The Human Genome: Can We Create Ourselves?
Session Notes

Agenda:

1. What is the genome?
2. What have we learned from it?
3. What can we do with it?
4. The Race
5. Discussion Points

Notes

1. What is the genome [Haymer 2002][Ridley]?
   1. genes located in the nuclei of cells
   2. two complete sets of the genome (except in egg and sperm cells): one from mom, one from dad.
      • 23 chapters or chromosomes
      • each chapter has thousands of stories or genes
      • each story made up of paragraphs or exons interrupted by ads or introns
      • each paragraph made up of words or codons
      • each word is written in letters or bases
   3. genes occur on chromosomes -- long, threadlike structures
   4. there are 23 pairs of chromosomes in the human cell
   5. genes contain coded instructions for the production of proteins
   6. proteins carry out all the tasks of the body's cells
   7. the DNA sequence of genes determines the structure and function of the proteins
   8. DNA = deoxyribonucleic acid
   9. genes are made of DNA
   10. DNA a complex molecule made of a string of nucleotides
   11. a nucleotide = the sugar deoxyribose + phosphoric acid + base
   12. all nucleotide have deoxyribose and phosphoric acid; the base can be one of four:
       1. A = adenine
       2. G = guanine
       3. C = cytosine
       4. T = thymine
   13. DNA molecule consists of two strands (helix), with bases in pairs to form the rungs (s. picture p. 87 2002 Yearbook)
       • A pairs with T
       • G pairs with C
   14. the sequence of bases along certain stretches of the DNA specify the production of ribonucleic acid (RNA)
       • made up of the same bases, except T is replaced by U = uracil
   15. RNA assembles a protein
       • text of gene copied into RNA, called messenger RNA
       • the messenger is edited to eliminate introns
       • a microscopic machine, the ribosome moves along the RNA translating each 3 letter codon into one letter of a different alphabet of 20 amino acids
       • each amino acid is attached to the last to form a protein
   16. In the RNA molecule, a sequence of three bases (a codon) encodes information corresponding to the production of a particular amino acid, the building block of a protein
   17. the order of codons specified by a gene spells out the sequence of amino acids making up a protein
   18. there is not one gene : one protein
       • the RNA created according to a gene's instruction can produce several different proteins.
       • scientists aren't clear on these mechanisms.
   19. only +1% of DNA in one chromosome is coded for proteins
       • some of the extra DNA regulates the function of adjacent genes
       • the remainder may be evolutionary left overs
   20. 26K to 40K genes
   21. When genes are replicated mistakes are sometimes made (mutations)
       • a base omitted
       • a wrong base inserted
       • whole paragraph inserted or omitted
       • 64 codons -> 20 amino acids -- room for error
2. What have we learned from it?
   1. genetic differences [Haymer 2002]
      1. each human's genome (except for identical twins/clones) are unique
      2. most differences due to polymorphisms: base changes in the DNA of an individual's body or sex cells
      3. the latter are passed to offspring
      4. caused by cell division or exposure to chemicals or radiation
      5. mutations are changes that cause the production of an altered protein
      6. millions of polymorphisms occur in human DNA
      7. single nucleotide polymorphisms, SNPs, snips: change in a single base at a particular location on a chromosome (e.g., one person has guanine at a point of chromosome 10; another has thymine.)
      8. if the snip occurs in a DNA sequence making up a gene, can cause the production of altered protein
      9. in some cases this can result in illness, or alter response to medication or treatment for a disease
      10. SNP Consortium formed in 1999 in Chicago by pharmaceutical companies, university research groups, and medical charities to locate SNPs
      11. some SNPs characteristically occur in women or men, or ethnic groups
   2. LUCA: the Last Universal Common Ancestor [Ridley: Chromosome 1]
      1. RNA evolved before proteins and DNA [p. 17]
         • ingredients of DNA made by modifying ingredients of RNA
         • DNA: Ts made from RNA's Us
         • many enzymes, thought made of protein, rely on RNA to work
         • RNA, unlike DNA + protein, can copy itself without assistance
         • a cell's most primitive and basic functions require the presence of RNA
         • RNA, unlike DNA, can act as a catalyst breaking up and joining molecules including RNA
      2. 'ur-gene': the first gene, a combined replicator-catalyst consuming chemicals around it to replicate itself
