? Seriously?

I don't think explaining what I do as a medicinal chemist is really that hard. Do I go into the nitty-gritty details of PK, no? Why would you? I don't expect someone an accountant to go into great detail about what they do on a day-to-day basis. Broad picture is quite simple to explain and most people get it.

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22. DV Henkel-Wallace on November 4, 2011 12:16 PM writes...

I'm not sure that "the dose makes the poison" is so hard to explain. I use water to explain that -- I think people understand that.

The hardest thing is to explain how non-deterministic the body is and how many layers of approximation go into determining efficacy, mechanism et al. One of my closest friends is a great (electrical) engineer but nevertheless has a hard time believing that we need animal models and can't just do everything in vitro.

More generally, I think people have what I consider an "automotive" model of the body: when their car makes a funny noise they take it to the mechanic and it is fixed. They expect the same from their drugs: they have symptom X and thus a visit to the doctor should result in table Y which will definitively make X go away.

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23. imarx on November 4, 2011 12:18 PM writes...

@21

Like I said, I have trouble with concise explanations, but I think it's come up when trying to explain to people what my day-to-day work is like and trying to explain the concept of building molecules through synthesis.

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24. dearieme on November 4, 2011 12:34 PM writes...

One problem arises from scientific shorthand. When we say that we need iron in our diet, we don't mean iron in metallic, elemental form. Nor calcium, sodium.......

The stereo business was more easily solved in olden times, when every reflective cove of scientific bent would have some pipe-cleaners to hand.

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25. C on November 4, 2011 12:34 PM writes...

Oh my. Where to start?

I think the hardest thing to explain to people is that anecdote does not equal data. Right on the heels of this problem is that data does not equal personal opinion.

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26. Bill O'Reilly on November 4, 2011 12:42 PM writes...

Tide goes in, tide goes out. You can't explain that!

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27. Anonymous on November 4, 2011 12:48 PM writes...

If you were to be shadowed by a person completely naive to the drug discovery world, I think they would be surprised by the following things:

1. We really don't know much about biology or how to manipulate it.

2. Chemists cannot make any compound they want; preparations for the ones we can make are riddled with uncertainty and complexity.

3. There is no real way to be 100 percent certain what effect a molecule will have upon a human (toxicity, etc.) outside of testing that molecule on a bunch of humans.

4. The vast majority of projects we work on will not lead to anything but a 'tombstone' publication (if you're lucky).

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28. Doug on November 4, 2011 12:51 PM writes...

Anything can be explained through analogy and the two best models I've run across are cars and sex; people understand those and if you can equate with /, they get it.

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29. Pete on November 4, 2011 12:52 PM writes...

A lot of the chemical concepts of Drug Discovery are much more easily explained when you've got molecular graphics handy and these days I believe that there's stuff that runs on cell phones. Using one's hands (quite literally) is a good way get the concept of chirality across. I've found the analogy with electrical plugs and sockets to to be a good way to explain aspects of molecular recognition (including FBDD). Where I struggle is explaining the concept of molecules to non-scientists and how molecular phenonomena are related to macroscopic phenomena.

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30. Chemjobber on November 4, 2011 1:25 PM writes...

F'n magnets -- how do they work?

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31. SAI on November 4, 2011 1:44 PM writes...

I'm a computer engineering student, the hardest thing that generally comes up is explaining to computer science majors how hardware description languages are fundamentally different from programming languages.

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32. Posted on November 4, 2011 1:53 PM writes...

#19 Hap-

I have figured out how to know if your post has posted. After hitting the "post" button, open another window and go to the page you are posting to. Most of the time, your post has posted in the new window, even if it hasn't posted in the original window.

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33. C on November 4, 2011 1:58 PM writes...

Oh my. Where to start?

I think the hardest thing to explain to people is that anecdote does not equal data. Right on the heels of this problem is convincing people that data does not equal personal opinion.

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34. Mama won't take my Kodachrome on November 4, 2011 2:00 PM writes...

I went to Wal-Mart to have some slide film processed (in my line of work we still use it.) The girl at the desk had absolutely no idea what to do with it. I even explained the E-6 process to her, and how the film inside the can would become the slides. All she kept asking me was how many prints I wanted.

She finally called her manager. He was a guy in his sixties who just smiled and shook his head.

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35. CR on November 4, 2011 2:21 PM writes...

@Pete, #29:

"A lot of the chemical concepts of Drug Discovery are much more easily explained when you've got molecular graphics handy and these days I believe that there's stuff that runs on cell phones."

I really and truly mean no offense by this; but, I'm a scientist and if someone at a party pulls out a molecular graphics program on their cell phone, I'll even walk away - Dork alert. No lay person needs that type of explanation.

@Anonymous, #27:

I think they might be able to grasp 1 -3 in your list; but they would have no comprehension what a 'tombstone' publication is.

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36. Thomas McEntee on November 4, 2011 2:26 PM writes...

