Robert L. Metzenberg Memorial Webpage

Robert  L.  Metzenberg



1950            Technician,  Dept.  of  Chemistry,  University  of  Chicago
1951-­1955    Graduate  assistant,  Dept.  of  Biology,  California  Institute  of  Technology
1955-­1958    Postdoctoral  fellow,  Dept.  of  Physiological  Chemistry,  University  of  Wisconsin,  Madison
1958-­1996    Assistant  Professor  to  Professor,  Dept.  of  Physiological  Chemistry,  University  of  Wisconsin,  Madison
1996-­           Professor  Emeritus,  Dept.  of  Biomolecular  Chemistry,  University  of  Wisconsin,  Madison
1996-­2002    Visiting/Research  Professor,  Dept.  of  Biological  Sciences,  Stanford  University
2002-­2005    Visiting  Professor,  Dept.  of  Chemistry  and  Biochemistry,  University  of  California,  Los  Angeles
2005-­           Adjunct  Professor,  Dept.  of  Biology,  California  State  University,  Northridge

Honors  and  Fellowships

1951            Phi  Beta  Kappa,  Summa  cum  Laude
1956            Thomas  Hunt  Morgan  Award,  Cal  Tech
1955-­1958    American  Cancer  Society  Postdoctoral  Fellow
1985-­1963    John  and  Mary  R.  Markle  Scholar
1963-­1973    U.S.P.H.S.  Research  Career  Development  Award
1977            John  Bascom  Professor  (undergraduate  teaching),  University  of  Wisconsin
1983            Guggenheim  Fellow,  Stanford  University
1990            President,  Genetics  Society  of  America
1994            Medical  School  Dean's  Award  for  Teaching,  University  of  Wisconsin
1996            Fellow  of  the  American  Academy  of  Microbiology
1997            Wisconsin  Medical  Alumni  Award
1997            Elected  to  National  Academy  of  Sciences
2005            Thomas  Hunt  Morgan  Medalist,  Genetics  Society  of  America

Contributed  by  Howard  Metzenberg

Robert  Metzenberg  was  born  in  Chicago,  Illinois,  on  June  11,  1930.  In  1951  he  graduated  Phi  Beta  Kappa  from  Pomona  College  in  Claremont,  California, where he  majored  in  Chemistry.  Between  1951  and  1955,  he  earned  a  PhD  at  California  Institute  of  Technology  in  the  Division  of  Biological  Sciences.  His teachers included  Herschel  Mitchell,  George  Beadle,  Ed  Lewis,  A.  H.  Sturtevant,  and  Max  Delbrück.  As  a  graduate  student  at  Cal  Tech,  he  met  his  wife Helene Fox, who  grew  up  in  Pasadena,  California.  They  were  married  on  June  26,  1954,  in  Vermont.

In  1955,  Bob  and  Helene  moved  east,  to  Madison,  Wisconsin.  Metzenberg  became  a  professor  in  the  University  of  Wisconsin,  Madison’s  Department of Physiological  Chemistry  (since  renamed  Biomolecular  Chemistry),  in  the  School  of  Medicine.  Throughout  his  career,  Robert  Metzenberg  conducted research on  genetic  regulation  and  metabolism  with  Neurospora  crassa,  a  fungus  that  is  studied  worldwide  as  a  model  eukaryotic  organism.  When  he was  elected  to the National  Academy  of  Sciences  in  1997,  the  academy  credited  him  with  the  discovery  that  a  cascade  of  positive-­  and  negative-­acting enzyme  products of regulatory  genes,  operating  together  as  a  feedback  mechanism,  can  act  to  govern  gene  expression.  In  2005  he  was  awarded  the Genetics  Society of America’s  Thomas  Hunt  Morgan  award  for  lifetime  achievement.

Following  his  retirement  from  the  University  of  Wisconsin  in  1996,  He  became  a  research  professor  at  Stanford  University.  Bob  and  Helene  relocated to Northridge,  California  in  2002,  so  that  Helene  and  Bob  could  live  near  family.  His  survivors  include  his  wife,  Helene,  sons  Howard  and  Stan, daughter-­in-­law Aida,  and  two  grandchildren.

Bob's  last  experiment

Memorial  tribute  to  Bob  Metzenberg

(Perspective by Eric Selker published in Genetics at bottom)

Bob  Metzenberg  gathered  friends  and  collaborators  around  him  so  easily.  On  the  science  side,  whenever  discussions  started  about  some  research project or proposal,  Bob  was  immediately  entrapped.  He  could  not  do  other  than  become  engaged,  make  certain  to  understand  the  research  questions,  and then often  to suggest  improvements  which  would  confirm  and  support  the  investigation.  There  seemed  to  be  nothing  more  rewarding  and  exciting  than  to imagine  a  new explanation  of  some  biological/biochemical  mystery,  and  then  consider  if  it  might  lead  to  additional  discoveries.

To  illustrate  his  considerate  and  generous  ways:  he  wouldn't  accept  full  credit  for  his  imaginative  proposals  but  often  passed  the  credits  on  to  his collaborators. He  wouldn't  accept  that  I  was  little  more  than  a  technician  cleaning  the  glassware  in  a  current  project.  He  proposed  that  because  my name  began  with  a  B,  I would  be  first  author  while  he  would  be  in  disguise  because  his  name  began  with  M  and  was  in  the  middle  of  the  alphabet of  the  five,  six,  or  so  suggested authors.  Of  course  he  regarded  the  investigation  (his  idea)  as  an  extraordinary  contribution.  It  is.  And  then  as  the  work went  on  there  was  a  flood  of  additional questions  raised  in  his  mind  that  would  be  investigated  as  follow  ups.  The  day  he  died  he  was  physically  at work  with  the  research  stocks,  all  the  while  knowing his  health  was  failing.

Bob  would  put  aside  or  modify  his  own  activities  to  assist  others  with  their  needs,  giving  up  the  convenience  and  ease  of  working  in  his  own  lab  at Wisconsin  to move  to  Stanford,  then  moving  on  from  Stanford,  setting  up  his  laboratory  at  home  so  that  he  would  be  there  to  assist  family  members with  their  needs. Notably,  he  could  not  stop  inventing  and  researching.  He  would  nicely  pull  such  a  wide  variety  of  others  into  collaboration  and assistance.  Though  his  field  was perhaps  molecular  biochemistry  he  could  and  would  look  through  a  microscope  or  across  a  bunsen  burner  or,  his choice,  an  alcohol  lamp.  Grow  cultures  and make  crosses  to  develop  the  right  mutant  strains.  Make  media  and  then  improve  the  chemical  contents  to better  support  his  creations.  Test  their  genetic characteristics and then insert or extract additional genes as needed.He was so complete.! am very much at a loss without him. We need his guidance.

-Ed Barry


I include in this e-mail a picture of the Yanofksy & Perkins groups at the time Bob was a member of the Perkins lab at Stanford. I knew Bob from his legendary work in Neurospora but I met him personally during the two summers that I spent at Stanford as a visiting scholar in Charley's lab in 1996 and 1999. At the time, Bob has retired from his University post and had decided that the Perkins lab was a fine place to spend his retired time as an active scientist. I was surprised and delighted by his brilliance and wit and by the interest that he showed to anyone coming to his desk to discuss a scientific problem. Finding him continuously  at  work  and tinkering with  fluffy  tester  plates  at  his  tiny  lab  bench  was  an  inspiring  sight.  The  presence  of  Charley,  David,  and  Bob  just  around  the corner  at  Stanford University  was  an  enriching  experience.  I'm  sure  that  Bob's  presence  in  the  fungal  research  community  will  be  sorely  missed.

The  group  picture  was  taken  in  September  1999  while  we  were  having  a  small  farewell  party  just  before  my  departure  after  spending  the  summer  in Charley's lab.  The  participants  in  the  picture  are  from  left  to  right:  Charley  Yanofsky,  Feng  Gong,  Vincent  Konan,  Bob  Metzenberg,  Bheong-­Uk  Lee, Kristin Black,  Joe Sarsero,  David  Perkins,  Namboori  B.  Raju,  Luis  Corrochano,  Janet  Elder.

- Luis  M.  Corrochano

Bob, Joan Bennett and David Perkins

I met  Bob  in  1961  at  the  very  first  Neurospora  Information  Conference  in  La  Jolla,  California.  The  meeting  was  free  for  all,  in  both  senses  of  the phrase, and Bob  and  I  began  talking  at  the  free  bar  after  the  last-­night  banquet.  Characteristically,  he  drank  Coke,  and  I  drank  Canadian  Club.  Even  as  I became  less articulate,  he  became  more  so,  and  I  remember  only  one  thing  from  that  night:  I  had  made  one  of  the  best  scientific  friends  of  my  life.

