Mark A Jobling

Investigative Genetics

PubMed

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Jobling Investigative Genetics 2013, 4:20
http://www.investigativegenetics.com/content/4/1/20OPINION Open AccessCuriosity in the genes: the DNA fingerprinting
story
Mark A JoblingIt is unusual for a scientific field to be associated with a
single individual, but in the case of the subject of the the-
matic series now being launched in Investigative Genetics,
this is surely so; Alec Jeffreys (Figure 1) is DNA finger-
printing. Having invented the method, he coined the per-
fect name for it - how different things might have been if
it had been called the tandem-repeat-based identification
technique (or something similarly dull). He realized its
potential and immediately applied, developed and refined
it. He then followed his nose to unravel the mystery of
the madly mutable minisatellites that make up DNA
fingerprints, and eventually to understand the engines of
genome variability that reside in recombination hotspots.
‘I think I was born a scientist’, he has said [1]. He certainly
seems to have been born with unquenchable enthusiasm
and curiosity, and it is this quality that has led him on his
extraordinary scientific journey.
The story of DNA fingerprinting has been told more
than once, but that is because it is such a good tale (its
inventor tells it very well himself [2]), and it deserves a
brief retelling here. Having noticed the sequence similarity
between core elements of tandem repeats in the myoglo-
bin gene and a few other known minisatellites, Alec made
a pure repeat probe, and radiolabelled and hybridized it to
Southern blots of restriction-digested DNA. The probe
cross-reacted with a set of hypervariable minisatellites,
and on the morning of Monday 11 September 1984 the
first fuzzy DNA fingerprint emerged from the developing
tank. In this ‘eureka moment’, Alec could immediately see
the diversity, and the pattern of inheritance in DNA from
a human pedigree. In his seminal paper [3] he foresaw
roles for the method in linkage analysis, in testing tumour
clonality, twin zygosity and paternity, in forensic typing,
and in dissecting fundamental aspects of mutation and
recombination processes. In one remarkably productive
year these ideas were developed in four further papers
[4-7], three of them in Nature.Correspondence: maj4@le.ac.uk
Department of Genetics, University of Leicester, University Road, Leicester
LE1 7RH, UK
© 2013 Jobling; licensee BioMed Central Ltd. T
Commons Attribution License (http://creativec
reproduction in any medium, provided the or
waiver (http://creativecommons.org/publicdom
stated.The first DNA fingerprinting application was in par-
entage testing [6]; normally it is the father who is in
doubt, but this unusual and challenging case was a ma-
ternity test, with paternal DNA unavailable. British nurse
Christiana Sarbah’s 13-year-old son Andrew was denied
re-entry to the United Kingdom after a visit to Ghana,
the immigration authorities suspecting that he was not
her child. Given three undisputed children for comparison,
it was possible to reconstruct the absent father’s DNA
fingerprint, and to strongly support the claimed maternity
over alternative relationships such as aunt-nephew - some-
thing that was not achieved with traditional protein poly-
morphisms such as blood groups. In an immigration
tribunal, the UK Home Office accepted the DNA evidence,
and allowed Andrew to stay with his mother and siblings.
It also stated that it would not contest future immigration
disputes where similar evidence was available, which effect-
ively broke a log-jam of such cases, but created an
avalanche of casework for the Jeffreys lab before the
methods were commercialized [8].
Hot on the heels of this came the first application of
DNA fingerprinting in forensic identification, in a case
that beautifully exemplifies the power of DNA evidence
to link crime-scenes, to exclude suspects, and to support
convictions. Work with Peter Gill and Dave Werrett had
shown that DNA fingerprints could be obtained from
old samples, and importantly that the method of differ-
ential lysis could yield male-specific information from
mixed rape-case samples [4]. When Leicestershire Police
suggested DNA fingerprinting be applied in a local mur-
der investigation it seemed straightforward - two 15-
year-old girls had been raped and strangled about 3
years apart with the same modus operandi, and a
suspect was in custody who had confessed to the second
killing. As expected, DNA profiles (now based on spe-
cific cloned minisatellites, known as single-locus probes)
from semen samples at both crime-scenes showed that
the same man was responsible in each case. The surprise,
though, was that the suspect matched neither scene - the
first DNA-based exoneration. A bold police decision thenhis is an Open Access article distributed under the terms of the Creative
ommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
iginal work is properly cited. The Creative Commons Public Domain Dedication
ain/zero/1.0/) applies to the data made available in this article, unless otherwise
Figure 1 Professor Sir Alec Jeffreys. (Picture taken by Colin
Brooks, courtesy University of Leicester) Prof Sir Alec Jeffreys has
provided informed consent for the publication of his photograph.
Jobling Investigative Genetics 2013, 4:20 Page 2 of 3
http://www.investigativegenetics.com/content/4/1/20triggered the first DNA-based mass screen to find the true
culprit. Blood samples were taken from 5,000 local men,
and following initial exclusion using protein polymor-
