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Maxwell  Berkow  







December  5,  2014  

Professor  Lampousis    






MHC  20301  


Herbert  Hauptman  

The  common  saying,  “knowledge  is  power,”  is  often  applied  to  the  field  of  

science,  but  it  would  be  difficult  to  find  a  more  applicable  use  than  when  describing  

the  work  of  Herbert  Hauptman.  Using  his  research  to  identify  the  structures  of  

molecules,  scientists  have  engineered  all  of  today’s  invaluable  drugs.  Although  the  

common  man  may  not  know  it,  he  or  someone  he  knows  has  had  their  life  saved  by  

Hauptman.  Whether  this  lack  of  appreciation  is  due  to  Hauptman’s  humble  nature  

or  the  public’s  inattention  to  the  scientific  research  that  keeps  them  alive,  this  man  

has  helped  to  drastically  increase  U.S.  life  expectancy  by  ten  years.  

Interestingly,  this  advancement  in  the  field  of  medicine  came  from  a  

mathematician.  Contrary  to  this  specification,  Hauptman  has  had  a  self-­‐described  

love  of  both  mathematics  and  science  ever  since  he  began  to  read.  This  interest  in  

science  may  have  been  the  reason  for  his  collaboration  in  chemistry  that  would  

eventually  win  him  his  Nobel  Prize.  The  New  York  City  native  attended  Townsend  

Harris  Hall  before  graduating  from  The  City  College  of  New  York  in  1937  with  a  

bachelor’s  degree  in  Mathematics  and  Columbia  University  two  years  later  with  a  

master’s  degree  in  the  same  field.  Afterwards,  the  United  States’  involvement  in  

World  War  Two  forced  Hauptman  to  take  a  break  from  his  studies  and  become  a  

Naval  weather  forecaster  in  the  South  Pacific.  

In  1947,  after  returning  from  the  war,  Hauptman  enrolled  in  a  Ph.D.  program  

at  the  University  of  Maryland  and  began  a  collaboration  at  Washington  D.C.’s  Naval  

Research  Center.  This  partnership,  with  physical  chemist  Jerome  Karle,  became  the  


Berkow  2  

focal  point  of  Hauptman’s  career.  The  research  he  did  on  x-­‐ray  crystallography,  a  

process  by  which  molecules  are  identified,  with  Karle  was  the  source  of  his  eventual  

Nobel  Prize  and  the  dissertation  that  earned  him  his  doctorate  in  1955.  He  and  Karle  

published  their  results  in  a  book,  Phase  Problem  I:  The  Centrosymmetric  Crystal,  but  

their  findings  were  quickly  dismissed  because  of  the  difficulty  of  the  problem  they  

had  solved.  The  question  of  determining  the  exact  structure  of  a  molecule  was  

considered  unsolvable  to  most  chemists  at  the  time.  It  would  take  until  the  1970s  

for  their  work  to  be  accepted  and  1985  for  it  to  be  recognized  with  the  Nobel  Prize  

in  Chemistry.  Hauptman  would  study  this  process  of  x-­‐ray  crystallography  for  the  

rest  of  his  career.    

In  1970,  not  wanting  to  shift  his  research  towards  laser-­‐guided  missiles,  

Hauptman  left  the  research  center.  He  continued  his  work  in  relation  to  endocrines  

at  the  Medical  Foundation  of  Buffalo.  He  became  the  director  of  research  for  the  

foundation  in  1972  and  its  president  in  1988.  By  this  time,  Hauptman  was  an  

internationally  renowned  scientist:  a  member  of  the  National  Academy  of  Sciences,  

honorary  degrees  from  universities  worldwide,  and  recipient  of  a  Nobel  Prize.  He  

became  the  first  mathematician  to  win  the  award  based  solely  on  his  work  in  

mathematics.  Due  to  these  distinctions  and  Hauptman’s  contributions  to  the  

foundation,  the  Medical  Foundation  of  Buffalo  has  since  been  renamed  the  

Hauptman-­‐Woodward  Institute.  Quoted  as  saying  “There  is  no  such  thing  as  

working  too  hard  or  too  long,”  Hauptman  exemplified  his  beliefs,  working  daily  at  

the  Hauptman-­‐Woodward  Institute  even  into  his  nineties.  He  died  on  October  23,  



Berkow  3  

X-­‐ray  crystallography  is  the  process  of  changing  a  compound  to  its  crystalline  

form  and  analyzing  the  scattering  patterns  observed  when  x-­‐rays  are  shone  on  this  

crystal.  Scientists  use  this  technique  to  determine  the  position  of  specific  atoms  in  a  

compound  and  create  an  image  of  the  molecule  in  three-­‐dimensional  space.  This  

knowledge  is  key  to  the  production  of  all  drugs.  It  provides  researchers  with  

information  about  the  substances  they  are  studying  and  molecules  they  have  

created,  both  of  which  are  vital  to  understand  how  a  proposed  treatment  may  

interact  with  the  body.  

Hauptman  and  Karle  made  this  process  into  what  it  is  today.  At  the  time  of  

their  research,  the  idea  of  calculating  the  position  of  an  atom  in  a  molecule  was  

actually  deemed  impossible  by  most  researchers.  Prior  to  their  research,  x-­‐ray  

crystallography  could  only  be  used  to  infer  the  structures  of  a  compound.  Chemists  

knew  that  there  was  a  relationship  between  the  scattering  patterns  of  the  x-­‐rays  and  

the  composition  of  the  molecule,  but  they  could  not  determine  the  exact  correlation.  

