Dna: The Secret of Life

by Watson, James

  On The Montel Williams Show, or Ricki Lake, or Jenny Jones, you can see the young women and men looking nervous. The host opens an envelope, gives the couple a meaningful look, and then reads the card. The woman covers her face with her hands and bursts into tears, while the man leaps into the air, pumping his fist. Alternatively, the woman leaps to her feet, pointing triumphantly at the man who remains slumped, shoulders bowed, in his seat. In either case, we have just seen one of the more outlandish applications of DNA fingerprinting – the ultimate in infotainment.

  Daytime television may make theater of the subject, but paternity testing is a serious business with a long tradition. Since the beginning of human history, much of one's life – its psychological, social, and legal realities – has depended on the identity of one's father. So, quite naturally, science has been drafted into the service of paternity testing ever since genetic techniques for distinguishing individuals were first developed. Until the advent of molecular genetics, blood itself was the most scientific clue to paternity. The patterns of inheritance were reliable and well understood, but with only a handful of blood groups to test for, the trait's power to discriminate was limited. Practically speaking, a test for blood type has limited power to exclude wrongly accused fathers, and it can never provide definitive affirmation of the right one. If our blood types are not compatible, I am assuredly not your father; but if they are, it's no certain proof that I am – the same will be true of any number of men who have the same blood type I have. Using other markers in addition to the familiar ABO blood group markers improves the resolving power of this kind of test but it still cannot match the statistical muscle of STR-typing: an STR-based genetic fingerprint can establish proof positive of paternity. And in the era of PCR, it is convenient enough to use.

  So convenient, in fact, that mail-order paternity testing companies do a thriving business. In some cities huge roadside billboards advertise a local paternity testing service with the none-too-subtle pitch line: "Who's the Daddy?" For a fee, these companies will mail you a DNA sampling kit that includes a swab to scrape some cells from the interior of the mouth. (Samples collected this way would not stand up in court. To be admissible, a DNA fingerprint must be based on a sample collected by a certified lab, which must verify the chain of evidence so as to prevent the sort of genetic switcheroo we saw in the Pitchfork case.) The tissue samples are sent by overnight courier to the testing laboratory, where the DNA is extracted.

  The child's DNA fingerprint is compared with that of the mother; any STR repeats present in the child but not in the mother are presumed to have come from the father, whoever he may be. If the fingerprint of a supposed father lacks any of these repeats, he must be excluded. If none are missing, the number of repeats allows us to quantify the likelihood that a match is definitive by the so-called Paternity Index (PI). This measures the chances that some man other than the actual father could have contributed a particular STR, and it varies in relation to how common a given STR is in the population. The PI for all STRs are multiplied together to give a Combined Paternity Index.

  Most paternity tests are, of course, handled with the utmost discretion (unless you happen to be on a talk show), but one recent analysis drew many headlines owing to the great historical interest in the alleged father. It had long been suspected that Thomas Jefferson, third president of the United States and the principal author of the Declaration of Independence, was more than a founding father: he was thought to have had one or more children by his slave Sally Hemings. The first accusation was made in 1802, just twelve years after the birth of a boy, Tom, who later took the last name of one of his subsequent masters, Woodson. In addition a strong resemblance to Jefferson had been widely remarked in Hemings's last son, Eston. DNA was destined to set the record straight.

  Jefferson had no legitimate male descendants so it is impossible to determine the markers on his Y chromosome. Instead, researchers took DNA samples from male descendants of Jefferson's paternal uncle, Field Jefferson (whose Y chromosome would have been identical to the president's), and compared them with samples from the male descendants of Tom and Eston. The results showed a distinct Jefferson fingerprint for the Y chromosome, but this DNA fingerprint was not present in the descendants of Tom Woodson. Jefferson's reputation had dodged that bullet. In Eston Hemings's descendants, however, the Jeffersonian Y chromosome signature came through loud and clear. But what the DNA cannot confirm beyond reasonable doubt is the source of that chromosome. We cannot say with certainty whether Eston's father was in fact Thomas Jefferson or some other male in the Jefferson lineage who might also have had access to Sally Hemings. Indeed, some suspicions have been cast on Isham Jefferson, the president's nephew.

