The history of genetic fingerprinting

You could say that the path that led to the discovery of genetic fingerprinting began for Professor Sir Alec Jeffreys when his father gave him a chemistry set and a microscope at the age of eight.

Scientists, he believes, like musicians are born not made, nonetheless he acknowledges that this parental encouragement played its part in his choice of vocation. It might have been disastrous, as he explained. "This was a real chemist's chemistry set, not a child's toy, and later, when I was 13 or 14, I got a face full of sulphuric acid, which is why I wear this beard now. I consider it a badge of honour."

Oxford and Amsterdam

At Oxford the young Alec Jeffreys did a four-year biochemistry degree before deciding that biochemistry was not for him. His real enthusiasm had been for the genetic component of his degree course, though looking back now he calls it "human genetics of the stone age era".

As a postdoctoral research fellow at the University of Amsterdam, his original plan was to work with yeast. "Then I met Dick Flavell and we started to work with mammalian genes. We didn't succeed in our original aims but we did develop a method for detecting specific genes in humans. It was crude but it gave us a glimpse into what human genes look like. We stumbled on the fact that mammalian genes look weird, they are not simple as in bacteria. They have gaps, so that in between the information sections of the genes were stretches of gobbledegook. Similar research led to a Nobel Prize for other teams working in the field, so you can see we were right in the centre of things."

Just as his two years in Amsterdam were up, while he was trying to decide between a second post doctoral term and an independent academic position, he received a phone call from Professor Bob Pritchard inviting him for interview for a temporary lecturership at Leicester.

Early work at Leicester

Speaking of the impression the University made on him, he said: "I liked it. Remember I had spent seven years at Oxford, where there is a collegiate system and less sense of a university. In Amsterdam I had worked in a research institute, which was prestigious but also had a different atmosphere. I liked the compact integrated campus at Leicester. The department was friendly, there was no obvious sense of power politics. Bob Pritchard made it clear I should just get on and do my research without interference from him, and I liked that."

Back in 1977 in Leicester, the new recruit to the University, aged just 27, in charge of a small laboratory and with one part-time technician, had considerable freedom. The technology now existed for the first time to look at genes, and he decided to study their inherited variation, shifting the focus from the products of genes such as blood groups, to DNA.

Those must have been exciting times in the genetics laboratory. "That year we found the first inherited DNA variation in one of our technicians. In 1978 we discovered you could detect variations in human DNA. Then we worked on mapping genes in disease diagnosis. By 1981 we could define our goal, which was highly variable DNA. We considered a number of approaches which didn't work, before looking at how genetic variations evolved. We stumbled on our clue, stuttered DNA, or 'minisatellites', which were highly variable. We had found a way of detecting lots of minisatellites variable enough to provide extremely informative genetic markers.

The 'eureka' moment

"My life changed on Monday morning at 9.05 am, 10 September 1984. What emerged was the world's first genetic fingerprint. In science it is unusual to have such a 'eureka' moment. We were getting extraordinarily variable patterns of DNA, including from our technician and her mother and father, as well as from non human samples. My first reaction to the results was 'this is too complicated', and then the penny dropped and I realised we had genetic fingerprinting."

It opened up a new area of science. The research team immediately grasped its applications, including crime, paternity and identical twins, as well as work on conservation and diversity among non-human species. Later that day Sir Alec's wife added another to the list - immigration. "That was when I realised this had a political dimension and that it could change the face of immigration disputes, especially where no documentary evidence existed."

First practical applications

The first 'real' immigration case came in March 1985, a decade earlier than Sir Alec had anticipated, driven by the demand from families and lawyers. "We even had people coming into our back garden, asking to be tested there and then, which of course I couldn't do, not being a licensed blood taker. If our first case had been forensic I believe it would have been challenged and the process may well have been damaged in the courts. But our first application was to save a young boy and it captured the public's sympathy and imagination. It was science helping an individual challenge authority. Of all the cases this is the one that means most to me. The court allowed me to let the family know we had proved their case, and I shall never forget the look in the mother's eyes."

The first paternity case came hot on the heels of that dispute and then - in Sir Alec's words - "the flood gates opened". At this point, all cases were dealt with by the Leicester laboratory. Sir Alec was a research fellow for the Lister Institute who gave him funding to take on another technician to enable them to run tests on a larger scale and for two years his was the only laboratory in the world doing this work. He describes it as 'exciting but exhausting', and had no regrets when ICI (now AstraZeneca) were granted a licence to set up Cellmark and put the research on a commercial level.

