The accidental discovery of DNA fingerprinting
Autoradiograph of the first genetic fingerprint, together with Alec Jeffreys’ lab book describing the experiment. 1984. Wellcome Images, CC-BY 4.0 Via Wikimedia Commons
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On the 7th March, 1985, a paper was published in the scientific journal Nature that changed the world.
Written by a team of three researchers at the University of Leicester: Alec Jeffreys, Victoria Wilson and Swee Lay Thein, the title, Hypervariable ‘minisatellite’ regions in human DNA’, and the jargon-filled results, talking about dispersed tandem-repeats and allelic variations, don’t provide much of a clue unless you know what you’re looking at.
But it’s this last sentence of the abstract that’s the real giveaway: “A probe based on a tandem-repeat of the core sequence can detect many highly variable loci simultaneously and can provide an individual-specific DNA ‘fingerprint’ of general use in human genetic analysis.”
So what did this team do, what did it mean, and what happened next?
Professor Sir Alec Jeffreys has always had the spirit of science and invention running in his DNA (if you believe in that kind of genetics…).
His Grandfather was an engineer and a prolific inventor who held many patents. One of them was for a method of creating photorealistic sculptures, where a customer could come into his shop, have a few photos taken,
and then come back the next day to pick up a picture-perfect statuette of their face, long before 3-D printing was even an inkling of an idea. Prime Minister Neville Chamberlain even counted among the happy clientele.
Grandpa Jeffreys’ inventiveness rubbed off on his son, and young Alec grew up in a household full of his dad’s gadgets and gimmicks. And it was his dad who bought Alec his first microscope and chemistry set - essential tools for any budding scientist.
Unfortunately, this enthusiasm for chemistry outweighed Alec’s sense of health and safety, resulting in the detonation of his aunt's apple tree and some nasty acid burns that still leave their scars today.
“You learn science very fast that way, but it was quite fun,” said Jeffreys in an interview in 2006.
Fortunately, this explosive incident didn’t put young Alec off science at all. He ended up at Oxford University for a degree in biochemistry and PhD in human genetics, and from there to a lab in Amsterdam, where he started working with some of the early tools that researchers were developing to study DNA.
In 1977 - the year that Fred Sanger invented his eponymous DNA sequencing technique - Jeffreys arrived in Leicester, complete with suitably 70s hair and beard, taking up the position of lecturer in the Department of Genetics.
Rather than focusing on investigating how information was stored within the sequence of DNA, he decided to take a different tack, instead looking at how DNA varied between people, so he could trace how different versions of genes linked to traits and diseases were inherited down the generations.
He and his colleagues started a systematic survey of one section of the human genome, trying to spot how it differed between individuals. But he soon realised this task was a lot tougher than he first imagined.
The variations between people were very hard to detect with the tools at the time, and not particularly informative. Surely, he figured, there must be other regions in the genome that were more variable - and easier to work on.
In the summer of 1984, Jeffreys and his team started working on a technique to detect so-called mini-satellites: short, stuttering sequences of DNA that are repeated over and over at certain places in the genome, like the same word repeated again again again again again at multiple points within a book.
But while the word is the same between all humans, the number of times it gets repeated in various locations throughout the genome is highly variable.
Their method for looking at mini-satellites worked like this. First extract DNA from cells and chop it into small bits using an enzyme that cuts DNA at specific sequences around the mini-satellite clusters. Run it all through a large slab of special science jelly, which separates all the fragments by size, from the largest to the smallest.
Then you stick all that DNA onto a piece of glorified paper, exactly preserving that pattern of fragments. Next, wash it with radioactively labelled mini-satellite DNA, slap a piece of X-ray film on top and leave it for a few days to see what you’ve got.
On the morning of 10th September 1984, at 9.05 am, Jeffreys developed the X-ray film from his latest experiment. As well as looking at DNA samples from related humans, he’d also included a few animal species too, just for kicks, really. What he saw on that pale blue film covered with rows of fuzzy black blobs and lines was absolutely astounding.
According to a 2009 interview in The Guardian, his first reaction was “'God, what a mess.'...Then I stared a bit longer - and the penny dropped."
He realised that the DNA from each species had its own particular pattern of mini-satellites, exactly like a personal bar code. Not only that, but each human had its own unique pattern:
For example, I might have 30 copies in one location, while you have 25, and someone else has 18. In another place of the genome I’ve got 17, you have 36, the third person has 40. All of these will generate a unique pattern of DNA fragments with different lengths.
Even more importantly, he saw that an individual person’s pattern was a composite containing elements of each of their parents mini-satellite patterns, and could be used to identify relatives from the same family.
This was something he figured out thanks to DNA samples donated by his lab technician and her mum and dad. Without intending to, Jeffreys had created the world’s first genetic fingerprint, as he and his team soon came to describe it.
