David Bedford

Alternating picture

Science

On this page I will to try to explain what I was doing between 1991 and 1997, when I was a scientist working in laboratories in England and California.

I don’t know if I will succeed in explaining exactly what I was doing, but I’m going to show some curious and beautiful pictures, some of the wonders of the world that scientists have uncovered. These wonders will include,

Streptomyces coelicolor A3(2)

beautiful blue bacteria!

Each round, grey-blue blob is a colony of bacteria growing on a clear nutrient jelly. See how the colonies are leaking out blue pigment?

Purple
the transformation of something whitey yellow into something purple!
Aspirin
the day I nearly made aspirin by accident!
Radio-active shoes
the time one of my Russian colleague’s shoes became radioactive!

 All this, and much, much more ...

I was a teenage genetic engineer

You may know that our bodies are mostly made up of cells. Every part of us, all cells, cells, cells. Skin cells, liver cells, muscle cells, brain cells (if we’re lucky) - all kind of cells, for all the parts of our body.

You began (as did I) as just one cell, a fertilised egg cell. It split in two, two split into four, four into eight, and on and on, splitting and growing until the number of cells reached somewhere in the trillions. Trillions of cells! Acting together as one marvel, walking, talking, being annoying (see later on!).

You can see cells under a microscope. Muscles cells are long, and can contract and release, as you might expect. Brain cells can appear empty - but there is so much going on inside!

I loved finding out about cells, but there was something more important to me. What makes the cells split and grow and arrange themselves into a body?

I knew the answer by then: the genes do it.

Inside every living cell, there are genes, long strands of a chemical called DNA, that can be read like a code. The cell reads the genes (here’s some DNA code: TTGCTAATTAACCTGG - spot how many letters it uses, they’re always the same, and not as many as the alphabet!) and by reading the genes, the cell will learn what to become, what to do, split in two or stay as it is, grow long into a muscle cell, or grow fat and round and live in the liver.

I wanted to study genes, and find out how they work. I was nineteen when I joined a lab and got my chance to have a go.

David Streptomyces

One day some college students came to the lab for the day, and I volunteered to show them around. It went well, with some curious would-be scientists asking appropriate questions and enjoying being shown the curious machinery, the Radioactive Room (for performing radioactive experiments), the Cold Room (for cold experiments), and the Dark Room (for dark experiments...).

There was a problem though. Two of the students were, every few minutes, sent into spasms of giggling and spluttering. I asked them if there was a problem, but they declined to answer. Their disruptions were annoying and distracting, and I was getting pretty annoyed because it was undermining my confidence, them laughing so uncontrollably, and for unfathomable reasons.

It got to the stage where I was thinking: radioactive shoes time.

During lunchtime I asked some of the saner-looking students about it, and they told me straight: the two buffoons were laughing at the badge I’d attached to my lab coat.

I looked at my badge, which I’d made myself with a sticker and a thick black pen. It said, ‘David Streptomyces’.

‘David’ so that the students would remember my name. And, underneath it, ‘Streptomyces’, to remind them what I was telling them about that day.

‘They think you’re called David Streptomyces,’ the saner-looking students explained, rolling their eyes in sympathy with me.

Actually, I thought it was funny too. Though Streptomyces is a fine-sounding name for the beasts I was studying - studied, in fact, for my entire time as a scientist.

Streptomyces are bacteria, ‘good’ bacteria as far as we are concerned. They grow in ordinary garden soil, and do little more than grow and make chemicals to kill off any other bacteria or funguses that might like to live too close.

It’s like a chemical war going on in the soil, and Streptomyces are the ones with the big guns.
Grow Streptomyces in a bottle, and you can extract from the soup an Aladdin’s cave of wondrous chemicals. This is how scientists have discovered most of the antibiotics we use. Chloramphenicol to cure eye infections. Streptomycin, erythromycin and many more to kill bacteria inside our bodies. There are chemicals that we can use as anti-cancer and anti-viral medicines, too.

And the only way Streptomyces lets itself be known is by making the characteristic smell you get by digging into fresh soil. That smell is the harmless chemical geosmin getting up your nose.

Streptomyces cells are like magical potion makers. Genes must be behind it, of course - strange and interesting genes, as it turned out.

For most of my science career, I joined a worldwide effort to study antibiotic genes in Streptomyces. If we changed the genes, engineered them, might we be able to change the chemicals they make, and make some new antibiotics? You betcha! Right now many ‘engineered’ chemicals from Streptomyces are being tested to see if they will make useful medicines for the future.

Publications

I wrote or contributed to several scientific ‘papers’ during my time as a scientist, and these were published in science magazines with names like Gene and Journal of Bacteriology. These papers told the results of my experiments, as well as the experiments of other scientists working alongside me - either in the same lab, or from labs across the world, particularly in the USA, Germany and Japan.

