An evening with Alec Jeffreys
The Biologist 63(4) p16-19
The inventor of DNA fingerprinting speaks to Alison Woollard about the scientists who inspired him and the 'eureka moment' that revolutionised forensic science
In 1984, Alec Jeffreys was in his lab in Leicester when an idea came to him. He had been researching genetic variation, and had suddenly realised the obvious and enormously significant application of the technique he had developed: the biological identification of any individual using only a tiny sample of their DNA.
By the 1990s, DNA fingerprinting had become a standard part of criminal investigations, as well as immigration disputes, paternity tests, war crime evidence gathering and more. Sir Alec now estimates that between 50 and 70 million people worldwide have been touched somehow by the drama of DNA identification, which, he says, "is almost always profound and life changing for the people involved".
Earlier this summer, the Society brought Sir Alec and The Biologist's Alison Woollard together in conversation in front of a live audience at the Science Museum's IMAX theatre in London.
Sir Alec began by explaining his somewhat unusual interests as a child growing up in suburban Oxford and then Luton. He revealed he was an "obsessive, precocious" child, fascinated with explosives and anything gory he could look at under his beloved Victorian microscope. His earliest scientific memory is his father doing experiments in the sitting room of their Oxford home, and it was his father who bought the chemistry set that lit up – quite literally – his passion for experimentation.
"If any of you buy a chemistry set now, it's a very anodyne affair. The thing my father bought me was made by a chemistry graduate from Oxford and it was the real McCoy – absolutely lethal. Among other things there was hydrochloric acid, sulphuric acid, nitric acid and sodium metal, which blows up in water."
Sir Alec began teaching himself chemistry, particularly organic chemistry.
"At age 12, I was doing syntheses in my kitchen that were probably undergraduate level. The house suffered disastrously."
He even wears a beard to hide a sulphuric acid scar from a childhood experiment to produce hydrogen cyanide gas.
By age 13, he was reading his hero Albert Einstein's theory of special relativity. Another hero of his was the Nobel Prize-winning biochemist Max Perutz, whose pioneering work helped deduce the structure of haemoglobin and myoglobin.
"I was so enamoured with the beautiful model of the structure of myoglobin in Scientific American, I tried to build it myself out of balsa wood. That's the kind of obsessive I was, and still am."
The first person in his family to go to university, Sir Alec left Luton Sixth Form College to study biochemistry at Merton College Oxford, a place he describes as "positively medieval, but delightful".
After graduating and doing a doctorate, he moved to the University of Leicester in 1977, where he remained until he retired four years ago. It was here, while studying genetic variation, that he laid the groundwork for his great invention.
"In the mid-1970s, we had no tools whatsoever to look at the genome, how it was organised, how information was stored, and certainly not to look at how it varied from person to person.
"I worked with Dick Flavell in Amsterdam, which helped us detect individual genes in that great tangle of DNA for the first time. When I returned to Leicester, I thought, what else can we do with that? The obvious thing was to look at variation between people's DNA, variation at the most fundamental level. We started a very amateurish programme and had our first variant detected in the DNA of one of our technicians in 1978."
Sir Alec's lab then set about testing whether the variant had been inherited, or was a mutation, by sampling the lab technician's parents, too.
"We got DNA samples from her parents and we could see she'd inherited it from her father. I remember breathing a sigh of relief because I knew that the likelihood of it being a new mutation was incredibly low, and so if things didn't match up, the most likely explanation was non-paternity. So already the thoughts about non-paternity in relation to DNA were there in 1978."
However, Sir Alec and colleagues quickly grew disenchanted with the types of variation they were studying. He describes it as "changing one letter at a time" in the genetic code.
Mary had a little lamb
Mary had a little limb
Mary hid a little limb
"We started thinking that in the immensity of the human genome there should be bits that were more variable than that."
Their focus shifted to stuttered DNA, where a section repeats over and over again.
Mary had a lit lit lit lit little lamb
The number of times that various segments repeated themselves varied greatly between individuals – greatly enough to ensure that the chances of two people having the same variants were infinitesimal.
Sir Alec can't remember the exact words he used when he had his sudden realisation of the power of the techniques he had developed.
"I don't know if I actually said 'eureka'," he recalls. "But that eureka moment really did happen. I was standing there in the dark room with a bit of film, and suddenly realised there was a door in front of me that I didn't even know existed that had suddenly swung open. And that door was the door of DNA-based identification."
Although DNA fingerprinting is now absolutely standard in criminal investigations, Jeffreys recalls a time when even his scientific peers refused to entertain the idea.
"People thought I'd gone insane. I remember standing up and giving a lunchtime talk to the department explaining what this stuttered DNA was and speculating that we could use this to catch criminals using semen recovered from rape victims.
"I'm not kidding, about a third of the audience fell about laughing. 'You just don't use DNA in criminal investigations; that's stupid,' they said."
It only made Jeffreys more determined. The first case to use the technology was an immigration dispute, where a DNA sample proved a young boy faced with deportation was a genuine member of a London family.
"That was in April 1985 and got a lot of press," says Jeffreys. "By the summer, we'd taken on paternity cases, and both these unlocked an absolute deluge of casework directed at us, as we were the only lab in the world that could do it. So the police were aware through the press that DNA identification was out there and was a powerful tool."
The following year, the police got in touch and Sir Alec found himself at the heart of a chilling criminal case. Two schoolgirls from Leicester had been brutally raped and murdered.
