At Last! Keeping a Competitive Edge in Science As I See It

Summer 2007

How do proteins fold in cells? The potential of chiral surfaces Synthetic success — at last! Keeping a competitive edge in science As I see it...

The UK pharmaceutical industry is, historically, a big success story for chemistry. Sarah Houlton talks to Richard Barker, director general of the Association of the British Pharmaceutical Industry , about competitiveness, government support and what the future holds for the sector

How did you end up working in the or psychologists with people who could do of the pipeline in 10 to 12 years. This is not get - pharmaceutical industry? molecular biology. Our impression is that the ting any easier. I’m a chemist by background, and my DPhil in number of molecular biologists hasn’t risen at What that means is that we’re very interested biological NMR taught me that the most inter - all in recent years. So if we’re really going to see in any technology that will help predict which esting chemical problems are actually in biol - bioscience as a major driver of economic medicines will succeed and which will fail – ogy, and the greatest potential for technology is growth and prosperity in this country in the predictive medicine techniques like biomarkers in addressing the problems of biology in med - next decades we need to address these issues. and bioimaging are going to be increasingly icine. I continue to believe that is the case – We will be approaching both of the two used to winnow down the potentially viable some of the most fascinating science is to be departments who deal with education in the clinical candidates in the early stages. done in biology and medicine. Whether this newly reformed government to ensure that they It will also be used to understand how the produces chemical drugs or biological drugs is understand not only what industry needs but medicines actually work, which I’m pleased to less important when you’ve the skill to be able what we understand the broader society needs. see with my NMR background! We’re going full to identify the structures of biological macro - circle: now NMR is being used in the form of molecules, and how they fit with the other What is the industry doing to ensure MRI to study how the blood flow in the brain is macromolecules or small molecules. We need its future success? modified by psychoactive drugs and how con - the ability to unravel the very complex systems Whatever you may read in the press, the indus - jugated antibodies reach active sites in the body, biology that is the cell and that is you and me. try continues to invest in very exciting research, for example. We are now able to do this by and is increasing the number of molecules in using chemical techniques and marrying them What needs to be done if the UK is to the pipeline – it’s up around 4,000 in the past with biology. keep its competitive edge in science? five years. For example, there are very many dif - I believe it’s very important to continue the ferent innovative potential cancer medicines in Does the industry get enough support flow of people studying hard sciences – chem - the pipeline. If people read that the pharma from government? istry, physics and mathematics – and at the ABPI industry is only doing minor modifications of I believe that the UK government, unlike many we are extremely determined to keep the pres - the successful drugs that we already have, then others, actually has a quite a positive view of sure on government to ensure we have a good that’s not borne out by the facts. what the industry brings to the country. It flow of high quality, practically skilled physical It’s also probably worth remembering that contributes billions of pounds to the economy: scientists coming through. the process of bringing the new medicines to last year we exported £4.2bn of medicines, We have, therefore, been very concerned the patient is an extremely long and uncertain more than we imported, but even more impor - about closures of chemistry departments. We one that requires huge investments – recent tantly we employ about 75,000 highly skilled also want to make sure that when the govern - numbers suggest it’s about £500m per medi - people, and about 250,000 others alongside ment publishes positive-looking figures of the cine. It’s so high as those that succeed also have them providing support. So I think the govern - number of newly qualified biologists, they’re to pay for those that drop out: we might start ment is smart enough to know that, in eco - not confusing people who are sports scientists with 5,000 to 10,000 molecules to get one out nomic terms, the industry has a huge contribu - tion to make. Thus far we have seen that, too, in a quite light touch regulation of prices. The Education: Education: Studied chemistry at CV Richard Barker Pharmaceutical Price Regulation Scheme, which Oxford before moving into biochemistry for sets prices, will evolve over the coming years, but we believe it’s a very sound basis for the a DPhil in biological NMR. This was pricing of most medicines. followed by a year’s postdoc in Munich, and But the area that as a society need to think a second in Leeds. hard about is the value of medicines and how we address the value of medicines. The National Career: After a spell working in the oil Institute for Clinical Excellence in England, and industry for Esso Petroleum, he spent 12 the Scottish Medicines Consortium in Wales, years with McKinsey as a management provide assessments that are often regarded by consultant, ultimately heading up its the health economics community and the pub - healthcare business in Europe. He moved to lic as a precise and objective science. But it can - not be: you cannot measure the suffering some - IBM to run its healthcare business, and one has from a disease and therefore the value relocated to the US. After a decade with of relieving that suffering narrowly in the way IBM, he moved into pharma with Chiron, that they do, using the cost per quality adjusted then a couple of early stage companies. He life year to quantify it. returned to the UK three years ago to the I think we need a very broad debate in soci - ety on how we should put a value on medicine. role of director general at ABPI. We recognise that the government and the NHS Interests: Richard loves the outdoors, have to use rationing to some extent as there is particularly walking in some of the more more medicine and more health intervention mountainous regions of the world, than we’ve got money to pay for. But we think we’ve got plenty of room to be able to be more including the Alps, Rockies, Andes and sophisticated and more thoughtful about the Himalayas. ‘I love to get a nice lungful of way health technologies are evaluated, and thin fresh air!’ ensure that the right patient gets the right med - icine at the right time.

2 Chem@Cam Summer 2007 Reluctant reactions Letters

Tomorrow’s chemists

Dear Editor I was fortunate enough to attend this year’s Chemistry open day in March, and I was really impressed with what I saw. It was wonderful to see hundreds of children carrying out chemistry experiments, and the enthusiasm of the students supervising them. The depart - ment is also extremely fortunate in hav - ing such a brilliant science communica - tor as Peter Wothers, whose talk really brought the chemistry of gases to life. It is also very important that they also got to see chemistry as a practical sub - ject, at a time when lessons including wet chemistry experiments are declin - ing in schools, and even in the early stages of some university courses. Poetic licence dle of the lecture. I recall that Dr Sugden The concerns about the numbers of was also very amused. young people studying science are I took Part II chemistry in 1963-4 growing in industry. If there are insuffi - Dear Editor and attended lectures from many of the cient good young chemists being The limerick which was quoted in the familiar names who have received trained, then in future we will struggle article ‘Preserving the chemical past’ recent mention in Chem@Cam . to fill our labs, and drug discovery will relating to Lord Todd in the Spring After Cambridge, I studied for a go the same way as much of the rest of 2007 edition of Chem@Cam reminded DPhil at Sussex. The chemistry depart - industry and increasingly be done in me of another amusing verse associated ment was a very new then and had places like India and China where the with chemistry at Cambridge. attracted several academic staff from universities are producing large num - Dr Sugden was lecturing on the Cambridge as well as Oxford and other bers of well-trained chemists. infrared spectroscopy of gases to a UK universities. My research supervisor For the pharmaceutical industry to physical chemistry group in the early was Colin Banwell, who had been a stu - survive in the UK, we need to ensure 1960s. On one of the blackboards, dent of Norman Sheppard. that our children are enthused about which was initially hidden from view, Soon after I started there, John chemistry. Events like the open day at someone had written in large bold Murrell brought his theoretical chem - Cambridge which show that chemistry chalk (with apologies to Lewis Carroll): istry group down from Sheffield. Ruth is fun are extremely important if chil - The time has come, the walrus said, Lynden-Bell was also there. I always dren are to be encouraged to study the To talk of many things look forward with particular interest to subject instead of the ‘easier’ options of delta J’s and delta n’s reading about chemistry at Lensfield that are growing in popularity at the and spectral lines with wings. Road in the late 50s early 60s in your expense of vital subjects like chemistry. Those who remember both Dr Sugden Alumni section. and their spectroscopy will readily Yours sincerely appreciate the gales of laughter which Kind regards, Tony Wood, vice-president and greeted the sudden appearance of this John Fleming head of discovery chemistry, verse when it was revealed in the mid - Chertsey, Surrey Pfizer Group R&D, Sandwich, Kent

Cover This newsletter is published three times a year by the University of Cambridge Chemistry Department. Opinions are not necessarily those of the editor, the department, or the university. Editor-in-Chief: Steve Ley Editor: Sarah Houlton Photographers: John Holman, Nathan Pitt, Caroline Hancox Contents Editorial Board: Brian Crysell, Jonathan Goodman, News 4 Rosemary Ley, Jeremy Sanders Address: Research 7 Chem@Cam , Department of Chemistry, Julia Parker, from Stuart Clarke’s University of Cambridge, Lensﬁeld Road Alumni 13 group, at work in the BP Institute Cambridge CB2 1EW Phone: 01223 763865 e-mail: [email protected] Chat lines 15 website: www.ch.cam.ac.uk Puzzle corner 18 Photograph: This publication is supported by Nathan Pitt and Caroline Hancox Cambridge University Press