I started studying chemistry seriously about 50 years ago. If you're like me, you're still learning and clarifying in your mind the principles that coalesced out of all those facts that made up your early chemical/science education. Most people never got beyond the facts level, facts in a language that was foreign to them. Try explaining kinetic vs. thermodynamic control, circular dichroism, enantiomeric excess, etc. to people who don't understand basic principals... I still struggle myself with polarized light.

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37. Nick K on November 4, 2011 2:37 PM writes...

Why are there so many multiple posts tonight? If this appears twice it isn't my fault as I pressed the post button only once.

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38. Chemjobber on November 4, 2011 2:47 PM writes...

If you're like me, you're still learning and clarifying in your mind the principles that coalesced out of all those facts that made up your early chemical/science education.

I'm probably not much like you, but yes, I'm still learning and clarifying.

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39. Jack Vinson on November 4, 2011 2:48 PM writes...

I am a chemical engineer, and I always find it entertaining when I need to say things like "chemical factory" instead of "chemical plant."

Now that I have been doing management consulting, I have borrowed from BASF: I help people who make things make them better.

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40. Anonymous on November 4, 2011 3:14 PM writes...

@CR (#37),

No offence taken and, rest assured, I don't have a molecular graphics app on my cell. Also when at at parties I prefer to avoid boring the others shitless trying to explain chirality and conformations.

The point that I was making is that many concepts that are tough to explain in words can be made a lot clearer using visual means. I once showed one of the catering staff (who also happens to be an artist) some stuff on the molecular graphics. The interaction between protein and ligand is a lot easier to show than explain with words.

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41. Capek on November 4, 2011 3:37 PM writes...

Why do like charges repel, and opposite charges attract? I can't explain that.

Also, how does a thermos bottle work? If I put in something hot, it keeps it hot. If I put in something cold, it keeps it cold. But how does it know which to do?

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42. Curious Wavefunction on November 4, 2011 4:22 PM writes...

Pete and CR: I have to say I beg to differ...a picture is worth a thousand words and saying that your work involves looking at pretty pictures like those on your phone may actually interest people. On the other hand, if someone walks away just because you showed them a picture of your work on your phone, they were probably not too interested in hearing you out in the first place so I don't think they deserve your attention.

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43. Curious Wavefunction on November 4, 2011 4:28 PM writes...

I also forgot to say that I think it depends a lot on what kind of layman you are talking about. There are the laymen who are avid general readers, who try to find out more about other fields of study and who are genuinely interested in the details of what you do. They deserve at least a somewhat detailed explanation and pictures on your iPhone.

On the other hand there are those for whom the question is only perfunctory and who are asking the question just to break the ice without being really interested in the actual answer. They don't *really* care about what you say. With these I will give it a three second try but after that won't waste my time.

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44. C on November 4, 2011 5:17 PM writes...

Nick - on the multiple posts. This morning each time I pushed the post button, the web browser just timed out with an error. When I reloaded the page a few minutes later my comment hadn't showed up so I tried again two more times. Two hours later, there were three posts. Sorry

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45. weirdo on November 4, 2011 5:27 PM writes...

Wait, wait, wait; stereochemistry??

"Right hand/left hand" doesn't do it? Mirror image?

I haven't found very many of friends that cannot understand that concept.

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46. John Novak on November 4, 2011 7:28 PM writes...

Conditional independence.

Relevant to artificial intelligence and-- based on the number of medical examples used to illustrate the principle in AI textbooks-- probably to medicinal chemistry, too.

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47. Lu on November 4, 2011 8:08 PM writes...

The hardest thing is to explain that genetic engineering is not as evil as it may seem and "organic" food is not as good as it's presented.

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48. Anonymous on November 4, 2011 8:37 PM writes...

Ever try explaining to elementary school children?
I give a demo in my kid's class every year. Its got to be REAL simple stuff. I've learned from these demo experiences how to distill down concepts to the most basic understandable level. I've found I'm better at discussing complex concepts with general lay people now, and as an added advantage, to my management. Children, lay people, big pharma management, they all seem about the same level, really...

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49. a chemist on November 4, 2011 9:28 PM writes...

I find if you say 'NMR' too quickly, non chemists often hear 'enema' and get very confused about what your work entails!

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50. Virgil on November 4, 2011 9:54 PM writes...

From a biologist's perspective (albeit one involved in the very earliest stages of drug discovery) the big thing grandma can't grasp, is why the cure for disease x I told her I discovered last year, isn't in the clinic already. Most folks have idea at all the time frame for drug development.

The other big one is explaining why we need animal research.... "why can't you use something else?" ... if they have a modicum of knowledge this is rapidly followed by.... "such as cell culture".

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51. Pete on November 5, 2011 5:07 AM writes...

CR/Wavefunction, Hopefully you've seen my comment that got posted anonymously as #40.