      3. before any other life, there existed RNA -- a riborganic world
      4. But RNA is an unstable substance
         • too hot, too large: error catastrophe -- a rapid decay of the message in their genes
         • one RNA invented by trial and error DNA and a system for making RNA copies from it
         • later amino acid tags, separating the 3 letter codons, in DNA joined together to form proteins
         • 3 letter codons became code for proteins -- the genetic code
      5. Now LUCA
         • we all evolved from LUCA
         • one possibility: she was bacterium-like
           • deep underground in fissures in hot igneous rock
           • fed on sulfur, iron, hydrogen, carbon
         • or possibly protozoa-like
           • cold climate
         • 3 letter codons mean the same in all creatures, simple and complex
           1. there is one, unified creation
           2. LUCA is EVE
           3. the unity of all life
           4. the primacy of RNA
   3. Our kinship with the chimpanzee [Ridley Chromosome 2]
      • all primates have 24 pairs of chromosomes, except humans
        • 2 ape chromosomes have fused together in the human
      • the rate at which genes accumulate spelling changes indicate relationship between species [p. 28]
        • spelling differences between gorillas and chimps is greater than between chimps and humans
        • humans and chimps split 5 to 10 million years
        • human = 98% chimps
        • chimp = 97% gorilla
   4. Genetically caused diseases [Ridley Chromosome 4]
      • CAG CAG CAG ... gene mutates and can cause Huntington's chorea (re. Arlo Guthrie)
      • if the gene is missing, Wolf-Hischhorn syndrome results
      • do not know much else about this gene
      • normally {CAG}^<=35
      • {CAG}^>=39 => Huntington's chorea 100%
      • other mutation of genes with C*G repeats cause neurological diseases
        • {CCG | CGG}^>=200 gene on X => mental retardation
        • {CTG}^50-1000 gene on chromosome 19 => myotonic dystrophy
      • anticipation: the number of repeats can increase each time the gene is copied (hence the disease is manifested late in life)
   5. Pleiotropy: multiple effects of multiple genes [Ridley Chromosome 5]
      • asthma
      • propensity or susceptibility to certain conditions
      • normal vs abnormal: in another age what trigger asthma, protected against worms.
   6. Intelligence [Ridley Chromosome 6]
      • alleles: alternative version of the same genetic 'paragraph', all equally fit
      • gene for intelligence?
        • DANGER: eugenics
        • intelligence: part genetic (twin studies); part environment
        • nature/nurture intimately intertwined
   7. X vs Y [Ridley Chromosome X and Y]
      • X chromosome pairs with Y
        • in male mammals and flies
        • in female butterflies and birds
        • XX in female mammals and flies; male birds and butterflies
      • (all other chromosomes pair with like 1 to 1, 2 to 2, etc)
      • one of the pair becomes inert (unlike other chromosome pairs where both are expressed)
      • X from mom
      • X or Y from dad
      • colorblindness, hæmophilia more common in men because gene is on X and there exist no spare X
      • genes good for men accumulated on the Y
      • genes good for women accumulated on the X
      • normally the two paired chromosomes swap genes, but not so with X and Y
        • gene using calcium on Y for antlers
        • gene using calcium on X for milk
      • gene on Y 'hijacked" genes on X
      • 'female' is the default in mammals ('male" is the default in birds and butterflies)
        • the SRY gene on the Y chromosome triggers the masculinisation of the embryo
        • between species SRY is 10x as varying
        • SRY fastest evolving
      • is there a "gay" gene?
        1. homosexuality highly heritable
        2. if man X is gay, most likely mother's brother is gay (runs in female line)
        3. gene on X chromosome?
           • same version of marker Xq28 shared by 75% of gay men
           • different version by 75% of straight men
        4. how could it survive, since gay men typically won't pass it along?
        5. has to have an advantage for females
        6. one theory:
           • 3 genes of Y chromosome: H-Y minor histocompatibility antigens
           • provokes a reaction in mom's immune system
           • which is likely to be stronger in successive male pregnancies (female babies don't produce the antigen)
           • these genes may be needed to switch on genes that contribute to the masculinisation of the brain
           • if mom's immune system is suppressing the genes, then the brain is not masculised even though the genitals are
   8. The genetics of genealogy [Ridley Chromosome 13]
