Worm

“Small Worm Makes History” BBC News

‘By 1998, researchers from the Sanger Centre in the UK and the Genome Sequencing Centre at Washington University reported that they had managed to sequence the entire genome of C. elegans.  Although, if you compare their bodies, a worm may not seem to be enough like a human to be of any use, the DNA code of a worm works in a very similar way to the DNA of a human. The same techniques that were used to sequence the worm DNA could be used to sequence the human DNA.’ YourGenome.org

“In a wonderful way, they are like miniature human beings.” Dr John Sulston, Director, Sanger Centre, UK

‘No one ought to feel surprise at much remaining as yet unexplained in regard to the origin of species and varieties, if he makes due allowance for our profound ignorance in regard to the mutual relations of all beings which live around us.’ Charles Darwin, Origin of Species, 1859

‘Small worm makes history - Scientists have taken an historic step forward in unravelling the mysteries of life. Researchers in the UK and the US have mapped all the genes in a small worm called Caenorhabditis elegans. It is the first animal for which this has been done. It has taken 15 years to complete and will have major implications for human health. Most people will never have heard of the creature which grows to about 1mm in length and lives in soil or among rotting plants, but it has much in common with man. Around 40% of the worm's genes - which hold all the instructions to build and maintain the creature - are also found in humans. This means that a study of C. elegans will also reveal much about the biological processes inside humans. C. elegans may be a much simpler lifeform but it also begins life as a single, fertilised cell and undergoes a series of cell divisions as it grows into an adult animal. During this process, it also develops complex tissues and organ systems. It even has a nervous system that can detect odour, taste, and respond to temperature and touch. .. Although it has taken until now to complete the worm genome, there are more than 200 labs around the world already engaged in C. elegans research.’ BBC News, 1998

‘I think there is much more in even the smallest creation of God, should it only be an ant, than wise men think.’ St Teresa of Avila?

“By looking at the genes that are needed to make worm muscles, we can learn quite directly about the genes that make human muscles - because they are the same." Dr John Sulston, Director, Sanger Centre, UK

‘Worm leads the way - Other scientists are in the process of sequencing the genomes of rats, cats, mice and pigs. Several simple organisms such as viruses and bacteria have already had their entire genetic blueprints sequenced. In animal terms, the big breakthrough came last year with the completion of the genome of worm Caenorthabditis elegans, the tiny worm that lives in soil. "C Elegans was the first multi-cellular animal to be sequenced," says Dr Patricia Kuwabara of the UK's Sanger Centre. "In part, it's because it had a small genome. There were also very good researchers who had the vision to see that sequencing an entire organism would lead to a lot of discoveries about basic biology, and may also provide insights into how genes are regulated in vertebrates such as ourselves." The worm's genetic blueprint has already proved useful in the study of the human brain condition Alzheimer’s disease.’ Monise Durrani, BBC Science

Worm, c.elegans

“In a wonderful way, they are like miniature human beings.” Dr John Sulston, Director, Sanger Centre, UK

The first,

as she was the first -

humble worm mother

muscling mud -

opened now

under skin,

her physical seal;

intimate

with her fleshless lettering,  

atomless string

of magic stars,

molecules of radiant chemistry

revealed, strung

shining in darkness,

to become the worm -

man plotting her galaxy.

First to be written,

as she was written first -

our small print,

cypher,

handbag-size;

just us,

simple, limbless,

stripped -

we who stayed in the mud,

leaving all that evolution

to those worm children

who were not at peace,

hearing the volume of the Word

turned up by time.

On sizzling grass I lie -

prickle-blades hissing,

sweating smeary green

blood on fried pink skin;

bury my forehead

at breathing roots -

such mother smell

wanting me to return,

otter to water,

slipping cool,

all belly and muscle,

from hurting sun -

my fingers healing,

feet, fussy dreams.