He  was  then  at  Wisconsin;;  I  had  taken  a  job  at  the  University  of  Michigan.  I  kept  seeing  Bob  at  meetings,  and  in  the  early  1970s,  our  labs exchanged  visits.  In Ann  Arbor,  Bob  inspired  one  of  my  most  daring  experiments  one  I  had  thought  impossible  if  he  had  not  said,  "Why  not?"  At  that point,  almost  whimsically,  he rattled  off  a  protocol  that  might  do  the  job,  and  within  a  month  we  accomplished  the  task.  This  was  his  habit:  using  his multitasking  imagination  to  explore,  at the  speed  of  light,  landscapes  of  possibilities  in  ways  Mozart  might  have  done  to  choose  harmony  and orchestration.  As  we,  his  friends,  coupled  our imaginations  to  his,  we  felt  that  even  his  hypothetical  dead  ends  were  more  illuminating  than  a  close scrutiny  of  quantitative  data.  He  proved  repeatedly  Francis Bacon's  point  that  the  truth  is  better  served  by  error  than  by  confusion.  He  remains  a  model of  how  much  sheer  fun  science  and  talking  about  science  could  be.

Out  of  context,  one  of  his  remarks  about  himself  might  sound  ridiculous:  "I  had  no  talent!"  But  the  context  is  illuminating.  Having  taken  instruction  in musical composition  in  earlier  times,  he  had  completed  several  string  quartets.  He  related  this  to  me  over  lunch  one  day  at  Stanford,  saying,  "They were competent,  but they  simply  followed  the  rules.  Derivative  of  Haydn  and  all.  But  I  discovered  I  simply  had  no  talent!"  This  not  only  illustrates  Bob's aesthetic  refinement,  but  his curious  blend  of  modesty  and  ambition,  an  ambition  to  use  his  mind  to  the  fullest.  It  also  explains  his  symphonic understanding  of  the  complex  biochemical systems  that  he  probed  with  a  sensitivity  to  detail,  subtle  complexity,  and  the  surprising  formal  beauty  of cascade  regulatory  systems.

Finally,  he  became  one  of  the  best  friends  of  all  of  us  in  our  scientific  community.  Always  good  humored  and  anxious  to  help,  he  willingly  suffered fools,  hoping at  first  he  might  show  them  to  the  light.  A  lack  of  success  would  then  bring  out  advice  in  an  advanced  play  on  words  that  at  least  he could  enjoy.  Finally,  the fools  would  retire,  yielding  Bob’s  attention  to  others  better  equipped  to  enjoy  it.  I  believe  Bob  made  few  enemies,  largely because  he  retained  a  reserve  that  few people  myself  included  fully  penetrated.  But  what  overlay  that  reserve  amounted  to  an  incomparable  friend  and scientist,  one  who  will  glow  in  the  dark  for  years to  come.

- Rowland Davis

Bob and Ron Morris

I  only  heard  this  week  that  Bob  Metzenberg  died.  It  has  been  quite  a  year  of  passage  for  icons  of  the  Neurospora  world.  The  message  I  pass  along is from February  1984,  and  I  think  if  provides  a  good  example  of  Bob's  sense  of  humor.  I  assume  many  people  received  correspondence  from  him  in  the typed postcard  format,  and  this  was  one  of  those.  It  was  just  before  I  attended  my  first  Neurospora  conference.  Bob  had  deposited  some  strains  which comprised  the so-­called  big  RFLP  mapping  kit,  as  the  first  paragraph  notes.  He  had  addressed  the  package  containing  them  to  Dr.  Craig  Wilson.  I kidded  him  about  awarding me  an  honorary  Ph.D.  and  his  response  is  in  the  second  paragraph.

Here's  a  quick  story  which  is  also  illustrative.  One  day  I  came  into  the  office  just  as  Patti  Hubbard  was  concluding  a  phone  conversation.  It  turned  out she  had been  talking  to  Bob.  She  had  a  perplexed  look  on  her  face,  and  when  I  gave  her  a  quizzical  look  in  return,  she  said  "Bob  Metzenberg  is  just too  nice!"

It  was  a  bit  hard  to  believe  anyone  could  be  such  a  nice  guy.


Bob,  like  David  Perkins,  was  one  of  the  finest  people  I  have  known  in  science.  He  deserves  a  lot  of  memorials.


During  a  conversation  in  2000,  I  asked  Bob  which  scientific  accomplishment  he  was  most  proud  of  in  his  career.  His  answer,  without  even  a  slight hesitation, was  the  use  of  RFLPs  for  genetic  mapping.  Although  Ray  White  and  David  Botstein  described  the  use  of  RFLPs  first  (1980),  Bob  had independently  worked out  the  concept  of  using  naturally  occurring  polymorphisms  for  genetic  mapping  and  his  group  published  in  1984  an  extensive RFLP map  of  Neurospora  crassa and  a  detailed  protocol  that  is  still  used  to  this  day.  I  was  struck  by  the  fact  that  one  of  his  most  prized  accomplishments was  strictly  personal  -­  no  glory  or credit,  just  the  satisfaction  of  doing  good  science.

- Wayne  Versaw



Bob  and  Michael  Freitag  Bob  and  Barbara  Valent

Bob  had  an  overall  knowledge  of  Neurospora.  He  was  interested  in  the  whole  organism  from  new  methods  to  isolate  tetrads,  new  mapping  procedures, biochemcal  genetics,  moecular  biology  and  new  techniques  in  working  with  DNA.  He  was  frequent  contributor  with  his  ideas  to  the  Neurospora Newsletter and later  to  the  Fungal  Genetics  Newsletter.  His  ideas  were  always  useful  and  unique.  He  was  a  wonderful  person  to  talk  to  you  about  your  reserach. He  always had  good  questions  and  ways  to  help  you  achieve  the  results  you  wanted.  We  shall  miss  Bob's  comments  about  research  and  Neurospora in  general.  His interest  in  Neurospora  did  not  end  with  his  retirement  to  California.  There  is  no  one  else  working  with  Neurospora  like  him.  He  made major  contributions  to  the field  of  Neurospora.

- Mary  Case


Bob  Metzenberg  had  not  a  thing  to  do  with  why  I  first  started  in  Neurospora,  but  an  enormous  impact  on  why  I  am  still  working  on  Neurospora.  For people  such as  myself  who  tend  to  become  tongue  tied  around  “giants  in  the  field”,  Bob  was  a  tonic.  He’d  relish  in  any  good  discussion  and  always cut  to  the  core  in  the most  matter  of  fact  way.  This  is  not  to  say  that  Bob  suffered  fools  with  what  would  be  described  as  the  milk  of  human kindness.  Bob  could  be  very  direct,  but was  never  unkind.  But  for  anyone  new  to  a  field,  he  was  just  the  kind  of  senior  person  who  personified  a field  with  which  you’d  want  to  be  associated.

Of  course,  his  knowledge  of  basic  genetics,  and  of  Neurospora  biology,  was  phenomenal.  The  problem  that  lacked  a  genetic  solution  simply  did  not exist  in Bob’s  book.  I  think  everyone  can  remember  one  scheme  or  another  that  Bob  cooked  up  to  solve  a  problem;;  they  were  always  really  clever (sometimes  a  bit  too clever),  presented  with  an  air  of  genuine  and  almost  breathless  enthusiasm,  and  relied  on  strains  or  aspects  of  Neurospora  biology that  most  folks  had forgotten,  if  they’d  ever  even  learned  them.  His  original  invocation  of  transvection  to  explain  what  became  MSUD  (I  remember saying, “huh”,  when  he  first explained  this  to  me),  and  his  extrapolation  of  this  to  other  problems  in  genetics  (like  haplo-­insufficiency),  was  one  such  example.

Another  was  his  novel  and ultimately  correct  interpretation  of  the  QA-­1F  and  QA-­1S  complementation  and  heterokaryon  data  in  terms  of  distinct  interacting proteins  –  in  1979,  well  before the  molecular  denouement.  And  of  course  his  analysis  of  the  genetic  cascade  in  phosphorous  regulation  was  rightly viewed  as  a  tour-­de-­force;;  you  know something  is  complicated  when  the  “summary  figure”  is  the  first  one  in  the  paper  rather  than  the  last.  Bob thought  deeply  about  problems,  cherished  the exceptions  to  prevailing  models,  and  brought  to  bear  on  everything  he  touched  both  a  native  and unquenchable  enthusiasm  as  well  as  a  synoptic  knowledge  of Neurospora  biology  and  genetics.  Such  are  the  people  that  define  fields.

Probably  the  thing  I  will  best  remember  about  Bob,  though,  is  his  wonderful  word  craft.  He  loved  to  use  words  in  the  way  a  carpenter  loves  to  use wood.  He was  an  artist  with  words.  I  still  have  notes  from  talks  and  discussions  where  he  dropped  verbal  gems,  and  some  I  have  since  adopted  for my  own.  I  remember one  discussion  about  heterokaryons  where  someone  (probably  me)  advanced  (without  sufficient  forethought)  the  idea  that  the  final nuclear  ratio  in  the heterokaryon  might  reflect  the  relative  numbers  of  homokaryotic  nuclei  mixed.  Bob  shot  back,  “Well,  that  sounds  good  if  you  say  it fast”,  which  was  indeed  true. It’s  a  phrase  I’ve  often  since  used  myself  for  glibly  pronounced  but  poorly  thought  out  explanations.  Another  was  the phrase  “low  hanging  fruits”  to  describe  the easy  scientific  pickings  available  when  a  field  is  newly  populated.

