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Professor Parry speaks at the Science Hons dinner after being presented with Rutherford Medal by Professor Mary Fowler, Rutherford’s great grand-daughter.

Muscle, hair and skin

Professor David Parry, the winner of the 2008 Rutherford medal, talks to Malcolm Wood about his career spent exploring the structure of proteins.

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Professor David Parry

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The Rutherford Medal

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The entire stock of rubber balls from Woolworths
in Oxford – as Professor Parry puts it – is seen
here as the base components of a model he
and John Squire constructed to show the
regulation of vertebrate skeletal muscle.
The basic mechanism, described by them in
1973, remains undisputed.

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Governor General Dame Silvia Cartwright and
Professor Parry unveil an official portrait of
Maurice Wilkins, New Zealand’s second Nobel
laureate, at Government House on the 50th
anniversary of the seminal work he carried out
into the structure of DNA in 1953. Wilkins was
one of Parry’s doctoral supervisors.

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Professor Parry and his wife at Alpbach in
Austria during some off-time from a workshop
on coiled coils, collagen and co-proteins. He
and John Squire have organised such
workshops every four years since 1993.

For someone who has just entered his retirement years – meaning a two-day working week in this case – Professor David Parry doesn’t look his age.
 
The 2008 Rutherford Medal winner is tall and whippet lean, and it is somehow right that as the world’s authority on the structure of hair (or more particularly keratin, which is its basic constituent) he should himself sport a full head of the stuff. It’s mostly grey admittedly, but then Parry knows professionally from his work with proteins that age will have its way.

But more of that later, for matters scientific are not top of Parry’s mind just now. Rather, he is thinking about the talk he will give when he goes on tour for the Royal Society. Where the tour will take him, he hasn’t been told quite yet, but it is likely to be small-town New Zealand: places where scientists on lecture tours are an uncommon event.

 He’s a bit apprehensive. These will be mixed audiences: some will be drawn to the hard science; others less so. So Parry is setting out to interleave his quite technical science with a more personal account of his own history and of how the world has changed around him in the half century since he began university study.

And it has changed, he muses, almost beyond recognition. Take information technology. Parry remembers the computer he worked with while doing his PhD at King’s College in mid-sixties London, the Elliott 803 (a room-sized machine boasting 8k of memory). “It had green, red and blue lights and they all flashed on and off. The magnetic tapes whirled around and the reader chewed up our precious spools of tape. This was a real computer and not the antiseptic ones we have today.”

Or take international travel. His first postdoctoral fellowship with the CSIRO’s Division of Protein Chemistry in Melbourne (where he met and married his wife and they had their first child) meant spending a month on the sea via the Suez Canal. His next bouts of extended travel were to Boston to work for the Children’s Cancer Research Foundation and Harvard Biophysics Department, then on to Oxford via the QE2 to work for the Laboratory of Molecular Biophysics, and finally to Massey in 1973 to take up a lectureship in physics. The plane travel was not long-haul as we know it, but an extended series of less-than-three-hour hops.

As a boy, Parry could never have foreseen the shape his career would take. In his final school years he had planned to go to Oxford on a maths scholarship, but when his father relocated to London he hurriedly revised his plans. He made a late application to several London University Colleges and was accepted by King’s College to study maths and physics, going on to graduate in 1963 with a job offer in hand: designing ship hulls for the British Scientific Civil Service.
But King’s College intervened once more. New Zealand-born Maurice Wilkins (who had won the Nobel Prize for physiology or medicine the year before for his part in determining the structure of DNA) and his colleague Arthur Elliott were looking for someone to take on a PhD determining the structure of synthetic proteins and polypeptides using the maths-and-physics heavy discipline of x-ray crystallography. Would Parry be interested? He would.

 It was a career-determining choice. He had opted to become a molecular biophysicist, and at a time when breakthroughs such as the solution of the primary structural motifs in proteins (proposed in 1951 by Linus Pauling and colleagues) and the determination of the structure of DNA (described by Watson and Crick in 1953 drawing on the work of Wilkins and Franklin) were relatively recent and the field was largely untilled.

As his Royal Society audiences will learn, Parry swiftly began notching up achievements. Between completing his PhD and arriving at Massey, Parry participated in some seminal work. At Harvard he helped decrypt the structure of the tropomyosin, a cable-like muscle component, and at Oxford he collaborated in assembling the first-ever sequence of the protein collagen (subsequently explaining in an elegantly designed modelling experiment why the sequence led to the collagen-forming bands in the fibrils). He also arrived at the mechanism by which muscles are switched on and off.
The last of these alone would have been enough to make Parry’s name.

At Massey Parry persisted with the line of research he had begun while at the CSIRO. There he had worked on wool proteins, now he would work with hair proteins. But call it wool or hair, it makes no difference, says Parry. In biochemical and structural terms the two are the same thing: a tough, resilient, outer layer that provides temperature regulation and protection from both the environment and predators.