‘Now the statistics are in, we can see/ how unconvincing our story is…/ No power that claims to be practical/ Would choose to embody itself like this in history./ And yet with a little effort we can work up something/ To prove how likely it all is,/ How suited we are to the sandy soil we spring from,/ To clay or loam, marshy or dry.’ Carl Dennis, Evolution

‘Worm Wins Nobel Prize - Three scientists have been jointly awarded the Nobel Prize for Medicine for their discoveries… All three made discoveries which will prove vital in the understanding of the life of the human cell - be it healthy or cancerous…Their finest work concerns an organism with fewer than 1,000 cells - the nematode worm…When doctors wanted to learn more about what happens to cells in the human body, they soon realised that humans themselves were far too complex to allow doctors to study every single division and differentiation. It was Professor Brenner's brainchild to use the nematode, which, at only 1mm long, and completely transparent, allows easy viewing of every cell division. In 1974, he showed that by adding a chemical compound, gene mutations could be induced in the worm - and that these mutations could have profound impacts on the development of the creature. This is the bedrock of much genetic science today - demonstrating the principle that our genes, if somehow mutated, might have a radical knock-on effect. This is the basis of the Nobel Prize award.’ BBC News

We are called from the Worm

We are called from the Worm -

which charmed itself from earth,

sang crumbs, water molecules;

understanding dark nutrients,

chemistry of the underworld -

writing her characters in mud;

perfecting her simple drawing

of muscle propulsion, impetus.

Small pink word talking compost

into form; our humble flesh-root

nudging, smudging darkness -

laying down her simple bodies

to formulate apes, hands, legs -

men’s eyes, her wildest dreams,

sum of her cultured creativity,

without nubs, stumps, buds -

no dreams wilder, more fantastic

than life’s organic fumblings -

like flowers will come from seed,

Earth systems - chemistry appear

in space - on a lonely planet,

peculiar with water and light.

‘For his own part, having helped to steer the report on the working draft of the human genome through to publication, he (Sulston) plans to return to doing what he always wanted - solving the final few problems that remain in the genome of the nematode worm.’ Georgina Ferry, Wellcome Trust

“RNA interference was first discovered in the obscure nematode worm. RNA plays a crucial role in de-coding information from the genes so that it can be used to build new proteins. But the nematode also uses tiny pieces of RNA to specifically switch off certain rogue genes that would otherwise cause it harm.” Sir Paul Nurse, Chief Executive, Cancer Research UK

‘The Wellcome Trust saw the opportunity to establish a world-class genome sequencing centre in the UK, using the high-throughput approach that the worm project had pioneered. In 1992 they founded the Sanger Centre jointly with the MRC, and invited John Sulston to be its first Director. It meant, among other things, that he could get the worm finished, and in December 1998 he and his colleagues published the complete sequence, the first of a multicellular organism. ‘I was not personally going for the human genome,’ he says. ‘It was more a question of wanting to get genomics going, and then more specifically to study the genome of the worm. But I also believed very strongly that the UK should become involved in large-scale genomics, and so when the opportunity came to head the Sanger Centre and help to make a serious attempt on the human, I was ready for it.” Many features of the worm sequencing project are very much in  evidence in the way Dr Sulston and his colleagues have managed their contribution to the human project. A prime example is…the strong, principled view of data release that the worm project pioneered.’ Wellcome Trust

C.elegans - ‘the elegant worm’

Heron balancing on supermodel legs -   

Leopard modelling couture in languid pose;

Siamese sniffing champagne dregs,

Butterfly balanced on champion rose -

Roe deer picking bound Chinese feet,

Hummingbird supping, blurred on the wing -

Species you could go to the Ritz to meet,

Even if the peacock turned up a bit bling -

But how can you have an ‘elegant’ worm?

Is this another weird scientist joke?

Another strange name just to confirm,

After a few post-lab beers, being a bit of a bloke?

Red in the face, hysterical, tieless,

(Obviously the same kind of mind

That called the gene central for making eyes, ‘eyeless’),

Well, I think it’s unkind - 

Perhaps the worm feels all inadequate -

Like she should be squeezed in a wee Gucci dress,

When single glove fingers are all that would fit -

Mind you, she’s about the right shape, shame about being limbless,

Though she does have the figure all women must strive for,

Would never have problems around the hips,

Is surely what’s in mind for the male designer -

But, alas, could never wear a pair of Manolo Blahniks.

