I had lunch with Quentin Crisp the week before he died. We met in the Bowery Bar in Manhattan on the Lower East Side for crab cakes and whisky, and for two hours I sat and gazed in wonder at an old man with mauve hair, the self-styled Stately Homo of England.
Gyles Brandreth, Sunday Telegraph, November 1999
The striking portrait of William Perkin by Arthur Cope, once in Perkin’s home, found its way to the National Portrait Gallery by Trafalgar Square in 1921. But today it is not on display next to Faraday or Darwin or the other eminent Victorian scientists in the little room set aside for them on the first floor. In the postcard rack in the shop, there is no room for him between Samuel Pepys and Beatrix Potter. The painting is in the basement, the receptionists think. In fact, the archivist locates it in a crate in a store-room south of the Thames, where it lives alongside hundreds of other men and women who are no longer trusted to excite the public imagination.
The bulk of Perkin’s life, or at least the material items that have survived it, lie in tissue and plastic envelopes in several large card boxes in another store-room, this one in the lower ground floor of the Museum of Science and Industry in Manchester. The items have been named The Perkin Collection by Peter Crichton Kirkpatrick, one of William Perkin’s grandchildren. For several years they were stored at Zeneca Specialties, the dyes and fine chemicals company established by demerger from ICI, but they moved a few miles to the Manchester museum when its archivist died. The collection contains some of the letters quoted here, some formal photographs, a collection of patent certificates, and some of the medals and citations awarded to Perkin on the big anniversaries. Then there are more unusual items: a slab of stained concrete floor from an unspecified Perkin laboratory (probably at Greenford Green); Perkin’s science lecture notes from the City of London School, written at the age of thirteen; samples of chemicals, dyed cloth and patent seals; a bow-tie worn at the American jubilee banquet at Delmonico’s; and the original 1856 notebook used by Perkin to denote the discovery of mauve. This small book, frayed but still firmly bound, contains the method of preparation of the colour, and some tests upon it. On several pages there are mauve fingerprints.
*
In the centre of a large glass display case on the first-floor landing of the chemistry block at Imperial College students may read a condensed history of their institution. They learn that in 1873 the Royal College of Chemistry moved to the New Science Schools in South Kensington, now the Henry Cole Wing of the Victoria and Albert Museum. This was called the Huxley building, and conditions were so crowded that some lectures were given at the Albert Hall, where students complained about the noise of the organ. It became part of the Royal College of Science in 1890. And the Royal College of Science became part of Imperial College in 1907. The display case contains a picture of Professor Hofmann but not of Perkin.
Beneath this there is an open science journal, undated but firmly rooted in the heart of Victoria’s reign, in which Hofmann presents his ‘Remarks on the Importance of Cultivating Experimental Science in a National Point of View’. It begins:
The present century, so rich in discoveries in every department of science, is more especially remarkable for the amount of human activity displayed and the success attained in the improvement of all material interests of society. The rapidity with which we are advancing in this direction is truly astonishing. Every year is fertile in discoveries in science, and almost every day brings forth some new and useful application of it to the purposes of life. Industry is in a state of perpetual advancement. Arts and manufactures which were supposed to have maintained perfection have been entirely superseded by the discovery of new principles and the introduction of new methods founded on them. It may indeed be safely affirmed that in no previous period in the history of the world has every branch of human industry undergone so thorough a revolution as that which has been affected during the last fifty years.
Three floors up, a 60-year-old man called David Phillips works in an office which contains a model of a sailing ship and several large holograms, including one of himself. Professor Phillips is the head of the chemistry department at Imperial, and in the autumn of 1999 he also became its Hofmann Professor, an enviable title which brought no additional wage but a firm bond with history. ‘They thought I should have his name,’ he explains, ‘even though my expertise is not the same as his was. But I was greatly flattered and gladly accepted.’