Always  a  ready  ear,  always  a  new  idea,  always  a  novel  screen  and  a  mutant  that  I  had  never  even  thought  of  thinking  about,  always  the  perfect  word and  the apt  phrase,  and  always  the  word  of  encouragement  for  science  that  he  thought  was  going  somewhere  –  how  could  anyone  not  want  to  work on Neurospora with  someone  like  Bob  Metzenberg  to  talk  to?

- Jay  Dunlap  


Bob  and  Colleagues

I  remembered  hearing  Bob's  name  for  the  first  time  from  my  Ph.D.  supervisor,  Louise  Glass.  Bob  was  Louise's  postdoctoral  mentor,  and  she  always had  the nicest  things  to  say  about  him.  According  to  Louise,  he  was  intelligent,  helpful,  kind,  and  witty.  Having  known  him  in  person,  he  was  all  of  the above,  and  then some.

My  first  encounter  with  Bob  was  in  a  conference.  Like  the  perfect  gentleman  that  he  was,  he  gave  me  encouragement  and  advice  on  my  project concerning mating-­type  genes  (which  incidentally,  were  first  characterized  by  his  and  Charley  Yanosky's  groups).  Even  as  the  legend  he  was,  he  never made  people  feel intimidated.

Upon  retirement,  Bob  moved  to  David  Perkins'  lab  at  Stanford  and  began  his  "second  career"  as  a  Visiting  Professor.  Having  been  informed  of  my imminent graduation,  Bob  invited  me  to  work  with  him  as  a  postdoctoral  fellow.  Although  I  had  my  mind  set  on  working  with  another  brilliant  scientist (Nancy  Keller)  at  the time,  I  could  not  pass  up  the  opportunity  to  learn  from  my  academic  grandfather  (and  risk  having  Louise  be  mad  at  me). 

My  best  memories  in  science  remain  to  be  my  tenure  at  Stanford.  I  remembered  having  daily  lunch  meetings  with  Bob,  Perkins,  Jacobson,  Raju,  and many other  visitors  (and  there  were  many  of  them,  especially  during  the  Asilomar  meetings  in  March).  The  conversations  were  not  just  about  the  crazy ideas  that  he had  (many  of  which  turned  out  to  be  big  discoveries  in  science).  Bob  was  extremely  well-­read  and  he  could  start  an  interesting conversation  on  any  topic  -­ history,  art,  politics,  cultures,  breweries,  and  the  taste  of  horse  meat,  just  to  name  a  few.

As  an  employer,  he  was  the  perfect  boss  -­  he  took  care  of  his  employees'  needs.  Many  of  his  protégés  went  on  to  have  a  very  successful  career. As a  friend, he  was  as  loyal  as  they  come.  During  Christmas  and  Thanksgiving,  he  would  open  his  home  to  me  (and  other  singles  alike)  and  made  me feel like  I  was  a  part of  his  extended  family.  I  remembered  singing  Christmas  carols  after  the  turkey  dinner,  and  Bob  would  be  able  to  play  any  song  you threw  at  him,  ad  lib.  That was  amazing  to  me,  considering  that  he  never  had  any  official  piano  training.

Bob  was  never  the  prototypic  principle  investigator.  You  would  never  find  him  paper  pushing  at  his  desk,  since  he  was  too  busy  working  on  the bench. He  was the  MacGyver  of  our  generation  -­  nothing  was  too  crazy  to  be  utilized  in  the  name  of  science  (e.g.  screws  joined  together  as  a  96-­pin  library replicator).  He would  rather  fabricate  an  instrument  himself  and  not  waste  taxpayers'  money.

Bob  was  a  mentor,  a  friend,  and  a  father  to  many  of  us.  He  will  be  sorely  missed.

- Patrick  Shiu


Bob  and  Mary  Anne  Nelson

Bob  was  a  very  special  person  to  me.  My  Ph.D.  is  in  Microbiology  from  the  University  of  Georgia  (1975)  and  my  research  was  under  the  direction  of Branch Howe.  My  problem  involved  genetic  crosses  of  N.  tetrasperma.  As  you  know,  in  N.  tetrasperma  normally  each  of  the  four  ascospores  resulting from  a fertilization  event  has  nuclei  of  both  mating  types  and  so  is  self  fertile.  This  does  not  lend  itself  to  genetic  anallysis  and  in  order  to  do  the research,  I  had  to  try to  find  the  RARE  dwarf  ascospores  which  would  hopefully  have  only  one  nucleus.  Things  were  not  going  well,  and  I  might  still be trying  to  get  enough  data except  for  the  help  of  Bob  Metzenberg.

Bob  had  produced  hybrids  between  N.  tetrasperma  and  N.  crassa.  The  hybrids  produced  asci  with  eight  ascospores  allowing  for  genetic  analysis. Bob sent  me cultures  that  were:  3tetra:1crassa;;  2tetra:2crassa;;  1tetra:3crassa.  I  was  able  to  cross  my  tetrasperma  mutants  to  these  hybrids  and  thus transfer the  genes)  we were  interested  in  to  an  N.  crassa  system  with  eight  ascospores/ascus  with  each  ascospore  containing  nuclei  of  only  one  mating type. From  this,  my  work  moved  along  and  I  was  able  to  map  and  analyze  the  genes  we  were  interested  in.  And,  also,  very  importantly,  to  complete my  degree. This  help,  which  Bob  so  willingly  gave  to  me,  is  characteristic  of  the  man  he  was  and  how  dedicated  he  was  to  science  and  how concerned  he  was  about others.

He  will  be  missed.

- Sare  Neville  Bennett


Bob  was  a  wonderful  scientist  and  intellectually  adventurous  person.  He  had  a  remarkable  grasp  of  metabolism  and  its  integration  into  the  physiology  of an organism.  From  the  time  I  began  an  independent  career,  Bob  was  my  resource  for  any  baffling  interaction  that  I  couldn't  make  heads  or  tails  of.  On one occasion  I  mentioned  a  peculiar  growth  behavior  of  a  mutant  in  the  glyoxalate  pathway.  Bob  always  greeted  such  puzzles  with  an  affectionate  broad grin.  This was  the  kind  of  problem  that  tickled  his  fancy,  even  though  it  was  my  problem.  Without  hesitation,  he  made  a  key  connection  between glyoxalate  metabolism and  gluconeogenesis  that  had  completely  eluded  my  students  and  me.  The  connection  he  made  formed  the  basis  for  many important  discoveries  in  my laboratory.  Like  so  many  of  his  colleagues,  I  found  my  career  influenced  by  Bob's  unique  scientific  style  and  generous spirit.

- Gerald  R.  Fink


Bob  was  always  very  interested  in  our  physical  mapping  work.  He  provided  advice  along  the  way  and  always  encouraged  me  to  finish  it  even  after the publication  of  the  sequence.  We  have  done  so,  and  he  would  be  pleased  to  know  that  we  have  finished  and  integrated  our  physical  map  of  N.  crassa with  his RFLP  map.  He  remains  an  inspiration  to  all  of  us,

- Jonathan  Arnold


Bob  and  Louise  Glass

Bob  is  and  has  been  an  inspiration  to  me,  both  on  a  personal  and  professional  level.  I  first  met  Bob  at  a  Keystone  meeting,  where  we  discussed possible  post-­ doctoral  projects.  I  was  semi-­comatose  (after  a  week  long  meeting  and  rooming  with  John  Hamer  and  Melanie  Yelton),  but  I  remember vividly  Bob's  passion and  enthusiasm  for  approaching  biological  issues.  I  had  never  met  anyone  before  who  showed  such  a  love  for  biology  and experimental  science.  That  passion continued  to  be  apparent  when  I  was  a  post-­doc  in  Bob's  lab.  Our  lab  meetings  often  dwelled  on  biological questions  other  than  projects  in  the  lab  and  how  to approach  them  on  an  experimental  level.  Since  leaving  Bob's  lab,  I  often  talked  with  him  about "how  Neurospora  does  it"  and  the  development  of  methods  for genetic  research.  I  will  sorely  miss  those  mind-­broadening,  educational  and  motivational discussions.  He  also  was  a  terrific  supporter  of  new  scientists  in Neurospora  biology,  including  new  assistant  professors,  post-­doctoral  associates, graduate  students  and  even  undergraduates;;  he  always  made  time  for  us.  In addition  to  being  the  most  inspirational  scientist  that  I  have  known,  Bob, along  with  David  Perkins,  was  also  the  most  selfless.  He  habitually  gave  out  strains and  ideas  prior  to  publication  and  refused  to  be  an  author  on publications  unless  he  actually  contributed  experimental  work.  Now  that  Bob  is  gone  (in  the physical  sense),  he  still  remains  an  inspiration  to  me.  I  often find  myself  asking  "How  would  Bob  approach  this  question?"  and  "What  kind  of  tools  need  to  be developed  to  help  to  address  this  aspect  of Neurospora  biology?"  and  sometimes,  I  think  I  hear  a  few  suggestions  that  help  me  along  the  way.

- Louise  Glass


Bob's  "retirement"  lab  and  outdoor  autoclave

Bob  Metzenberg  and  the  FGSC

In  comments  after  being  awarded  the  2005  Thomas  Hunt  Morgan  Award  at  the  23rd  Fungal  Genetics  Conference,  Bob  Metzenberg  took  a  moment  to acknowledge  the  role  of  the  Fungal  Genetics  Stock  Center  in  providing  an  even  playing  field  for  scientists  interested  in  fungal  genetics.  He  called  the FGSC  an "open  source"  for  fungal  genetics,  comparing  it  to  the  open  source  software  movement.  This  was  not  just  a  passing  comment,  but  rather  the culmination  of  a career  of  support  and  use  of  the  resources  at  the  FGSC.