Chem@Cam Summer 2007 3 News

Three of the distinguished t t i

lecturers who have visited P

the department recently… a h

The chemists’ league t

Melville lecturer David a N

Tirrell from Caltech, who s

Klinowski and Jeremy Sanders have an o t

spoke about non-canonical o

h-index of 51. h amino acids in P Two chemists who left us recently are macromolecular design, also there: Andy Holmes, with and Paul evolution and analysis… Raithby. Of the younger generation of Cambridge chemists, David Wales is the closest to making the list, with an h-index of 47. As might be expected for … Merck lecturer Shu Kobayashi from Tokyo a ranking method that relies on volume visited in May, and spoke of publications, quite a few of our about catalytic reactions retired chemists feature in the list, too. in aqueous media… Dudley Williams, with a h-index of 76, is the highest ranked of these, closely followed by Jack Lewis on 74 and Nick Alan Fersht – highest Cambridge chemist… Handy with 71. Ray Freeman, Brian Johnson, David Buckingham, Olga Several Cambridge chemists feature in a Kennard and Alan Battersby all scored at new ‘league table’. Compiled by Henry least 50 too. Schaefer and Amy Peterson at the You can peruse the full list at University of Georgia, it ranks chemists www.rsc.org/chemistryworld/News/ by h-index score. 2007/April/23040701.asp …and Fraser Stoddart, director of the California The highest ranked is Alan Fersht, in NanoSystems Institute 14th place, who also has the distinction and Fred Kavli Chair of of being the British chemist who is fur - Nanosystems Science at thest up the list. UCLA, who spoke on The h-index was devised by physicist molecular memories Jorge Hirsch in 2005 as a measure of research impact. The h-index is the number of papers a scientist has pub - lished that have been cited at least that number of times. So Alan’s h-index score of 97 means that he’s published 97 papers that have each been cited at least 97 times. Several other Cambridge chemists also feature on the list of those with an Salters students’ success The Impington t h-index of at least 50. Chris Dobson t Village College i P

weighs in with 86, Dave King’s score is team dressed and n a h 58, Steve Ley’s 53, and both Jack …with Chris Dobson not far behind ready for action t a N

: o t o h Chemistry’s part in Science Festival award P The Cambridge Science Festival – of which our Open Day festivities are a part – won the prestigious Public Body Award from the Directory of Social Change. This is the first time the DSC awards have been made. Just after the department open day in The award was given to the festival for March, we hosted a group of school its work with the community to achieve students as part of the Salters’ Festival of shared social change objectives. The Chemistry. This is the third year in a row three shortlisted nominees were voted we;ve taken part, and 20 teams of four on by charity professionals and the gen - kids from year 8 or 9 came to do some eral public, and Cambridge romped chemistry in our teaching labs. home with more than half the votes. ‘It’s a competition, and they did two ‘We’re absolutely delighted to receive experiments,’ explains organiser James the award, and very pleased to be Keeler. ‘One of the experiments we inspiring the next generation of scien - devised ourselves, and it involved col - tists,’ says Nicola Buckley, the univer - umn chromatograpy. It was really quite sity’s festivals and outreach coordinator. complex, as they had to pack, load, run The prize included a cartoon drawn and collect fractions from the column. specially for the winner from photos Those who did it well were amazing.’ submitted by the university. Eagle-eyed The day finished with Peter Wother’s readers will be able to spot the rather ‘It’s a Gas!’ lecture which, once again, Not just a flash in the fine likeness of Peter Wothers in action! was rapturously received. pan – Peter Wothers blows things up in cartoon style

4 Chem@Cam Summer 2007 www.ch.cam.ac.uk

Computational developments Winning experiments

At this year’s Open Day, we sent two t t i P

The computer ofﬁcers have plenty of panels of highly qualiﬁed judges n a news to report, with both new people around all the activities, and asked them h t a

and new services appearing in recent to judge each activity for their presenta - N

: s months. First of all, there are two new tion, content and fun. o t o computer officers: Philip Marsden and The scoring was remarkably close in h Greg Willatt. the end but the winners were clear cut. P Philip has actually been around in the First prizes of champagne and a £100 department for a while, having finished voucher went to Jen Ryder and the Blue his PhD with Bobby Glen in 2006, and Goo group from the Unilever Centre, spending the past year on a temporary and Joel Gustafsson and the Lambert contract as a computer officer in the group for Going Cryobananas. Unilever Centre. He’s now on a full- Champagne and £50 vouchers went time contract, mainly focusing on to those in second place: Nick Johnson Windows admin, and is currently and the Klenerman group for the mar - implementing an active directory vellously messy cornflour slime, and domain in the Unilever. Jessops’ Paul Franklyn for Cambridge Greg, meanwhile, joins us from BT, First prize winners Jen Ryder (above) and Joel Gustafsson (below) Blue Prints. and is working in the Unilever and the collecting their champagne from Head of Department Bill Jones Those in third place also got cham - theoretical sector, supporting users with pagne: Alistair Boyer and the Ley group hardware and software problems. for chemiluminescence, and Lech- The Windows active directory system Gustav Milrov and the Market Gardeners that’s being developed and expanded in for the fruit & veg batteries. the department has big advantages for Thanks must go to our fantastic jun - those involved in collaborative work. In ior judges, Rosie (13), Georgie (13), the Unilever, however, it’s being taken a Hugh (9) and Toby (9), and their some - step further. There will be centralised what more aged helpers, Stuart Clarke file storage and common file shares and Brian Johnson. across research groups, increased secu - In addition, the organisers gave RSC rity, and standard software packages like books to several people, in recognition Office will be deployed over the net - of their efforts: Silvia Gonzalez and Tom work so if it becomes corrupted it will Anderson for supervising the molecular be repaired or reinstalled automatically. models, Louise O’Brien, who designed And if the worst happens, it will be the element trail, and Chris Mitchell for faster to recover broken machines. his services to Open Day over the past ‘This will all result in less time being three years. spent by us fixing machines,’ claims computer officer Mike Rose. ‘This will lead to happy computer officers with more time to work on projects benefi - Olga’s A little golden artwork cial to the rest of the department. And award many of the active domain develop - The scanning tunnelling microscope ments will be adoped department-wide Congratulations image, showing gold nano-clusters in the future.’ to Olga Kennard, embedded in islands of nitrogen diox - New software is available, too. founding ide on a Au{111} surface at 77K. director of the Chemistry is paying for a university- ‘When NO 2 adsorbs on this surface, it wide licence for Hyperchem, and we Cambridge forms islands,’ Stephen explains. Neigh - have led the negotiations for a three- Crystallographic bouring islands are arranged in a meso - year site licence across 13 departments Data Centre, scopically ordered fashion as a result of for Mathematica. who has been the interaction of their stress fields and ‘It’s expensive commercial software awarded the the pre-existing “herringbone” recon - that is very broad, and provides a sys - Gmelin-Beilstein struction pattern of the Au{111} surface. tematic interface to all sorts of compu - Medal by ‘When the islands grow to a certain tations, from traditional numeric and the German size, they start to lift the reconstruction, symbolic computation to data format Chemical “squeezing out” excess gold atoms in conversion, and the creation of user Society for her what we term a massively cooperative interfaces,’ Mike explains. contributions to restructuring process, involving con - Meanwhile, there has been an open- chemical infor - certed motion of around 100 Au atoms. access wireless network up and running matics. She will The ejected atoms aggregate into a around the department for a few be presented Artwork from the King group featured string of nano-clusters, each containing months now. with the award prominently in Angewandte Chemie four to five gold atoms, marking the ‘It’s aimed at visitors and confer - at the Third earlier this year. The image, illustrating a positions at which they were ejected.’ ences, and is available in the Cybercafe, German paper by Stephen Driver, Tianfu Zhang Stephen, Dave and first-year PhD stu - library, Unilever Centre offices and the Conference on and Dave King entitled ‘Massively coop - dent Mary Ross, in partnership with BP theoretical sector,’ Mike says. ‘Access Chemical erative adsorbate-induced surface Alternative Energy, are now starting to to the open-access wireless network Informatics in restructuring and nanocluster forma - explore the potential catalytic reactivity is, as it says on the tin, absolutely open November tion’, was used as a Frontispiece image. of these Au nano-clusters in a series of and unrestricted.’ ‘It’s nearly a front cover!’ says Stephen. follow-up experiments.