Professor Phillips is a physical chemist, which means he’s interested in quantitative aspects of reaction, kinetics and dynamics. Most of his work involves light and lasers. He teaches several courses each term, and has come to realise that while his students are exceptionally bright and motivated, they don’t know much about the history of their subject, which he thinks is a shame. ‘Perkin was one of the greats of chemistry,’ he reasons. ‘Although there is no chair named after him, the college does have a Perkin Laboratory.’
Over the last ten years, Professor Phillips has been involved in the development of dyes for the treatment of cancer. These are dyes injected into the bloodstream of a patient which diffuse throughout the body within a couple of heartbeats. They are then lost through the normal mechanisms – the liver and spleen – and are excreted. But the dyes used are selected because they are selectively retained in tumour tissue. If you wait a couple of days after the injection, there is more dye in a tumour than there will be in the normal surrounding tissue. So then you blast the area with a high-powered laser and, if all goes to plan, destroy the tumour.
The dyes are called phthalocyanines, big plate-like molecules used predominantly as pigments and food dyes. In the 1970s there was a lot of work synthesising the structure of these molecules, experimenting with the introduction of new substituents around the rings.
The dyes are based on molecules that go back to 1913, when a man called Meyer-Betz began experimenting with pigments called porphyrins, widespread throughout nature and in haemoglobin. He injected himself with haematoporphyrins, and then, for reasons best known to himself, went out in sunlight and suffered severe burns (the porphyrins were a sensitising agent in his skin, absorbed sunlight, and fried him). Not much was made of this until it was realised that this action might be applied to cancer treatment by aiming high intensity light into a diseased organ. And it was not until the emergence of very intense diode lasers in the mid-1990s that the beam could be focused down accurately into fibres and inserted into the body.
Professor Phillips strayed into this area when he was working for the detergent company Unilever. The company was interested in developing a cold-water washing powder, a bleaching formulation that would work in the developing world.
‘One of the things that occurred to us was that you could use sunlight,’ Professor Phillips remembers, ‘so we began looking for an additive [a colour-free dye] that became active in sunlight and destroyed the stains. The dye absorbs light, becomes excited and therefore has a lot of excess energy, and the excess energy is transferred to oxygen, which is in the water or the fabric, and it creates an excited state of oxygen called singlet oxygen. This then attacks the chemicals which are in the stain.’
But Unilever was beaten to the market by Procter and Gamble, so Phillips and his team stopped doing that work. ‘But at the time I met a medic who alerted me to the fact that a dye had been announced that had been used for this photo-dynamic therapy of tumours. We wondered, “Wouldn’t it be interesting if our bleaching dye actually had this effect as well?” We got a project going, and it’s been one of those astonishing things that have been successful at every turn.’
Tens of thousands of patients have been treated in this way. The treatment is designed for primary tumours, and as yet is unable to treat rogue cells throughout the body. It is very widely used in ear, nose and throat cancers, and has saved a great amount of brutally disfiguring surgery. When Professor Phillips lectures on this subject he shows his audience some slides of a woman who developed a melanoma on her nose, a patient who would normally require surgery t
o excavate the bridge of her nose and a large part of her cheek; probably she would have lost an eye as well. The new treatment, however, takes half an hour, and after two weeks you cannot find a scar.
Photo-dynamic therapy is very widely used in colon cancer, and has had some success in surface brain tumours – as a cleaning-up process after surgery. The most exciting uses are in pancreatic tumours, where surgery is often considered hopeless. There has also been some success with prostrate and bladder cancers, and with breast tumours.
‘It’s been very satisfying,’ Professor Phillips says. He calls his dye work ‘a novel application of a casual observation’, one of the frequent cases of serendipity in his line of business. ‘I suppose you could draw a parallel with Perkin, who was looking for a medical application and found a dye, while we were working with dyes and found a medical application.’
