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polymerase chain reaction

Polymerase chain reaction (PCR) is a laboratory technique for amplifying small quantities of deoxyribonucleic acid (DNA) into amounts large enough for detailed genetic analysis, invented by Kary Mullis in 1983 and central to modern forensic DNA work, including several tests of hair and other trace samples connected to reported anomalous encounters.

Molecular biology / forensic science · Kary Mullis · 1983

Polymerase chain reaction (PCR) is a laboratory technique for amplifying small quantities of deoxyribonucleic acid (DNA) into amounts large enough for detailed genetic analysis, creating a very large quantity of the originally extracted material.1 The method was conceived in April 1983 by Kary Mullis, who arrived at the idea one Friday night while driving to his cabin in the Anderson Valley, Mendocino County, California.2 Mullis is credited with the initial concept that led to PCR,3 and he was awarded the 1993 Nobel Prize in Chemistry for the technique.4 Modern forensic DNA work was made possible by PCR.5

In forensic science, PCR is used to profile DNA extracted from minimal biological material. In David Berryman’s September 22, 2002 Radio National interview on Polymerase Chain Reaction (PCR) crime-scene contamination, broadcast on Radio National (ABC), David Berryman explained that forensic DNA profiling commonly uses PCR amplification of variable regions of DNA called short tandem repeats (STRs), because forensic samples such as a single hair or the DNA in fingerprint cells contain very little material.6 Henry C. Lee said that most forensic DNA techniques are powered by PCR, a process permitting faithful reproduction of very small amounts of DNA into large amounts of identical copies.7 He said PCR allows investigators to obtain a DNA profile from postage stamps, coffee cups, and single hairs.8

The Anomaly Physical Evidence Group (APEG) directed its discussions with Bill Chalker toward using PCR amplification and sequencing of mitochondrial DNA on a hair sample from the Peter Khoury alien abduction case to test the credibility of abduction accounts.9 Preparing the samples involved a prolonged extraction step at elevated temperatures, fragmentation of the hair, and repeated boiling and freezing with dry ice to release the DNA from its protein structure before purification and PCR amplification.10 UFO Research New South Wales assisted with funding the preliminary PCR “human consensus” DNA comparisons.11 A preliminary mitochondrial DNA PCR profiling comparison against the human consensus, carried out on both Peter Khoury’s hair sample and a sample from Mike Wood’s daughter as part of the mitochondrial DNA PCR profiling comparison of Mike Wood’s daughter’s hair sample against human consensus, found both within the normal human range but different from each other.12 Vivian Khoury’s hair sample did not produce PCR amplification products, which analysts concluded might have been due to chemical treatment.13 A specialised ribosomal PCR DNA profiling was also undertaken on samples from Betty Hill’s dress, as part of Betty Hill’s 1961 dress DNA analysis, to extract non-human DNA alongside standard assessments.14 Kary Mullis did not personally carry out the PCR testing of the Khoury hair samples described in Chalker’s account.15

According to Hair of the Alien, four PCR products were obtained in total from this work: two from the tall blond alien hair and two from Peter Khoury’s own hair, but none from his wife’s hair, which may have been chemically treated and had never come into direct contact with the alien hair.16 The same source states that a 2-centimetre portion of the thin blond hair shaft, cut from just above the root, required extensive grinding to release its DNA, and that no contaminating DNA was found on any outer part of the sample.17 According to the source, PCR studies of that hair shaft, part of the hair-shaft mitochondrial DNA hypervariable region I analysis of Peter Khoury’s alien hair sample (Phase One, 1998-1999), revealed unusual mitochondrial DNA of Chinese genetics carrying a rare 16,108 C-to-T mutation, recorded as the Chinese Mongoloid mitochondrial DNA substitution found in Peter Khoury’s alien hair shaft.18 According to the same source, both sides of the mitochondrial hypervariable region I were amplified by PCR for 37 or 33 cycles respectively, while a nuclear region coding for the CCR5 gene was amplified for 40 cycles.19 A later stage of testing, the Phase Two hair-root DNA analysis of Peter Khoury’s alien hair sample revealing Basque/Gaelic mitochondrial DNA, found that two different samples from the hair root gave two different mitochondrial DNA sequences within the same PCR run: a 16255C genotype for six of seven clones from the soft root, and a 16304 sequence from the hard keratin at the base of the shaft, matching the shaft result from the first round of testing.20