Something that I did want to make clear is that if somebody at a party wanted to find out about what I do and where it fits in the grander scheme of things then I'd would certainly have a go at explaining. This is the duty of any scientist and it must not be shirked. If it's a dinner party my advice is to consider the use of food and cutlery as props (provided that the occasion is not too posh).

At the same time, in social situations I do not assume that everybody with whom I interact will find what I do to be utterly fascinating. As Wavefuncton correctly points out, not all laypersons are identical. When I was showing molecular graphics to my artist friend (who was in catering where I used to work) we talked about the irregular shapes of molecular surfaces and their lack of corners.


Permalink to Comment

52. processchemist on November 5, 2011 6:22 AM writes...

The most crucial and hardest thing to explain (to a bench chemist too) is runaway behaviour in scaling up reactions. Most of the times I said "your cooling capacity grows like a square function, your heat generation like a cubic one" the standard answer was "So what?".

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53. Anonymous on November 5, 2011 8:15 AM writes...

As a high school chemistry teacher the answer to that one is easy - the mole. Once you get it, it's easy, but if you don't, it's all just blah, blah, blah. And there's only a limited number of ways that you can explain that it is just a number.

Permalink to Comment

54. david on November 5, 2011 8:17 AM writes...

I find it hard to explain that there are different types of evidence which carry different levels of predictive value. Newspaper articles often use the phrase "New study shows..." without stating the type of study or level of evidence.

Finding that a compound prevents some cellular process in a dish doesn't mean we've cured cancer in people. Finding an epidemiologic link between a drug and a side effect doesn't mean the drug causes the side effect. A group of anecdotes isn't data. An open-label pilot study in 10 people without a control group doesn't mean that the FDA should approve the drug immediately and otherwise is keeping cures away from the public.

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55. anon the II on November 5, 2011 9:37 AM writes...

What's hardest to explain is why, with so much education and experience, I don't have a job.

Permalink to Comment

56. maja on November 5, 2011 9:40 AM writes...

I couldn't agree more with david. Sometimes for me is hard to explain that type of enzyme inhibition is not a tool for determination of inhibitor binding site on enzyme target! Sometimes its hard to explain even to biochemists. They do not make the difference between the things they just believe in and things which are proved by adequate methods. In this case that means X-ray crystallography or NMR data instead of kinetic measurements.

Permalink to Comment

57. Anon on November 5, 2011 3:36 PM writes...

Hard to explain succinctly?

Women.

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58. Susurrus on November 5, 2011 6:07 PM writes...

My Mom has a difficult time understanding why Milkweed extract won't cure cancer. I think un-doing the damage done to our profession by the snake-oil peddlers is the most difficult thing to work around.

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59. RKN on November 5, 2011 9:19 PM writes...

GWAS studies. Trying to explain the important difference between "X causes Y" and "X is significantly associated with Y".

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60. Puhn on November 6, 2011 3:03 PM writes...

There is this other side of the problem - that thinks that we've learned and became common sense with years - may prevent us understand something new and radically simpler...

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61. cliffintokyo on November 7, 2011 4:07 AM writes...

How about trying to explain in lay terms that:
the areas under the peaks of an HPLC trace represent the relative amounts of the compounds present, except that they don't until you correct for the differences in absorbtivity between the different molecular species present!
(....after some thought)

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62. Guppy on November 7, 2011 9:02 AM writes...

Regarding Selenium poisoning -- you could start by explaining Iron poisoning, as that element is more familiar to people. In addition, it happens in the real-world much more often (mostly to young children who swallow too many Vitamins).

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63. Jim on November 7, 2011 10:14 AM writes...

I end up explaining the overall drug discovery process moreso than what part I specifically play in that process (in vivo biology), so what is usually the most difficult to explain is the whole regulatory/clinical process. In part, it's difficult to explain because it's not my area of expertise, and in part because it's, well, it's the FDA.

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64. silverpie on November 7, 2011 3:27 PM writes...

"It's like trying to say that cyanide is a vitamin"

How soon we forget... it's been tried. Amygdalin

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65. Jonadab on November 7, 2011 11:17 PM writes...

> try getting across to someone that there's an
> essential nutritional element that's also poisonous.

One word: salt. Selenium is obscure: most laypersons are aware neither that it's an essential nutrient nor that it's poisonous in excessive doses. Salt, however, is... let's just say it's less obscure. Most adults are aware (if not from their own doctor then from information regarding their parents' or grandparents' medical issues) that too much salt can be bad.

Or, for that matter, how about just plain *food*? If you eat no food at all, you're not long for this world. If you eat too much food, you can definitely harm yourself that way as well. Just about anyone should be able to understand that much.

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66. ScienceySophie on November 9, 2011 11:09 AM writes...

I still can't explain electrochemistry to people properly.

I gave an interesting introductory talk to some electronic engineers who despite knowing how to shuttle electrons about in electric circuits, have no idea about the chemistry inside which makes the current flow in the first place.

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