Interview with Sir Alec Jeffreys
by Mary Rice
Professor Sir Alec Jeffreys FRS heads the Department of Genetics at the University of Leicester, England, UK. He will be giving the lecture “Processes of allelic and ectopic recombination in the human genome” in the symposium “Cytogenetics” at ESHG 2008 on Sunday, June 1, 2008 at 17.15 hrs.
Professor Jeffreys will describe his current work, which uses single DNA molecule methods to explore patterns and processes of recombination in the human genome, including dynamic analysis of allelic and ectopic exchanges, to understand how recombination impacts on human DNA diversity and on the origin of copy number variation. He talked to Mary Rice about his current and previous work.
“Currently I am looking at instability in human DNA, looking at how changes arise when DNA is transmitted from parent to child – if this didn’t happen we would all be clones of one other. We are trying to understand what kind of processes take place during mutation and recombination and how they impact on genetic diversity. This builds naturally on my previous work on genetic fingerprinting, but scientifically is very much more challenging. We are also analysing mutations caused by external agents such as ionising radiation,” says Alec Jeffreys.
Eureka moments are rare in science, and he remembers his as if it were yesterday. ”It was 9.05 am on Monday 10 September 1984. In the context of studying the genetics of repeat DNA sequences, my technician and I were looking at DNA from members of the same family when we noticed distinctive patterns. Even though we were looking at a smudgy mess, the implications were quite clear. It dawned on us that individual genetic profiles had been revealed and that we could trace the links between family members. We realised that variations in the genetic code could be used to identify individuals.” The rest of the day was spent both thinking about possible uses of the technology and looking to see whether DNA could be recovered from old samples such as blood stains. “I ran round picking my finger and dropping spots of blood all over the place and tested them for DNA when they were dry. The distinctive patterns were still there.”
Jeffreys had discovered genetic fingerprinting, the technique behind DNA identification, possibly the best-known application of molecular genetics. Two or three months later he had managed to transform the “complicated mess” of the first DNA fingerprint into clean patterns where the genetic uniqueness of each individual could be clearly seen. Within weeks of the first publication of his research in Nature, he began to be solicited to use the technique in all kinds of different situations. Until its commercialisation some two years later, Jeffreys’ lab was the only one in the world that could carry out genetic fingerprinting, and he was asked for help to solve all kinds of cases from all over the world.
The use of DNA profiling that has given Jeffreys the greatest pleasure is in immigration cases, where it can be used to show that people belong to the same family and allow parents and children to stay together. “My technician and I had thought about paternity disputes and criminal cases, but when I went home on the evening of the discovery my wife said to me ‘Why not immigration disputes?’ Perhaps my proudest moment was when we used the technique in a disputed immigration case to confirm the identity of a British boy threatened with deportation whose family was originally from Ghana.” The DNA results showed that the boy was indeed a full member of the family. “I saw the family’s reaction and their happiness at the immigration tribunal and it was wonderful.”
The first use of the technique in a criminal case also pleased him. In the English county of Leicestershire, where Jeffreys made the discovery and where he has worked ever since, two young girls were raped and murdered in 1983 and 1986. Semen samples were taken from the bodies and the DNA analysed. The prime suspect was Richard Buckland, a 17 year old local man, who confessed to the second murder under questioning. However, Jeffreys’ analysis of the DNA samples showed that both murders had been carried out by the same man, and that he was not the suspect in custody. Thus Buckland became the first ever person to be exonerated by DNA fingerprinting, and the same technique allowed the real perpetrator to be identified, charged and imprisoned.
Other uses he is less happy with. “I do have significant concerns about recent developments with the UK National DNA Database, on which the profiles of suspects who have been cleared of crimes now remain for life. This is potentially discriminatory, and measures should be taken to ensure that particular groups are not targeted. For example, it is estimated that 40% of all young black men in the UK, many of whom have no criminal record, are on this database, and that is a real concern. In addition, if you are storing the DNA of millions of people, there are bound to be some errors in identification and there is a risk that current procedures using this database to identify suspects would not necessarily trap these errors. When DNA profiling was first commercialised, I was shocked to hear that one of the companies involved was describing the technology as infallible. There is always room for human error.”
Some of the other uses suggested for DNA profiling have amused him. “I remember, in the early days, getting a letter from someone who ran holiday cottages in North Wales asking if they could use my technique to find out who had urinated in their beds”, he laughs. “Of course, if the National DNA Database gets much bigger, they may find their answer there!”
Jeffreys can remember being interested in science from around the age of five, but the transforming moment of his life came when he was eight and his father bought him “a fantastically dangerous chemistry set, of the kind that would be totally illegal nowadays”. This was quickly followed by the gift of a Victorian microscope, which started his interest in biology. His parents were extremely supportive of these activities. “My father is a technologist with a considerable bent for adventure, and his father in turn was a prolific inventor with a number of patents to his name. I think there must be a science gene in the family.”
Even in retrospect, he doesn’t think that he would have been tempted to follow any other path. “When I was a boy I had the usual ideas about becoming a jet plane pilot ands so on, but I think from the outset that I always wanted to be a scientist and I really cannot conceive of any more satisfying vocation.” Outside science, he confesses a liking for ‘rubbishy historical novels” and says that he is “possibly the world’s worst surfer.”
Does he have any plans for retirement? “I’m 58 now and just starting to think about it, but I can’t imagine that I will ever give up science completely.”