This is part of the series of blog articles called “A Writer’s Guide…”, check out this article by writer Sarena on being a Biochemist.
Being a Biochemist
Overview -What is biochemistry?
The human body is driven by countless chemical reactions, occurring at every moment. These reactions give rise to life, and biochemistry encompasses the study of all of these reactions, as well as what happens when they go wrong, causing diseases.
In other words, biochemistry is quite literally the chemistry of biological organisms. We’re talking small things in the body. Proteins, DNA, mitochondria, cells, cell membranes, and signalling pathways.
Biochemistry overlaps with many otherrelated fields, such as genetics, microbiology, molecular biology, biology, pharmacology, physiology, and a lot of ‘ology’s.
So, the field can be quite broad and widely applicable, but this article will focus on biochemistry in academia: research done in laboratories, particularly in universities.
Biochem is fundamentally just investigating what all sciences seek to learn: “what is this, what does it do, what happens if it stops doing the thing”.
However, most funding bodies and popular public interest are really only interested in “can this be used to treat disease?”
EVERYONE wants to cure cancer, right? So this research is normally conducted and discussed in terms of what it might cure. Some examples:
- Protein misfolding in terms of Alzheimer’s disease.
- Failed signalling pathways in terms of cell death and cancer.
- Antibody generation in terms of autoimmune diseases.
You get the idea.
The keywords I would apply to the discipline are: innovation, stress, and impact. It is an extremely competitive field, and I will outline the causes and effects of this later.
What is a biochemist?
“Biochemist” can apply to anyone working in or studying biochemistry, andistherefore a quite broad term.
Generally speaking, biochemists are extremely intelligent, highly motivated individuals (although I don’t necessarily put myself in that category).
It is the competitiveness of the field that means that only the brilliant AND the motivated remain. We are practicing Darwinists, you see: survival of the fittest.
Because “biochemist” is a broad term, I’ll break it into categories, which fall under the relevant qualifications.
1. Undergraduate student
High school completion is a must, and a good completion score is generally required for the sciences. Each country will have its own alternate university entrance pathways, so I’ll skip that.
In Australia, where the writer of this article is based, students typically do a generic “Bachelor of Science”, and then are free to choose their major and minor areas of speciality.
Biochemistry students will need to study basic biology and chemistry in first year, and then start to specialise. They don’t need to (and often don’t) know what they want to do when they start their degree.
Courses contain theory and laboratory/practical components, and due to the broadness of the field and its overlap with other disciplines, there’s a lot to remember, and students sometimes drop out or switch at this stage.
Although, technically, students have the skills necessary to work in a research lab after finishing their bachelors, due to educational inflation they will never be able to get a job in a research lab.
Biochemists with only a bachelors will typically move into what we loosely term “industry”. This can be many things: food and beverage testing laboratories (for bacterial contaminations, GMOs, nutritional composition testing, Quality Assurance (QA), etc), soil testing, waste/sewerage testing, pharmacies, pathology labs, etc.
We’ll focus on those who continue in academia.
2. Honours/Masters students
If you want to work in a research lab, this is a must. Once upon a time, perhaps 30 years ago, a simple undergraduate degree would’ve been enough, but nowadays, I’m sure we’re all aware that there’s just not enough jobs.
Things are more competitive. Although undergraduate classes have a practical/laboratory component, it’s just not enough for research professionals to consider “experience”.
Honours is a one-year course at the end of a bachelor’s degree in which students have a project, mostly directed by their supervisor, and must deliver a report (a miniature thesis) at the end.
This will typically mean 6-8 months of lab work, and a minor coursework component.
Masters is largely similar, except that it is two years long, and the fee structures can be different, making it the more expensive option.
So why would anyone choose that, you ask? Honours has a minimum grade requirement, typically a distinction average (70%+), and Masters is much easier to get into. There is also a larger coursework component in Masters, normally comprising the first year.