All proteins are built from different combinations of about 20 amino acids. In the case of hair, the structure of keratin is based on the α-helix. This resembles a spiral staircase with amino acids as runners. Two of these structures come together and wind around one another to form a coiled coil rather like a ship’s rope.

One of Parry’s achievements has been to establish that the basis of the coils is a set sequence of seven amino acids – a heptad – broken up by ‘stutters’, ‘stammers’ and ‘skips’, the terms applied when certain predictable numbers of amino acids are missing.

“The heptad repeat is an extremely common feature in a very large number of proteins, but it just wasn’t recognised,” says Parry.

This “delightful simplicity”, as he puts it in one of his papers, means that one day soon it may be possible to bioengineer new forms of coiled coil proteins with biomedical and other applications.

What, then, is the relationship between the keratin in skin and the keratin in hair? At the base of the hair follicle, he explains, the structures of hair and the surrounding skin are virtually identical.

“But as the cells die the hair molecules rearrange themselves, disulphide bonds form, and the thing becomes very stiff and rigid,” Parry explains.

These same disulphide bonds, which form many of the links between the coiled coils, are the reason why burning hair has that distinctive smell, and it is also these bonds that are rearranged when hair is permed.
As for what happens to proteins with age, the news is mostly bad. Parry has collaborated in investigations into the state of horse tendons as they age and has shown that the delicate collagen connective tissues known as fibrils undergo a distinctive change: “In an older horse the fibrils are very small; all the big ones have gone.”

Age brings other unwanted changes too. Tissues, such as the skin, which were plump with lubricating water, become increasingly desiccated as we age, and most – not quite all, he says – of the cosmetic remedies on offer are little more than upmarket forms of grease.

Perhaps the strangest of Parry’s projects has been an investigation of collagen in the cornea of the eye. For the cornea to be transparent, the collagen fibres must have the same diameter and be evenly spaced. But over the years researchers had produced results that showed the diameters of the fibrils varied widely across the species, a result Parry doubted. It must, he thought, be an artefact produced by variations in methodology.

He talked to the veterinary department at the Auckland Zoo and soon strange packages began arriving.
‘Every time an animal died – from natural causes I might say – they would post the eyes to us and we would extract the cornea.”

He rattles off a Noah’s ark of animals: “...salamander, possum, stoat, stingray, hippopotamus...”
“So we treated all these species in the same way and all, except the bony fish, had fibrils of the same size,” he says with amused satisfaction.

“That was an easy piece of work, but quite fun – it is all fun.”

Except when it isn’t. In Parry’s later career, as he increasingly took on responsibilities within the international science community, the amount of travel he had to do became a trial. In 1990 he was elected to the Council of the International Union for Pure and Applied Biophysics, serving for 12 years in roles including vice president and president. In 1999 he was elected to the executive board of the International Council for Science (ICSU) – science’s equivalent of the United Nations – which is headquartered in Paris.

“Initially that meant only one or two meetings a year, but after three years I became vice president and the chair of one of the major subcommittees.”

Six times a year Parry would set aside his duties as head of Massey’s Institute of Fundamental Science to head for the most unromantic return trip to the city of lights. “It really killed me: a day-and-a-half there, a two-day meeting, and then a day-and-a-half back. A miserable existence.” At Massey a backlog of work and correspondence would await his return.

So while more golf, tramping, gardening and family time are on his list of aspirations, more travel isn’t. For the most part it is far more convenient to collaborate electronically, and again Parry marvels at the way things have changed.

“When I came to New Zealand in ’73 if you wanted to collaborate you literally had to write a letter to somebody and it would take a week to get there, and a week there and a week back. Then came faxes, then, at last, e-mails.”

Parry is much sought after as a co-researcher, and not just because of his expertise, he admits.
Being 12 hours out of sync with Europe has its advantages – “I can work while they sleep,” and, besides, there is another pragmatic line of reasoning: “I am not competing for same [nationally-based] pot of money that they are.”

Over the years and in the course of compiling more than 200 published research papers (plus editing and co-authoring a number of books) Parry’s tally of co-authors has topped 250.

“I have been collaborating with someone in Oxford and we just published a paper together.

“Coincidentally, I was at a big conference on intermediate filaments in Oxford later that year, so I got to meet him for the first time. Turns out he is about six foot eight and graduated from Otago.”

How does he feel about the recognition of the importance of fundamental science in New Zealand? It has improved greatly, he says, with it now being more widely recognised by government that successful applied science could not exist without its vibrant sibling.

In his own case, his early work explaining how muscles are triggered has found application in such things as meat processing (electrical stimulation makes for more tender meat) and he has worked with an Auckland-based plastic surgeon to foster techniques to minimise scarring.

But acknowledging the place of fundamental science is not enough in itself. More funding is needed, particularly, he says, for that mainstay for New Zealand science – the Marsden Fund.

As for the Rutherford medal, he knew he had been put in for it, but as a first timer he didn’t rate his chances.
“Most times you need to be there for quite a few years before you become a serious contender, and often you never get to the top of the pile at all.” It must, he says, with genuinely unassuming self deprecation, have been an easy year.

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