1998 Australia Prize

Awarded in 1998 for excellence in the field of Molecular Genetics

Professor Sir Alec Jeffreys

Australia Prize winner Professor Sir Alec Jeffreys remembers the exact moment he accidentally stumbled upon one of the most effective tools in modern crime detection. It was 9am, Monday September 15, 1984 when Sir Alec removed some X-ray film from the developing tank and experienced a rare moment in science, an absolute eureka. “I thought - My God what have we got here - but it was so blindingly obvious,” he says. “We’d been looking for good genetic markers for basic genetic analysis and had stumbled on a way of establishing a human’s genetic identification. By the afternoon we’d named our discovery DNA fingerprinting.”

To understand how Sir Alec and his team at the University of Leicester came up with DNA fingerprinting, and subsequent enhancements of the technology, one must go back to the late 1970s when they began a search for regions in human DNA that were variable between people. They hoped their work would enable them to map genes and develop diagnoses for inherited diseases.

At the time, Sir Alec concentrated his search for variable bits of DNA in regions where the DNA code is repeated, or stuttered. Each human chromosome is one long DNA molecule with four different chemical letters written down its length, ten of millions of times.

If you were to slide down that almost endless string of DNA, the letters would look random, but at certain points you’d hit segments where the sequence repeated. If an ordinary segment of DNA read ‘Mary had a little lamb’, one of these stuttered regions would read something like ‘Mary had aaaaaaaaaaaaaaaa little lamb’.

“People had already stumbled over several of these stuttered regions of DNA purely by accident,” says Sir Alec. “We wanted to find a way to get to them any time we wanted.”

While continuing his work on stuttering DNA, Sir Alec became involved in a side project looking at the evolution of genes. “One of the genes we were interested in was myoglobin, a gene which produces the red pigment found in muscle,” says Sir Alec. “It’s a relative of the gene which codes for haemoglobin, the oxygen carrying pigment in blood. We knew that myoglobin had split from haemoglobin about half a billion years ago so we thought it would take us back to some ancient events in gene evolution.”

When Sir Alec isolated the myoglobin gene, he found it contained stuttered bits of DNA, plus a strong clue that these stutters occurred at particular chemical motifs within the DNA. “There was also a suggestion [in that gene] that if these stuttered bits of DNA varied from one person to another, and if we developed a chemical probe which could latch on to this chemical motif that was shared between different stuttered regions in a person’s DNA - called minisatellites - we could isolate a lot of stuttered DNA regions at once and thereby develop good markers for genetic analysis.”

Back now to 9am, Monday September 15, 1984 and standing in the dark room with his freshly developed x-ray film, Sir Alec could see that not only had the experiment worked - he could see lots of the so-called minisatellites - but the pattern they made varied quite extraordinarily from one person to another.

Sir Alec and his team spent the rest of that morning discussing the practical implications of their discovery. “In theory, we knew it could be used for forensic identification and for paternity testing. It could also be used to establish whether twins were identical - important information in transplantation operations. It could be applied to bone marrow grafts to see if they’d taken or not,” says Sir Alec. “We could also see that the technique working on animals and birds. We could figure out how creatures are related to one another - if you want to understand the natural history of a species, this is basic information. We could also see it being applied to conservation biology. The list of applications seemed endless and that’s how it’s turned out.”

By afternoon on September 15, Sir Alec and his team were pricking their fingers, smearing blood on tissues and bits of glass to see if they could produce DNA fingerprints from this “evidence”. They found they could. “It was a classic case of basic science coming up with a technology which could be applied to a problem in an unanticipated way,” says Sir Alec.

A DNA fingerprint appears as a pattern of bands or stripes on x-ray film. The technology’s applications for forensic science are obvious: It can determine whether two biological samples come from the same person. It can be used to establish family relationships because the banded patterns the technology produces are simply inherited.

“Half the bands from a child’s DNA fingerprint come from its mother and half from its father,” says Sir Alec. “In paternity testing, you take the child’s banding pattern and that of the mother and the alleged father. The bands on the child’s DNA fingerprint that are not from the mother must be inherited from the true father. And no two people have the same DNA fingerprint, other than identical twins.”

In late 1984, lawyers involved in an immigration case contacted Sir Alec about using his technology. The case involved a Ghanaian family who had become UK citizens. One of the children, a teenage boy, had returned to Ghana and then when he tried to re-enter Britain, immigration authorities suspected that he was not a member of the family, but a substitute, and denied him entry.

Traditional blood group typing could not resolve the case. (The boy’s father was unknown - there were two possible candidates.) Sir Alec took blood samples from the boy, the mother, and the three children who were undisputedly hers and used their DNA fingerprints to reconstruct the DNA fingerprint of the unknown father. “We then compared the DNA fingerprint of the mother and the missing father with the DNA fingerprint of the boy,” says Sir Alec. “Every one of the boy’s genetics characteristics could be found in the woman and the missing father’s three other children. It was overwhelming evidence that the boy was a full member of the family and it also informed the mother as to the identity of the boy’s father.”