Genetic profiling as a forensic tool

At this time the forensic implications of genetic fingerprinting were emerging. The original process proved to be inadequate for this, and so from 1985 Sir Alec and his team developed a variation which they called "genetic profiling" for forensic use.

Again, its first application caught the public mood. Two young girls were raped and murdered in the Enderby area of Leicestershire. A man who had been arrested had confessed to one murder but not the other, and the police decided to use genetic profiling, thinking to prove him guilty of both cases. Against all expectation he was found to be innocent of both. Then the hunt was on to find a genetic profile among the entire male population of the area that matched samples taken from the two victims. No match was found, until Colin Pitchfork was overheard boasting of how he had persuaded a friend to give a sample on his behalf. The case was solved.

How did Sir Alec feel when Pitchfork was finally convicted? "I felt relief because he was a serial murderer and would kill again, and because if the operation had failed then the public's perception of forensic DNA would have been shattered. Also, here was a serial killer in the region who knew what I was doing and where I worked and where my family lived. That feels very uncomfortable so on a personal level it was a great relief when he was trapped."

Advances in genetic profiling

The original technology used to catch Pitchfork is now largely obsolete, though still in use in some laboratories around the world. But the techniques have been speeded up and simplified. In the UK we now have a national database of 2.5 million genetic profiles from convicted criminals which the police say is one of the most powerful tools in their fight against crime. While there is some concern amongst civil rights activists, Sir Alec feels it would be "criminally irresponsible" not to maintain the database and would mean that rapists and murderers who are now identifiable would be able to continue unstopped. However, he does take civil rights seriously and is concerned with the fact that suspects' DNA profiles are also being stored on police records. He sees this as discriminatory, though notes that this potential infringement of civil rights of minority groups would largely disappear if everybody was "fingerprinted".

"Where it is a matter of identification of genetic disease I feel insurance companies and their like have no right to genetic information. This is private property and no one other than the individual concerned should have that information. We all carry within us the equivalent of three lethal genetic variants, so why should insurance companies have access to information on selected cases? The information should only be used if it helps the individual, for instance if there is a treatment for the disease."

Not all Sir Alec's cases have been so intense nor with such portentous implications. In the early 1990s he received a phone call from the producer of BBC Television's "Jim'll fix It". There were twins, 11-year-old girls, who wanted to know if they were identical or not. Could he help? Since identical twins are the only people who share genetic fingerprints, Sir Alec could certainly help. "Cellmark Diagnostics leapt on this, it was fun. Once we had the results we went down to the studio, set up the DNA fingerprints behind a curtain and invited the girls to draw the curtain. They saw for themselves that they were identical. Then I had the opportunity to explain the scientific processes to an audience of 20 million people."

Beyond genetic fingerprinting: Chernobyl

Since the late 1980s Professor Sir Alec Jeffreys has been examining the ways DNA mutates and crosses over (reshuffles its chromosomes), looking at minisatellites and the spontaneous ways in which they add and lose stutters.

With Professor Yuri Dubrova from the NI Vavilov Institute of General Genetics, Moscow, he has studied 79 families in the region around Chernobyl in Belarus, the scene of the 1986 nuclear accident, to find out whether the environment we live in influences this mutation, or whether it all comes from our genes.

The research concentrates on three groups of people who have been exposed to radiation:

• Those exposed by accident, such as survivors of the Chernobyl disaster or the bombing of Hiroshima and Nagasaki;
• Those deliberately exposed in the sense they live near nuclear test weapon sites;
• Those deliberately exposed, for example in the treatment of cancers.

Results so far have been perplexing. In the Chernobyl region the genetic mutation rate was found to be unusually high. In other words parents in that area pass on mutations to their children more than elsewhere. But it is impossible to point the finger of accusation at radiation alone. For instance, the population of Belarus is more stressed than in non-contaminated environments, and people's health may be affected by stress-related behaviour like smoking. However, those living near nuclear weapon test sites also show increased levels of heritable mutation, suggesting a direct effect of radiation. On the other hand sperm from men undergoing radiation for cancer treatment shows no change in genetic mutation at all, nor do samples from the remaining survivors of Hiroshima and Nagasaki.

Questions to be explored include whether Chernobyl families living in more contaminated areas show more genetic mutation than those in clearer districts, or whether the way people receive the radiation is significant, i.e. from a single bomb blast as opposed to living in a contaminated environment and consuming radioactive material in food and drink.

It is a project that will, Sir Alec foresees, take him to retirement. For a scientist who enjoys venturing into the unknown he seems well content to take up the challenge.