Some students have a knee-jerk reaction to lab workduring this time. Usually, students are guided and nurtured by their supervisor, who supports them to gain the skills required, and move their project in a positive direction.
esn’t always happen. Some supervisors are terrific, and some are terrifically not. Some supervisors work students to the point of mental breakdowns, some don’t help students at all, some just shouldn’t interact with other humans.
Remember these problems for the “PhD candidate section”, as it applies equally there. Also, some students simply put too much stress on themselves. Six months of lab work isn’t long enough to get impactful results, but some students don’t realise this.
Some quit and go into industry, others quit science altogether, while some finish and move into…
3. Research Assistants
Real lab work. An actual wage. Sounds great!Research assistants (RAs) don’t have their own projects, they merely assist other’s, typically those of Research Fellows (see below).
They are generally employed on 1-year contracts, so while the job security isn’t ideal, it’s not too difficult to find new work: RAs are the cheapest form of lab labour, after students.
Technological advancements mean that there are more and more robotics being used in biochem, which could put the future of RAs into doubt,but so far, it’s merely meant that experiments can be performed faster, rather than replacing someone’s job. Perhaps, in another twenty years, this may change.
I consider RAs to be the lowest stress positions of the career ladder I’m presenting to you. They are merely expected to assist, and therefore they work reasonable hours.
There is also room for flexibility in work hours, where earlier or later hours can often negotiated. Working part time is also a possibility, wheremany elect to not work on Fridays, making it a reasonable job to hold while raising a family, or writing on the side 😉
So, low-stress RAs can look on, or even laugh (in a sad, very concerned way), at the others in the lab who are killing themselves for their work.
The pay is probably on-par with some other entry-level job sat similar education levels. But, it is a dead-end career, unless one moves into industry, or proceeds onto…
4. Doctor of Philosophy (PhD) students
PhDs typically go for 3-6 years depending on country, Australia has recently tried capping degrees at 3.5 years.
For the same reasons as in Honours, a PhD can be either a reasonable or a horrifyingly traumatic experience. However, students don’t pay: they can finally start receiving a stipend, although funding is competitive and dependent on honours/masters grades, or previous experience/research output.
The average stipend is roughly 1/4 – 1/3 of the average wage, but can be supplemented by teaching in undergraduate labs or other scholarships.
Again, some discover they love to teach, while some discover that they shouldn’t interact with other humans more than is necessary.
However, teaching is encouraged for all students in their second year. Another major difference is that PhD students have two supervisors, which helps relieve the stress if one isa bad supervisor.
There are milestones at the end of each year, comprising short reports and oral presentations,and a final thesis of a five-digit word count thesis.
Students are expected to do occasional professional development workshops, as well as present poster presentations at conferences and talks to boost their CV.
Four years is a long time to sustain high levels of stress however, and again, many leave for industry, but are able to enter at higher level positions than they could at lower education levels.
The major metric of success in science is research output, which can be clearly seen by the number of papers published and the significance of those papers.
Hopefully, PhD candidates are able to publish more than one paper during their time, which would help them get…
5. Research Fellowships
Research Fellowships are generally awarded for 1-3 year periods. A fellowship pays a scientist’s wage during that period, and sometimes some lab expenses too.
They are very competitive, and often prompt scientists to move to distant countries if they find a good position there.
As long as one can speak passable English, language or cultural backgrounds are no barrier, and biochemistry labs are full of culturally diverse personnel.
Research Fellows report to a Chief Investigator (CI), known more commonly as lab heads. Lab heads have all the funding for things, and functionally “own” the lab (note, the University/place of employment actually owns everything, including all the patents and research that scientists conduct with their own blood, sweat, and tears).
Funding is still competitive, and can run out, leaving biochemists unemployed.So they work hard, some doing 70 or 80 hour weeks, as well as going to talks and conferences.
However, despite the added stress, time spent in lab, and qualifications, the pay is not a huge step above that of RAs: 1/6 – 1/3more.
At this stage, Research Fellows can take on students. Since researchers have typically been in a lab for at least six years by now, some struggle with the incompetence of inexperienced undergraduate/honours students, while some shine, and start moving towards teaching positions, lecturing, etc.