Chem@Cam Summer 2007 5 News Recognition for Richard Two more prizes for Steve

Richard Layﬁeld: ‘shocked and stunned’

Steve was presented Steve Ley has another couple of addi - with the ACS tions to his collection of awards. He Richard Layfield has been awarded the ‘I was shocked and stunned when I award by John picked up the American Chemical Meldola Medal by the Royal Society of heard I was getting the medal!’ Richard Chan of sponsors Society’s award for creative work in Chemistry. The medal is given every year says. ‘I’d completely forgotten about the Sigma Aldrich (left) synthetic organic chemistry in Chicago to British chemists under the age of application for it. But it’s really nice and ACS president back in March, the first Brit to be given 32 for ‘promising original investigations to get external recognition of my work Catherine Hunt the annual prize since his former in chemistry’. like this.’ postdoc supervisor Derek Barton won it Richard is being honoured for his Sadly, however, Richard is leaving us in 1989. ‘innovative and imaginative contribu - for pastures new – after eight happy Then, in June, he was given the Paul tions to the organometallic chemistry of years in the department he’s off to take Karrer Gold Medal by the University of magnesium and manganese’. It will be up a lectureship in inorganic chemistry Zürich. This is given every year in hon - presented at a ceremony in November, at Manchester this autumn. Having our of the former Zürich professor, and and as part of the prize, Richard is grown up as a die-hard Leeds United Steve won for his contributions to attending this year’s IUPAC general fan, he claims he’s extremely glad his chemical synthesis as related to natural assembly in Turin. office looks east over the Pennines… and biologically active molecules. Jonathan joins inorganic sector Academic ing his group of students and postdocs promotions… from Geneva to Cambridge over the fol - lowing few months. Chemistry was very successful in this His group studies self-assembly in year’s round of university senior aca - water, creating remarkably complex and demic promotions. beautiful structures from simple inor - As of 1 October, four of our scientists ganic and organic components. Jeremy will take up personal chairs: Shankar Sanders – recently promoted to head of Balasubramanian, Wilhelm Huck, Bill inorganic – says, ‘We are all delighted by Jones and David Klenerman. Jonathan’s appointment and look for - Jane Clarke will also become a reader ward to working with him. We also on the same date, funded by the greatly appreciate Eric Walters’ generous Wellcome Trust. Congratulations to all. donation of a Next Generation Fellowship which has enabled us to …and departures recruit Jonathan and his group.’ Jonathan explains that the NGF will Two of our research fellows are moving make getting his group up and running on to pastures new to further their Jonathan’s getting The department has appointed Jonathan in Cambridge much easier and quicker. independent research careers. a helping hand in Nitschke to a university lectureship in ‘It means I’ll avoid losing momentum in Julian Huppert, a former student of his impending move inorganic chemistry, and to a Next my current research programme,’ he Shankar Balasubramanian and currently to Cambridge Generation Fellowship funded by the says. ‘It will allow me to pay for a post - a research fellow at Trinity, has been Walters-Kundert Charitable Trust. grad student and a postdoc to come appointed to a Research Councils UK Jonathan, who is American, obtained with me from Geneva; had this not been Fellowship, leading to a lectureship, in his PhD in organometallic chemistry possible, it would have taken a long time computational biology in the physics with Don Tilley at Berkeley, and was a to recover from losing them! It also department here in Cambridge. postdoctoral fellow with Jean-Marie means I’ll be able to replace kit that I And Michal Sharon, Dorothy Lehn in Strasbourg for two years before have to leave behind. I’m sincerely Hodgkin research fellow with Carol moving to a junior faculty position in grateful to Eric and I’m really looking Robinson, has been appointed to a lec - Geneva in 2003. He will be taking up forward to continuing my academic tureship at the Weizmann Institute in his post from 1 October, gradually mov - adventure in Cambridge.’ Israel. We wish them both all the best.

6 Chem@Cam Summer 2007 Research

It’s taken more than two decades, but Steve Ley’s group has finally completed the total synthesis of the insect antifeedant azadirachtin, a world first. A long time coming The project, started during Steve’s time at Imperial College and continued in Cambridge when he moved here back in 1992, has taxed more than 40 PhD students and postdocs over the years. Azadirachtin has been a target for total synthesis in many research groups around the world for years. The mole - cule is an attractive target partly because of its biological activity, and partly because it’s so fiendishly complicated. It was first isolated from the neem tree in 1968, and it took another 17 years for the correct structure to be elucidated and synthetic efforts to begin in earnest. The neem tree is native to India, and has many uses – its twigs are used as toothpicks, powdered extracts are used for stomach complaints and an oil as a topical antimalarial, for example. It also has very low mammalian toxicity. ‘Its t t i

mystical properties have fascinated peo - P

n ple for centuries, being mentioned way a h t back in ancient Sanskrit writings,’ Steve a N

: says. ‘But the most important is its insect o t o antifeedant activity – azadirachtin h deters insects from feeding. It’s a bit like P a slimming pill for insects! We became best equipment and people to help solve interested in it because we thought we Azadirachtin has taxed many organic these problems. It’s a major achievement might be able to learn a lesson from chemists around the world for 22 years, for UK chemistry, particularly when you nature – if it has learnt how to protect consider how many groups around the itself against predatory insect attack, but Steve Ley’s group has finally world have been looking at the problem.’ then maybe by studying it we might be completed the first total synthesis Steve is a great believer that cham - able to find alternatives to conventional, pagne is the best reward for a successful more toxic insecticides.’ synthesis, and azadirachtin proved such To describe the molecule as compli - allene. This was beautifully set up for a a beast to make that a beast of a bottle cated is something of an understate - radical cyclisation reaction that created was required. So in July the group cele - ment. It has 16 contiguous chiral cen - the right hand side skeleton of the mol - brated the success with a Balthazar of tres, seven of which are tetrasubstituted. ecule, with all the carbon atoms and champagne – that’s 16 bottles in one, or And there is a diverse array of oxygen stereochemistry falling into place. 12 litres. functionality – there’s a reactive enol Along the way, many important dis - ‘This molecule has been one of the ether, a strained coveries have been made, not least that biggest synthetic challenges of my acetal, an epoxide, a fragments of the molecule have career,’ Steve concludes. ‘Many very tal - secondary antifeedant and growth disrupting ented people have worked on the prob - hydroxyl properties. ‘We hope to be lem over the years, and it’s a fantastic group, a cyclic able to use result for all of them that we’ve finally ether, an ester, this tamed it.’ an ace tate, a informa - Michael tion to gen - Born: Stamford, Lincolnshire . acceptor and erate new struc - Status: Married to Rose, who works for him in the a hemiac - tures that mimic department. Their daughter Becky is a molecular etal. ‘It’s a the activity of the natural prod - biologist, and produced Steve’s first grandchild, “who’s who” uct,’ he claims. Eloise, last year y

of oxygen func - The work over the 22 years has also e Education: A chemistry degree from Loughborough, tionality, all in one molecule!’ Steve says. L generated a large number of innovative followed by a PhD there with Harry Heaney They decided to try and make the synthetic solutions to the challenges pre - e v Career: After a postdoc with Leo Paquette at Ohio molecule in two halves, and then join sented by the molecule. Its complexity e the two parts together. ‘It seemed a means extremely selective chemistry is t State, he moved to Imperial College to work for strategically sensible approach, but required. ‘It’s very difﬁcult to make S Derek Barton. He was appointed a lecturer there in maybe it was chemically naïve!’ Steve changes in the presence of such a diverse 1975, made a professor in 1985 and head of department in 1989, and moved to the BP 1702 says. ‘As it turned out, joining the two array of oxygen atoms,’ Steve says. ‘You V fragments proved far from trivial and correct one thing, and then something C chair of chemistry in Cambridge in 1992 resisted all our best efforts, and we had else comes and bites you. Interests: Nice wine, nice food, nice cars and opera. to devise a different strategy.’ ‘And the synthesis wouldn’t have been He also collects Chinese snuff bottles In the end, with the left hand skeleton possible without the advances in mass Did you know? Steve has been known to sleep in in place, they used a Claisen enol ether spectrometry and NMR that have been skips full of autumn leaves, but these days he much rearrangement reaction, with a gold cat - made in recent years, and the depart - prefers ﬁve-star hotels! alyst or microwave heating, to create an ment is fortunate in having some of the

Chem@Cam Summer 2007 7 Research

tionally much more challenging to study – I now know why!’ Sophie is looking at how some larger A fold in time proteins fold, and whether what has been found for the smaller fragments can be applied to them. One protein she’s studying, green fluorescent pro - Most protein folding studies have been carried out in isolation, but tein or GFP, is found in a jellyfish and what happens in real cells, where there are many other interactions? fluoresces green under blue light. ‘We knew before we started that, in compar - That’s one of the questions Sophie Jackson is looking to answer ison to the smaller proteins, there are really large kinetic barriers to folding,’ she says. ‘We’ve been carrying out sin - gle molecule studies in collaboration with Dave Klenerman in the depart - ment. His nanopipette technology is perfect for looking at what’s going on in proteins like this, and GFP is an ideal candidate to study.’ What they’ve managed to do is find direct evidence of intermediate states in the folding process. These states had been inferred from studies on bulk pro - teins, but being able to look at single molecules means they now have proof of precisely what intermediates are formed during the folding process. ‘We’ve also got direct evidence of paral - lel pathways,’ she adds. We collaborate with Peter Hore’s group in Oxford

x using ﬂuorine NMR, and along with the o c n NMR studies we’ve done in the depart - a H ment we’ve managed to identify parts e n i l of the protein that we believe are key to o r a the folding process.’ C