Bob  Metzenberg  has  deposited  254  strains  into  the  FGSC  collection  including  231  Neurospora  crassa  strains  as  well  as  N.  sitophila,  and  N.  tetrasperma strains,  interspecific  hybrid  strains  and  even  Gelasinospora  strains.  The  first  strain  Bob  deposited,  FGSC  1769,  reached  the  FGSC  in  October  of  1969  in a group  of  eleven  strains.  They  were  described  as  hybrids  between  N.  crassa  and  N.  sitophila  useful  for  transferring  genes  between  species  (Metzenberg and Algren,  1969).  Demonstrating  the  value  of  long-­term  collections,  most  of  these  strains  were  not  requested  from  the  FGSC  until  after  2000  but  have been distributed  a  number  of  times  since  then.

Correspondence  between  Bob  and  Bill  Ogata,  the  first  FGSC  curator,  suggests  that  strain  1226  which  has  the  genotype  rib(76R5)  and  which  was deposited  by Walter  S.  McNutt  in  1965  may  be  Bob  Metzenberg's  first  strain  deposited  into  the  FGSC.  This  is  the  level  of  detail  that  early correspondence  between  Bob  and FGSC  director  Ray  Barratt  included.

The  next  group  of  strains  deposited  were  aryl  sulfatase  mutants  of  N.  crassa  which  were  the  first  of  a  number  of  mineral  metabolism  strains  Bob developed. These  ars-­1  strains  were  the  result  of  UV  irradiation  but  also  coincided  with  a  description  of  variation  in  aryl  sulfatase  proteins  among  wild strains  from  a number  of  Neurospora  species.

Many  later  strains  were  specific  purpose  strains  such  as  RFLP  mapping,  heterokaryon  maintenance  or  manipulation  or  even  transformation  strains.  These were  all  useful  and  widely  used.

Bob  was  also  very  supportive  of  the  evolution  of  the  FGSC  into  a  repository  for  molecular  genetic  materials  and  first  suggested  this  in  a  January  1980 letter  to Bill  Ogata.  The  FGSC  collection  of  molecular  clones  now  numbers  nearly  650  plasmids.  Of  these,  up  to  ten  percent  were  deposited  by  Bob Metzenberg  or  his academic  progeny  (or  theirs).

Bob  also  used  the  resources  in  the  FGSC  collection.  Since  1987  he  ordered  317  strains,  including  mutants,  wild  type  strains,  and  many  strains  with translocations  or  inversions.  Bob  also  used  the  molecular  resources  he  promoted  and  received  nine  plasmids  and  three  gene  libraries. 

Bob  supported  the  FGSC  in  other  ways.  He  donated  a  supply  of  the  cell  wall  synthesis  inhibitor  polyoxin  B  to  assure  that  it  would  remain  available. He  was generous  with  his  energy,  ideas  and  time.  This  is  truly  a  remarkable  heritage  and  establishes  Bob  Metzenberg  as  one  of  the  giants  upon  whose shoulders future  generations  will  stand.

- Kevin  McCluskey

Bob  and  Colleagues  (Mary  Anne  Nelson,  Tom  Randal,   Bob,  his  car,  Mary  Anne  Nelson  and  Seogchan  Kang
Jeff  Grotelueschen  and  David  Butler)  on  a  collecting  trip on  a  collecting  trip

I’ve  known  Bob  since  the  second  Neurospora  Information  Conference,  at  Rice  University  in  1964,  when  I  was  a  young  graduate  student.  That’s  a  long friendship,  and  I’ll  certainly  miss  him.  He  was  one  of  the  giants  of  our  community,  with  a  phenomenal  intellect  and  a  propensity  for  thinking  out  of  the box.  He gave  us  sulphur  and  phosphorus  uptake  and  metabolism,  regulatory  cascades,  RFLP  mapping,  tRNA  and  rRNA  genes,  and  so  much  more  from his  own  work. He  gave  so  many  of  us,  so  freely,  novel  insights  and  suggestions  regarding  our  own  research.  Over  the  last  few  years,  I’ve  really appreciated  his  support  and encouragement  as  the  e-­Compendium  has  been  developed,  but  that  was  typical  of  Bob.  He  was  one  of  the  key  people who  set  the  style  of  the  Neurospora community  –  that  of  cooperation  and  mutual  support,  and  that  may  be  as  important  to  us  in  the  future  as  his research  output.

- Al  Radford

Bob  and  P.  Maruthi  Mohan & Bob  at  the  bench

My  meeting  with  this  noble  soul  was  very  short,  but  his  work  is  of  great  influence.  My  first  attempt  to  meet  him  in  Wisconsin  could  only  materialize with  a  brief telephonic  talk.  He  was  gentle  and  apologetic  that  he  cannot  meet  on  that  day  (in  1988),  but  was  willing  to  help  with  the  lab  protocols  for preparation  of protoplasts  and  transformation.  Only  in  2003  I  got  the  oppurtunity  to  meet  this  extraordinary  scientist  with  a  pleasing  smile.

- P.  Maruthi  Mohan


Bob before Helene & Bob after Helene

Bob  and  Helene  were  married  for  53  years.  Helene  was  an  important  contributor  to  Bob's  love  of  life  and  the  pursuit  of  science.

(Perpsective for Genetics)


Kooert L. lVIetzenoerg, June 11, • :;U-JWY 1: lJenencist


Copyright © 2008 by the Genetics Society of America


Anecdotal, Historical and Critical Commentaries on Genetics

Edited by James F. Crow and William F. Dove

Robert L. Metzenberg, June 11, 1930–July 15, 2007: Geneticist

Extraordinaire and ‘‘Model Human’’

Eric U. Selker1

Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229

The genetics world was saddened by the recent death of Bob Metzenberg. We invited Eric Selker to write an informal biography and tribute and several others to write remembrances. These illustrate the high esteem in which he was held by his colleagues. Among other honors, Bob was elected to the National Academy of Sciences and in 2005 was awarded the Thomas Hunt Morgan Medal by the Genetics Society of America.

J. F. Crow and W. F. Dove

first met Bob Metzenberg (Figure 1) when he came to Reed College to give the Gabriel Lester Memorial Lecture in 1974. He made a convincing case for using the fungus Neurospora crassa to investigate gene regulation in eukaryotes. This was, of course, before DNA-mediated transformation of Neurospora and other eukaryotes, before the invention of recombinant DNA techniques, and even before a reliable method of extracting nucleic acids from Neurospora had been described. However, as anyone who has heard Bob give a presentation, formally or informally, knows, he had a knack for arranging information into tight stories and his special blend of humor and style ensured that even potentially sleepy undergraduates remained tuned in. Bob described his investigations on regulation of sulfur and phosphorus utilization at a time when little was understood about gene regulation in eukaryotes. His identification of mul- tiple regulatory mutants and his demonstration that the underlying genes exist in a hierarchy to turn on families of unlinked structural genes was clearly a major advance. Indeed, Bob was the first to discover a cascade of positive- and negative-acting products of regulatory genes acting to govern eukaryotic gene expression. These studies fore- shadowed the discovery of similar signal transduction systems in other organisms. Bob Metzenberg was not a person who tooted his own horn, however. ½For example, he was not the type who ‘‘casually’’ mentioned that he was a member of the National Academy of Sciences, was awarded a MERIT grant, and had one of the longest-

1Author e-mail:

Genetics 178: 611–619 (February 2008)

running National Institutes of Health grants ever (over
38 years) or that he had been awarded a slew of other prestigious honors, including the Thomas Hunt Morgan Medal (Selker et al. 2005).]
Visiting the Metzenberg laboratory 4 years later left me with two other strong impressions of Bob: his approachability and the breadth and depth of his in- tellectual tool chest. I discovered that he was a chemist disguised as a geneticist. The disguise was effective be- cause he was an extraordinary geneticist, but his core of chemistry served him well: as an award-winning bio- chemistry professor, as a molecular biologist, and as an advisor for thousands of students and colleagues who learned to seek his advice. Those who interacted with Bob quickly discovered that the value of his extensive knowledge base was amplified by his uncommon imag- ination and by his legendary generosity. Gerry Fink recently noted,

Bob was a wonderful scientist and intellectually adventur- ous person. He had a remarkable grasp of metabolism and its integration into the physiology of an organism. From the time I began an independent career, Bob was my resource for any baffling interaction that I couldn’t make heads or tails of. On one occasion I mentioned a peculiar growth behavior of a mutant in the glyoxalate pathway. Bob always greeted such puzzles with an affectionate broad grin. This was the kind of problem that tickled his fancy, even though it was my problem. Without hesitation, he made a key connection between glyoxalate metabolism and gluconeogenesis that had completely eluded my stu- dents and me. The connection he made formed the basis for many important discoveries in my laboratory. Like so many of his colleagues, I found my career influenced by Bob’s unique scientific style and generous spirit.


