The Nature Biotechnology 2000 Millennial quiz

As you write all four digits of the year wrongly on your checks for the first time for a 1000 years, its good to know that some things never change. Once again, its time for Nature Biotechnology to take a quizzical look back at events not only from the past 12 months, but also from the past decade, the past century, and (ambitiously) the preceding 1000 years. Answers provided on opposite page.

1. Merger mania. 1999 was the year of the biotechnology merger. But who merged with/acquired or was acquired by the following:

a) Anergen in January and Ribi ImmunoChem in June

b) Acacia Biosciences in February

c) ChromaXome in March

d) Pioneer Hi-Bred in March and CombiChem in October

e) PolyMasc Pharmaceuticals in May

f) Proteus in May

g) Chiroscience in June

h) Genentech in June

i) Sugen in June

j) Peptimmune in July and Cell Genesys in October

k) Cytel in July

2. Making a move. Which “brilliant strategist” was appointed to the scientific advisory board of Infectech (Sharon, PA) in July?

3. Frankenquestions. Can you stitch together answers to the following?

a) Who are “Captain Swing”, the “Minnesota Bolt Weevils”, and “Seeds of Resistance”?

b) Progress of which crop technology came to a halt in October?

c) Who decided, in January, that genetic engineering was not “organic”?

d) Which monarch stood up in June for rats and a scientific dissident?

e) Who in July accused the US Food & Drug Administration (Rockville, MD) of “deliberately unleash[ing] a host of potentially harmful foods [onto] American dinner plates”?

f) What have GM foods got in common with agent orange, polychlorinated biphenyls, and dioxin?

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5. Zyming slang. Biotechnology brought us abzymes and ribozymes. But what is a snorbozyme?

6. Order from chaos. Arrange in chronological order the following mergers/acquisitions from the 1990s:

a) Amersham/Nycomed

b) Celltech/Chiroscience

c) Chiron/Cetus

d) Ciba-Geigy/Chiron

e) Eli Lilly/Sphinx

f) Glaxo/Affymax

g) Hoffmann-La Roche/Genentech

h) Sandoz/Ciba-Geigy

i) Sphinx/Genesis

j) Zeneca/Astra

7. Added value. The success of an IPO can reflect both a company's true value as well the financial climate at the time. Order the following companies according to the size of their IPO:

a) Cephalon

b) Interneuron Pharmaceuticals

c) Affymetrix

d) BioMarin

e) Cantab

f) Chiroscience

g) Myriad

h) Nanogen

i) Neurex

j) Spiros

8. It's a fix. Namers of biotechnology companies seem to work with a limited palate. Which suffixes or prefixes do each of the following groups of companies share?

a) _Lining (Berlin, Germany); _pharm (Hannover, Germany); _Tec (Hamburg, Germany; _Tect (Rostock, Germany

b) _genics (New York, NY); _soma (London, UK); _sense Pharma (Göttingen, Germany); _toxin (Meckesheim, Germany)

c) _tagen (Malvern, PA); Vir_ Vision (Woburn, MA); Aqua_ (Berlin, Germany); InVi_ (Berlin, Germany)

d) Cor_ (Irvine, CA); Gel_ (Waltham, MA); Bion_ Laboratories (Munich, Germany); An_Biologics (Gaithersburg, MD); Apo_ (Weston, Ontario, Canada)

e) Ara_ (Hayward, CA); Para_ Genetics. (Research Triangle Park, NC); Pharma_ (Salt Lake City, UT); Para_ Therapeutics (Cambridge, UK)

9. Arrange in chronological order the following terms and (for an extra thrill) name the people that coined them.

Antibiotic; Bacteriophage; Bacterium; Biochemistry; Biolistics; Biology; Biotechnology; Chromosome; Cytoplasm; Enzyme; Gene, genotype, and phenotype; Genetic engineering; Hormone; Molecular biology; Photosynthesis; Protein; Vitamin.

10. The art of biotechnology. What is (or will be) GFP-K9?

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12. Connections. Who or what links the following:

a) The end of the overlapping triplet code and the worm genome

b) Proof of semiconservative replication and the biological warfare convention

c) The operon, messenger RNA, and microbial growth kinetics theory

d) Oligonucleotide sequencing and Biogen

e) Old English “healer” and the hemolytic protein, hirudin

f) Variola virus and Genentech

g) Seymour Benzer's 1957 concept of the smallest unit of function of the gene and biotechnology supply company located in Pine Brook, NJ

h) Researchers at The Instititute for Genomic Research in 1995 and Richard Friedrich Johannes Pfeiffer and Shibasaburo Kitasato in 1892

13. The DNA question

Which C demonstrated constant ratio between the frequency of bases in DNA?

Which G discovered a “transforming principle” in pneumococci in 1928?

Which T was a nucleic acid chemist who established the nature of the link between the sugar residue and ring nitrogen in nucleotides?