Recently the emphasis has switched to examining whether a number of other, microbial, diseases might also be susceptible to the same treatment. ‘We’ve shown in a large number of cases involving bacteria and fungi and yeasts that you can deactivate these beasts by adding the dye, irradiate with red light, and you knock these fellows out. We’ve been doing work with a dental hospital, knocking out oral microbes, and knocking out gut microbes in the lab. And you can destroy a lot of viruses this way – including HIV.*
‘Chemistry now is a very dynamic subject,’ Professor Phillips believes. ‘It used to be said, up until about 1986, that chemistry was not exactly dead, but it was felt that we were mopping up. It was felt that there weren’t going to be any spectacular new breakthroughs, and we understood it all; we were filling in bits of knowledge, and then applying it. But then Harry Kroto discovered Buckminsterfullerene [a molecule in which 60 carbon atoms resemble the structure of a geodesic dome], and there’s a whole new family of carbon-based compounds which we didn’t know existed. So chemistry is far from dead.’
In 1999 there were six new companies established on the back of research work at Imperial. ‘It’s a great trend,’ Professor Phillips says. ‘When I arrived here, there were still professors who would throw their hands up in horror if you were too involved in industry. There was this feeling that people who were very good at science shouldn’t dirty their hands. It was believed that that path was only for the second-raters.’
*
In April 1944, eighty-eight years after Perkin’s first failure, Robert Woodward, probably the leading American synthesiser of his generation, finally discovered how to make quinine. It was still the most effective treatment for malaria.
Its formula – C20H24N2O2 – had been identified in 1908 by Paul Rabe at the University of Jena, but only successful synthesis confirmed this formula. The need had never been as pressing as during the Second World War. The Japanese occupied the Dutch East Indies and cut off the main source of quinine, and American troops were suffering. As it turned out, Woodward’s work (and that of his post-doctoral student William von Eggers Doering) proved too complex to be commercially viable – it needed fifteen steps just to reach quinotoxin, one of quinine’s main constituents and the starting point of synthesis. But their work contributed to the formulation of other treatments, and suggested that the eradication of this most persistent of killers was but years away.
The cause of malarial transmission had been identified in 1897, with the aid of synthetic dyes. In Secunderabad, India, the British poet and public health worker Ronald Ross located the malarial parasite in the body of a mosquito that had previously fed on an infected patient. Malaria was found to be caused by four species of protozoan parasites, the most lethal being Plasmodium falciparum. The parasites are transmitted by the saliva of female Anopheles mosquitoes, found primarily in sub-Saharan Africa, and are able to kill within a day of the onset of symptoms.
The first recorded case of a cure by a quinine substitute fell, by accident, to Paul Ehrlich, who found that the methylene blue dye he had used to locate the malaria in a German sailor also eradicated it. But there was no effective laboratory trial to analyse this treatment, and the true era of synthetic anti-malarials began only after the identification of avian malaria (thus enabling controlled tests), and after the disease had ravaged Western armies. The breakthrough came with mepacrine in 1930, a German discovery made after some 14,000 different compounds had been tested to resemble substances close to both methylene blue and the molecular structure of quinine identified by Rabe. The drug was valuable to all sides in the Second World War: chemists at ICI cracked the formula by 1938 and made in the region of 2,000 million tablets annually for soldiers in the Far East. But there were many side effects: mepacrine betrayed its origin as a dyestuff by its yellow colour, and it tended to turn the skin of its users the same shade. New variants soon followed – chloroquine, nivaquine, proguanil and mefloquine (brand name Lariam) – but these too caused side-effects, and in time malaria evolved resistance to them all. In the late 1990s, a new anti-bacterial drug called fosmidomycin was being developed in Germany with promising early results in mice. By analysing the genome of Plasmodium falciparum, a key enzyme may be inhibited; the research is being conducted at Justus Liebig University, Giessen.
Why is this still of concern? There are 300 to 500 million new cases of malaria each year, of which 1.5 to 2.7 million will result in death, most of them children under the age of five. Clearly the control of the disease has been only partially successful, although it is often regarded in the West as yesterday’s complaint.