: s GFP has a very complex set of paral - o t o

h lel folding pathways, with large num - P bers of intermediate states. ‘We’ve started off by looking at unfolding Looking back, Sophie Jackson is a little enzyme that eats itself!’ she says. pathways using the single molecule surprised that she ended up a biological Undeterred, she stayed in Alan’s studies, and have managed to find evi - chemist. Studying chemistry at Oxford, group for 18 months after her PhD, and dence that the protein can unfold she even chose quantum chemistry as a after two years with Stuart Schreiber at through some intermediate state,’ supplementary subject. ‘I look back on Harvard, she returned to Cambridge in Sophie says. ‘This is interesting, as most that now and can’t help thinking, with 1995 as a Royal Society University intermediate states are so transient and hindsight, that choosing biochemistry Research Fellow to embark on her inde - unstable that they are impossible to instead would have made more sense!’ pendent research career. ‘I started off observe. But there is a fast-track to she says. ‘But I’d not enjoyed biology at with a protein folding project, and over unfolding, too, so we can look at both school, and it was only in my last year at the past decade it’s branched out in lots routes. It’s been fascinating finding evi - Oxford that I had any exposure to biolog - of different directions,’ she says. ‘In dence of parallel pathways and seeing ical systems. I spent a month isolating the recent years, there has been a lot of intermediate states we otherwise protein plastocyanin from spinach to work on smaller and smaller proteins wouldn’t be able to see, but we’ve also look at electron transfer processes. And I that fold faster and faster. established that it’s a fabulous method - found that I really love research, and that ology to apply to the problem.’ there are so many really amazing biolog - FAST FOLDING Sophie has also been looking at is ical systems out there.’ While there was something of a transat - knotted proteins – proteins where the Having started a PhD at Imperial with lantic battle to find the fastest folding long chain of amino acids has a knot Alan Fersht, after a year she moved with protein, it was actually driven by a desire tied in it. ‘For decades people assumed Alan to Cambridge in 1988. ‘The first to have experimental results on systems that these structures would never exist year was pretty difficult as I had huge that were small enough for computa - because it was one thing to fold a pro - amounts of biochemistry and molecular tional folders to tackle. But many of these tein, but quite another to tie it in a knot,’ biology to learn,’ she recalls. But she proteins are just fragments, and most of she explains. ‘But in the past five years or learnt a huge amount across the two proj - the proteins in our bodies are signifi - so, it has become clear that there are ects she worked on, one of which was cantly larger. So I wondered whether the quite a few proteins that do, in fact, have looking at how a very small protein folds, rules that have been found for these knots in them. We have no idea at the and the other was on the enzyme subtil - small, simple proteins can really be moment why they are knotted and what isin, which is used in washing powder. applied to these larger, more complex kind of functional purpose the knot ‘The process of making subtilisin using systems. There’s a big gap in our knowl - serves, but we are now starting to get Bacillus bacteria is very smelly, and it was edge of how these large proteins with some clues about how they fold.’ hard work trying to measure small complex structures fold, and as these sys - About 300 knotted proteins are changes in biological activity in an tems are experimentally and computa - known so far, and these cover a whole

8 Chem@Cam Summer 2007 www.ch.cam.ac.uk

Born: Preston, Lancashire. She was a premature protein starts to function, and past ity and activity, and there is a linear rela - twin, and her only two months in Preston were spent which further stability doesn’t add a tionship rather than a threshold for n great deal to the activity. Or is it a more activity. ‘We are getting similar results in o in hospital with her brother. They grew up in Cheshire.

s linear relationship where as you cells and in vitro, which is encouraging,

k Education: Studied chemistry at Oxford, followed by

c increase the stability, you increase the because otherwise it would negate all a PhD with Alan Fersht, ﬁrst at Imperial, then a function? Where diseases are caused by the huge number of experiments that

J Cambridge.

misfolded proteins, more than 80% have been carried out in water rather e

i Career: After 18 months postdoc with Alan, she result from stability issues – the protein than in cells!’ she says. ‘I never really h moved to Harvard for two years postdoc with Stuart no longer works because it’s no longer believed it would, but it’s important to p

o Schreiber. She came back to Cambridge as a Royal stable enough to fold.’ be able to prove it.’

S Society University Research Fellow in 1995, and is These kinds of studies are important if Another important area of work in now a Senior Lecturer. we are to be sure that it is fair to translate Sophie’s group is on molecular chaper - Interests: She spends much of her spare time all the knowledge that has been gained ones – proteins that help other proteins V from in vitro studies to the real world in fold correctly. ‘There are many different C engaged in craft-y pursuits. She makes stained glass windows, many of which are presents for friends vivo . ‘Our preliminary studies suggest chaperones in our cells,’ she explains. who are getting married, and the first two she made that there we do indeed see loss of func - ‘We’ve been focusing on HSP90, which were of protein structures! She also makes glass tion for proteins that are very desta - is interesting for many different reasons,’ fusion jewellery. Away from the crafts, she loves bilised, and pretty much normal func - she says. ‘Most chaperones are fairly non- walking, including going on hiking holidays in tion for proteins that are only slightly specific, but this one works on a specific mountainous regions of the world. destabilised,’ she says. subset of client proteins. While these Did you know? Sophie spent last New Year dancing ‘But it’s much more difficult to work in proteins are very diverse in their struc - around a campfire in the Sahara desert with Bedouins. cells than in vitro , because it’s hard to iso - tures and functions, many play critical late what we’re looking at from every - roles in cellular processes. The question thing else that’s going on around it. You is, what is the common feature of all of gamut of different protein types, func - can do the same experiment many times the proteins HSP90 recognises?’ tions and structures, and there are also in the lab and get the same result every several different types of knots. Sophie time, but once you move into cells, they’re ANTITUMOUR ACTIVITY started off with a simple protein YibK, very different from each other, even if There are about 100 of them now, and which is a methyltransferase enzyme they’ve been cultured in vitro . We have to about 90% are associated with cancer, with a trefoil knot, and is trying to work do repeat experiments to get averages of so it’s perhaps unsurprising that the nat - out precisely when in the protein folding behaviour – it’s much more a statistical ural product geldanamycin, which sequence the knot is tied. ‘It’s not that big problem of collecting enough data.’ binds to HSP90, has very potent antitu - a protein, and as well as a lot of kinetic Processes in cells are extremely com - mour activity. ‘If you knock out the analysis we’ve been looking at other plex: the activity that’s being studied activity of HSP90, all of the client pro - members of the same family of proteins may be influenced by many different teins that need it to function stop work - that aren’t knotted,’ she says. ‘We’re factors, such as ions or other proteins. ing,’ Sophie explains. ‘So instead of establishing the fact that it’s possible to ‘You also have to make sure that each of inhibiting one specific cancer-causing unfold and refold a knotted protein in the mutant proteins is expressed to pathway, as many anticancer drugs do, it vitro, and the knot can be retied effi - exactly the same amount, but there knocks out a whole collection of path - ciently, both rapidly and spontaneously.’ that’s an assumption and there may be ways at the same time. It’s becoming clear that proteins have some variability,’ Sophie explains. ‘But ‘It’s interesting how the pharma no problems in knotting themselves. ‘A Sophie and the in vitro, it’s simple to measure exactly industry’s ideas change,’ she adds. mutation in one protein that has been current members how much there is, and you know for ‘Specificity used to be essential, but the found to have a double knot is known of her group – sure when you do experiments that the problem with that is that cancer cells to be associated with Parkinson’s dis - David Pina, concentration is the same.’ have so many different interconnecting ease, so that could be very interesting to Shimobi Onuoha In general, she says, there seems to be pathways they can develop resistance to investigate further,’ she concludes. and Anna Mallam a reasonable correlation between stabil - the drugs. Now several companies have ‘These are completely novel systems, drugs that target HSP90 in development and traditional folding mechanisms because taking it out blocks so many can’t be used to suggest how they fold. different pathways.’ I can’t yet tell you how proteins fold Sophie’s trying to understand some into knots, but we’re carrying out of the basic aspects of HSP90’s structure numerous different experiments and a and function. ‘It’s actually a very com - lot of protein engineering to find out. plex system,’ she says. ‘It doesn’t work Maybe this time next year we’ll have alone, but alongside a whole host of co- more of an idea!’ chaperones, and while it’s beginning to Protein folders have been making become clear what some of these do, measurements on stability and folding for others we still have no idea. in vitro for a couple of decades, but ‘We’ve been combining a number of does all the knowledge they’ve accumu - biophysical techniques, such as mass lated actually translate to what’s hap - spectrometry in conjunction with Carol pening in vivo within cells? ‘It’s a really Robinson’s group, to try and find out important question, but it’s very techni - what’s going on. We’ve been using mass cally challenging,’ Sophie says. ‘We’ve spec, for example, to look at what hap - developed an assay of ubiquitin, a small pens to the whole protein in drug bind - protein that’s extremely widespread, ing. Remarkably, we find there are very and have introduced mutants with dif - long-range effects – there are changes in ferent stabilities to see how stability the shape of the client protein not just at correlates with function. One of the the end of the protein where binding questions we want to ask is whether occurs, but much further away, too. there’s a threshold stability at which the Technically, it’s extremely challenging.’