      • 1980s: Luigi Luca Cavalli-Sforza: variations in simple genes ('classical polymorphisms') indicate 5 different gene frequency contour maps in Europe
        1. SE to NW follows archaeological data of neolithic farmer's migration from the Middle East 9500 years ago
        2. steep hill in NE: Uralic (e.g., Finnish and Estonian and Hungarian) speakers
        3. radiation gout from the Ukrainian steppes, reflects the expansion of pastoral nomads from the Volga-Don region in 3000 BCE
        4. peaks in Greece, southern Italy and western Turkey -- the Greeks of the first and second millennium BCE
        5. steep little peak in the Basque country, possibly pre-neolithic
3. What can we do with it?
   • helpful (?)
     1. Committee for the Prevention of Jewish Genetic Disease [Ridley, p 191]
        • organizes testing of schoolchildren's blood
        • matchmakers call a hotline and quote the two anonymous numbers of the couple
        • if both carriers of the same mutation for Tay-Sachs disease or cystic fibrosis, advised against marriage
        • very successful: cystic fibrosis virtually eliminated in American Jewish population
        • been criticized (1993 in NYTimes) as eugenic
     2. [Haymer 2002] Using the knowledge of SNPs, physicians can have access to the genetically programmed details of how your body words, allowing vastly more accurate diagnosis and more effective prescription of drugs and other treatments
        • knowing what proteins a patient's tumor cells produce, a physician can target them for treatment
        • predict susceptibility to disease and so modify behavior, such as heart-disease
        • your SNP profile on a card: for a computer to specify treatment and appropriate medication
        • cystic fibrosis: SNPs on the CFTR gene
        • pharmacogenetics: specifying drugs to match your SNP profile
        • Alzheimer's treatment by tacrine: patients with a gene that codes for protein apolipoprotein E won't response
     3. Cure cancer
     4. gene therapy, manipulation of genes to treat and cure disease [Haymer 2002]
        1. disable virus to make it harmless
        2. splice normal human gene into the virus' genetic material
        3. virus is mixed in lab with cells removed from patient
        4. virus transfers desired gene into the cells
        5. cells injected into patient and new gene will code for the protein that was absent
        • cystic fibrosis
        • brain tumors
        • melanoma
        • sever combined immunodeficiency disease (the bubble boy syndrome)
     5. anthropologists: comparisons of genetic traits of ethnic groups to track migration of prehistoric people
     6. biologists: comparisons of humans and animals to understand evolution
     7. Prevention [Ridley Chromosome 19]
        • is it morally wrong not to develop technology that can cure?
        • is it morally wrong to have a cure and not use it wherever it is needed?
        • the apolipoprotein genes (APO): A, B, C, and E. APOE is on Chromosome 19
          1. APO Epsilon and APO Beta needed to work to dispose of cholesterol and triglyceride properly.
          2. If they do not work, build up of fat in bloodstream (on the walls as atheroscelerosis), resulting in a coronary.
          3. three varieties of APOE, E₂, E₃, E₄, each with a different efficiency of removing triglyceride
          4. so genetic screening of which brand can aid in determining susceptibility to heart attack and a warning to manage diet
        • But there is also a correlation of the APOE to Alzheimer's
          1. no E₄, 21% chance and mean age is 84
          2. one E₄, 47% chance and mean age is 75
          3. two E₄s, 91% chance and mean age is 68
          4. more likely among whites and more likely among women: other genes are involved
          5. now what would have happened if a journalist in 1979 managed to get some of Reagan's DNA and tested it to discover he would likely have Alzheimer's in office?
        • should we test for an incurable disease or genetic condition?
          1. what if there are methods to slow its onslaught?
          2. to volunteer for experimental drugs
          3. what about insurance companies? should they know that you are at risk?
          4. note difference between smoking (an insurance bias for a choice) and having the APOE₄ gene (an insurance bias for a natural condition)
   • bad (?) --- consider Gattaca
     1. Eugenics [Ridley Chromosome 21]
        • genetic screening: amniocentesis
          1. check for three chromosome 21s = Downs
          2. abort (why bring into the world the incapacitated)
          3. not abort (still children of God)
          4. eugenics at work
        • eugenics
          1. coined in 1885 by Francis Galton, Darwin's cousin as the process of selective breeding of humans