  Centuries of national reverence, then, are no protection against the harsh revealing light of DNA evidence. Nor, it seems, is any amount of celebrity or money. When the Brazilian model Luciana Morad claimed that Mick Jagger was the father of her son (whom she named Lucas Morad Jagger), the Rolling Stone denied it and demanded DNA testing. Perhaps Jagger was bluffing, hoping that the threat of a forensic denouement would weaken Ms. Morad's resolve and induce her to drop the case. But she did not. The tests were positive, and Jagger found himself legally obliged to contribute to the upbringing of his son. Boris Becker, too, submitted to a paternity test over a girl born to Russian model Angela Ermakova. The tabloids had a field day with stories that the tennis star believed himself the victim of a blackmail scheme contrived by the Russian mafia – the lurid details of how this plot was supposedly perpetrated are best left in the pages of the tabloids. Suffice it to say that when the DNA results were in, the swaggering Becker acknowledged his deed and pledged to support his daughter.

  DNA fingerprinting to identify a child's biological relatives has been applied to causes rather more uplifting than those of Messrs. Jagger and Becker. In Argentina, between 1975 and 1983, 15,000 people were quietly eliminated for holding opinions unpopular with the ruling military junta. Many of the children of the "disappeared" were subsequently placed in orphanages or adopted illegally by military officers. Having lost their own children to the regime, the mothers of the disappeared then set about finding their children's children – to reclaim their grandchildren. Las Abuelas (grand– mothers) drew attention to their nationwide quest by marching every Thursday in the central square in Buenos Aires. They continue their search to this day. Once a child has been located, genetic fingerprinting methods can be used to determine who is related. Since 1984, Mary-Claire King – whom we encountered earlier grappling with another set of relationships, that between humans and chimpanzees – has provided Las Abuelas with the genetic analysis needed to reunite families torn apart by eight nightmarish years of misrule.

  DNA fingerprinting has come a long way since its first forensic applications. It is now a staple of our popular culture, a consumer good for the genealogically curious; a mousetrap in the ongoing spectacle of "gotcha" we play with celebrities and with those ordinary folk who wish only to be on television. But its most serious application remains in the resolution of legal questions involving life and death. The United States is the only nation in the Western world that still imposes the death penalty. Between 1976, when the Supreme Court reinstated capital punishment after a ten-year hiatus, and 2001, 749 convicts were put to death, and by the end of that period there were 3,593 prisoners on death row. It is against this background that we need to examine the work of the Innocence Project, and its founders, Barry Scheck and Peter Neufeld, some of the earliest and staunchest critics of DNA fingerprinting, at least as it was first practiced. Since the early days, Scheck, Neufeld, and other defense attorneys have come to realize that the forensic technology they opposed is actually a powerful tool for justice – more capable, in fact, of exculpating the innocent than of convicting the guilty. Proving innocence merely requires finding a single mismatch between a defendant's DNA fingerprint and that taken from the crime scene; proving guilt, on the other hand, requires demonstrating statisticall
y that the chances of someone other than the accused having the specified fingerprint are negligible.

  As of November 2002, the work of lawyers and students in Innocence Projects (there is now a whole network of them, based at law schools throughout the country) has led to the exoneration of 117 wrongfully convicted individuals. In Illinois, six of these mistaken convictions had resulted in death sentences, leading Governor George Ryan to take a remarkable and – given popular support for law-and-order palliatives like capital punishment – politically dangerous step of imposing an indefinite moratorium on executions in the state. In addition, Ryan appointed a special commission to review the handling of capital cases; published in April 2002, this commission's report listed among its strongest recommendations that provision be made to facilitate DNA testing of all defendants and convicts in the state's criminal justice system.