The titles of these papers make me smile for all the sciency words they use. When I read them aloud to my daughter, she howled with pleasure and told me the words were ‘brain tickling’!

1991
Characterisation of a gene conferring bialaphos resistance in Streptomyces coelicolor A3(2).
By David J Bedford, Cinzia G Lewis and Mark J Buttner. Published in Gene.

This was a project I did as part of my studies when I was nineteen, in my second year at university. It worked out so well I was able to write it up, with my supervisor (later also to be my PhD supervisor) Professor Mark Buttner. It was my first look at a gene, and it made the chemical bialaphos, which happens to kill weeds and so can be sprayed on to crops as a herbicide.

I found out where the gene started and stopped and generally what it looked like - just a standard sort of gene, but a good place for me to start.

1995
Two genes involved in the phase-variable phiC31 resistance mechanism of Streptomyces coelicolor A3(2).
By David J Bedford, Carole Laity and Mark J Buttner. Published in Journal of Bacteriology.

I made a diversion from studying the chemicals made by Streptomyces, and instead (and for my PhD qualification) I spent three years studying a virus that infects Streptomyces. In other words, our tiny bacteria gets infected with an even tinier virus... All kinds of bacteria can get viruses that kill them off. In fact, in Russia in particular, there was a lot of interest in giving sick people bacterial viruses to drink. The viruses wouldn’t hurt the person at all - they’d just kill the bacteria that was making them sick. It’s a good idea.

1995
Expression of a functional fungal polyketide synthase in the bacterium Streptomyces coelicolor A3(2).
By David J Bedford, E. Schweizer, D A Hopwood and C Khosla. Published in Journal of Bacteriology.

This was probably the neatest experiment I ever did, taking a gene from a fungus and putting it into our bacteria. It wasn’t as simple as it might have been, because fungus genes are odd. This one had a big piece of junk in the middle of it - Junk DNA. Humans are full of Junk DNA too, which makes things complicated. The fungus gene was complicated enough though, and the first thing I had to do was remove the junk. Next, I engineered the gene, making it look more like one that Streptomyces would recognise. And it worked! When I put the new gene inside Streptomyces it made the chemical it was supposed to make, 6-methylsalicylic acid. Which is almost the same as aspirin! Spot the difference?

Aspirin 6-methylsalicylic acid

This paper also has the names of two important professors who I had the pleasure and honour of working with closely, and from whom I gained enough wisdom not to have fallen flat on my backside when I decided to switch careers: David Hopwood at the John Innes Centre in the UK, and Chaitan Khosla at Stanford University in the USA.

1996
A functional chimeric modular polyketide synthase generated via domain replacement.
By David J Bedford, J R Jacobsen, G. Luo, D E Cane and C. Khosla. Published in Chemistry and Biology.

More genetic engineering, this time of a massive gene that makes the equally massive antibiotic erythromycin.

1998
The granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tü22: sequence analysis and expression in a heterologous host.
By Ichinose K, Bedford D J, Tornus D, Bechthold A, Bibb M J, Revill W P, Floss H G, Hopwood D A. Published in Chemistry and Biology.

purple imageThis time I put a cluster of 20 or more genes into Streptomyces, and had my biggest pleasure when the Streptomyces turned purple! That’s what should have happened, because the genes I put in were supposed to make an antibiotic, granaticin, which happens to be purple. But even so, there were many reasons the experiment might not have worked, and the immediate success was sweet.

1999
Cloning and characterisation of a gene cluster from Streptomyces cyanogenus S136 probably involved in landomycin biosynthesis.
By Lucia Westrich, Silvie Domann, Bettina Faust, David Bedford, David A Hopwood, and Andreas Bechthold. Published in FEMS Microbiology Letters.
I don’t know too much about this paper, except I remember making one of many fine friends in Andreas Bechthold, a German scientist. I think I gave Andreas some genes or DNA to work on, and clearly he remembered me when he came to write up his experiments years later.

2001
Functional Complementation of Pyran Ring Formation in Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2) by Ketoreductase Genes for Granaticin Biosynthesis.
Koji Ichinose, Takaaki Taguchi, David J. Bedford, Yutaka Ebizuka, and David A. Hopwood. Published in Journal of Bacteriology.
This paper reports work that was mainly done by other people, quite a while after I stopped being a scientist. It is mightily encouraging to know that my contribution was useful and is being continued. I am also delighted to see that, in 2001, my last scientific paper overlapped in time with publication of my first children’s books, as if one career slipped seamlessly into another... which is comforting to imagine.

As for the Russian’s radioactive shoes? Well, who knows how they became radioactive - I’m not entirely sure. They were put in a safe place and left while the radiation decayed naturally. They could still be in the lab - if you want to know the place, it’s the cupboard under the sink, the one to the left, wrapped in a see-through bag. They’ll probably be okay to wear by now, so long as their owner’s feet haven’t grown...