Which A demonstrated unequivocally the nature of G's transforming principle?

14. Emancipation? The Nobels started in 1901, but only six women have won prizes for their work in biology this century. The citations and the dates of their awards are given below, but who are they?

a) Glycogen breakdown, 1947

b) X-ray crystallography of biological molecules, 1964

c) Mobile genetic elements, 1983

d) Nerve growth factor, 1986

e) Rational drug development, 1988

f) Genetic control of early embryonic development, 1995

15. Of the following pairs, which came first?

a) Crystallographic studies of DNA or elucidation of the last of the 20 amino acids?

b) Correct enumeration of human chromosomes or elucidation of DNA structure?

c) Approval of recombinant insulin or sequencing of human insulin receptor?

Box 3

Box 1: 4. What would we do without…Match the biotechnological breakthroughs to the correct researcher(s) and arrange in chronological order.

2-D Electrophoresis of proteins David Baltimore and Howard Temin

Automatic amino acid analyzer Paul Berg

DNA–DNA hybridization Ralph Brinster and Richard Palmiter

Electron microscope Charles Cantor

Hollow fiber enzyme reactor H. Ghobind Khorana

Monoclonal antibodies A.J. Kluyver and L.H.C. Perquin

Oligonucleotide sequencing Georges Kohler and Cesar Milstein

Oligonucleotide synthesis M. Kroll and Ernst August Friedrich Ruska

Oligopeptide synthesis Archer J. P. Martin and Richard L. M. Synge

Partition chromatography for amino acid analysis Alan Maxam, Wally Gilbert, Fred Sanger. S. Nicklen and Alan Coulson

PCR R. B. Merrifield

Peptide sequencing P.R. Rony

Pulse field gel electrophoresis Fred Sanger

Radioimmunoassay Edwin Southern

Recombinant DNA P.H. J O'Farrell

Reverse transcriptase Marc van Montagu and Jeff Schell

Shake-flask culture William Howard Stein, Stanford Moor and Spackman

Ti plasmid Theodor Svedberg

Transgenic animals by microinjection R. Yalow and Solomon Aaron Berson

Ultracentrifuge Kary B. Mullis

Yeast artificial chromosomes. Maynard Olson

Box 2: 11. Because of a Y2K problem, the Nature Biotechnology computer has malfunctioned while aligning dates with scientific notables from the distant past. Can you match the names to the correct years?

~965–1038 Pioneer genetic mapper Alfred Henry Sturtevant

1170–1250 Leonardo da Vinci

~1219–1292: Microscopist Antony van Leeuwenhoek

~1285–1349 Classifier and taxonomist Carolus Linnaeus

1323–1382 Philosopher Francis Bacon

1452–1524 Francis Crick

~1478–1553 Writer Hieronymus Francastorius

1516–1565 Naturalist and taxonomist Konrad Gesner

1561–1626 Ali Al-hazen, who studied optics

1632–1723 Mathematician Leonardo Pisano (Fibonacci)

1707–1778 Chemist and microbiologist Louis Pasteur

1737–1798 Mathematician Nicole d'Oresme

1803–1873 Biologist Luigi Galvani

1822–1895 Organic chemist Justus von Leibig

1891–1970 Roger Bacon

1916– William of Ockham

Box 3: Answers to quiz

1. (a) Corixa; (b) Rosetta Inpharmatics; (c) TerraGen Discovery; (d) DuPont; (e) Valentis; (f) Therapeutic Antibodies; (g) Celltech; (h) Hoffmann-La Roche; (i) Pharmacia & UpJohn; (j) Genzyme; (k) Epimmune.

2. Susan Polgar, womens' world chess champion.

3. (a) Eco-warriors claiming responsibility for trashing GM crops in the USA; (b) Monsanto's “terminator” gene technology; (c) The US Department of Agriculture, following a barrage of public responses to its initial proposals that GM crops could be organic; (d) Prince Charles, heir to the British throne, who declared Arpad Pusztai a national hero after he fed poisonous potatoes to rats; (e) The Alliance for BioIntegrity, a collection of biotechnology activists, religious leaders, consumer representatives, scientists, and chefs; (f) PR virtuosos Monsanto.

4. 1925, the ultracentrifuge introduced by Svedberg; 1932, Kroll and Ruska describe the electron microscope; 1933, Kluyer and Perquin introduce shake flask culture; 1941–1944, Martin and Synge work on amino acid chromatographic separation; 1949–1950, Sanger devises peptide sequencing; 1958, Stein, Moore, and Spackman describe automated protein sequencing; 1959–1960, Yalow and Berson report the first radioimmunoassay; 1963, Merrifield accomplishes oligopeptide synthesis; 1970, Baltimore and Temin isolate reverse transcriptase; 1971, Rony develops the hollow fiber enzyme reactor; 1972, Berg carries out first recombinant DNA experiments; 1972, Khorana introduces the oligonucleotide synthesis method; 1975, Kohler and Milstein produce monoclonal antibodies; 1975, O'Farrell devises 2-D electrophoresis of proteins; 1975, Southern demonstrates DNA–DNA hybridization; 1977, Maxam, Gilbert, Sanger, Nicklen, and Schell introduce oligonucleotide sequencing; 1981, Brinster and Palmiter create transgenic animals via microinjection; 1983, Montagu and Schell isolate Ti plasmid; 1983, Mullis “invents” PCR; 1984, Cantor describes pulsed field gel electrophoresis; 1987, Olson creates yeast artificial chromosomes.