  By no means has all DNA testing of those who insist on their innocence led to the overturning of convictions. James Hanratty was convicted of one of the most notorious murders in twentieth-century Britain. He accosted a young couple, shot the man fatally, and raped the woman before shooting her five times and leaving her for dead. Despite his insistence that he'd been miles away when the crime occurred, Hanratty was found guilty and sentenced to hang. In 1962, he became one of the last criminals to be executed in Britain.

  Hanratty died proclaiming his innocence, and his family began a posthumous campaign to clear his name. Their efforts became a cause célèbre: they succeeded in compelling the authorities to have DNA extracted from the female victim's semen-stained underwear and from the handkerchief that had masked the assailant's face; both samples were then compared with DNA fingerprints from Hanratty's brother and mother. To their chagrin, it was determined that the crime scene DNA had indeed come from a member of the Hanratty family. Still unsatisfied, the Hanrattys had their black sheep's body exhumed in 2000 in order to retrieve tissue samples for DNA extraction. That more direct analysis showed it was unequivocally Hanratty's DNA on the underwear and the handkerchief. Finally, grasping for straws, the family argued, following the recently successful Simpson defense, that the sample sources had been handled improperly and become contaminated. But the Lord Chief Justice proved less distractable than the Simpson jury. He rejected this claim out of hand: "The DNA evidence establishes beyond doubt that James Hanratty was the murderer."

  26. A plasmid as viewed by the electron microscope

  27. Herb Boyer and Stanley Cohen, the world's first genetic engineers

  28. Recombinant DNA: cloning a gene

  29. Paul Berg with his viral Honda

  30. A P4 laboratory, the ultrasafe facility required for biomedical research on lethal bugs such as the Ebola virus or for developing biological weapons. During the late 1970s, scientists using genetic engineering methods to do research on human DNA were also required to use a P4 laboratory.

  31 and 32. Wally Gilbert (left) and Fred Sanger, sequence kings

  33. TIME magazine marks the birth of the biotechnology business (and looks forward to a royal wedding).

  34. The Sanger method of DNA sequencing

  35. Phil Leder with his "Harvard" onco-mouse

  36. The effect of eons of artificial selection: corn and its wild

  37. Bt cotton: cotton genetically engineered to produce insecticidal Bt toxin thrives while a non-Bt crop is trashed by pest insects.

  38. The full complement of human chromosomes highlighted by chromosome-specific fluorescent stains. The total number of chromosomes in each cell's nucleus is 46—two full sets, one from each parent. The genome is one set: twenty-three chromosomes— twenty-three very long DNA molecules.

  39. Kary Mullis, inventor of PCR

  40. Amplifying the DNA region you're interested in: the polymerase chain reaction

  41. The genome project goes commercial: William Haseltine and Craig Venter.

  42. International collaboration: British and American scientists were the first to complete the sequencing of the genome of a complex organism, the nematode, C. elegans. The project's leaders, Bob Waterston and John Sulston, still found time to relax.

  43. Mass production meets DNA sequencing: MIT's Whitehead Institute.

  44. What our genome looks like: the major features of a small human chromosome, number 20

  45. Barbara McClintock, discoverer of mobile genetic elements

  46. Fruit fly faces. On the left is a normal individual, with a fair of feathery antennae protruding from its forehead. On the right is an antennapedia mutant, in which the antennae have been replaced by fully formed legs.

  47. Proteomics: the 3-D structure of a cancer-causing protein, BCR-ABL. The fusion of the two genes caused by a chromosomal abnormality leads to the production of this protein, which stimulates cell proliferation and may cause a form of leukemia. Shown in purple is a small molecule drug, Gleevec, which inhibits BCR-ABL function (see chapter 5). It is with 3-D information like this that drugs will in the future be designed to target particular proteins. This representation of BCR-ABL's structure does not show the details of the atoms or individual amino acids, but nevertheless accurately reflects the protein's layout.

  48. Mary-Claire King

  49. The mitochondrial DNA human family tree

  50. Out of Africa and beyond: Our species originated in Africa and spread out from there. Estimated colonization dates are based on mtDNA data.