David Berryman has drawn attention to the potential for deliberate contamination of crime scenes with PCR products.21 In his Radio National interview, Berryman said PCR has contamination issues in the laboratory and that a crime scene can be deliberately contaminated using PCR products as the diagnostic test.22 He said this does not require planting hairs or a fingerprint, but can be done by covering the whole scene with DNA PCR products.23 He said it requires only easy access to a publicly available PCR kit and amplifier, comparable in difficulty to buying a litre of milk at a supermarket.24 He said the PCR reaction itself requires no special skill or significant resources and can be performed at home on a stove using publicly available information.25 He said that, based on his data, squirting PCR products around a crime scene is enough to contaminate it virtually beyond any possibility of recovering a genuine DNA profile.26 He was concerned that while considerable effort had gone into resolving PCR-related contamination issues in laboratory settings, the impact of deliberate PCR contamination in the field, at crime scenes, seemed largely ignored.27 Bill Chalker said he considered it certain that Peter Khoury had no knowledge, in 1992, of the forensic PCR contamination techniques only later discussed in the field.28 Chalker also said he considered it very difficult, though not impossible, to fabricate a PCR “brew” containing the same rare genetic substitutions found in the Khoury hair sample, given the rarity of the profile and its unusual attributes near the root and at the shaft.29 Debate continues about the factors that might affect the accuracy of standard PCR-based DNA profiling.30

PCR also featured in the investigation of the 2000-09 Gary Lowrey alien claw discovery. According to Hair of the Alien, six separate rounds of DNA analysis, using different and sometimes novel approaches, were carried out on the claw sample, including a new PCR reaction using novel primers targeting the most conserved DNA sequences on Earth, in order to resolve the case.31 The source notes that molluscs, particularly snails and slugs, secrete a thick mucus containing inhibitors of many enzymes fundamental to molecular biology, including PCR enzymes.32 It states that rigorous DNA analysis using a novel set of oligonucleotide primers for PCR ultimately resolved the identity of the claw sample.33

