How do we know so much about biochemistry?

X-ray crystallography and nuclear magnetic resonance crystallography are two techniques used to determine the structure of molecules.

When I googled “History of Chemistry,” I found this interesting site along with hyperlinks.

For starters:

“The earliest practical knowledge of chemistry was concerned with metallurgy, pottery, and dyes; these crafts were developed with considerable skill, but with no understanding of the principles involved, as early as 3500 B.C. in Egypt and Mesopotamia.

The basic ideas of element and compound were first formulated by the Greek philosophers during the period from 500 to 300 B.C. Opinion varied, but it was generally believed that four elements (fire, air, water, and earth) combined to form all things. Aristotle’s definition of a simple body as “one into which other bodies can be decomposed and which itself is not capable of being divided” is close to the modern definition of element.”

Then, one thing led to another.

I literally took entire classes on this while in college (Chemistry major) and a lot of the concepts are still tough for me to grasp sometimes especially when you get down into the super-minute details like subatomic structure.

The links you’ve got so far are a good start though.

cracks knuckles Well, seeing as I am a biochemist, perhaps I can take a crack at this. Though I would prefer some more specific questions, as this is rather broad. But I can go into a little on all of your questions.

Sequencing: We’ve got a huge number of techniques now, one of the first and most successful was Edman Degredation, which if you’re careful (and paired with other techniques such as proteolytic cleavage) can give you a sequence, though it’s rather tricky to do well. The most recent and powerful technique now is Tandem Mass Spectrometry, which can give you an unknown protein’s sequence in a day if you’re lucky and good. Basically it all revolves around slowly degrading the protein and seeing what falls off. Take that, pair it with powerful computer software, and you can figure out your sequence.

Along these lines, as @nikipedia mentioned, X-Ray and NMR spectroscopy can be used to determine angles and structure, as well as sequence, though sequence is very hard to determine just from those techniques alone. But NMR and X-Ray can give detailed structural information, especially related to bond angles and connectivity.

As to “They can’t just use a microscope to look at the molecules”, that’s actually not true. Scanning Electron Microscopy and more so Transmission Electron Microscopy can get very high resolution, with TEM getting down to almost single atom resolution. This has been used to determine the structure of proteins in ‘large’ molecules such as virus particles, though it has a lower resolution then X-Ray (~1 nm, as opposed to < .2 nm). Lastly, Atomic Force Microscopy has actually gotten down to single atom resolution, even further technically, though that involves a lot of signal averaging over lots of images.

However, a lot of knowledge on bond angles and things of that nature come from physics and physical chemistry, which informs biochemistry just as much as it does other branches of chemistry.

As to chemical reactions, there’s two things there. First, biochemistry owes a lot to the work of organic chemists (which i am decidedly not one), as most biological reactions fall under the umbrella of organic reactions, and physical organic chemistry has given us lots of tools to determine the exact pathway a reaction takes. However, in more complex biological systems, such as the photosynthetic pathway you mentioned, we use a combination of biochemical and genetic techniques, such as looking at where a protein appears in a genome and what’s around it (linked proteins tend to appear in a genome in close proximity, many times one right after another), then creating those proteins for study, along with organic and biochemical techniques (to determine how a single enzyme does it’s thing) like NMR and/or rapid kinetic spectroscopy.

And now I’m really late for work, so I should leave. But that’s a brief overview on many of the questions you bring up, if you want to get more specific into one I’ll be happy to give you more detail.

I would argue that, “we” don’t know very much. Purists of chemistry and biology however have been working together experimenting for quite some time now. Trial and error, finding patterns, using computer simulations and such. I don’t think it can be covered in one answer here. I mean it sounds like this topic would be at least a 3 and ½ lecture in college. And even then maybe a 1 and ½ lab class attached to it. This is a ton of information you’re asking and I can’t imagine this subject being broken down to layman’s terms.

@_Whitetigress , I was not looking for the gritty details, just a broad outline of what can be done. The answers that @nikipedia and @BhacSsylan gave are helpful, though it still seems a bit mysterious. To find a DNA sequence, I assume it is first necessary to isolate DNA. Then you have to collect a bunch of it. How do you go about doing that? Can DNA be crystallized? I would imagine there is a lot of hard work that went into coming up with the proper techniques. The guy who figured out photosynthesis got a Nobel prize for his efforts, as did the people who first figured out the structure of DNA.

I love questions of the “how do we know what we know?” variety. GQ.

Yes, I think above answers focus too much on recent technology rather than historic roots. Chemistry appeared in the 18C, pioneered by Lavoisier, Dalton, Boyle, Priestly et al. By applying the modern scientific method they established atomic theory that left alchemy in its dust. Chemistry continued to develop during the 19C culminating in the periodic table of elements. The quantum physics revolution of the early 20C nailed it down & established a bottom-up understanding of how atoms form molecules. Chemical bonds are seen to emerge from the equations of particle physics.

The progression of disciplines has been: chemistry—> organic chemistry—> biochemistry—> molecular biology.

Organic chemistry and biochemistry also put an end to the mystical notion of vitalism. Biology is just chemistry.

There’s a nice Wikipedia article on the History of biochemistry.

Plus: Organic chemistry: History.