Chem@Cam Summer 2007 9 Research

also have an effect on the sort of reactions that could happen, as the orientation Asymmetric surfaces could have an influence on whether it can pick up another atom from the surface. So Many industrially important molecules even though deposition of the molecules are chiral – they can exist in two differ - on the surface might not be hugely chi - ent forms, or enantiomers, which are rally selective, the orientation could be mirror images of each other, a bit like a really important.’ pair of hands. A common way of mak - He’s focusing on a small group of ing just one of the two enantiomers molecules to probe these effects, starting involves chiral catalysts, where a metal with two pairs of related molecules – core is attached to a chiral ligand to glycine and alanine, and pyruvic and induce asymmetry in the product. But lactic acids – the first of each pair being what if the surface of the metal itself achiral, the second chiral, and the basic were chiral – could the resulting prod - chemistry of converting the first to the uct be made selectively without any second is well understood. ‘We’ve been chiral ligands? putting these molecules on copper sur - That’s one of the questions Steve faces, and we find there is a very defi - Jenkins is trying to answer with his com - nite triangular binding arrangement, puter models. ‘It would be really useful if with each molecule attached to three we could get a surface to act catalytically copper atoms,’ he says. ‘On achiral sur - x o

in a chirally selective way, either so it c faces, both enantiomers of a chiral mol - n would only react with one enantiomer in a ecule can bind equally well, but on chi - H

e a starting material that is a mixture of n ral surfaces the necessary three-atom i l o both, or perhaps so it would direct a r sites are aligned differently with respect a reaction towards giving more of one C to the two enantiomers. It should have product than the other,’ he says. quite a marked effect.’ The first problem is getting that chi - He’s also started looking at the reac - ral surface in the first place. There are, Could chiral surfaces be used as tion pathway for the conversion of essentially, three ways of doing this. pyruvic acid to lactic acid, calculating One way would be to use a bulk mate - selective chiral catalysts? Steve the energies of the intermediates that rial that is chiral to start with, but the Jenkins is trying to find out are formed on the surface along the range of these materials is very limited, way. ‘At the moment this is being done and typically comprises minerals like on an achiral surface, but eventually we quartz, which aren’t known for their tifying the plane orientation, these are want to do this on a chiral surface as catalytic properties. The second alterna - ‘low index’ surfaces, {100}, {110} and well, in the hope that one enantiomer tive is to take an achiral surface and {111}. More recently, however, interest of lactic acid would be formed prefer - attach chiral molecules to modify its in high index surfaces, such as {421} or entially,’ he says. ‘But the calculations are properties, but for this you need to have {643}, has been growing, driven by the much larger! Other people in the sur - a supply of homochiral modifier mole - knowledge that they have a more com - face chemistry group are doing practi - cules to begin with. plex surface structure, and potentially cal experiments to see whether the cal - It’s the third possibility that Steve surface chirality as well. culations are right, and we’re trying to finds fascinating. ‘What about a material ‘When you cut the crystal at certain point them in the direction of interest - that’s achiral in bulk, but has a surface angles, rows of atoms make up an array ing experiments on the basis of our cal - that is intrinsically chiral?’ he wonders. of parallel steps, forming regular ridges culations. And the next important ques - ‘That would give you access to a much like a sheet of corrugated iron, while tion we’re keen to answer is whether it wider variety of materials, such as the cutting at other angles can create kinks really is possible to use chiral surfaces to transition metals that are familiar as cat - in those steps,’ Steve says. ‘For a while induce chirality in a reaction.’ alysts. It all hinges on the angle at now it has been recognised that these which you slice the crystal, as the structural kinks can be associated with Born: Manchester, but moved to Weston-super-Mare arrangement of atoms on the surface surface chirality, and many people have aged 5, so considers himself a West Country boy varies depending on that angle.’ assumed that kinks and chirality are s Education: Studied theoretical physics at Exeter,

Surface science studies have histori - inextricably linked. Our recent work has n i followed by a PhD there, also in theoretical physics, cally tended to focus upon just a few shown that this is not the case, however, k and a three-year postdoc. He moved to Cambridge – different angles of cut, corresponding as we have identiﬁed surfaces that are n e and into chemistry! – in 1997 as a postdoc with

to simple crystal planes with high sym - chiral without kinks, and others that are J

Dave King, and has been a Royal Society University

metry and low energy. In the Miller kinked without chirality!’ e Research Fellow since 2001. Index notation,which provides a con - Together with colleague Steph Pratt, v e venient three-digit code uniquely iden - he has just completed a comprehensive t Status: Lives in Soham with fiancée Vicky, who’s just analysis of surface structure and sym - S finished an MA in Communication, Media and metry for a number of important crys - Culture at Anglia Ruskin University. tal types, set to be published in Surface Interests: Reading non-fiction – especially history V

Science Reports later this year. C and archaeology. He spends much of the rest of his Steve believes that any chiral catalytic spare time creating raytraced digital art, often selectivity that one of these surfaces will inspired by his scientiﬁc work. He’s also an occasional have will be more subtle than simply one runner, and did a half marathon last year. enantiomer sticking to the surface, and Did you know? Steve once ate 60 packs of Wotsits the other not. ‘What would probably hap - trying to complete a set of collectable freebies, and pen is that the two would both stick, but still goes green at the thought of them more than 20 Chiral surfaces with a kink: D and L {421} in different orientations,’ he says. ‘That dif - years later! are mirror images of each other ference might be detectable, and it might

10 Chem@Cam Summer 2007 www.ch.cam.ac.uk What to do next after a PhD?

The chemistry department organised its optimise our personalities, through first residential Local GradSchool at undertaking the carefully designed tasks Wyboston Lakes conference centre back and activities. It was also an opportunity in April. Over a long weekend, more to try some absolutely new things in a than 50 second and third year postgrads safe environment. I found the person - from across the school of physical alised feedback from tutors and group ciences attended the event. participants to be especially useful. The development of transferable skills He added that attending the weekend is increasingly being seen as an impor - helped him redefine his understanding tant element of a PhD, but the challenges of a career. ‘It is something that every - of completing the research project make body searches for, adapts to, and it difficult for a postgrad to find the time pursues in a quite customised way,’ to stand back and assess where they are he says. ‘It made me recognise the now, and what they want to do next. importance of identifying values deep A GradSchool offers a number of ben - rooted inside us, and how these can efits for participants. It is designed to determine our selection and choice of assess and develop personal effective - careers, and, ultimately our profes - ness, networking and teamwork, com - sional satisfaction.’ munication, and career management He believes the GradSchool was a skills away from the workplace. It allows great opportunity. ‘I was able to identify, the students to identify ways in which measure and organise my energies, gifts they can develop themselves, to see the and skills with vision, in order that I relevance of their skills in different envi - may pursue the right field of interest as ronments, and feel more able to pro - my future career.’ mote themselves and their abilities. Feedback from participants iden - Third year student Muhammad tified that the event had been edu - Khurram Naseem Qureshi was enthusi - cational and a valuable use of time, astic about the weekend. ‘It was some - although it was found very inten - where outside of this world where I sive, undertaken at a fast pace, and views expressed: ‘It was a thor - Khurrum bending identified new dimensions both within run for very long hours over all oughly exhausting experience – but over backwards myself and other fellow participants,’ he four days. I feel a great sense of achievement.’ during one of explains. ‘I discovered how we can all One quote from the feedback Christine Wilson, transferable skills the activities help each other be more self-aware and forms summarised the majority of training programme coordinator The Corporate Associates Scheme

Accelrys Thanks to the generosity of the depart - upcoming events, colloquia, and Insense ment’s Corporate Associates, we have updates about the department; Akubio been able to benefit the education and I Complimentary subscriptions to Jeol environment for students and staff. For Department publications, including Johnson Matthey Amura example, the Associates pay for univer - Chem@Cam; Astex Therapeutics sity-wide access to SciFinder Scholar I Access to emerging Cambridge Kodak and ChemOffice. They also make signifi - research via conferences, special brief - Astra Zeneca cant contributions to the library for ings and various publications; Merck Sharp & Dohme journal subscriptions. Moreover, plans I Priority notification of and free Research Laboratories Biotica are afoot to provide new undergraduate access to departmental research lectures; chemistry exam prizes and new faculty I Ability to hold 'Welcome Stalls' in Novartis Boehringer Ingelheim teaching awards, and the CAS has the department entrance hall; I Pfizer BP funded four summer studentships. Preferential conference rates for Corporate Associate membership not Corporate Associate members; Proctor & Gamble BP Institute only provides essential support for the I Free access to the teaching lectures department, but also provides numer - held within the department; Roche Bristol-Myers Squibb ous benefits to help members work with I The full services of the Corporate us and achieve their business objectives. Relations team to facilitate interaction Shell Global Solutions Cambridge BioTechnology Members enjoy many benefits through with students, staff, and other parts of their enhanced partnership with the the University of Cambridge to help The Society of Cambridge Display Technology Department, such as: achieve your corporate objectives. Chemical Industry

CambridgeSoft I Visibility within the department; If your organisation would be interested Shell Global Solutions Dow I Invitations to recognition days and in joining the Corporate Associates networking events at the department; Scheme, then please email Jane Snaith at Solexa ETRI I Access to the department library [email protected], or call Syngenta and photocopying/printing facilities; 01223 336537. GlaxoSmithKline I Regular communications about We look forward to hearing from you! Unilever

Chem@Cam Summer 2007 11 Science The chemists of the future?