Robert Metzenberg was born on June 11, 1930, in Chicago, where his great-grandfather had settled. Apparently Bob’s great-great-great-grandfather, the

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Figure 1.—Bob Metzenberg. Bob loved thinking about science in his free time. The handwriting in the background is from letters written by him while waiting for planes. In one he suggested a possible way to recognize N-methyl adenine in conjunction with the Church–Gilbert genomic sequencing method. The two additional people in the bottom image are Joan Bennett and David Perkins.

‘‘Stammvater,’’ or first Metzenberg with a surname, was a fairly successful furrier, dyer, and leather worker in Germany. Bob owed his life to the fact that one of his great-great-great-grandfather’s sons decided to stay in Ireland after going there to buy a supply of leather. After I told Bob about visiting Germany to participate in a tri- bute to relatives of mine lost in the Holocaust, he wrote to me that he had tried to trace relatives who had lived on the Continent but his research invariably led to ‘ in Buchenwald gestorben’’ (died in Buchenwald). He concluded,

It seems that nobody in my patronymic family survived the Holocaust. I have no living relative on the Continent on my mother’s side either.. . . The Holocaust was much talked about in my family when I was a small child. I have no doubt that horror of it was, and is, the defining core of my life. I have never lost my gratitude for having been born in this country, nor have I ever taken my luck for granted.

From an early age Bob lived intensely and made the most of life. Growing up, he focused on competitive swimming, photography, and baseball and excelled in
arithmetic and spelling at the expense of English and art. He earned spending money mowing lawns, which financed movies, dates, etc. He cared about the world and idolized Adlai Stevenson. After graduating from high school, Bob headed west to Pomona College and made firm ties in California.
At Pomona, Bob majored in chemistry and minored in physics and biology, which he noted were ‘‘almost immiscible with chemistry’’ at the time. His Pomona and life-long buddy George Becker reflected,

The Chemistry Department was anything but stuffy. Prof. R. Nelson Smith and his partner Corwin Hansch were constantly pranking one another and set the tone for their students. Partly as a result of his own DNA and certainly as a result of being in that Chemistry Depart- ment, ‘‘Metz’’ was emboldened to pull pranks constantly. No one enjoyed it more.

Becker also noted,

Metz was bright, very bright and used to astonish his friends by ‘‘testing out’’ of classes. He seemed to be able to

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avoid taking beginning classes and in doing so he was very self denigrating saying he was ‘‘lucky’’ etc.

In 1951 Bob graduated Phi Beta Kappa and enrolled in the Division of Biological Sciences at the California Institute of Technology for graduate studies. He worked with Herschel Mitchell on the synthesis of certain amino acids and interacted with an impressive group of ge- neticists and biochemists, including George Beadle, Ed Lewis, A. H. Sturtevant, and Max Delbru¨ ck. Matt Mesel- son commented, ‘‘Bob greatly helped to make CalTech the humane and intellectually exciting place it was in those days.’’
Bob did manage to find time for necessary fun,
however. For example, Bob Lester recalls ‘‘many fine memories of extracurricular hijinks while we were still bachelors, e.g., skinny dipping on a hot deserted beach in Mexico with Bob and Len Hertzenberg and paying for the sunburn where the sun doesn’t usually shine.’’
While at CalTech, Bob married Helene Fox of Pasa-
dena, and afterwards they moved to Madison, Wisconsin, so that he could do postdoctoral research in the De- partment of Physiological Chemistry at the University of Wisconsin School of Medicine. Bob worked with Philip Cohen on enzymatic reactions involved in urea synthesis in mammals and amphibians, but he became increas- ingly interested in the underlying gene regulation. He therefore took a 1-year visiting scientist position in the group of Ernst Hadorn in Zurich to do some ‘‘reading and listening’’ and to get ‘‘hands-on experience in de- velopmental genetics.’’ In 1958 Bob returned to the Department of Physiological Chemistry as an assistant professor and decided to study the regulation of enzyme synthesis in a simple eukaryote. He chose Neurospora, with which he had become familiar as a graduate stu- dent. He wanted to answer such questions as: (1) How many genes are involved in the regulation of typical families of adaptive enzymes?, (2) Do these genes act by preventing the activity of spontaneously active genes or by engendering the activity of otherwise inactive genes?, (3) If several genes are involved in the regulation of such pathways, do they exist as parallel, alternative sig- naling mechanisms or as a hierarchical series?, and (4) Do the structural and regulatory genes involved in a family of adaptive enzymes tend to map close together or are they scattered throughout the genome? In a tour de force, in the 1970s Bob and his colleagues answered all of these questions for genes required during depri- vation of phosphorus or sulfur.
In 1977 Bob visited Stanford, where I was a graduate
student, and we exchanged notes about our respective efforts to clone interesting Neurospora genes. After I extolled the virtues of building genomic libraries in phage rather than in plasmids, Bob invited me to visit his lab to help them set up some things. My visit, in May
1978, was pivotal for me, leading to decades of enjoyable collaborations and enduring friendships. Although
neither of us had been successful in isolating the genes in which we were most interested, we tried to make the best of those that came relatively easily, such as rDNA genes. A joint ‘ side project,’’ to characterize the 5S rRNA genes of Neurospora, became central to both of our ef- forts (Selker et al. 1981). We exchanged countless let- ters and phone calls on everything from technical details to potential mechanisms of concerted evolution of dispersed genes. Bob’s colorful writing livened up even mundane topics. Here are a few snippets from a rep- resentative letter of 1981:

That should be impossible, I think, because there should be no RI site with lambda sequences on both sides of it. I’m trying again, and hope nothing so interesting happens next time.


Well, that’s all woolgathering at this point, but the experiments to be done are fairly obvious. Or at least some of them are. Give me your thoughts on this too!


Everything seems to violate common sense, but perhaps a few solid facts will shape it up.


I couldn’t help thinking of something wild: parsley is one of those plants, along with (at least) celery and parsnips, that contain psoralens at quite substantial concen- trations.. . . It would certainly be interesting if the gene in a living plant ever turned into snapback DNA in response to infection or injury, but I admit it’s a crazy idea.

Two years later, when I joined Bob’s lab after a stint in Germany, I found him still working on the 5S genes. In an application for a Guggenheim Fellowship (awarded for his sabbatical in 1983), Bob commented, ‘‘In the last couple of years, accidental events have sparked my interest in a biological problem on which I had not previously done any research.’’ To map the 5S RNA genes, Bob developed RFLP mapping for Neurospora (Metzenberg et al. 1984, 1985). In reference to this, Wayne Versaw, Bob’s last graduate student wrote,

During a conversation in 2000, I asked Bob which sci- entific accomplishment he was most proud of in his career. His answer, without even a slight hesitation, was the use of RFLPs for genetic mapping. Although Ray White and David Botstein described the use of RFLPs first (1980), Bob had independently worked out the concept of using naturally occurring polymorphisms for genetic mapping and his group published in 1984 an extensive RFLP map of Neurospora crassa and a detailed protocol that is still used to this day. I was struck by the fact that one of his most prized accomplishments was strictly personal—no glory or credit, just the satisfaction of doing good science.

In the late 1980s and early 1990s, Bob and members of his laboratory made important contributions in other areas, including characterizing the structure and func-

614 E. U. Selker

Figure 2.—Bob and his home laboratory. Clockwise from top left: Bob, January 2007;

‘‘stockroom’’; microscope and work table; ‘‘auto-


tion of mating genes of Neurospora (Glass et al. 1988,
1990a,b; Metzenberg 1990; Metzenberg and Glass
1990; Nelson and Metzenberg 1992; Randall and Metzenberg 1995; Ferreira et al. 1998), discovering a premeiotic process resulting in drastic changes in the number of tandem rDNA repeats in the genome (Butler and Metzenberg 1989) and isolating and characterizing the phosphorus family genes (Mann et al. 1988; Kang and Metzenberg 1993; Peleg et al.
1996) that Bob had identified genetically in the early
1970s (for review, see Metzenberg 1979). He also continued to design and share imaginative technical advances, such as a method to use ‘‘sheltered RIP’’ (repeat-induced point mutation) to identify and study essential genes (Harkness et al. 1994) and a new chemical method to couple DNA to glass slides for microarray experiments (Dolan et al. 2001). Mary Case noted,

Bob had an overall knowledge of Neurospora. He was interested in the whole organism from new methods to isolate tetrads, new mapping procedures, biochemi- cal genetics, molecular biology and new techniques in working with DNA. He was a frequent contributor with his ideas to the Neurospora Newsletter and later to the Fungal Genetics Newsletter. His ideas were al- ways useful and unique. He was a wonderful person to talk to you about your research. He always had good questions and ways to help you achieve the results you wanted.. . .