"Following the second murder, a young man was acting suspiciously and was arrested, and he confessed to the second, but not to the first. The police were stuck. They approached me asking whether our DNA technology could be used to look at forensic samples to prove his guilt in the second murder but also to tie him to the first one."
However, this historic criminal case, the first of millions to use DNA fingerprinting, would prove to be anything but straightforward. Sir Alec's lab found that the two semen samples matched each other, but did not match the suspect. He had to tell the police that the man who had confessed was not the murderer.
Did he ever doubt his findings?
"Yep. When I stood up there and said 'there's no doubt' I had a huge doubt. My blood ran cold. This was a chilling case. I'd spent my entire career up until that point in a lab or lecturing. Then suddenly to be faced with these highly intimate samples from murder victims – you could feel the temperature in the lab drop. But then to get that exclusion of someone who was assumed to be guilty, that really worried me."
After the Forensic Science Service backed up Sir Alec's findings, the original suspect was exonerated.
The manhunt resumed, and more than a thousand local men were asked to voluntarily provide blood samples to help whittle down the suspects.
"In the end, the idea that this was voluntary went out the window – you can imagine the social pressure in the community. 'Oh, so and so down the road hasn't given a blood sample; what's he hiding?' So everyone came forward. It was a very interesting social experiment."
Eventually, a match was found and Colin Pitchfork was convicted and sentenced to life in prison. The historic case went on to be dramatised in the TV mini-series Code of a Killer, starring John Simm.
However, says Sir Alec: "The first time DNA fingerprinting was used in a criminal case was to exonerate and not establish guilt – that's a really important point."
He is keen to stress the importance of fundamental research and its role in the DNA fingerprinting story. The best description of how his discovery came about, according to Sir Alec, has been provided by his grandson as part of a school project, in which he said: "One day my grandad was messing around in the lab and he accidentally invented DNA fingerprinting."
Sir Alec told the audience: "This discovery was an accidental product of blue skies research, and that's a really important political message. If you don't support blue skies research, you're not going to get weird and wonderful technologies emerging."
Jeffreys was wise enough to patent his remarkably useful technique, which has barely changed despite the advances in DNA technology since, because to use newer DNA markers would invalidate all the existing records stretching back decades. He says much of the royalties were ploughed back into biomedical research. The family's one extravagance, he says, is a seaside cottage in Cornwall.
Although no-one has kept track of how many cases have used DNA fingerprinting since, Jeffreys thinks it is "a reasonable estimate" to say that between 50 and 70 million people have now been touched by his technology. "Remember every time it is deployed it is a drama for the person involved. Exonerating a man from death row, or proving who the parents of a child are."
This is an edited account of 'An Evening with Alec Jeffreys', the Society's fundraising event from earlier this summer. The Society is grateful to Unilever for sponsoring the event. Listen to the event in full here.
Sir Alec Jeffreys FRSB FRS is a British geneticist who developed the techniques for DNA fingerprinting and DNA profiling which are now used worldwide in forensic science and other identity disputes. He is a professor of genetics at the University of Leicester and was knighted for services to genetics in 1994.
Are we the same or different?
Sir Alec was asked how DNA can be used as an extremely sensitive identification tool when we hear so often that humans are genetically 99.9% similar and even share 98% of their DNA sequence with chimps.
“It’s no problem because of the size of the genome. If you look at the enormity of the human and chimp genome and ask what that 1 or 2% difference means, in terms of numbers of positions that vary you’re talking tens of millions.
“So the highly variable bits that we exploited for DNA fingerprinting make up only a tiny fraction of the genome, but within these confined regions the variation is spectacular. The original technique presented patterns on x-ray patterns that are completely unique to individuals. The only exception is identical twins.”
How does the stutter happen? How is it allowed in the genome?
“The first system used bits where the stutter is quite long – we know now that the process that drives that is aberrant myotic recombination. When your maternal and paternal chromosomes line up and are separated and passed into a sperm or egg, the DNA is shuffled, and that can go wrong and can drive variation. The technology moved on and we moved to more simple sections of DNA called simple tandem repeats. Our best guess how they change is aberrations in replication and repair. The genome is not perfect and can’t filter out all the errors.”
Sir Alec was asked whether it should be compulsory to have your DNA on a national police database.
“What is the benefit to an innocent individual? None. Is there a risk? Yes. There could be a mistake or glitch, or a partial match that means I am brought into a criminal investigation. Politicians will say ‘if you’ve got nothing to hide…’ but that is naïve and misleading.
“More interestingly, is anyone ever going to try it? A number of years ago, the United Arab Emirates passed legislation making it mandatory to be on the DNA database. I pressed the forensic people when I was over in Dubai about how far they’d got with this. It seemed to be going very slowly.
“Kuwait has also rushed through similar legislation in response to a terrible bombing at a Shiite mosque. DNA is crucial in the fight against terrorism, as anyone who has been following the hunt for the Paris attackers will know. But whether it merits putting the whole population on a database, for the same reason above I would raise very serious doubts.
“You should ask the question, what other use would that database be put to? They would say it would be used to clear up serious crime. What else? Well, there is a real risk of a massive invasion of genetic privacy. For example, you could use that list to scan the entire population for every single instance of non-paternity and identify the true father. That is dynamite. I’m not suggesting they would do that; I’m suggesting it’s a risk. As is state surveillance.”