  51. DNA fingerprinting using STRs. The DNA of two suspects is compared to DNA recovered from the crime scene. The fingerprint of B matches that of the crime scene DNA.

  Today short tandem repeats (STRs) have replaced RFLPs as the keys to genetic identification. STRs, in which sequences of two to four bases recur as many as seventeen times, are the segments routinely amplified by PCR. For example, D7S820 is a region on chromosome 7 where the sequence AGAT can occur between 7 and 14 times. It happens that DNA polymerase, the enzyme that copies DNA, does a bad job of copying these repeating chunks of DNA—it tends to get the count wrong—so there is a high mutation rate in copy number of the AGAT sequence at D7S820. To put it another way, there is a great deal of variation in the number of AGAT copies among individual humans. With two copies of chromosome 7 (one from our father, the other from our mother), we typically have a different AGAT repeat count on each—say, 8 on one and 11 on the other. This is not to say, however, that an individual cannot be homozygous for a particular repeat count (e.g., 11 and 11). If we carry out DNA fingerprint analysis on a crime-scene blood sample and find it matches a suspect's fingerprint for D7S820 (say, 8 and 11 repeats), we have one indication of a match but not conclusive proof. After all, many others also have an 8/11 genotype for D7S820. It's therefore necessary to look at multiple regions; the more regions in which the crime scene DNA matches a suspect's, the greater the probability of a match, and the more remote the chances that the crime scene DNA could have come from anyone else. Under the FBI's system, a DNA fingerprint is produced from the analysis of twelve such regions, plus a marker that determines the sex of the individual from whom the DNA sample is derived.

  52. Alec Jeffreys, father of DNA fingerprinting

  53. Nancy Wexler holding a child with early-onset Huntington disease, Lake Maracaibo, Venezuela

  54. Genetic mapping of a disease gene. For convenience, only two generations and a few individuals are shown. If the analysis is to be statistically powerful, information is required from a large number of related individuals.

  55. David Vetter, whose inherited immune system disorder made him susceptible to the slightest infection, was raised in a sterile world and became the original "bubble boy."

  56 and 57. Fluorescent staining for chromosome number. A cell nucleus (dark blue) is probed for chromosome 10 (light blue) and chromosome 21 (pink). The image on the far left shows a normal karyotype with two copies of each chromosome; in the other, we see a Down karyotype, which has an extra copy of chromosome 21.

  58. Trofim Lysenko measuring wheat plants in a rare burst of empiricism
on a collective farm near Odessa, Ukraine

  59 and 60. The impact of just one gene. At top, a normal mouse mother is highly attentive to her offspring. The mother below, lacking a functional fos-B gene, ignores her newborns.

  61 and 62. The cultural wonder that is Homo sapiens. Two contrasting notions of chic: Paris 1950s and the highlands of Papua New Guinea. Evolutionary psychology seeks the common denominators underlying all our widely divergent behavior.

  Usually the strongest objection to reopening a case comes from the district attorney, who is understandably reluctant to see a hard-won conviction subject to post-trial scrutiny. But sometimes such rigidity can be self-defeating, and if prosecutors have now learned that genetic evidence can nail a case, they should also recognize that DNA may also be the surest way to keep one shut. The example of Benjamin LaGuer illustrates the point. Sentenced in 1984 to forty years in prison for a rape in Worcester, Massachusetts, he never stopped protesting his innocence. Like Hanratty, he attracted a retinue of rich and famous sympathizers, who in 2001 arranged and paid for samples of DNA to be analyzed. The results must have surprised them all: LaGuer was the rapist. One can imagine that a man facing forty years behind bars rightly imagined he had nothing to lose in making such a demand. But ironically, it had taken two years to get the district attorney's office to agree to the DNA fingerprinting. As an editorial in the St. Petersburg Times sensibly remarked, "In hindsight, the prosecutor could have wasted less time arguing and gotten the pleasure of saying 'I told you so' much sooner had he consented early on to the DNA test."