phisms, the remaining 500 were tested using the new
DNA technology. None matched, but the stalemate was
broken when Ian Kelly, a colleague of the perpetrator
Colin Pitchfork, told friends that he had been persuaded
to provide a blood sample on his workmate’s behalf. The
eventual DNA profile from Pitchfork himself matched the
crime-scenes, he was convicted, and he remains incarcer-
ated today.
As well as human DNA, that first autoradiograph had
included samples from various other species, and showed
that the core minisatellite probes also detected hyper-
variable loci in non-human genomes [1]. Applications
promptly followed in mice [9], cats and dogs [10], and
birds [11,12]. Perhaps the last hurrah of true DNA finger-
printing came with the autoradiograph published to
confirm that Dolly the sheep was indeed a clone [13].
I first encountered Alec when he gave a barn-storming
talk to the 1991 International Congress of Human Genetics,
in Washington DC. His subject there, described with
his trademark enthusiasm, was a near-magical trick that
detected and mapped the sequence variation betweenindividual repeat units within a minisatellite, revealing a
mind-boggling degree of diversity. He had embraced PCR
early, showing that profiling could be done from trace
amounts of DNA [14], then developing his improbable
method - minisatellite-variant-repeat (MVR) PCR [15].
With a Y-chromosomal minisatellite in hand [16], I
wanted to try it too, and came to Leicester in 1992, finding
the same hospitable environment that Alec discovered
fifteen years earlier, and, in Alec himself, a generous
sponsor. MVR-PCR was perhaps the ultimate DNA
fingerprint, but instead of impacting on forensic ana-
lysis, it turned out to be a key tool in understanding the
complex recombination processes that drive minisatellite
diversity [17]. Forensic DNA testing was moving towards
short tandem repeats (STRs), and after using these
markers in a collaboration with Erika Hagelberg to iden-
tify the skeletal remains of a murder victim [18], and of
Josef Mengele [19], Alec’s research interests shifted away
from forensics. He has, however, maintained his willing-
ness to engage in public debate about forensic genetics
and DNA databases.
Alec himself deplores the bean-counting that goes on
in judging science these days, but nonetheless it is worth
noting that he has well over 200 publications, an h-
index of 67, and over 21,000 citations of his work, a figure
that continues to grow. Since joining the University of
Leicester in 1977, he has enhanced the reputation of the
place enormously, as can be confirmed by a casual glance
at almost any piece of University publicity. It was some-
thing of a surprise when he retired in September 2012
since his enthusiasm for experimental science and his
continuing technical élan seemed likely to keep him at the
bench, pipette in hand, forever. Our Vice-Chancellor, dur-
ing the valedictory address, noted the irreplaceability of
Alec, but said that he took some comfort from the fact
that ‘at least we now have Richard III’ [20]. The amuse-
ment expressed by Alec at being supplanted by the
skeletal and wormy [21] remains of a long-dead king
can be imagined.
DNA fingerprinting has also, of course, had a massive
impact on society. Indeed, it is hard to think of another
modern scientist whose work has had the societal reach
of Alec’s. His list of prizes and honorary degrees is al-
most absurdly long (particularly when set beside those
of his departmental colleagues), but it is the public rec-
ognition that is particularly telling - Midlander of the
Year (1989), Honorary Freeman of the City of Leicester
(1993), and Morgan Stanley Greatest Briton (2007). An-
other honour that many UK celebrities quietly crave is an
appearance on BBC Radio 4′s long-running programme
Desert Island Discs. Participants must choose eight re-
cords they would take to a desert island and use them to
punctuate an interview about their lives; it is said that
many a deceased public figure is found to have their disc
Jobling Investigative Genetics 2013, 4:20 Page 3 of 3
http://www.investigativegenetics.com/content/4/1/20list stored safely away in preparation for the call. Alec was
called [22], and his appearance shook middle England out
of its slumber by including Feel the Beat, by Trance DJ
‘Darude’, among his chosen records.
As well as a spectacular researcher, Alec has been a
highly valued colleague in Leicester - a modest and truly
collegiate person who has been a popular teacher of
undergraduates, who has shown an almost superhuman
ability to unfailingly ask a pertinent question at the end
of a seminar (no matter how boring or impenetrable it
was), and who has been generous with his advice and
support.
These days our universities, institutes and funders
spend a lot of time beating us over the head with de-
mands for our research strategies, translational research
plans, and pathways to impact. As Alec has said [23], ‘If
someone had told me in 1980, ‘Go away and figure out a
way of identifying people with DNA’, I would have sat
there looking very stupid and got nowhere at all’. The
story of DNA fingerprinting is a reminder that following
your nose, and your scientific enthusiasm, can get you a
long way.
Competing interests
The author declares that he has no competing interests.
Received: 12 September 2013 Accepted: 17 September 2013
Published: 18 November 2013References
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doi:10.1186/2041-2223-4-20
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Curiosity in the genes: the DNA fingerprinting story

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