6. Chief Investigators / Lab heads
Who are these mystical creatures? Do they even exist? What goes on in their heads? Who knows.
While it’s true that some lab heads don’t know what happens in their labs, deferring almost everything to their lab manager (a kind of research fellow), these are the best of the best.
They have gone through all those years of study and stress, and continued undeterred. They have succeeded in having a spectacular research output, having the insight, critical thinking ability, people skills, and luck (yes, luck, most scientists will agree that luck is a legitimate factor!) for things to go their way.
Like unicorns, they’re a varied bunch, some majestic purple, some muscular and green…
Kidding, but still, they’re a cut above the rest. Ideally they go to many conferences to hear new ideas, techniques, find new collaborators, but otherwise they spend large amounts of their time writing grants and supporting the research fellows working for them.
Their name appears on every paper their lab publishes. But, like all the rest of these ranks, they can’t just sit back and relax.
Funding is still competitive, coming mostly from the government, but sometimes the private sector if their lab can develop a viable drug, so they need to keep their lab’s research output high (read, keep loading pressure onto their underlings).
Also, if their funding runs dry, the entire lab closes, and all of its students and researchers need to move elsewhere.
Some professors teach lectures, or administerundergraduate, honours, or PhD courses.
Great! So now you know the basics of the qualification levels!
Funding! It’s super competitive! And every time the government announces a budget cut, research is normally cut, reducing the already too-few jobs available.
The uncertainty of future funding is the dark cloud that hangs over most scientists’ heads.
Because biochemistry typically looks at disease, if a new drug or therapy is produced, they can often sell the idea to pharmaceutical companies, who then gain the intellectual property, and pay the vast sums of money it takes to get the drug through clinical trials, most of which fail.
So it’s ALL about research output and results. If you have a good publication record, you have more chance of your grants being approved, because you can prove that you can deliver on your grant aims.
However, what if the project you’ve been working on for years and which you’re finally making progress on, is suddenly published… by someone else.
You had most of your results. You were already in the process ofwriting it into a paper. But bam, a scientific journal just released a paper that shows results similar to what you’ve got, but a little more complete, therefore rendering all of your last few years of research obsolete.
This is called getting scooped. It’s why there’s pressure to publish results ASAP, and not hold on and wait for better results.
However, if you wait for better results, you could publish something with more impact, so it’s important to balance the two. It’s also a good idea to “keep your friends close and your enemies closer”.
Also, the bigger and more interesting the topic, the more funding that field will get, but also the more people working in that field.
So again, everyone wants to cure cancer… But what if someone else cures it first? You get nothing. No honourable mention. No pat on the back. You just have start again, move onto something new. Years wasted.
Opportunities of funding diminished.So it’s important to stay up to date with new publications and developments in the field as well as your competition, because what would be worse than getting scooped? Not realising for months that you’ve been scooped.
It’s not SO bad, since many biochemists work on more than one project at once, but it is still a very, very big deal, and really does happen to people.
PPE and OHS
Scientists generally wear jeans and runners. No nonsense. Get the job done. Nobody cares what you look like. Hair tied back or kept short.
The only uniform is that enclosed shoes are a must: if you drop chemicals, they will fall down and splash your feet. Pants are also a good idea, but not enforced. (Worth noting that Australia routinely has days over 30 °C (~86 °F), so good luck enforcing pants!).
In terms of lab wear however, you’ve all seen the long white lab coats, gloves, and goggles, even if only on tv. They’re real. They get worn.
Some people are slack, and breach OHS sometimes by not wearing them, especially late at night when no-one’s around, but these are bad people and we must shun them.Shuuun.
Other Personal Protective Equipment (PPE) to note are noise cancelling earmuffs for things such as sonicators, and face shields for things such as liquid nitrogen.
Equipment and techniques
Oh boy, here we are. Are you ready for some jargon? Let’s get started!
I’ll try to explain a common workflowfor a protein-based project, but workflows vary greatly, as do projects.It is lengthy and jargon-y, and that’s science in a nutshell.