When the Home Office dropped its case against the boy, Sir Alec had the privilege of giving the boy’s mother the good news. “It was a golden moment to see the look on that poor woman’s face when she heard that her two year nightmare had ended,” he says.

Sir Alec says he’s glad DNA fingerprinting was used in an immigration dispute and not a criminal case first up, as the technology’s limitations for forensic analysis soon became apparent. For a start, a lot of good quality DNA is required to obtain a good DNA fingerprint. “But often at crime scenes, there’s not enough biological evidence to attempt a match with the DNA of a suspect,” says Sir Alec. “Old DNA can also be degraded and this can cause serious problems of interpretation in court.”

The second limitation comes when there’s a long interval between the collection of a DNA sample from a crime scene and the taking of a sample from a suspect. “The nature of the test means that the pattern, while completely reproducible in a single experiment, can subtlety shift from one experiment to another,” says Sir Alec. “These patterns are not black and white like a barcode. They’re grey codes with light and dark patterns. If you do a second test some time after the first, some of the faint bands might disappear or get darker. There’s also the problem of aligning the two patterns for comparison. It can be done by eye, but that’s not acceptable evidence in court.”

In 1985, Jeffreys and his team developed a technology which overcame these limitations. Called DNA profiling, it enabled them to isolate individual minisatellites and produce a pattern on X-ray film with just two bands per individual: one from the person’s mother and one from their father. “These patterns are now much simpler to read and interpret, and you can store them on a computer data base,” says Sir Alec. “You can also develop them using much less DNA.”

Sir Alec used this new technology to help solve one of Britain’s most notorious crimes this century, the Enderby murders. An “immature” young man with a record of minor sex offences was arrested after two young school girls were raped and murdered three years apart. The man confessed to one of the murders but denied any knowledge of the other.

Sir Alec was asked to look at the forensic evidence in both cases. Using DNA profiling, he found that semen samples from the crime scene did not match the DNA of the man police suspected of committing the crimes. “The police subsequently dropped the case against that man,” says Sir Alec, “And he became the first person ever proven innocent by DNA analysis. If we hadn’t developed the technology, I’m confident he would have been gaoled for life.”

The police then embarked on the world’s first DNA-based manhunt, screening the local community and successfully flushing out the true perpetrator who was gaoled for life for each of his crimes.

These days, the use of DNA profiling sees 30 per cent of accused in British rape cases exonerated. “The technology provides powerful evidence that allows courts to arrived at solid decisions in criminal cases,” says Sir Alec. “It’s also led to a swathe of longstanding convictions around the world being overturned. Some of these people had been in gaol for over a decade before molecular evidence proved their innocence.”

DNA profiling is now standard in forensic laboratories, but it’s fast being replaced by DNA amplification. It’s a technology which allows a forensic scientist to take a trace amount of DNA and copy it a billion times to give enough material to type. Sir Alec used DNA amplification to identify the skeletal remains of Josef Mengele, the Auschwitz camp doctor whose experimentation on Jewish prisoners earned him the title Angel of Death.

Mengele evaded the Allies at the end of the Second World War and fled to South America. Someone who was thought to be Mengele drowned at sea in 1979 and was buried in Brazil. In 1985 the remains were exhumed and examined by forensic anthropologists who invited Sir Alec to subject them to DNA analysis. “We compared DNA from the bones with DNA from Mengele’s mother and son who were still alive,” he says. “The DNA matched up, the genetic constitution of the bones was what one would have predicted for Josef Mengele and so his case was closed.”

Three years ago, Britain launched the first national criminal DNA data base. Under British law, anyone now convicted of a serious offence has their DNA profile stored on a data base. “If they re-offend and leave biological evidence,” says Sir Alec, “they can be apprehended. The DNA information of 250,000 people is now stored on that database and it’s already proved very successful at linking unsolved crimes, identifying possible perpetrators and giving police new leads.”

Professor Sir Alec Jeffreys says the basic science of DNA profiling has been solved. “It’s now a matter of speeding up the processing of biological evidence and getting rid of a few glitches,” he says.

Sir Alec says his discovery of DNA fingerprinting took his life in a direction he never thought possible. “But I have not abandoned the pure science I was involved in before my discovery,” he says.

These days, Sir Alec and his team are studying the effects of chronic irradiation such as that which has followed the melt down of the nuclear reactor at Chernobyl in the Ukraine 12 years ago.

They’ve found a systematic increase in the mutation rate in Belarus families affected by Chernobyl - the first direct evidence that radiation induces inherited mutation in humans. “The scale of mutations we’re seeing is way beyond what you’d predict from the physics,” says Sir Alec. “Most of these mutations almost certainly do not have disabling consequences but at the moment we’re trying to establish some of the biological properties of this process”.

Sir Alec says he’s thrilled to be named one of the winners of the 1998 Australia Prize. “I know Australia well and I dearly love the place,” he says. His younger brother lives just outside Sydney. “Australia is a small country in terms of population and such countries tend to go in for solving applied problems in science rather than pure science problems,” says Sir Alec. “Australia is the great exception to this rule, so to be recognised by Australia in this way is very exciting”.