          2. Karl Pearson (early 1900s): nation (Britain) must operate selective breeding to stay ahead of Germany
          3. and caught on in Germany based on Nietzsche (superman) and Haeckel (biological destiny)
          4. at first just a popular, volunteer project
          5. then dysgenics: keeping the "weakest" from breeding -- the mentally disabled, other races, criminals, etc.
          6. In the USA, the Immigration Restriction Act of 1924 resulted from eugenics campaign to keep non- Anglos out of the country
          7. sterilization laws passed in USA between 1910 and 1935: >100K people sterilized for 'feeble-mindedness' through 1970s
          8. likewise other Protestant countries
          9. no such laws ever in Britain, though the source of much eugenics philosophy
             • most Britons were in favor: socialists, liberals, and conservatives pre-WWII, including H. G. Wells and Winston Churchill
             • Josiah Wedgewood, MP resisted it and demonstrated the cruelty and oppressive nature of eugenics: requiring the full might of the nation over the individual
             • eventually scientists recognizing heredity was not a prime cause of "feeble-mindedness", the Labour party recognizing eugenics as class warfare, along with the RC church turned on eugenics
             • ... and the Nazis did it
          10. no such laws in RC countries
        • eugenics: inevitably cruel and oppressive
        • possible new routes to eugenics:
          1. genes for intelligence
          2. germline gene therapy
          3. prenatal diagnosis and screening
        • 'laissez-faire' or private eugenics: each individual through screening makes their own decision of the preferred child
          • choosing boys over girls (India)
          • choosing more intelligent babies
        • but to outlaw screening could be just as cruel -- not to detect curable conditions for example.
        • genetic screening: for private people to make private decisions
        • eugenics: the state making national decisions
     2. Discriminate against people with "bad" genes (insurance companies, employers)
     3. Make "designer babies"
     4. medical forensics: SNP profiles to identify criminals
   • future possibilities
     • how proteins do their jobs in cells
       • how do healing proteins work?
       • how do protective proteins of the immune system work?
     • study of the proteome: the complete set of human proteins
       • Proteomics
       • Protein Structure Initiative
   • ELSI, affiliate with HGP, group of health care professionals, historians, legal scholars, and religious leaders to study ethical implications
4. The Race [Haymer 2000][Haymer 2001][Haymer 2002]
   • J. Craig Venter, of Celera Genomics Corporation (Rockville, MD)
     • formed May 1998
     • private company
     • to be done by 2001
     • plans to patent about 200 genes linked to common diseases
     • uses whole-genome shotgun sequencing
       1. entire set of genetic material from multiple copies of chromosomes broken down into millions of fragments using restriction enzymes
       2. nucleotides in the fragments are all sequenced by machines
       3. high speed computers determine original order of fragments by looking for overlapping sequences of nucleotides
     • decoded all of the nucleotides by April 2000, but not ordered
   • Human Genome Project (HGP)
     • began as a result of scientists looking for genetic causes of cystic fibrosis, Huntington's disease, and breast cancer
     • US National Institutes of Health, US Dept. of Energy, the Sanger Centre in England, research institutions in Japan, German, and other countries
     • Francis Collins, leader
     • to develop a comprehensive description of the h. gen.
     • free of charge by anyone
     • develop physical map of genome using "markers", easy-to-find sequences on the chromosomes
       1. chromosome map of genetic markers
       2. (biochemical scissors) to randomly slice up chromosomes into segments to be readable by sequencing machines
       3. sequence the stretches of DNA between markers, one nucleotide at a time by machines
       4. put the fragments back together
     • responding to Ventor, gave priority to sequencing the gene-rich regions of the genome
   • The prize
     • new drugs and other products worth billions of $$
     • the US Patent office allows newly discovered genes to be patented!
       • first researcher determining the nucleotide sequence of a gene and the function of the protein coded for by the gene can claim exclusive rights to the information
       • the scientist can then license these rights for a fee or royalty
       • the commodification of the elements of life
     • June 26, 2000 Collins and Venter announced they had completed a "rough draft" of the human genome