5. An artificial ribozyme targeted to the nucleolus comprising a hammerhead ribozyme fused to small nucleolar RNA.

6. 1990 (g); 1991 (c); 1992 (d); 1993 (i); 1994 (e); 1995 (f); 1996 (h); 1997 (a); 1998 (j); 1999 (b).

7. Affymetrix ($90 M) 1996 (c); Spiros ($88 M) 1997 (j); Chiroscience ($76 M) 1994 (f); BioMarin ($67 M) 1999 (d); Nanogen ($64 M) 1998 (h); Cephalon ($60 M) 1991 (a); Myriad ($46 M) 1995 (g); Neurex ($16.3 M) 1993 (i); Cantab ($10 M) 1992 (e); Interneuron Pharmaceuticals ($9.3 M) 1990 (b).

8. (a) Cell; (b) anti; (c) tek; (d) tex; (e) digm;

9. Biology (1800), Karl Friederich Burdach; Protein (1838), Gerardus Johannes Mulder; Bacterium (1872), Ferdinand Julius Cohn; Enzyme (1877), Wilhelm Friedrich Kühne; Cytoplasm (1882), Eduard Strasburger; Chromosome (1888), Heinrich Wilhelm Gottfried Waldeyer; Photosynthesis (1898), Charles Reid Barnes; Biochemistry (1903), Carl Neuberg; Hormone (1905), Ernest Henry Starling; Gene, genotype and phenotype (1909), Wilhelm Johannsen; Vitamin (actually “vitamine” 1911), Casimir Funk; Bacteriophage (1917), Felix Hubert d'Herelle; Biotechnology (1919), Karl Ereky; Molecular biology (1938), Warren Weaver; Antibiotic (1941), Selman Abraham Waksman; Genetic engineering (1963), Edward Lawrie Tatum; Biolistics (1984), John Sanford.

10. A glow-in-the-dark green dog envisaged by artist, Eduardo Kac.

11. ~965–1038, Ali Al-hazen, expert on optics; 1170–1250, Leonardo Pisano (Fibonacci), a mathematician whose number series is eminently relevant to biology; ~1219–1292, Roger Bacon who set the basis of empiricism; ~1285–1349, William of Ockham, who enunciated Ockham's Razor, which Tina Turner restated as “Simply the Best”; 1323–1382, Nicole d'Oresme, who invented coordinate geometry before Descartes; 1452–1524 Leonardo da Vinci Polymath inventor and artist; ~1478–1553, Hieronymus Francastorius who wrote “On Contagion”, the first book on contagious infection; 1516–1565, Konrad Gesner, naturalist and taxonomist; 1561–1626, Francis Bacon who conceived the notion of the “crucial experiment”; 1632–1723, Antony van Leeuwenhoek, microscopist; 1707–1778, Carolus Linnaeus, classifier and taxonomist; 1737–1798, Luigi Galvani, discoverer of animal electricity; 1803—1873, Justus von Leibig, organic chemist; 1822–1895, Louis Pasteur, chemist and microbiologist; 1891-1970, Alfred Henry Sturtevant, pioneer genetic mapper; 1916– Francis Crick, elucidator of DNA structure.

12. (a) Sydney Brenner; (b) Matthew Meselson; (c) Jacques Monod; (d) Walter Gilbert (e); Leech means “healer” is also the source of hirudin; (f) 1977: Genentech was founded and smallpox was confounded; (g) Cistron [Biotechnology]; (h) Haemophilus influenzae; Pfeiffer and Kitasato isolated it, TIGR sequenced it.

13. C is for Erwin Chargaff; G is for Fredrick Griffiths; T is for Alexander Todd; A is for Oswald Avery.

14. (a) Gerty Theresa Cori; (b) Dorothy Hodgkin; (c) Barbara McClintock; (d) Rita Levi-Montalcini; (e) Gertrude Elion; (f) Christiane Nüsslein-Volhard

15. (a) William Astbury made the first X-ray crystallography study of DNA in 1938; Cumming Rose discovered threonine only three years before; (b) It was not until 1956, three years after Watson and Crick did their stuff, that Joe-Hin Tjio and Johan Albert Levan revised a 1898 estimate of the human chromosome count down from 24 pairs to 23 pairs; (c) Eli Lilly's Humulin was approved in the US in 1982, whereas the insulin receptor was sequenced three years later.