Bob’s generosity and creativity together yielded count- less contributions to the community. A typical multi-page letter from Bob in 1991, describing a new idea for iden- tifying recessive mutations in essential genes, started with, ‘‘I have no special reason to think you need this
procedure, but I wanted to give you, Mary Anne and
Louise copies of this in case it proves useful.’’ Immediately before ‘‘retiring’’ in 1996, Bob and his
postdoctoral fellow discovered a remarkable and un- expected new epigenetic phenomenon in Neuros- pora, initially called meiotic transvection and later renamed ‘‘MSUD’’ for meiotic silencing by unpaired DNA (Aramayo and Metzenberg 1996; Shiu et al. 2001). Elegant work, largely devised and carried out by Bob independently, showed that any sequence that is un- paired during meiosis elicits an RNAi-like mechanism that silences all homologous sequences in the genome, paired or unpaired, for the duration of meiosis. The finding that MSUD is mechanistically related to RNAi came from one of Bob’s characteristically imaginative genetic schemes for selecting suppressor mutations.
As detailed below in the remembrance by Namboori B. Raju and David J. Jacobson, while fighting cancer, Bob worked his last 10 years as an emeritus professor, first at Stanford, followed by UCLA, California State University at Northridge, and, finally, up until his final day, in his home laboratory (see Figure 2).
In his marvelous style, in January of 2007, Bob wrote a piece entitled ‘‘Research in your retirement house’’ (p. 7 of pdf), which starts out:

Retirement can be one of the most productive and satisfying times of your scientific career. All you need is a spare, dedicated room, an understanding and patient companion, neighbors who don’t suspect you of brewing up anthrax bacilli, and a small amount of money.

He goes on, suggesting,‘‘do not be shy about doing a bit of dumpster-diving at an institution near you’’ and

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notes that ‘‘younger people will see you as a harmless eccentric.’’ He then proceeds to explain that when normal job constraints are suddenly removed, ‘‘one discovers how severely they limit our ability to follow up high-risk, high-payoff ideas.’’


Bob’s enjoyable and interesting style was not only evident in his writing and speaking—it came through in all aspects of his life. He made the extra effort to add flair, consistent with his entry in a ‘‘Grandfather Re- members’’ book that he filled out when his granddaugh- ter was born in 1985. He said that a simple statement that sums up his attitude about life is: ‘‘it should be enjoyed and lived with a little enthusiasm and flair. We should be ready to leave when it’s over.’’
Clearly, Bob had no shortage of ‘‘enthusiasm and flair.’’ Craig Wilson, who was curator of the Fungal Genetics Stock Center, contributed the following from a typical Metzenberg postcard:

I apologize for calling you Doctor, and didn’t know whether it applied or not. When people ask me if I like to be called Dr. or what, I tell them my real preference would be to be called ‘‘Oh, Venerable One,’’ but too often it comes out

‘‘Venereal One.’’ My second favorite name is ‘‘Bob.’’

Probably everyone who interacted with Bob has at least one example of his humor coupled with his hu- mility. I selected the following examples from e-mails that Bob sent me over the last few years, written while already fighting for his life:

Thank you for your kind words. I still think they made a clerical error and some poor secretary is going to be fired.


Sorry it’s taken me several days to answer your letter. My mind seemed to be going ta-pocketa on one cylinder, but this morning a second cylinder seems to be coughing fitfully into action. Let me try to state the problem to see if I have got it right.


Some or all of you may tell me I have devised the Neurospora equivalent of an appendix transplant. I await your criticisms! Alternatively, would anybody be willing to pick a few interesting, obviously essential genes and try a proof-of-principle? I would try to be helpful.


I finally clicked into Genetics, and, lo and behold, there I was. At last I understand how a ‘‘woman of a certain age’’ feels when she gets an extreme makeover at a top-of-the- line spa and likes the stranger she sees in the mirror. I haven’t forgotten that, despite your kind profile, I’m still me, warts and all. Nevertheless, it was more than generous of you to airbrush them out.


As far as I am concerned, fruitcakes are one of the crowning achievements of Western civilization, and will

persist after the Sistine Chapel has crumbled into ruins and the late Beethoven Quartets have been forgotten. Well, almost, anyway.


With a little luck, I will be around for a long time to bedevil my friends and family, but if that’s not in the cards, I want things to be left reasonably shipshape.


I’m sorry it took me five days to respond to your letter. It was my druggy week, and I have been sleeping most of every day and spending my waking hours wandering on a strange, cratered planet on which I am the only life form. Finally yesterday I started to return to earth, and today I even drove into UCLA and got some samples ready for Patrick to work on tomorrow. The next two weeks will be fine—then it all starts over again, unfortunately. I should count my blessings: hardly anyone has it so easy.


Thank you so much for the letter, which is full of interesting ideas that I want to study further. It cheered me up to be hearing and thinking science again!


You were correct in guessing that I might be full of poisons that would keep me from responding promptly or even lucidly. It has been a less than perfect month, which finally culminated in a substantial stay in the hospital with a pulmonary embolism. Since I have only three of my original five lobes, losing function in one of them was very unwelcome. I am, thank goodness, now discharged from the hospital. However, no more bungee-jumping, sky- diving, or street-fighting allowed; I will be on blood- thinners from here on out.

After nearly succumbing to pneumonia in January
2006, Bob wrote,

... a few people have told me from time to time that I have walked the earth with no baggage, and that I am a completely uncomplicated person. I wish it were true, but the right moment to correct this impression has never presented itself. But after I go to that Big Lab Bench in the Sky, someone may say so again. I don’t want to have my character prettied up any more than my physical remains. I’ve elected you to say ‘‘It ain’t so!’’

The fact is that Bob’s character and credentials are not at all in need of being ‘‘prettied up’’: they are impressive in their native state. Bob was a model scientist, continuously doing research with his own hands and overflowing with ideas, energy, and flair. He was a natural tinkerer and educator who also inspired others to try ‘‘wild’’ things. Moreover, he was a model human being: caring and generous with a great sense of humor. And in spite of his talents, Bob was exceptionally modest. He was complex, but only in a positive way. We will continue to miss him tremendously.


The following remembrances are from colleagues at the University of Wisconsin, where Bob Metzenberg

616 E. U. Selker

joined the faculty in 1958 as an assistant professor of physiological chemistry. Bob’s role on the faculty of that department in the medical school is expressed by his colleague Larry Kahan:
When I joined the Physiological Chemistry Depart- ment in 1973, I was given the opportunity of sitting in on Bob’s lectures to the medical students. I did this with more than a little interest since I was slated to take over some of those lectures the following year. I was surprised and impressed by the way in which Bob could take as relatively dry a subject as the biochemistry of blood clotting and weave in everything from European history to the similarities between genetic dissection of a pathway and biochemical dissection of a pathway in ways that captured the interest of the medical students. His lectures had everything—basic biochemical and genetic principles, clinical examples, and a good deal of very dry humor. Bob made it clear to the students that he was not just teaching them biochemical facts: he was also preparing them to understand and incorporate the biochemistry that they would encounter in the several decades of their careers as physicians.
Behind the scenes I had some long discussions about
teaching philosophy with Bob. At the time, the medical school was starting up a new, independent study cur- riculum. Bob had some very definite ideas about teach- ing, particularly about the value of integrating the basic science courses of the first semester by studying the sub- jects concurrently rather than serially, the unique learn- ing gained from hands-on laboratory experiences, the value of the lecture as a teaching method, and the proper way to test students, which were at odds with the then- current philosophy of the medical school. He was instru- mental in arriving at a compromise that maintained some of these elements even in the new independent study curriculum (eventually abandoned several years later).
Bob was truly a dedicated teacher. He loved being in
the laboratory with students during the enzyme kinetics laboratory, walking around and pointing out that they could see the tubes changing color as the reaction pro- ceeded. His lectures were classics. When introducing the subject of prenatal diagnosis, Bob began with the following:

‘‘A Whimsical Example Illustrating the Principle.’’ I have chosen prenatal diagnosis of Transylvanian Vampirism to emphasize that we don’t need to know the relation between the gene and phenotype to apply this method. The analysis is made possible by linkage of the gene governing this trait to the gene which determines round vs. square toenails. Vampirism is caused by homozygosis for the recessive allele, vp (genetic constitution vp/vp). Heterozygotes and homozygotes (Vp/vp and Vp/Vp, re- spectively) are not vampires. In the romance of the century, Melanie Moozendoodle and Gary Gazinkus courted, wed, and started procreating. Unbeknownst to them they were both descendants of the infamous Vlad Tepes the Impaler (Count Dracula) and were hetero- zygotes of constitution Vp/vp. This came to light when

their firstborn turned out to be a vampire.. . . When Melanie became pregnant again, she decided that nurs- ing one child from her jugular vein was enough. Gary, who was taking half the night feedings, agreed. Yet they knew that there was one chance in four the fetus she was carrying would be a homozygote, like its older sibling. The hollow saber incisors characteristic of vp/vp homozygotes appear only at birth, so there is no way this can be directly observed in the fetus. Can any predictions be made?

Bob then proceeded by analysis of linkage of the vampirism gene to the toenail-shape gene to the conclusion that:

The new Gazinkus child is the joy of her parents’ lives. The only sign of her heterozygous condition is that, like the parents themselves, she gets a craving for blood sausage when the moon is full.