  1. PCR creates a very large quantity of originally extracted DNA, making more detailed analysis possible
    “The PCR step, in simple terms, creates a very large quantity of the originally extracted DNA, making it possible to analyze the DNA in more detail.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch12:9141-9281
  2. Mullis conceived PCR in April 1983 while driving to his Anderson Valley cabin, Mendocino County, California
    “On a Friday night in April 1983, Mullis was driving up to his Anderson Valley cabin in Mendocino County in northern California... Mullis made one of the great discoveries of modern chemistry—the polymerase chain reaction (PCR)”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch13:256-507
  3. Mullis is credited with the initial concept that led to PCR
    “Dr. Kary Mullis is credited with the initial concept that led to the PCR technique, a discovery that ultimately earned him the 1993 Nobel Prize in chemistry.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch7:5369-5516
  4. Mullis was awarded the 1993 Nobel Prize in Chemistry for PCR
    “a discovery that ultimately earned him the 1993 Nobel Prize in chemistry”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch7:5453-5516
  5. Modern DNA forensic work was made possible by PCR
    “Such work was made possible only through a remarkable breakthrough, the PCR (polymerase chain reaction) procedure.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch7:5253-5357
  6. Berryman explained PCR amplification of STRs is used because forensic samples contain very little material
    “The most common way of doing the forensic analysis at the moment is using PCR amplification of variable regions of DNA, called ‘short hand and repeats’ or STRs, but with forensics in particular, you often work with very small amounts of material—it might be a single hair or even the DNA contained in the cells on a fingerprint on a stamp, or something like that—so you’ve really got very little DNA, there’s not really enough there to do any analysis on, somehow you’ve got to increase the amount, and that’s done by PCR.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:65862-66380
  7. Henry C. Lee said PCR permits faithful reproduction of very small amounts of DNA into large amounts of identical copies
    “[Most] of the forensic techniques are generally powered by polymerase chain reaction, or PCR, a revolutionary process that permits the faithful reproduction of small, sometimes even vanishingly small, amounts of DNA. The process produces large amounts (identical copies) of DNA”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch7:6821-7094
  8. Henry C. Lee said PCR allows a DNA profile from postage stamps, coffee cups, and single hairs
    “allows investigators to obtain a DNA profile from postage stamps, coffee cups, and even single hairs.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch7:7106-7201
  9. APEG's discussions with Chalker focused on PCR amplification and sequencing of mitochondrial DNA on Khoury's hair sample
    “Our discussions then focused on the fact that techniques like polymerase chain reaction (PCR) amplification and sequencing of mitochondrial DNA on the hair sample might provide a real challenge to the credibility of abduction stories”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch12:4689-4915
  10. Extraction process: elevated-temperature extraction, fragmentation, boiling and freezing to release and purify DNA before PCR
    “Following a prolonged extraction step at elevated temperatures, fragmentation of the hair into smaller pieces, and repeated boiling and freezing with dry ice, the DNA from each was released from its protein structure, purified, and prepared for the PCR amplification step.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch12:8867-9134
  11. UFO Research New South Wales assisted with funding the preliminary PCR human-consensus DNA comparisons
    “UFOR (NSW) assisted with the funding of these preliminary PCR “human consensus” DNA comparisons.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:21698-21782
  12. Preliminary mtDNA PCR comparison found Khoury's and Mike Wood's daughter's samples both within normal human range but different from each other
    “Ultimately we did the preliminary step of undertaking a mitochondrial DNA PCR profiling comparison against the “human consensus” on both the “alien hair” and Mike’s daughter’s sample. While different, both were within the normal “human consensus” DNA range.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch15:33177-33428
  13. Vivian Khoury's hair sample did not produce PCR amplification products, possibly due to chemical treatment
    “Vivian’s hair sample did not produce PCR amplification products; the analysts concluded that this might have been due to chemical treatment.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch12:9645-9775
  14. Specialised ribosomal PCR DNA profiling undertaken on Betty Hill's dress samples to extract non-human DNA
    “A specialized (ribosomal) PCR DNA profiling was undertaken to extract non-human DNA along with standard assessments.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch18:5123-5227
  15. Kary Mullis did not personally carry out the PCR testing of Khoury's alien hair samples described in Chalker's book
    “It needs to be made clear that Kary Mullis did not carry out the PCR DNA testing of the Khoury hair samples detailed in this book.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:1302-1427
  16. Four PCR products obtained: two from the alien hair, two from Khoury's hair, none from his wife's hair
    “Four PCR products were obtained in total: two from the hair of the tall blond female (both left and right), two from the young man who collected the hair (both left and right), but none from his wife whose hair may have been chemically treated, so as to make recovery of DNA difficult (and who never came into direct contact with the alien hair).”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch22:10152-10492
  17. 2cm hair shaft portion required extensive grinding to release DNA; no contaminating DNA found on outer part
    “we analysed a 2 cm portion of thin blond hair shaft, which was cut from just above the root. That hard hair shaft required extensive grinding to release its DNA; no contaminating DNA was found on any outer part.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch22:28167-28373