One  major  difficulty  in  x-­‐ray  crystallography  is  the  phase  problem.  Inconveniently,  

the  x-­‐ray  detector  can  record  the  intensity  of  different  beams  but  not  the  phases  of  

each  electromagnetic  wave.  This  limitation  means  that  vital  information,  such  as  

electron  density  distribution  in  the  crystal,  is  lost.  Hauptman  used  probability  

theory  to  devise  a  series  of  equations,  called  “direct  methods”,  that  could  determine  

the  phase  and  translate  the  diffraction  patterns  to  pinpoint  the  positions  of  atoms  in  

a  small  compound.  In  the  1980s  Hauptman  addressed  this  limitation,  applying  his  

research  to  larger  molecules  and  successfully  altering  his  equations  to  do  so.  

Although  they  had  revolutionized  medicine  and  the  pharmaceutical  industry,  


Berkow  4  

Hauptman  and  Karle’s  theories  were  dismissed,  unused  until  they  were  finally  

accepted  twenty  years  later.  

Hauptman’s  formulas  even  reduced  the  time  required  to  determine  a  

compound’s  structure.  During  the  1960s,  it  could  take  two  years  to  find  the  

structure  of  an  antibiotic  with  only  fifteen  atoms.  Using  Hauptmann  and  Karle’s  

research,  it  became  possible  to  determine  the  structure  of  a  compound  with  100  

atoms.  Hauptman’s  later  improvements  to  his  own  direct  methods,  made  from  his  

research  at  the  Hauptman-­‐Woodward  Institute,  further  increased  this  limit  to  1000  

atoms.  Currently,  using  direct  methods  in  conjunction  with  modern  computing  

capabilities,  it  is  possible  to  quickly  determine  the  position  of  atoms  in  a  protein  

with  over  ten  thousand  atoms.  A  determination  that  once  took  years  to  complete  is  

now  done  in  hours  with  much  larger  molecules.  Although  computing  power  has  a  lot  

to  do  with  this  increase  in  efficiency,  the  impact  of  Hauptman’s  research  is  


In  an  interview  with  the  Associated  Press,  Eaton  Lattman,  chief  executive  of  

the  Hauptman-­‐Woodward  Institute  stated,  “I  don’t  think  there’s  a  single  

pharmaceutical  that’s  been  developed  in  the  last  30  years  that  hasn’t  been  studied  

using  derivations  of  what  Dr.  Hauptman  and  his  colleagues  won  the  Nobel  Prize  for.”  

Although  Hauptman’s  influence  on  modern  medicine  is  demonstrated  by  his  

prestige  and  awards,  Lattman’s  quote  is  a  much  greater  measure  of  his  work.  

Hauptman’s  dedication  to  scientific  advancement  led  him  to  further  his  research  

even  after  decades  without  recognition.  The  lasting  impact  of  his  work  shows  that  

society  will  forever  be  indebted  to  this  commitment.  


Berkow  5  

Works  Cited  


Grimes,  William.  "Herbert  A.  Hauptman,  Nobel  Laureate,  Dies  at  94."  The  New  York  

Times.  The  New  York  Times,  24  Oct.  2011.  Web.  28  Nov.  2014.  


Hauptman,  Herbert.  "A  Minimal  Principle  in  X-­‐Ray  Crystallography:  Starting  in  a  

Small  Way."  Proceedings  of  the  Royal  Society  A:  Mathematical,  Physical  and  

Engineering  Sciences  442.1914  (1993):  3-­‐12.  JSTOR.  Web.  30  Sept.  2014.  


Hauptman,  Herbert  Aaron.  An  N-­‐Dimensional  Euclidean  Algorithm.  Thesis.  

University  of  Maryland,  College  Park,  1954.  N.p.:  n.p.,  n.d.  Print.  


"Herbert  A.  Hauptman  -­‐  Biographical".  Nobel  Media  AB  2014.  Web.  1  

Oct  2014.




Hauptman,  Herbert.  Crystal  Structure  Determination:  The  Role  of  the  Cosine  

Semivarients.  New  York:  Plenum,  1972.  Print.  


"Herbert  A.  Hauptman,  PhD."  Hwi's  Nobel  Laureate.  Hauptman-­‐Woodward  Medical  

Research  Institute,  n.d.  Web.  28  Nov.  2014.  


"Herbert  Hauptman."  Jewish  Virtual  Library.  N.p.,  n.d.  Web.  28  Sept.  2014.



Hauptman,  Herbert  Aaron,  and  Jerome  Karle.  Solution  of  the  Phase  Problem.  I.  The  

Centrosystemmetric  Crystal.  Wilmington,  DE:  American  Crystallographic  

Association,  1953.  Print.  


Hauptman,  H.  "The  Direct  Methods  of  X-­‐ray  Crystallography."  Science  233.4760  

(1986):  178-­‐83.  JSTOR.  Web.  02  Oct.  2014.  


Lamont,  Paul.  "Herbert  Hauptman:  Portrait  of  a  Laureate."  Herbert  Hauptman:  

Portrait  of  a  Laureate.  PBS.  22  June  2008.  Television.  


"".  Nobel  Media  AB  2014.  Web.  3  Oct  2014.




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