After capturing the students’ interest, Bob then went on to introduce the students to prenatal diagnosis through the use of closely linked RFLPs.
Bob’s knowledge was truly encyclopedic. It was well known and appreciated that if you had a really strange question you could not answer that Bob was the person to ask, no matter how unrelated the question might be to his teaching or research. I took frequent advantage of this, and he never disappointed. He was always willing to take on extra teaching to help out a colleague, some- times giving a lecture literally on a moment’s notice.
Finally, Bob really cared about the students. He was willing to spend hours going over the material with students who were having difficulty. He delighted in working with students who wanted to extend the material that he had covered.
Within the mega-university of Wisconsin, as in many a research university, a faculty member could fully occupy himself with his research program and his departmental responsibilities. Not so, Bob Metzenberg, as explained in the following by Bill Dove:
Bob and I first came together as pioneers. Working with Walter Plaut (zoology) and Millard Susman (ge- netics), we (physiological chemistry and cancer biology) crossed the college and departmental matrix of the mega-university that is Wisconsin. We were driven only by our shared enthusiasm for the emergent fields of molecular genetics and molecular cell biology and by our enjoyment of the spectrum of undergraduates in this land-grant university who chose to join us to explore new fields of inquiry without boundaries. Our guiding educational principle was the importance of ‘‘The Experiment.’’ For a full year, we four designed a set of novel experiments in cell biology, biochemistry, and genetics. For decades afterward, Bob continued to de- sign experiments for Biocore as it grew from a cottage industry to one of the bulwarks of undergraduate edu- cation in biology at Wisconsin. Indeed, The Experiment was Bob’s lifeblood—for his own science and then for his teaching of others.

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Another example of Bob’s talent for explanation of seemingly subtle ideas is offered here by Millard Susman:

In the Biocore course, Bob wanted to make the point that the various scientific disciplines were distinguished by the methods that they used and by the kinds of questions that they asked. He told the students that a biochemist who wanted to understand a motor car would grind it up, reducing it to a pile of little chunks, and then would separate the chunks from one another, studying each chunk separately to try to figure out what it did and how it did it. An anatomist would get a huge band saw and slice the car like a salami. The anatomist would then study the slices individually and in sequence to try to figure out the contours of the individual parts and to determine which parts were connected to one another and how they are connected. A geneticist would work with the whole car, removing one bit at a time—a valve here, a gear there—- and see how the removal of that one part affected the operation of the car. It was an immediately comprehen- sible and memorable analogy.

Bob’s life at Wisconsin, in the university and in the community, knew no boundaries. During the three decades following our foray into the wilderness of Biocore, many of our encounters involved mutually enjoyed musical events. Bob had a finely tuned sensitiv- ity to the differences among people—beyond the student body at Wisconsin. We would often exchange postcards from new travel discoveries. We and our wives jointly came forward to help preserve Wisconsin’s classical American Player’s Theater (APT), where Bob again demonstrated his ability to cross disciplines. Discovering with Louise Glass and others that the different alleles of the highly polymorphic mating- type loci of fungi each arose from a distinct sequence origin, Bob consulted with the classics professor of Beloit College who was directing one of the plays at APT. From that consultation was born the neologism
Bob Metzenberg’s quick sense of humor was en- hanced by his ability to recall facts and events that allowed him to view events in unusual ways. Both within and outside of the laboratory and classroom he was well known for his encyclopedic knowledge of tastes and smells. Jim Dahlberg has noted how these latter abilities made him a very popular expert at wine-tasting gather- ings. He was said to have a ‘‘gas-chromatographic nose’’ for ketones and esters. He was a cofounder and an active member of a tasting group that still meets regularly, and his wry comments kept the group from becoming too serious about itself.
The decade in California, described below, generated the end of this story. We continued to exchange mes- sages about new ideas, and in 2005 Bob stepped for- ward to write a masterly essay on one of his Caltech mentors, Norman Horowitz, for the Perspectives article in Genetics (Metzenberg 2005). Our last encounter was in January 2006 when Alexandra and I briefly visited Bob and Helene in Northridge. Again, The Experiment
took first place. Bob announced that he was publishing with Patrick Shiu and others a study on the perinuclear localization of the RNA-directed RNA polymerase in- volved in meiosis in silencing the expression of unpaired genomic sequences (Shiu et al. 2006). This article was important enough to elicit a ‘‘Comment’’ (Kelly 2006).
‘‘I chose to submit this to the Proceedings by Track II,’’ said Bob, eschewing the option of coordinating its review himself as an Academy member. This message was cut from the same cloth as the final word of Bob’s tribute to Horowitz (Metzenberg 2005, p. 1448):

Somehow, Norm always managed to tell the truth without becoming a scold. There can never be enough of such people, and his legacy must be kept alive.

Operating outside the traditional academic bor- ders, enriching the scientific communities of Caltech, Wisconsin, Stanford, and Neurospora, engaging dis- ciplines beyond science, Bob Metzenberg created a remarkable life from three elements: experiment, com- munication, and truth.


Rowland Davis (University of California at Irvine):
I met Bob in 1961 at the very first Neurospora Information Conference in La Jolla, California. The meeting was free for all, in both senses of the phrase, and Bob and I began talking at the free bar after the last- night banquet. Characteristically, he drank Coke, and I drank Canadian Club. Even as I became less articulate, he became more so, and I remember only one thing from that night: I had made one of the best scientific friends of my life.
Bob was then at Wisconsin. I had taken a job at the University of Michigan. I kept seeing Bob at meetings, and in the early 1970s, our labs exchanged visits. In Ann Arbor, Bob inspired one of my most daring experiments— one I had thought impossible if he had not said, ‘‘Why not?’’ At that point, almost whimsically, he rattled off a protocol that might do the job, and within a month we accomplished the task. This was his habit: using his multi-tasking imagination to explore, at the speed of light, landscapes of possibilities in ways that Mozart might have used to choose harmony and orchestration. As we, his friends, coupled our imaginations to his, we felt that even his hypothetical dead ends were more illuminating than a close scrutiny of quantitative data. He proved repeatedly Francis Bacon’s point that the truth is better served by error than by confusion. He remains a model of how much sheer fun science—and talking about science—could be.
Out of context, one of his remarks about himself
might sound ridiculous: ‘‘I had no talent!’’ But the context is illuminating. Having taken instruction in musical composition earlier in life, he had completed several string quartets. He related this to me over lunch

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one day at Stanford, saying, ‘‘They were competent, but they simply followed the rules. Derivative of Haydn and all. But I discovered I simply had no talent!’’ This illustrates not only Bob’s aesthetic refinement, but also his curious blend of modesty and ambition, an ambition to use his mind to the fullest. It also explains his symphonic understanding of the complex biochemical systems that he probed with a sensitivity to detail, subtle complexity, and the surprising formal beauty of cascade regulatory systems.
Finally, Bob became one of the best friends of all of us in our scientific community. Always good humored and anxious to help, he willingly suffered fools, hoping at first that he might show them the light. A lack of success would then bring out advice in an advanced play on words that at least he could enjoy. Finally, the fools would retire, yielding Bob’s attention to others better equipped to enjoy it. I believe Bob made few enemies, largely because he retained a reserve that few people— myself included—fully penetrated. But what overlay that reserve amounted to an incomparable friend and scientist, one who will glow in the dark for years to come.
Namboori B. Raju and David J. Jacobson (Stanford University) interacted with Bob after he retired from Wisconsin and provided the following comments on his time in California:
Bob Metzenberg was no stranger to California; he was here first as a student and later as a retiree. When Bob retired from the University of Wisconsin in 1996, he returned to California to be closer to his family. His two sons live in California: Howard in San Francisco and Stan in Northridge near Los Angeles. Bob chose Stanford for continuing his Neurospora research, mainly because of David Perkins and Charley Yanofsky in the Department of Biological Sciences. This was Bob’s second sojourn at Stanford, the first being a 6-month sabbatical in the Perkins laboratory in 1983. Bob’s re- search interests had long overlapped with those of the Perkins lab, especially in the areas of Neurospora sexual biology (Metzenberg 1995), mating-type genes, rRNA genes, and, more recently, meiotic silencing (Shiu et al.
2001). He was at ease with classical genetics as well as with molecular biology, and he practiced both at Stanford. In early collaborations, Bob provided molecular data for the analysis of a chromosome rearrangement, which has a breakpoint in the nucleolus organizer region that is com- posed of 150–200 rDNA repeats (Perkins et al. 1986).
In January 1996, Bob and his postdoc Rodolfo Aramayo settled into the Perkins lab. Here, Bob contin- ued his seminal research on a new phenomenon first called transvection, and since renamed meiotic silencing by unpaired DNA (MSUD) (Aramayo and Metzenberg
1996; Shiu et al. 2001). After Rodolfo left for a faculty position at Texas A&M in 1997, Bob, together with Patrick Shiu, Namboori Raju, and Denise Zickler in France, greatly extended meiotic silencing studies by
ectopically inserting single genes (at the his-3 locus), whose function is essential for meiotic progression. When such strains are crossed with wild type, the un- paired DNA sequences trigger RNAi-mediated silencing processes involving the RNA-directed RNA polymerases and dicers, in addition to several other components. Consequently, ascus development is abnormal in het- erozygous crosses because of meiotic silencing of un- paired genes, but their development is completely normal in homozygous crosses. Bob isolated two sup- pressor mutants of meiotic silencing, Sad-1 and Sad-2, whose wild-type gene functions are essential for meiotic silencing (Shiu et al. 2001, 2006; Shiu and Metzenberg
2002). The availability of GFP-tagged histone H1 and b-tubulin genes greatly facilitated the visual demonstra- tion of meiotic silencing and its suppression during ascus development (Freitag et al. 2004; Raju et al. 2007; Jacobson et al. 2008). Shiu and Raju had the privilege of collaborating with Bob on several of these research projects. The last of five joint articles with Raju was published in May 2007, barely 2 months before Bob passed away (Raju et al. 2007). Bob was extremely pleased that the article was among the ‘‘Issue High- lights’’ and that our Neurospora image was featured on the cover of Genetics.
Bob’s arrival at Stanford was warmly celebrated during a local Neurospora information conference on the Stanford campus in March 1996. His presence at Stanford also brought together Neurospora workers for
1-day ‘‘joint lab meetings’’ from the nearby University of California campuses of Berkeley and Santa Cruz. Bob especially enjoyed interactions with students and post- docs and often gave them valuable advice for solving their technical problems. During the 7 years at Stanford, Bob made many friends both in his host department and in the medical school. He also taught a biochem- istry course. Lunchtime conversations in the Perkins lab were very lively, with Bob doing most of the talking. He was always bubbling with new ideas and hypotheses, which he often tested within the next few weeks. It was during his time at Stanford that Bob started to suffer his own health problems, although this did not affect his productivity, as evidenced by his election to the National Academy of Sciences and being awarded the Genetics Society of America’s Thomas Hunt Morgan Medal.
In 2003, Bob moved to Northridge mainly to be close
to and help his son’s family. In southern California, he spent some time as a guest in the Department of Chemistry and Biochemistry at the University of California, Los Angeles, and afterward in the Depart- ment of Biology at California State University at North- ridge. However, he spent most of his work hours in his converted home laboratory. Bob’s enthusiasm for re- search was clearly seen in an essay on how to conduct research after retirement ( pdf/newsletter_jan07.pdf). He was actively thinking