Several large pharmaceuticals companies face accusations that they care little for most victims of malaria because these people could never afford to pay for the end-product of successful research. But there is much growing evidence that malaria is once again on the rise in Europe and in other areas where it was once considered eradicated. Some blame the increase on the banning of the toxic and environmentally destructive pesticide DDT in the 1970s.
At the beginning of 2000 there were a number of anti-malarial vaccine trials in progress, and one of the most promising emerged at the Naval Medical Research Center at Rockville, Maryland. As in Giessen, the project involves DNA, specifically the DNA of the malaria parasite Plasmodium falciparum, injected into humans. The programme is directed by Captain Steve Hoffman, a specialist in tropical medicine for almost twenty years and a long-standing member of the World Health Organisation’s malaria steering committees. The DNA that he administers is incorporated into the body’s cells. It enters the nucleus, where it is transcribed by the human cell into RNA, which is then transported out of the nucleus and translated into protein. The body then recognises this protein as foreign material, and mounts an immune response against it.
Malaria may just be the beginning; if the DNA vaccine works in principle it may herald similar vaccines against HIV, hepatitis C and other infections. Dr Hoffman’s first proof of protection (in mice) was published in 1994. The first human trials (in twenty volunteers recruited by posters and newspaper advertisements) were published in 1998. A far more complex clinical trial began in January 2000, and three more are planned.
Artificial dyes are employed every step of the way – in the analysis of the Plasmodium chromosome, in blood tests, in the examination of the vaccine results. ‘We use Wright-Giemsa stain for blood smears,’ Dr Hoffman says. ‘We have also used acridine orange for staining and diagnosing malaria in the past.’
Dr Hoffman liked the symmetry his work created with Perkin’s struggle for quinine. Slowly, one Victorian adventure was reaching its intended conclusion.
*
Of all the contemporary uses for synthetic dyes, none would have bemused William Perkin as much as their employment in the detection of crime and infidelity.
In October 1999 the first international conference on forensic human identification took place over three days at the Queen Elizabeth II Conference Centre in Westminster. People leapt up to the podium to address the issues of dye work in scene-of-crime ball-of-foot evidence, the fluctuating value of personal ear-prints, and the DNA identifi
cation of the victims of Swissair Flight 111.
In the exhibition hall, Scott Higgins, European product manager for PE Applied Biosystems, was marketing his human identification products. PE Applied Biosystems is the life sciences division of the Perkin-Elmer Corporation, a company well versed in genetic analysis, molecular diagnostics and microbial identification. PE’s science plays an important role in gene discovery and genetic disease research; the other division of the PE Corporation is Celera Genomics, the private company responsible for the deciphering of the human genetic code.
The basis of the technology is based on dRhodamine gel dyes, a method of separating both proteins and DNA. The company has developed a technology of running fluorescently labelled DNA patterns past a detector, providing a different-coloured peak for each base. As Higgins explained, ‘You had your G, your A, your T and your C (the basic codes of DNA), and each would have a different colour. Red is a T, the black should actually be yellow but it doesn’t print out so well, the A is green, and the C is blue.’
This analysis is used in criminal intelligence databases for generating and storing profiles of suspects. It is also used to analyse stains from crime scenes – any biological substance – blood, semen, hair. The sensitivity of the technology enables it to generate a profile from flakes of skin. It is frequently used in analyses of disaster scenes, and is increasingly employed as a security device. ‘In the United States wealthy people take mouthwash samples of a child,’ Higgins explains. ‘And then if there is a kidnapping that child can be easily identified.’
A less complex forensic home-testing kit with a similar aim has been selling well in Tokyo. Here, wives who suspect their partners of cheating have been able to buy two chemical aerosol sprays that detect the presence of semen in underwear. You use the sprays on the garment one after the other. If fresh semen is present, it will turn bright green.
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