The department was packed with kids for this year’s open day. John Holman, Nathan Pitt and Caroline Hancox were on hand to photograph the fun

A strange white film covered most floors Many of the usual favourite hands-on in the department on the morning of experiments were available. I cannot Monday 19 March. What had happened? mention everyone by name, but the Had the Jones group experiments with cryo bananas show from Joel and the pharmaceutical powders gone wrong? Lambert Group also had an ice-cream Was there a dandruff epidemic? stall where fresh ingredients were con - No, it was the spectacular cornflour verted into a decadent ice-cream with activity at Open Day. Nick Johnson and just the right amount of liquid nitrogen. his team had a swimming pool of corn - And Jen Ryder switched Prussian Blue flour slime to show off the delights of for Blue Goo and with the Unilever polymer science. The swimming pool Group sent hordes of children home was constructed by our own workshops with multicoloured putty. and filled with about 100kg of corn - Open Day would not happen without flour. Nick’s explanation of non- the support of the sponsors. We are Newtonian fluids while walking on again very grateful to Eric Walters and water was nothing short of a miracle. the Walters Kundert Trust for the gener - ous support that underpinned all the IT’S A GAS activities. We also thank Kimberley- Peter Wothers’ lecture this year, It’s a Clark, Fisher Scientific, Cochranes and Gas!, went off like the many flaming the RSC. And thanks to the St.John’s hydrogen balloons used in the demon - Ambulance team who were in atten - stration – spectacular! A DVD of the talk dance, although they had a remarkably will be available in the autumn. boring afternoon. For the first time in New this year was a huge display by the organisers’ collective memory, there the Centre for Atmospheric Science and were no incidents requiring St John’s the British Antarctic Survey, who attendance. Are we 100% safe? Only showed everything from weather bal - through proper risk assessment and... lons to inflatable penguins. Thanks to …and so on to next year’s Open Day, Rebecca and all in CAS for this. Also new which will take place on Saturday 16 this year was the Virtual Zone. Tucked March. Watch out for publicity regard - away in the Unilever Centre, visitors ing new activities and competitions for used computers to visualise molecules, researchers. Details will be announced at the ones that were on display in the www-openday.ch.cam.ac.uk smelly Model Zone. Thanks to Jonathan Around 2000 members of the public Goodman and Ramla Shahid for setting came through our doors, and about 200 this up and proving that virtual chem - students, researchers, staff and academ - istry can be part of these public displays. ics helped out. Thanks to all of you who And thanks to Silvia Gonzalez-Calera worked so hard and brilliantly. Special and Tom Anderson for the fragrant thanks must go to Emma Powney for Model Zone where ball-and-stick mod - her brilliant and hard work in the lead- els of chemicals in everyday smells up to event and on the actual day. (pleasant ones!) could be constructed. Paul Barker

12 Chem@Cam Summer 2007 Science day

Chem@Cam Summer 2007 13 Alumni

The photo of 1960s theoretical chemists in the last Chem@Cam generated lots of name sug - gestions. Here’s the correspondence, and the Theoretical identiﬁcation full collection of names has been collated under the photo. We’re now missing just one, if all our suggestions are accurate – second right on the middle row. There’s also some confusion about whether Bryan Nicholson is in the photo and, if so, which face he is. Any further suggestions would be gratefully received!

Dear Editor, The photo was taken when Christopher Longuet-Higgins had just announced that he was leaving the subject of theoretical chemistry and moving into artificial intelligence. A small conference was organised at Cambridge, of his students and former students, to celebrate his achievements. The date was early 1960s. It might have been summer 1963, or possibly 1965 (I was away in the US on sabbatical for the academic year 1963-64). Many of us presented short papers on our current activities. I have this photo enlarged and framed on my office wall. I myself worked with Christopher as a postdoc for Front row: Andrew Hudson, Mark Child, Ruth Lynden-Bell, John Murrell, Christopher Longuet-Higgins, Lionel Salem, Ian Mills, one year, 1956-57, when I had just returned Bill Dixon, Colin Thomson; Middle row: Robert Lloyd Evans, Terry Miller, Anthony Stone, Alan Carrington, Andrew from two years at the University of Minnesota.) McLachlan, Peter Todd, ???, Bill Jones; Back row: Gavin Currie, Paul Dyer, Douglas Abraham(s?), Steve Graham (or Ted Edgar?) I should be able to provide all the missing names, but of course I am failing at that game, and a rather fetching shirt is Douglas Abraham – Dear Editor, despite being familiar with all the faces. grand master of the Ising model and the like I can throw some light on the Carrington photo However, I can do some. To the left of Anthony and a professor in the department of theoretical identities. I was not there so it wasn’t 1963- Stone is a youthful-looking Terry Miller, now physics in Oxford. 1966, but I remember all but one of them, full professor at Ohio State (he was post-docing He taught me during the year I spent in although I can’t put a name to all of them. It with Alan Carrington, who was a director of Oxford, before I returned to Cambridge to fin - does not look like an annual department photo; research in Cambridge with Longuet-Higgins at ish my PhD with Antony Stone after my Oxford there’s no secretary. Many on the front row had the time). Terry Miller now runs the Columbus supervisor, Charles Coulson, died. left before I arrived, but those at the back over - Conference, the big annual spectroscopy con - Yours sincerely, lapped with me and were there after 1966. ference in the US. Robert Tough On the far left of the front row is Andy To the left of Mark Child is a man who went Hudson, a student of Alan Carrington 1962-65, to the department of chemistry at Canterbury, Dear Editor who postdoced in New Zealand, was a lecturer where he was a lecturer for many years. He did The very tall guy, second from the left, is cer - at Sussex, and is now retired ESR research. He must be retired now. tainly Paul N. Dyer, who graduated with a First At the far right of the front row is Colin Ian Mills, Emeritus Professor of Chemistry in 1965. Best wishes for an excellent magazine. Dixon?, a postdoc with Alan C 63-64?, then a University of Reading Jim Miller, Department of Chemistry, lecturer at St Andrews. He drove an Armstrong- Loughborough University Sidley car in which he survived a serious acci - Dear Editor dent. I think he has since died. I was a student of Colin Reese between 1964–67 Dear Editor, Second left on the middle row is Terry Miller, and remember some of the people in the photo I think that the person at the right on the back a student with Alan Carrington on a Marshal of the department of theoretical chemistry pub - row is Steve Graham. Scholarship from 1965-68, so he went with lished in the latest Chem@Cam (which I find a He was an undergraduate at Queens and Alan to Southampton. He’s now a professor at very interesting read, even though chemistry no became a PhD student in about 1963. Ohio State, where he runs the annual Columbus longer plays any part in my life). Stu Whittington, Department of Chemistry, Spectroscopy conference. In the middle row on the left is Robert Lloyd University of Toronto Third from the right of the middle row is Evans who published some work on string the - Peter Todd, a student of Alan Carrington 1961- ory after he left Cambridge. In the middle wear - Dear Editor, 64, who I think went to work at Esso in Cheshire ing glasses is Bryan Nicholson who gained a As the ? in the front row next to Mark Child, I On the left of the back row is Gavin Currie, a Fellowship at Trinity College and studied at can identify a few more of the people in the student of Alan C, 1965-68?, in Cambridge and Harvard (I think). He is no longer in chemistry. photograph. At the other end of the front row Southampton? He drove a Morris Minor, post - Now for a few guesses. On the right of the beyond Ian Mills are Bill Dixon and Colin doced at NRC Ottawa, and then worked for back row is probably Ted Edgar, and to his right Thomson. Peter Todd is next to Andrew Statistics Canada, possibly on the build up to the is possibly Douglas Abrams. McLachlan. The photograph was taken at a sym - Montreal Olympics The picture will have been taken between posium held to mark the move of Christopher Next to him is Paul Dyer, a student of Alan C 1964–67 because Robert shared a flat with me Longuet-Higgins from Cambridge to 1965-68, at Cambridge and Southampton. And during our time at Cambridge. Edinburgh. It was probably taken in 1967 – it next to him is Douglas Abrahams, a statistical Keep up the good work on the magazine! was after I took up an appointment at the mechanician, subsequently a lecturer at Oxford. Yours sincerely University of Sussex in 1966. Some of us in the The name of the last person on the right David Martin, Marple Bridge, Stockport photo met up again many years later at the escapes me, but he worked with Christopher in memorial Service held for Christopher the molecular symmetry group, and may have Dear Editor, Longuet-Higgins in Brighton. gone to Africa after his PhD. I can identify one of the back row of the theo - Yours Best wishes retical group on page 13 of the spring 2007 Andrew Hudson Richard Moss issue. The young man with glasses, dark hair Piltdown, East Sussex Penrith, Cumbria