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about various experiments and writing his final paper just a couple of weeks before he passed away.
Bob’s energy for work was surpassed only by his ded- ication to others. He was devoted to his family, friends, and colleagues. His years in California were spent as much helping others as doing research. Bob’s sacrifices were legendary, even close to his own end. On learning that his close friend David Perkins was critically ill at the end of 2006, Bob, very ill himself, drove with his son the 7 hr from Northridge to Palo Alto to see David in the hospital. Although David was heavily sedated and un- responsive, Bob spent more than an hour at David’s side, analyzing the situation and making sure the best possible care was being provided. He flew home the next day, catching pneumonia on the plane, but with the satisfaction that he was able to do what he could for his friend.

Eric Selker thanks Joan Bennett, Stan Metzenberg, Mary Anne Nelson, Patricia Pukkila, and Matthew Sachs for contributing some of the photographs reprinted here. He also thanks Helene Metzenberg and friends and colleagues of Bob Metzenberg who contributed remembrances and he regrets that not all could be included in this brief tribute. A more complete collection of pictures and remembrances can be found at lab_research/bob%20website/bob%20memorial%20webpage.html. Above all, he wants to express his appreciation for Bob, who enriched his life and made this article relatively easy to write.


Aramayo, R., and R. L. Metzenberg, 1996 Meiotic transvection in fungi. Cell 86: 103–113.

Butler, D. K., and R. L. Metzenberg, 1989 Premeiotic change of nucleolus organizer size in Neurospora. Genetics 122: 783–791.

Dolan, P. L., Y. Wu, L. K. Ista, R. L. Metzenberg, M. A. Nelson et al.,

2001 Robust and efficient synthetic method for forming DNA

microarrays. Nucleic Acids Res. 29: E107.

Ferreira, A. V., Z. An, R. L. Metzenberg and N. L. Glass,

1998 Characterization of mat A-2, mat A-3 and DmatA mating- type mutants of Neurospora crassa. Genetics 148: 1069–1079.

Freitag, M., P. C. Hickey, N. B. Raju, E. U. Selker and N. D. Read,

2004 GFP as a tool to analyze the organization, dynamics and function of nuclei and microtubules in Neurospora crassa. Fungal Genet. Biol. 41: 897–910.

Glass, N. L., S. J. Vollmer, C. Staben, J. Grotelueschen, R. L.

Metzenberg et al., 1988 DNAs of the two mating-type alleles of Neurospora crassa are highly dissimilar. Science 241: 570–573.

Glass, N. L., J. Grotelueschen and R. L. Metzenberg, 1990a Neu- rospora crassa A mating-type region. Proc. Natl. Acad. Sci. USA 87:


Glass, N. L., R. L. Metzenberg and N. B. Raju, 1990b Homothallic sordariaceae from nature: the absence of strains containing only the a mating type sequence. Exp. Mycol. 14: 274–289.

Harkness, T. A. A., R. L. Metzenberg, H. Schneider, R. Lill, W.

Neupert et al., 1994 Inactivation of the Neurospora crassa gene encoding the mitochondrial protein import receptor MOM19 by the technique of ‘‘sheltered RIP.’’ Genetics 136: 107–118.

Jacobson, D. J., N. B. Raju and M. Freitag, 2008 Evidence for the ab- sence of meiotic silence in Neurospora tetrasperma. Fungal Genet. Biol. (in press).

Kang, S., and R. L. Metzenberg, 1993 Insertional mutagenesis in

Neurospora crassa: cloning and molecular analysis of the preg1 gene controlling the activity of the transcriptional activator NUC-1. Genetics 133: 193–202.

Kelly, W. G., 2006 Standing guard: perinuclear localization of an

RNA-dependent RNA polymerase. Proc. Natl. Acad. Sci. USA

103: 2007–2008.

Mann, B. J., R. A. Akins, A. M. Lambowitz and R. L. Metzenberg,

1988 The structural gene for a phosphorus-repressible phos- phate permease in Neurospora crassa can complement a mutation in positive regulatory gene nuc-1. Mol. Cell. Biol. 8: 1376–1379.

Metzenberg, R. L., 1979 Implications of some genetic control mechanisms in Neurospora. Microbiol. Rev. 43: 361–383.

Metzenberg, R. L., 1990 The role of similarity and difference in

fungal mating. Genetics 125: 457–462.

Metzenberg, R. L., 1995 The sexual cycle in Neurospora: from fer- tilization to ascospore discharge, in Biotechnology of Ectomycorrhi- zae, edited by V. Stocchi et al. Plenum Press, New York.

Metzenberg, R. L., 2005 Norman Harold Horowitz, 1915–2005.

Genetics 171: 1445–1448.

Metzenberg, R. L., and N. L. Glass, 1990 Mating type and mating strategies in Neurospora. BioEssays 12: 53–59.

Metzenberg, R. L., J. N. Stevens, E. U. Selker and E. Morzycka- Wroblewska, 1984 A method for finding the genetic map po- sition of cloned DNA fragments. Neurospora Newsl. 31: 35–39. Metzenberg, R. L., J. N. Stevens, E. U. Selker and E. Morzycka- Wroblewska, 1985 Identification and chromosomal distribu-

tion of 5S rRNA genes in Neurospora crassa. Proc. Natl. Acad. Sci. USA 82: 2067–2071.

Nelson, M. A., and R. L. Metzenberg, 1992 Sexual development genes of Neurospora crassa. Genetics 132: 149–162.

Peleg, Y., R. Aramayo, S. Kang, J. G. Hall and R. L. Metzenberg,

1996 NUC-2, a component of the phosphate-regulated signal transduction pathway in Neurospora crassa, is an ankyrin repeat

protein. Mol. Gen. Genet. 252: 709–716.

Perkins, D. D., R. L. Metzenberg, N. B. Raju, E. U. Selker and E. G. Barry, 1986 Reversal of a Neurospora translocation by crossing over involving displaced rDNA, and methylation of the rDNA segments that result from recombination. Genetics

114: 791–817.

Randall, T. A., and R. L. Metzenberg, 1995 Species-specific and mating type-specific DNA regions adjacent to mating type idio- morphs in the genus Neurospora. Genetics 141: 119–136.

Raju, N. B., R. L. Metzenberg and P. K. T. Shiu, 2007 Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNA. Genetics 176: 43–52.

Selker, E. U., C. Yanofsky, K. Driftmier, R. L. Metzenberg, B. Alzner-DeWeerd et al., 1981 Dispersed 5S RNA genes in N. crassa: structure, expression and evolution. Cell 24: 819–828.

Selker, E. U., R. H. Davis and D. D. Perkins, 2005 The 2005

Thomas Hunt Morgan Medal: Robert L. Metzenberg. Genetics

169: 503–505.

Shiu, P. K., N. B. Raju, D. Zickler and R. L. Metzenberg,

2001 Meiotic silencing by unpaired DNA. Cell 107: 905–916. Shiu, P. K. T., and R. L. Metzenberg, 2002 Meiotic silencing by un-

paired DNA: properties, regulation and suppression. Genetics

161: 1483–1495.

Shiu, P. K. T., D. Zickler, N. B. Raju, G. Ruprich-Robert and R. L.

Metzenberg, 2006 SAD-2 is required for meiotic silencing by unpaired DNA and perinuclear localizataion of SAD-1 RNA-

directed RNA polymerase. Proc. Natl. Acad. Sci. USA 103: