Biochemists and biophysicists

Three parts of your work where AI is already doing real lifting, and what stays yours.

• Wet chemistry1874–1926

  Wet chemistry and fermentation analysis (spectroscopy, titration, colorimetry)

  The founding generation of biochemists worked with the analytical tools of late 19th-century chemistry: colorimetry, wet titration, fractional precipitation, and elementary spectroscopy. Eduard Buchner's 1897 demonstration of cell-free fermentation in yeast extract was the field's foundational experimental moment, proving that enzymatic chemistry could proceed outside a living cell and therefore be studied chemically. The techniques of this era could measure the products and stoichiometry of biochemical reactions but could not reveal the molecular structures responsible for them. Equipment was simple glassware, waterbaths, and beam balances; the limiting factor was the scientist's ability to design a clean chemical assay for a biological process.

• Enzyme crystallization1926–1960

  Enzyme crystallization, ultracentrifuge, and paper chromatography

  James Sumner's 1926 crystallization of urease proved that enzymes are pure proteins and gave structural biochemistry its first toehold. The Svedberg ultracentrifuge (introduced 1924) allowed determination of protein molecular weights for the first time. Paper chromatography (Martin and Synge, 1941 Nobel 1952) transformed amino acid and small-molecule separation from a days-long effort to a single-afternoon technique. These tools let biochemists begin characterizing the molecular composition of enzymes and metabolic intermediates, building toward the complete descriptions of the citric acid cycle (Krebs, 1937) and the metabolic map. The era's hallmark was the move from measuring what reactions happened to identifying which molecules were involved.

  Effect on the work

  These analytical advances created demand for PhD biochemists across university medical schools and the growing pharmaceutical industry. By 1950 biochemistry departments existed at all major research universities and medical schools, and industrial employment (at Eli Lilly, Merck, Pfizer, and a dozen others) was growing rapidly around vitamins, antibiotics, and hormone production.

• X-ray crystallography1953–1990

  X-ray crystallography and the DNA double helix (structural biology era 1.0)

  X-ray crystallography had been applied to small molecules since the Braggs' 1912-1913 work, but it became a biology tool in the 1950s and 1960s when Rosalind Franklin's fiber diffraction data helped reveal the DNA double helix (1953) and David Phillips's group solved the first protein crystal structure at atomic resolution, lysozyme, in 1965. The Protein Data Bank was founded in 1971 with seven initial structures. By 1980 it held a few hundred; by 1990 a few thousand. X-ray crystallography transformed biochemistry's central question: not just what molecules are involved in a biological process, but what three-dimensional architecture makes them work. The era created the discipline of structural biology and made the biochemist's core skill set include cloning, protein expression, crystal growth, and synchrotron data collection.

  Effect on the work

  Structural biology created a new subspecialty of biochemistry that commanded premium salaries in pharmaceutical drug discovery. Structure-based drug design (pioneered at companies like Agouron Pharmaceuticals, founded 1984) became a major driver of industrial biochemist hiring through the 1990s. The number of structural biology positions at pharmaceutical companies grew rapidly with each new synchrotron beamline and protein expressed.

• NMR spectroscopy for protein structure…1984–2005

  NMR spectroscopy for protein structure in solution (Wuthrich method)

  Kurt Wuthrich at ETH Zurich developed 2D NMR methods in the early 1980s that could determine protein structures in solution rather than requiring crystals. This was transformative: many biologically important proteins (membrane proteins, intrinsically disordered proteins, signaling proteins in their physiological states) do not crystallize well or at all. Wuthrich received the 2002 Nobel Prize in Chemistry for this work. NMR created a second experimental pillar for structural biochemists and biophysicists and generated a new market for NMR spectroscopists at pharmaceutical companies and academic NMR centers.