14 Chem@Cam Summer 2007 Chat lines

Some of the photos Regular readers of Chem@Cam will are reproduced remember that back in Autumn 2005 we Portraits of the 1950s here; the rest will published an article by Antony be published in the Barrington Brown about the iconic pho - After only a brief time with Esso leges, and also some scientists individually, next issue. While tograph that he took of Crick, Watson and Research as an analytical chemist, I in their place of work. In case you might we know a lot the DNA model. Antony’s been back in returned to Cambridge to set up as a be interested, I’m sending you prints of about some of the contact, with more photos. He writes... photographer in Park Street opposite the some chemists taken in the 1950s. subjects, we’re a ADC. My studio and all the adjoining All my portrait negatives are soon little hazy about a number of the Dear Editor properties were demolished when the going to the National Portrait Gallery. others, and would You will recall that you kindly published multi-storey carpark was built. Yours sincerely, love to hear from a couple of reminiscences of my time in Much of my photographic work was Antony Barrington Brown anyone who can Cambridge in 1948–51. portraying dons at the behest of their col - Warminster, Wilts tell us more.

Left: Ralph Gilson, taken in 1957. Gilson was Todd’s administrator in Manchester, and moved with him to Cambridge Right: George Kenner, 1953. A porphyrin chemist who went to Liverpool, and enthused Alan Battersby in the subject Far right: B.R. Brown, 1953. A marvellously ﬁlthy labcoat, but who is he?

Far left: J.H. Schulman, 1953. Does anyone know any more about who he is? Left: Morris Sugden, 1953. Physical chemist whose prime interest was in combustion, with a sideline in microwave spectroscopy Right: John Lennard-Jones, theoretical chemist famous for the Lennard-Jones potential t t i P n a It’s a very small world… h t a N

: Yusuf Hamied, chairman of Indian drug the plane, and it turned out she was a o t o company Cipla and a former student Cambridge chemist. Not only that, she h P with Lord Todd, is a regular visitor to was extremely complimentary about the department, and generously paid for how great the Todd-Hamied room is for the conversion of cold, uncomfortable having meetings in. Room G19 into the wonderful space On his next Cambridge visit, Yusuf that is the Todd-Hamied room, complete popped in to see how the room was with exhibits about the life and work of looking, and it turned out that Jeremy his former supervisor. had been doing a little detective work. Earlier in the year, Yusuf was back in Armed only with the knowledge that she Cambridge to be inducted into the was a PhD student from India, he’d man - University Guild of Benefactors in aged to determine that the young woman recognition of his donations to both in question was Sunita Kumari, who’s in chemistry and Christ’s. At the ceremony, Shankar Bala subramanian’s group. his wife Farida told Jeremy Sanders an Jeremy arranged for the pair to meet interesting tale – on a recent ﬂight to up in the Todd-Hamied room, and pho - Delhi at Christmas she’d got chatting to tographer Nathan Pitt was on hand to the young woman sitting next to her on record Yusuf’s delight at meeting her.

Chem@Cam Summer 2007 15 Chat lines Nic’s front page fame

my dad and I headed uphill to look at the planes dropping water on the fire to try and control it, and as I’d taken my camera with me I took loads of photos.’ He sent a picture to the Athens News, which his parents get every week, and thought it would be amusing if they spotted his picture in the paper after he’d gone home. They used the dramatic shot of the plane emptying its water on the front page. And yes, it was spotted! He says it was really sad watching the The fires caused devastation, but olive groves burn. ‘An olive tree takes 20 made for some years to become productive, and we dramatic photos could see people’s livelihoods literally going up in smoke,’ he says. When Nic Davies, the technician who runs Greece was incredibly hot while Nic the Part Ib lab, was visiting his parents in was out there – when he arrived at the Greece this summer, he managed to get end of June the temperature was an one of his photos on the front page of the astonishing 47°C! It stayed over 40° for national English language newspaper. the next week, before cooling down to a ‘Greece was on fire for two or three positively chilly 38°. ‘I was really glad to weeks because of the heatwave,’ Nic says. cool down when I got home as it was ‘Fires were raging about 5km from my far too hot for me,’ he says. ‘And I’d for - parents’ house in the Peloponnese, and we gotten what clouds look like – I’d not saw the smoke billowing over the hills. So seen one while I was out there!’

Mykola Karabyn says a sad farewell Comings & Oliver Norris David Hadaway to Irene Derungs goings Ernesto Sarah Maslen (William) Prist Catherine Gibbs Ollero, who worked New staff Irma with him in the Sian Bunnage Leavers Kvarinskaite lecture theatres Carlos Davies Anthea Danute Bramford Retired Griksiene Angela Locks Chris Rayner Another little Spring t t i P

n a h t a N

: o t o h P

Smile, please! Thanks to a mix-up by one of Chem@Cam ’s spies, last issue’s report of two boys born on the same day was slightly inaccurate – Tanya Radic’s son Marko was actually born the day before Stuart Mackenzie’s son Fraser. However, it does give us a good This issue’s ‘aaaaaah’ moment comes in Oliver takes a quick excuse for a bonus baby photo. This one the shape of Oliver Spring, son of Dave. snooze before of the marvellously smily Marko was Born on 27 May at the Rosie maternity his next feed taken by photographer John Holman hospital, he weighed in at 7lb 5oz and for his passport. Dave reports that all went well. ‘As Marko’s a New Zealand citizen by Daughter Elizabeth was born in descent, he needed a photo with his August 2005, so Dave and his wife birth certiﬁcate to get into the NZ Lauren are being kept rather busy. ‘He’s books,’ Tanya explains. ‘So it seemed putting on a lot of weight,’ he claims. sensible to get him a passport at the ‘He’s a hungry boy and complains if Marko practises his best cheesy grin same time.’ he’s not being fed every two hours…’

16 Chem@Cam Summer 2007 i ’ i www.ch.cam.ac.uk x o c n a H

e n i l o Fun and games r a C

: s o t o

This year’s sports day was held at the Leys School h playing ﬁelds, with the usual mix of sports like P football, cricket, rounders, boules and croquet. Caroline Hancox had her camera at the ready

Chem@Cam Summer 2007 17 Puzzle corner

£20 prizes are Last issue’s winners on offer for both puzzles. Chemical crossword In case any readers remain bamboo - final letters IMS (familiar as the acronym Send entries Graham Quartley’s latest Chemical zled, the correct answers are: for Intra Model Sets. by email to Crossword produced another fine crop Across: 1. SUPErB; 5. POTaSH; 9. I must now sit quietly in the shade [email protected] of entries. Correct answers came from: PaNdAs; 10. LaScAr; 11. CHeAtS; 13. with a cold compress on my over-heated or by snail mail Michael Aicken (who continued his TiErS; 14. OAr; 15. ReAl; 16. AlKAlINe; brow to recover. to pub theme with one of a hostelry he 19. URn; 21. CoSmOPOLiTaN; 24. Unfortunately for Roger, Chem@Cam , found on holiday in Cornwall), M.W. SUNSHINe; 26. NOWHeRe; 28. BOOTh; Chem@Cam’s normally impeccable Department Pascoe, David Norman, W.G. Roberts, 30. AlGa; 31. GaSbAg; 32. CURbS; 33. archaeological filing system appears to of Chemistry, Peter Keefe (who spotted Chem@Cam ’s ThIn; 34. SAcCHArIn; 35. SLaY; DOWN: have separated the solution from the University of deliberate error – ‘I must be getting old 1. SPaTiAl; 2. UNdEr; 3. PAsS; 4. question... so he’ll have to wait until Cambridge, at 78, as I cannot tell the difference BLaCKSmITh; 5. PArSnIP; 6. TaCO; 7. next time for the correct answer. Anyone Lensfield Road, between SPaNiSH and SPaNiSH!), Jim SHeAr; 8. HAt; 12. STeRn; 15. else have any further suggestions, or are Cambridge Dunn, Clifford Price (who claims it ReInSTiGaTe; 16. AlCoHOLiC; 17. you all stumped? helped to while away a long trans- AlONe; 18. NeON; 19. UNHeAlThY; 20. Atlantic flight, a joint effort from the BiNBAgS; 22. LiONeSS; 23. TaW; 25. SO; Walker family of Bovey Tracey, Ed Moll, 27. ReGaIn; 29. BrUIn; 32. CAr. Reginald Lewis (who says that his win in This issue’s puzzles last issue’s Chemdoku prompted a con - Hidden identity temporary of his to write to him – so The ‘Hidden Identity’ problem had Pb Pd Pr there are at least two 80+ year olds read - the entire readership bamboozled. ing the magazine, which at least goes However, we did have this marvellously some way to helping those who only creative contribution from Roger Po P had to learn about 90 elements keep up Duffett. He says: to date), John Salthouse (who reports After lateral broodings that have Po Pu that he’s now retired but was up at caused me to dip into areas of my sub - Cambridge from 1959–65, doing his conscious that I have not visited for PhD from 1925–65 under the supervi - some time, I wish to submit for your Pa P Pu Po Pb sion of Tom Waddington, before moving delectation the following solution. with him to Warwick, and then put in 30 It is evident that the noun that Pt Pr years as a lecturer/senior lecturer at emerges from the progression from HI Manchester), J. Billingsley, Bill Collier to LO is associated with an allusion to he Pt (who sais, ‘What a delightful crossword, Fall of Man‚ as described in Genesis and what a pleasant change from the Chapter 3 verse 24. Times Jumbo! My daughter – also a ‘So He drove out the man; and He Pb Pa chemist – and I had a good chuckle over placed at the east of the garden of Eden some of the answers), Paul Littlewood, Cherubims, and a flaming sword Pa Pu Richard Brown (who answered whirling around to guard the way of the Chem@Cam ’s plea for nice postcards tree of life.’ and sent in one of a stained glass win - As a stranger to the nuances of Po Pa Pt Pd dow), Richard Moss, Keith Parsons, Tom Cambridge politics, I can neither iden - Banfield, Ian Potts (who claims it was tify the man who has fallen from grace It’s back to the old Chemdoku this elementary only in the chemical sense), nor the constituents of the angelic host. month, only this time it’s been set by Paul Stickland (who claims Trinity 1951 However, the 9-letter noun is undoubt - Keith Parsons, which rather saves and hence must be another of our septu - edly Cherubims, even though the Chem@Cam the bother of devising one agenarian readers), John Malone, John Hebrew plural formation does not actu - herself. Keith calls his puzzle Pseudoku, Carpenter, David Thompson (who says ally permit this word. Nevertheless, and the nine chemical elements whose he’s been in the fertiliser industry ever English speakers frequently use it in symbols start with P (hence the P) are since he left St John’s in 1964, Roger preference to Cherubs‚ which has a to be arranged in the grid such that, Duffett, Annette Quartly (who says she’s slightly erotic connotation, or with an extra (hence the E) rule, none married to the setter but did it herself!) Cherubim, which seems insufficiently of the elements is repeated along each and Keith Preston. plural to define such a multiplicity of main diagonal, as well as in each row, And the winner is… David Thompson. elevated entities. column and 3x3 square. He adds… ‘5 across caused me some The word is derived as follows. amusement. Potash in the fertiliser busi - SIX AND II are the atomic numbers of Transmutation ness refers to potassium chloride, C and He. Graham Quartly’s back with a transmu - although the analysts still prefer to refer to YOUR LUMINOUS GUIDING CLUE is tation problem. He says: the oxide form in representing the potas - Ru (Ruthenium), an invaluable element We all know the parlour game of sium content, even though the oxide is not in solar technology. changing one word into another by there – t’would be an interesting problem BE ELEMENTARY is a double bluff, changing a letter at a time. This can be to keep potassium oxide in the huge quan - not referring to Beryllium but heard as taken on at a chemical level to turn lead tities that mineral fertilisers are needed in. B (Boron). into gold, viz. I’ve had no end of problems over the years HMM! An inquisitor with a less LEAD – LOAD – GOAD – GOLD. in the business trying to explain to non- labyrinthine mind, or less addicted to The challenge is to turn a chemical ele - chemists what is going on! It is almost as erotic fantasies, would have stopped at ment of more than four letters into bad as trying to explain to a marketing Cherubs. However, his desire for a 9-let - another, by once change of letter at a type why urea only has 46% N – they ask ter noun has caused him to resort to a time, at each stage leaving a valid why we can’t sell the more concentrated paired alignment in a Hidden Markov English word, with no proper nouns form before you dilute it!’ Model (HMM), thereby introducing the allowed. The fastest transmutation wins!

18 Chem@Cam Summer 2007 People in the know

‘I had the task of struggling to look after the very old engines as we travelled Maintaining order around the Mediterranean and other European seas,’ he says. ‘After ﬁve years, and with not much leave to speak of, I decided I wanted to spend more time on Our roving reporter Don Flory talks to senior building service land with my wife, Grace.’ He’d been technician John Palmer about his Irish roots and naval past married for three years, having met his wife at a disco when he was with HMS Sultan in Gosport, where her father was x o

c serving in the Fleet-Air-Arm. By this n a time, they had a year-old daughter Angela H e

n (a son, Michael, was to arrive four years i l o r later), and John felt he couldn’t say no a C

: when Grace asked him to leave the ship. o t o ‘I left the old tug, and we moved to h P Newcastle for a year, the Navy having decided I could spend some time with HMS Exeter, a destroyer that was being built in the Swan Hunter shipyard on Tyneside. My job was as officer’s writer, a sort of secretary aiding the com - mander of the ship,’ he explains. But they were soon heading back south to Gosport, with John back studying at HMS Sultan’s engineering school where, at last, he became fully qualified as an engineering technician. By this time, John had been in the Navy for 11 years – rather more than the four he originally signed up for – but his final three years of service were to prove the most exciting and interesting. Up to then, he had hardly travelled far on the high seas, but his transfer to the It only takes a brief word from John office, and I thought, “What the hell!” engine rooms of the aircraft carrier HMS Palmer to tell you that he hails from the and joined up. At that time, there was Invincible at Portsmouth was to change Emerald Isle, but whether his lively, sea - very little going on in Belfast, and it all that. The ship was home to more than manlike gait indicates years of service seemed there was little hope for the a thousand seamen, and carried dozens in the Navy is debatable! John, the future, and with the conflict in full of aircraft, and John finished his Navy department’s senior building service swing I thought signing on for four days travelling to the Far East, Caribbean technician and maintenance supervisor, years in the Navy would be a way of and Mediterranean, which he describes has worked in Lensfield Road for nearly getting out and starting a new life.’ as a fantastic experience, all paid for by a decade, and his maintenance group John had never been away from home Her Majesty’s Government. now consists of three electricians, two before, so it was with some apprehen - But in 1986, 14 years after signing plumbers and a carpenter. sion that he made the long trek from up, it was time to move on. ‘My daugh - ‘The original parts of the building are Belfast to Plymouth to join a land-based ter was 10 and my son five, and it was a bit of a pain in the backside!’ he says. training centre at HMS Raleigh. After a time for them to have a more stable ‘There are lots of leaks and problems few weeks being instilled with Navy dis - existence,’ he says. ‘I found a job at a like that. But I love working here.’ cipline, he transferred to HMS Sultan, a computer company in Harston near John was born in Belfast and spent land-based engineering school in Cambridge, and managed to get a house his schooldays there, and it was soon Gosport, where he spent six weeks doing in the village under a government hous - after he left school in the late 1960s that basic training and learning something of ing scheme, where we still live.’ the sectarian violence took hold. the workings of naval machinery. But after seven years as its building ‘Luckily for me, I lived in a quieter services technician, the company folded Unionist part of the city, well away from TOUR OF DUTY and he was made redundant. After five the large “no-go” divided estates. dur - His first proper placement, as an engi - years at a local water treatment com - ing the early days of the conflict,’ he neering mechanic, was on an odd- pany, John came to work at Lensfield explains. Nevertheless, it was always looking ship called HMS Blake, a sec - Road in 1998. ‘I really enjoy working in devastating to discover that someone he ond world war destroyer that had been the chemistry department,’ he says. knew had been shot, and especially so converted to take helicopters. After a ‘Every day is different, and I get to meet when four of his old schoolfriends spell on board travelling around the UK so many interesting people.’ were killed in the violence. and the Mediterranean, and a further His activities outside work – three From school, he became an appren - tour of duty on HMS Matapan, a sonar nights at the gym every week aside – are tice fitter at a textile manufacturer in trials ship travelling around the UK, somewhat limited as his wife is now Belfast, but towards the end of this John joined HMS Reclaim. At that time, disabled with rheumatoid arthritis, but apprenticeship he broke his ankle, it was the oldest ship in the Navy – a they now have four grandchildren, being off work for three months before King solver class tug – used as a deep- three boys and a girl. Could it be that being made redundant. ‘I hung around sea diving ship for testing sea-diving John’s tales of life in the Navy will Belfast for six months, then one day I equipment, and which had a diving prompt them one day to follow in their was walking past a Navy recruiting bell and decompression chambers. grandfather’s footsteps?

Chem@Cam Summer 2007 19 Look! I can see the chemistry department from here!

Chem@Cam is written, edited and produced

by S ARAH H OULTON

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