This will be the most technically detailed information in this article, so you may skip it if you want.
However, if you want to write about a scientist whose experiments are going badly, then please, read on for dat juicy info. Google things as you will.
1. Protein expression
Since, apparently unnecessary human experimentation is bad, or something, ethics laws forbid us from taking the proteins out ofhealthy humans.
I know, real bummer, right?
So we have to make it the long way, which is more efficient anyway.
You order the gene that encodes the protein you’re interested in online. You use enzymes to cut what’s called a plasmid, or vector (which is a circular ring of DNA that bacteria uses) and then use another enzyme to stick your gene into where you’ve cut.
You can check that your cloning worked at this point using a DNA gel (outlined below). Then, you transform it into bacteria such as E. coli (which basically involves stressing out bacteria enough that they swallow your plasmid construct), and then grow itovernight in a nice, warm, rotating incubator, which mixes the media in the flask so that the bacteria are very happy in their delicious broth of yuck (contains salt, amino acids, and yeast extract) (it smells warm and yeasty, but once bacteria’s grown in it, it can smell either weirdly yeasty or YUCK, OMG, LIKE WHAT EVEN IS THAT, WHAT HAS DIED IN THIS LAB?!?!).
Because bacteria are obviously very different from humans, some proteins can’t be expressed in bacteria, and need to be expressed in either insect cells or mammalian cells (mammalian cells used are typically cancer cells, such as HeLa cells, which will grow forever and ever).
Then you add something such as IPTG, which activates transcription of your gene, and the cells express protein (i.e. make the protein by joining together amino acids) non-stop. When you have enough protein (trial and error to find out what “enough” is, but proteins are typically unstable and will degrade if you leave it too long), say, 24 hours, you harvest the cells in a centrifuge (which involves spinning the culture very fast to create more force, thousands of times the force of gravity), and it pulls the cells down into a compact pellet (a gooey clump of yucky cells), separated from the liquid media they were floating in.
You can freeze the pellet in liquid nitrogen, and store the cells in a -80°C freezer for years. Remember your PPE for liquid nitrogen. Lab gloves make your hands more sensitive to the cold, so special gloves are used.
Burns from liquid nitrogen (LN2) can leave you scarred for life. LN2 also expands in volume about 700x when it evaporates, which can quickly push out the air of small rooms (ie. Elevators) and cause the scientist to asphyxiate.
Both the scarring and the asphyxiating are things that have happened in real life, but nowadaysall liquid nitrogen facilities have oxygen monitors and security protocols in place preventing you from doing stupid things like going into a lift with liquid nitrogen.
2. Protein purification
Then, you can resuspend your cells in lysis buffer. The solution at this point looks like more yuck juice, a greyish brown ooze.
Cell lysis can be done with a sonicator (which breaks open the cells using ultrasonic sound waves to let out all the protein (amongst other things comprising the cells’ guts)).Remember PPE.
Without earmuffs the sound would be painful, and you would soon go deaf or develop tinnitus. With earmuffs a muffled high-pitched shriek is what you hear,just at the edge of your hearing range.
Then, you spin it down in a centrifuge again to clear the unwanted crap (cell debris).
Next, you would filter your lysate through a syringe, and then bind your lysate to some kind of affinity column, to separate the protein we want from all of the other crap.
This is getting lengthy, isn’t it?
Fun news: LAB WORK IS NORMALLY LENGTHY AND BORING.
An affinity column could be something such as micro beads with a charged metal bound, such as nickel, which would bind a certain tag called a His tag, typically comprising histidine residues (which you should’ve cloned in right at the start).
Your tagged protein will bind the metal, while all the other gunk will flow through. You wash it, and then elute your protein off (for Histidine tags, using a high salt buffer will work).
Then you cut the tag off using another enzyme, pass it back through the column, this time catching the flow through.
Additional purification steps are normally required.