• Recombinant DNA expression1990–2013

  Recombinant DNA expression, PCR, and genomics tools (molecular biology toolbox)

  PCR (Mullis, 1983; Nobel 1993), recombinant expression systems (E. coli, baculovirus, mammalian cells), and the human genome project (completed 2003) gave biochemists an entirely new relationship with their starting materials. Before recombinant DNA, a biochemist studying an enzyme had to purify it from the native biological source, often kilograms of tissue. After, any gene could be expressed in bacteria and purified in milligram quantities in days. This compressed the bottleneck of biochemistry from protein isolation to experimental design. The genomics era then provided every protein sequence in every organism, creating the target landscape that structural and mechanistic biochemists would spend the next two decades characterizing.

  Effect on the work

  The molecular biology toolbox dramatically expanded what one PhD biochemist could accomplish in a year and increased industrial employment in pharmaceutical target identification and validation. Biotechnology industry employment of biochemists grew from near zero in 1980 to a substantial fraction of the profession by 2000, driven by Genentech, Amgen, Biogen, and a wave of startups using recombinant proteins as drugs.

• Cryo-EM resolution revolution2013–2021

  Cryo-EM resolution revolution (direct electron detectors, 2013; Nobel Prize 2017)

  In 2013, a new generation of direct electron detectors replaced the photographic film and CCD cameras used in cryo-electron microscopy, enabling the collection of movie-mode data that could correct for beam-induced sample motion in post-processing. The resolution of cryo-EM structures jumped from several Angstroms to a few Angstroms within two years -- a leap that made cryo-EM competitive with and often superior to X-ray crystallography for large complexes. Jacques Dubochet, Joachim Frank, and Richard Henderson received the 2017 Nobel Prize in Chemistry for the foundational cryo-EM methods. By 2020, cryo-EM had become the primary method for determining structures of membrane proteins, ribosomes, viral capsids, and multi-megadalton assemblies that had resisted crystallization for decades. This opened structural biochemistry to a new class of biologically relevant targets and drove large investments in cryo-EM facilities at universities, national laboratories, and pharmaceutical companies.

  Effect on the work

  The cryo-EM revolution created strong demand for structural biologists with cryo-EM expertise and for the software engineers building the ML-accelerated data processing pipelines (CryoSPARC, RELION). Pharmaceutical companies built in-house cryo-EM facilities; academic cryo-EM centers expanded rapidly. A generation of biochemists trained in crystallography retrained or hired cryo-EM specialists.

• AI structure prediction2021–present

  AI structure prediction and generative protein design (AlphaFold 2 onward)

  AlphaFold 2, released by DeepMind in July 2021, solved the 50-year-old protein folding problem for most single-chain proteins. AlphaFold 3 (May 2024) extended accurate structure prediction to protein-DNA, protein-RNA, and protein-small molecule co-complexes with approximately 80% success on novel drug-target interactions, making experimental structure determination optional for many hypothesis-testing applications. RFdiffusion (Baker Lab, July 2023) and ProteinMPNN (Baker Lab, 2022) together enabled generative protein design: a biochemist can now computationally design a novel enzyme or high-affinity molecular binder, generate hundreds of candidate structures in a day, and synthesize only the top-scoring ones for experimental validation. CryoSPARC v4 and ModelAngelo (DeepMind, 2024) automated the cryo-EM data processing and model-building steps that previously required weeks of manual work. ML interatomic potentials (MACE, NequIP) now run molecular dynamics at near-quantum accuracy 100-10,000x faster than traditional methods. These are not incremental improvements: they represent a categorical shift in what one biochemist can accomplish per unit of time, and they are the largest technology disruption in the profession's history since X-ray crystallography.

  Effect on the work

  BLS projects 6% employment growth for 19-1021 through 2034 despite this disruption, reflecting that AI tools augment rather than replace the experimental judgment, mechanism elucidation, and instrument-level expertise at the core of the role. The pharmaceutical and AI drug discovery sector (EvolutionaryScale, Isomorphic Labs, Generate Biomedicines, Recursion) is creating new biochemist roles focused on designing and validating AI-generated molecular structures -- a job category that did not exist in 2020.