Discussion Points

1. Consider the movie Gattaca
   • genetically pure future
   • natural born and flawed Vincent ('InValid') assume the identity of a genetic better
   • to achieve dream of space travel
   • uses a DNA broker to find Jerome: genetically perfect, but paralyze in an accident
   • humans becoming automata
   • genetic renegades constantly sought in constant policing
   • "There is no gene for the human spirit"
   • Issues
     1. s. here and here
     2. designer children
     3. genetic profiling
     4. human freedom vs genetic determinism

2. [Haymer 2002, p. 97] Single nucleotide polymorphisms (SNPs) are variations among the genes of individuals in which a single base (genetic building bloc) differs from one person to another at a particular point in the DNA of a chromosome. The SNP in a gene determine whether an individual:
   • develops a certain illness,
   • how he or she reacts to a medication, and
   • other physical characteristics of the person.
   In the future, an SNP profile may contain all the details of one's genetic code.

   Questions:

   • Would you want to know your SNP profile?
   • If you found out that you had a gene that increased risk for an incurable disease, what would you do?
   • Do you think a school, employer, or insurance company should know what kinds of genes you have?
   • would you tell your family and friends about your genetic flaws?
   • Would you ask them about theirs?

3. [Haymer 2002, p. 97] Scientists may someday have enough understanding of genes and proteins to enable them to manipulate genes in sperm, eggs, or unborn children to produce humans that have superior intelligence, improved athletic ability, or enhanced physical appearance.

   Questions:

   • Do you think scientists should be allowed to attempt such experiments?
   • Would this research be ethical?
   • Whose standards of intelligence, ability, or appearance would be applied?
   • Should laws be passed to ban such experiments?
   • would you consider using genetic technology to produce certain desirable traits in your own children?
   • If so, what traits would you desire?
   • Are new laws needed to guard against such practices?

4. Questions [Haymer 2002]:
   • should an individual be tested for incurable diseases?
   • what psychological/spiritual impact might there be on knowing your genetic makeup?
   • Is it right to own and sell genetic information?
   • should there be increased federal oversight of the use of genetic information and technology?
   • what should our response be if a scientist attempts to "improve" the human species?
5. Given our understanding of the human genome, what does it mean to be a human?
6. What does it mean to have a soul?

Web sites [Haymer 2002]

• Celera Genomics
• Human Genome Central
• Human Genome Project Information
• Genome Guide: Home sapiens

References

1. Haymer, David; The Genome Race Is On; World Book Science Year 2000
2. Haymer, David; Genetics; World Book Science Year 2001
3. Haymer, David; What's Next For the Human Genome?; World Book Science Year 2002
4. Ridley, Matt; Genome: The Autobiography of a Species in 23 Chapters; HarperCollins; New York 1999.