He says, "It was an absolute Eureka moment. It was a blinding flash. In five golden minutes, my research career went whizzing off in a completely new direction.”
Not bad for a completely accidental discovery, or as Jeffrey’s grandson Ewan described it in a school project, “My grandad was messing about in his lab one day when he discovered genetic fingerprinting.”
Jeffreys immediately called his team together to start brainstorming ideas for how to use their new profiling technique. Paternity testing was an obvious one, as revealed by that very first experiment.But there were other applications too.
What about crime scenes? Would it be possible to get enough DNA from bloodstains or other biological remnants left at the scene of a crime to identify a perpetrator? Or even to track down the identity of an unknown victim? And it was Jeffreys’s wife, Sue, who suggested that this newfangled fingerprinting technique might be a way of reuniting families separated by immigration disputes.
The Leicester team published their paper describing the technique in March 1985. It got a fair bit of pick-up in the media, and almost immediately the university switchboard was jammed with calls from people desperate to use DNA fingerprinting to solve their problems.
Within a month, Jeffreys and his team had taken on and solved his first case - the Ghana immigration dispute, which we’ll come to a bit later. By mid-1985 they had taken on their first paternity case, kick-starting an industry that’s still keeping dubious daytime TV shows fed with drama to this day.
This was also the first time DNA fingerprinting was used in a court of law, in a magistrate’s court, signalling that the legal profession was going to have to embark on a pretty steep learning curve to get to grips with all this genetics stuff.
By 1987 the first DNA profiling company, Cellmark, was set up by licensing Jeffreys’ technology from the University. In the same year came the first criminal case, when a combination of DNA evidence and outstanding police work was used to solve the murders of two Leicestershire schoolgirls, Lynda Mann and Dawn Ashworth, who I’ll talk about later on.
This case was the launchpad for forensic genetics, and within a year DNA profiling was being used by police forces worldwide.
By the early 90s, the techniques for DNA profiling took a leap forward with the invention of the polymerase chain reaction, or PCR. Exactly how this works - and the curious drug-fuelled story behind its discovery - is a topic for a future podcast.
Basically it’s a kind of ‘photocopier’ for DNA, allowing scientists to see how many copies of each mini-satellite are present at various locations in the genome in a matter of hours, rather than the days or weeks required for Jeffrey’s original technique.
PCR-based fingerprinting also needed far smaller amounts of DNA to get a decent profile, making it feasible for use in situations like crime scene investigations where only tiny samples could be gathered. And it’s not just human crimes that can be solved with DNA fingerprints…
When I heard him speak at a recent event in Leicester celebrating the 35th anniversary of his seminal paper, Jeffreys told the story of one a man in the UK who had an adult male and female golden eagle, both of which he was licensed to keep. But he also had three fluffy little eaglets.
And as everyone knew it was impossible to breed golden eagles in captivity, so he must have stolen them from the wild. This is a serious criminal offence warranting a serious fine and potentially a prison sentence.
Jeffreys’ lab set about doing the world’s first golden eagle paternity test. They found out that the birds were in fact all one family group, and in an instant, the man went from a potential wildlife criminal to a wildlife hero as the first person ever to breed these majestic birds in captivity!
Wildlife crime might seem low down the list of international criminal priorities, but it actually has huge financial and environmental impact globally. This is particularly pressing given that illegal wildlife trafficking increases the chances of transmission of novel pathogens like viruses from animals to humans.
There are plenty of uses for genetic fingerprinting in conservation too - whether that’s figuring out the family relationships of wild or captive animals to keep an eye on inbreeding, or just monitoring and studying wild populations by looking at the traces of DNA they leave behind in their droppings.
The applications of genetic fingerprinting are almost endless. Today it’s used in agriculture, medicine, biodiversity research, and much, much more. DNA profiling has confirmed the identities of remains of the great and the not-so-great, from the murdered Russian Romanov dynasty to the infamous Nazi Josef Mengele.
Jeffreys’ Leicester colleague Turi King confirmed that the skeleton in a local car park was likely to be Richard the Third - and you can hear more about that story in episode 7 or our recent miniseries, New Light on Old Britons.
Genetic fingerprinting has solved horrific crimes and exonerated innocent prisoners. It was used to confirm that Dolly the sheep was a true clone, and is being put to work proving the pedigree (or otherwise) of prize puppies and other valuable animals. There are even ‘poo-printing’ services that use DNA profiling to identify dogs with irresponsible owners who persistently fail to scoop that poop.
Unsurprisingly, Jeffreys has received many honours and awards all over the world. But the strangest recognition by far is from Sir Alexander Fleming College, a British school in Trujillo, Peru, which has named one of its houses after him, complete with DNA-based headbands. It’s not exactly a Nobel Prize, but it’s certainly an original way to celebrate the inventor behind one of the most important and powerful techniques in genetics. Go Jeffreys!