  18. PCR studies of the hair shaft revealed unusual mitochondrial DNA of Chinese genetics with a rare 16,108 C-to-T mutation
    “Those studies revealed an unusual mitochondrial DNA of Chinese genetics, with a rare mutation 16,108 C-to-T, plus four other mutations 16,129, 16,162, 16,172, 16,304 in hypervariable region I (HVRI).”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch22:28506-28699
  19. Hypervariable region I amplified for 37/33 cycles; CCR5 nuclear region amplified for 40 cycles
    “Our PCR methods also remain the same, where both the left and right-hand sides of mitochondrial HVRI (hypervariable region I, nucleotides 16,020-16,400) were amplified for 37 or 33 cycles respectively; while one small nuclear region which codes for CCR5 was amplified for 40 cycles.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch22:30406-30681
  20. Two hair-root samples gave two different mtDNA sequences (16255C and 16304) within the same PCR run
    “Two different samples from the hair root gave two different DNA sequences, within the same PCR: 162555 genotype for 6/7 clones from the soft root (i.e., the skin area of the “donor”) and 16, 304 again (as in the shaft result from the first round of testing) from the hard keratin inside the base of the hard shaft of the hair).”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:74624-74945
  21. Berryman drew attention to the potential for deliberate PCR contamination of crime scenes
    “has been drawing attention to the potential of deliberate contamination of crime scenes with PCR products”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:65657-65754
  22. Berryman said PCR has lab contamination issues and a scene can be deliberately contaminated with PCR products
    “if people want to contaminate a crime scene, using PCR as the diagnostic test is a bit problematic because, as I said, you can contaminate a crime scene using PCR products.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:66538-66701
  23. Berryman said contamination needs no planted hairs or fingerprints, only covering the scene with PCR products
    “You don’t have to distribute hairs or try to put a fingerprint on a wall in the space that looks like it was accidentally put there during a crime—you can just cover the whole scene with DNA PCR products.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:66711-66906
  24. Berryman said it requires only a publicly available PCR kit and amplifier
    “firstly, get access to the kit and amplifier, and that’s easy to do, it’s just publicly available information—it’s like going down to the supermarket and buying a litre of milk, it’s not hard to do”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:66979-67174
  25. Berryman said the PCR reaction needs no special skill and can be done at home on a stove
    “then, do the PCR reaction and once again, that’s easy to do, it’s all publicly available information, it doesn’t require any skill or any significant resource—in fact, you can do it at home on your stove.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:67178-67376
  26. Berryman said squirting PCR products around a scene is enough to defeat genuine profiling
    “Then just go to a crime scene and squirt it around, and that’s enough to contaminate a crime scene from our data, virtually beyond any possibility of recovering a genuine profile.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:67383-67554
  27. Berryman was concerned field contamination at crime scenes seemed largely ignored compared to lab efforts
    “What concerned Berryman was that, while there was plenty of effort in resolving such PCR-related contamination issues in a lab environment, the impact of deliberate PCR contamination in the field, i.e., at crime scenes, seemed largely ignored.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:67564-67799
  28. Chalker said he was certain Khoury had no knowledge in 1992 of PCR contamination techniques
    “Before someone suggests it, the chances of Peter Khoury having this sort of knowledge, only now being discussed and debated in the field of forensics, were certainly nil back in 1992 and pretty much the same even now.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:68034-68247
  29. Chalker said fabricating a matching PCR 'brew' would be very difficult though not impossible
    “The dilemma now would be how anyone could fabricate a PCR “brew” in a similar way that would contain the same rare genetic substitutions. Impossible? No, but very difficult, given the rarity of the DNA profile and its unusual attributes near the root and at the shaft of the hair.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch23:68252-68527
  30. Debate continues about factors affecting the accuracy of standard PCR-based DNA profiling
    “Even with standard PCR-based DNA profiling, considerable debate continues about factors that might affect its accuracy.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch21:481-591
  31. Six rounds of DNA analysis, including a new PCR with novel primers, were carried out in the Gary Lowrey claw case
    “six separate rounds of subsequent DNA analysis, using different and sometimes very novel approaches, were carried out to bring this case to a conclusion. It was necessary to invent a new polymerase chain reaction using novel primers to the most conserved DNA sequences on Earth in order to finally resolve this case.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch18:27313-27624
  32. Molluscs secrete mucus containing inhibitors of PCR and other molecular-biology enzymes
    “Mollusks, particularly snails and slugs, secrete a thick mucus that contains multiple inhibitors of many of the common enzymes that are fundamental to molecular biology and DNA analysis, including polymerase chain reaction enzymes and those used in standard molecular cloning.”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch18:28131-28399
  33. A novel set of oligonucleotide PCR primers ultimately resolved the claw sample's identity
    “Ultimately however rigorous DNA analysis using a novel set of oligonucleotide primers for the polymerase chain reaction solved the puzzle”
    Hair of the Alien: DNA and Other Forensic Evidence for Alien Abductions ch18:28635-28766

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