3. Gel filtration chromatography
A gel filtration column is a long, thin, porous tube connected to a computer, and it separates things based on size. You run your sample through it and collect the fractions that your protein is in (often having to test it on an SDS-PAGE gel to make sure, see below), and then concentrate it in a centrifugal concentrator.
Just so you know, all of that is weeks of work, if not months, and if something goes wrong, it can take a long time to trouble-shoot.
Sometimes to decision must be made to cut your losses and abort the project, andmove on to something else.
Examples of things that can go wrong are: low protein yields from the bacteria, protein unable to bind to the affinity column, protein degradation, and nothing or very little coming out of the gel fil column.
Protein might also precipitate at any point, forming little (normally white) floaty bits made out of ruined hopes and dreams.
Now, after weeks of slavery, IF EVERYTHING GOES RIGHT, you can now do actual experiments.Inspiring, isn’t it.
Used for looking at proteins. Most biochemists do something involving proteins sooner or later.
Note, proteins are involved in basically everything in your body: They interact with and translate DNA, produce more proteins, help form the cell wall, send messengers through cells, build muscle fibres and give cells shape, transport things about, etc.
SDS Polyacrylamide Gel Electrophoresis runs an electric current through a gel that you’ve loaded
your sample into, and it pushes your sample along it.
The polyacrylamide gel is porous (you can easily change how dense it is), and smaller proteins travel through it faster than big ones, which means that it separates proteins based on size. Then you take the gel out and put a dye on it that binds only to proteins (eg. Coomassie stain).
This lets you see that you HAVE protein in your samples, and tells you whether your protein has degraded (fallen apart or been cleaved by something else) or not, as well as how pure it is.
Here’s an example of a good gel (from https://www.thermofisher.com/au/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-electrophoresis.htmlwhich also contains informational videos, and https://en.wikipedia.org/wiki/SDS-PAGE)
GREAT, now here are some bad ones! Follow the link for more, as well as an explanation of what went wrong! https://www.ruf.rice.edu/~bioslabs/studies/sds-page/sdsgoofs.html
Very similar to SDS-PAGE, except that DNA is typically smaller, and behaves a little differently. The gel is made out of agarose, basically seaweed jelly protein.
Theses might be binding assays, to see what your protein binds to, or structural studies to determine what the protein LOOKS like at a microscopic level.
Both of these have the end result of learning what a protein does, and how to change that function.
My favourite structural techniques are cryo-electron microscopy and x-ray crystallography, which are just as cool as they sound, but are too lengthy and complex to explain.
If you’re interested in learning more, find a nice, heavy textbook. We studied from “Molecular Biology of the Cell” (Alberts), and “Molecular Cell Biology” (Lodish).
As mentioned before, papers are the most important indicator of success. They tend to be jargon filled, hard to read by those outside the field, and are often hidden behind a pay wall.
They need to be completely accurate, and the experiments mentioned within must be repeatable. It’s usually the end of a scientist’s career if they lie, make stuff up, or fabricate results. Nobody will hire or give funding to someone with the reputation of a liar and cheater.
Here is my lab’s most recent paper, for some shameless self-promotion. It is also hidden behind a pay wall, but abstracts are designed to give you an overview of the paper’s key points.
Wow, wasn’t that an adventure.
Biochemistry is full of hard-working, intelligent people, who often love what they do enough to not demand too much money for it.
They work long hours, normally doing time consuming, tedious, boring experiments, but it is definitely worth it:
To advance human knowledge, and to cure disease.
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About Sarena Flanigan
Sarena lives in Melbourne, Australia. She is a Research Assistant in a biochemistry research lab at Monash University, and thankfully she realized that she’s too obsessed with fantasy to undertake a PhD, before doing her PhD.
She has dreams of getting her fantasy novel Light in the Darkness published, and in the meantime is writing other things such as this.
Normally there’s more magic in the things she writes.She also loves video games, music, painting, reading, and writing.
I hope you liked this article and if you have any questions for Sarena, please drop them in the comments below. Check out all the current “A Writer’s Guide” articles on their new page for easy access.
Do you have knowledge of a skill or occupation you could write about?
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