To make matters worse she’s also known

As a ‘model organism’, convenient tool,

To find out how everyone else on earth has grown,

So without a Prada bag probably feels a fool -

And not much can be done about her lack of hair,

Also bosoms, fish-lips, Lopez-butt, ears -

But if you’re looking for midriff she’s got acres to spare,

Even more than Britney Spears.

But maybe our scientist with worms before the eyes,

Saw more in her than blackbird’s lunch -

Living, compact memory, simple streamlined beauty, he sighs,

Sensing the rungs of Science’s ladder; just a hunch.

‘Professor Sulston took Sydney Brenner's work and went further with it. He managed to develop a way of studying every single cell division in the nematode worm. On the way he mapped out the sequence of cell changes and divisions in the developing nervous system of the worm, finding out that this was the same in every single worm. His key find, however, was the fact that certain cells, rather than keeping on dividing forever, simply died at a certain point in the development of the creature. This cell death appeared to be programmed. By looking at a cell on the point of this "apoptosis", or programmed cell death, he was able to map out exactly which genes were involved in this necessary biological process. In particular, he found a gene called nuc-1 which seemed to be vital to the whole process. He found a mutation of nuc-1, in which the cell died - but without the DNA within it being broken down - a key part of the process. This is important because it is the failure of cells to die "properly" at the correct point that it is at the root of many cancers - and the "overenthusiasm" of cells to die which maximises the damage from strokes, Alzheimer's disease or heart attacks. If apoptosis could be initiated within a tumour, or halted around the site of a stroke, then this would be a massive medical breakthrough. Sulston's first sequence of the nematode was in fact the first ever complete genome produced of an animal…Once again, Professor Horvitz built further on the foundations laid by Brenner and Sulston. He found two proper "death genes" - if these were not present, then cells did not die when they should. In addition, he found a third gene which interacted with the other two to protect against cell death. And he made a jump to humans, identifying a gene on the human genome which appeared similar to one of the two "death genes". Further work has discovered that most of the genes involved in cell death in the nematode have their counterpart in the human genome. It is this progression into the human genome which offers promise for treatments which either encourage or protect against cell death.’ BBC News

‘Men have found cells/ sensitive to light in the hearts of snails.’ Ronald Johnson, Beam 4

nuc-1

Simple pink word of Earth Omega -

founded on formula darkness crumbs,

life learning the right time to die;

principle of compost, fruit, seed -

hearing the Alpha of the beginning,

ecstatic full stop written even then.

How the worm has come to understand light -

written pink stars, sisters tiny as the Milky Way;

inhabiting darkness, sparking chemical switches,

igniting earth into feathers and bone, hair, wings -

how could she dream of limbs and fingers -

what thought, spirit, infiltrated her existence.

“I love Cerion [a type of snail] with all my heart and intellect.” Stephen Jay Gould, Research Biologist

‘…a toad has the most beautiful eye of any living creature. It is like gold, or more exactly it is like the golden-coloured semi-precious stone which one sometimes sees in signet-rings, and which I think is called chrysoberyl… I mention the spawning of toads because it is one of the phenomena of spring  which most deeply appeal to me, and because the toad, unlike the skylark and the primrose, has never had much of a boost from the poets.’ George Orwell, The Collected Esssays, Journalism and Letters of George Orwell, Volume 4, 1945-50, Penguin Books, 1970

‘A jewel in your head? Toad,/ you’ve put one in mine,/ a tiny radiance in a dark place.’ Toad, Norman MacCaig 1910-96

‘Dr John Sulston claims that he became Director of the Sanger Center, spearheading the UK’s contribution to large-scale human genome sequencing, only because he couldn’t see how else he would get the funding to finish his real life’s work, the genome sequence of the nematode worm.’ Wellcome Trust

"The approach of shotgun sequencing by the Sanger method and clone-by-clone analysis as developed for the nematode underpins today's announcement. All of genomic biology rests on these foundations - the work with the nematode illuminated the path forward while others were still discussing the route. The complex code of the human requires all to work together - openly, freely, without restriction - if we are to realise the benefits it may bring. This ethos, which stems in part from the researchers who pioneered the field, lives today in the work of the Human Genome Project.” Sir Aaron Klug, OM, President of the Royal Society