TheTheJapaneseSociety Japanese Society for Chemical Regulation of Plants (JSCRP){JSCRP)

sckS retadiSftssen - Regulation ot Plant Growth & Developrnent Vol, 39, Ne 2, 260-266,2004 tttttlil1!I･ History of GibberellinResearch in the U.K. and

Iiit1litlPersonal Reflections

/.II"''j1 Jake MacMillan

School of Chemistry, University of Bristol, Bristol BS8ITS, U,K.

>. Introductien ･ north of London, The Frythe (Fig, 2) has an interesting Kd There are several accounts of the history of the history (see Knaggs unknown date). It was commandeer-

gibberellins (e.g., Stowe and Yamaki 1957; Stodola 195,8; ed by British Mj]itary Intelligence at the beginning of World

Tamura 1969, 1977; Phinney 1983). My remit from the War II and became Station IX of the Special Military

Editor was to write a review article on the history of Executive (SOE). In the grounds ofthe house temporary

gibberellin research in the U.K. especially focussing on my luboratories were consttucted in huts and many ingenious

own research activities, It is an appropriate time to do se deyices of war were devised as descrLbed by Boyce and

In 1946 the with wartime since it marks the 50th anniversary ofthe first publications Everett (2003). site its labora- on gibberellin research in the U,K, (Curtis and Cross 1954; tories was taken over by ICI for long-term academic and

Cross 1954). I have had to rely on my memory since my multi-disciplinary research, independent of the more

original notebooks and correspondence have been gradua]ly ttpplied research in the ]Cl manufac/turing divisions. Ini-

discarded over the years. Fortunate]y fbr me, I have an tially named the Butterwick,Laboratories they were subse-

aide-memoire through my article, Reflections of a Bio- quently re-named the Akers Research Laboratories.

Frythe was the organic Chemist (MacMillan 1996). Unfortunately forthe. Work on the gibberellinsat the initiatedin

reader of this article there is some overlap. Another limita- fo11owing jnteresting way. In 19flO there appeared in

tion relates to documentation and, because of space limita- Chemical Abstracts (Chem Abs 1950) twelve successive

tions, a heavy reliance on review articles is made. tt has abstracts of papers by Yabuta, Sumiki and their co-workers

"bakanue" also not been possible to mention the names of many of the on the biochemical studies of the , Parts people who have contributed to gibberellin research in the VII-XVLII, that had been published in the Journal of the

U.K. To them I apologise. Agrjcultural Chemical Society of Japan from 1940 to 1944.

X Early days These abstracts, describing the isolation and biological x.ti. Studies on the gibbevellins in the U.K. began in the properties of gibberellin A, caught the eye of Dr,A.W.

early 1950s at the Imperial Chemical Industries (ICI) labo- Sexton, then at the ICI Dyestuffs Divi/lsion. He brought this

ratories at the Frythe, an old country house some 25 miles work to the attention of P.W, Brian at the Frythe with the

suggestion that he might find gibberellin A a rewarding

study. How right Sexton was and how fortunate that Brian

was there to act on th{s suggestion. Brian, originally a

mycologist, was a brilliafit scientist who had been engaged

in a study of the antibiotics from acidic heath soils in close

collaboration with a group of chei:Lists led by J.F. Grove,

Brian acted on Sexten's suggestion by screening cu]tures of

Gibberella flijikuroi. He and his colleagues did not suc- ceed in isolating the gibbereLlin A o:r the Japanese scientists

but instead isolated a compound with similar properties

which was named (Curtis and Cross 1954 ;

Borrow et aL. 1955). At about the same time Stodola and

Fig.1 The author his colleagues (1955) in the USA had also isolated ti

ditzIt7ftpm\ft-1 The japanese Society for Chemical Regulation of Plants

NII-Electronic Library Service TheTheJapaneseSociety Japanese Society for Chemical Regulation of Plants{JSCRP)Plants (JSCRP)

retzotsftsuaenvol. 39,No, 2, 2004 261

HO

Fig.3 Structure ofGibberertic Acid. 'and For structures of ull t36 presently khown gibberellins .thier occurrence in plants, fungi and bacteria see http/1! www. plant-hormones,infolgainfo,asp

F;g. 2 The Frythe from the east biology. There were two other important factors. Firstly, the selected strain 917 of GthbereVa fLofikuroi produced mixture of gibberel]in X, shown (Cross 1954) to be identi- predo,minantly one gibberellin, gibberellic acid, unlike the

cal to gibberellic acid, and a second gibbere]Lin. This Japanese strain which was subsequently found to produce at

prompted Takahashi et al, (1955) to re-examine the origi- least four (Takahashi et a], 1955, 1957). SecondlyL at the

nal gibberellin A and showed that it contained a mixture of Frythe there were biologists and chemists who were in close

compounds, three which they named gibberellins Ai, A2 collaboration. By the early 1950s therefore the chemists

and A3. Gibberellin A, Was identical to the second gibber- and biologists had made significant progress in the produc-

ellin of Stodo]a et al. (1955) and gibberellin A, was identi- tion, chemistry and biolegy of gibberellic acid. As noted

ca] to acid. Thus initially there were three by Tamura this came as a shock to Sumiki when he gibberellic (1977),

trivial names, gibberellic acid, gibberellin A3 and gibberel- visited the Frythe in 1953 since the first publication on

lin X, used for the same compound. Although the groups gibberetlic acid from the IC[ group had yet to be published.

in the USA and Japan conceded that the name gibberellic StruCt"re of

acid had precedence and, although the British group used tsfi:iedM::tl:eaFnrdytffeheMiCal9ibberemc the name gibberellic acid fbr many more years, the name ln the decade fo11owing the first publication (Cross i954) gibberellin A,, usually abbreviated to GA,, is now generally until the Akers Research Laboratories c[osed in 1964, the

used, as origina]ly suggested by Stowe and Yamaki (1957). IC[ chemists made a detai]ed study of the ehemistry and

This is consistent with the procedure, suggested later by structure of gibberelljc acid. As explajned in the Introduc-

MacMillan and Takahashi (1968) for the allocation of tion this work can not be described in detail with cited

trivial names to the gibberellins. literature references. But most of it has been descrjbed in

Tl has been often been stated in reviews that Brian and his several review articles (BrLan et al. 1960; Grove 1961 ;

group were fortunute in obtainjng a strain 917 that provided Cross et al. (1961), By 1959 the chemical structure and high yields of gibbere]lic acid. However, examination of absolute stereochemistry, shown in (Figure 3), had been

the paper by Borrow et al. (1955) shows that it was a determined (Cross et aL, 19S9b). The absolute stereo-

methodical survey of 21 strains and a detai]ed study of the chemistry was later confirmed outside the Frythe group at

conditions ofculture that led to the initial relatively high Glasgow University (McCapra et al. 1966). The determi-

yields approaching 200mg per ]itre of culture fiuid in nation of the chemical structure of gibberellic acid is one of

submerged culture. Subsequent]y yie]ds were greatly in- the last examples of the dete.rmination of the structure of a

creased by further development ofsubmerged culture, first in mainly by the classical methods of degrada-

convcrted Hoover washing muchine and eventually in indus- tion although nuclear magnetie resonance and optical rota-

tria] fermentoFs [for further details see the review by Vass tory dispersion were used late in the work (Cross et al, 1959 and JeH'ereys (1979)]. Thus, ear]y on gibberelll'c aeid was a, b).

available to the ICI reseurchers at the Frythe in amounts The determination of the structure of gibbere]]in A, was

that facil{tated the subsequent studjes on its chemistry and important in that it put subsequent studies on a sound

NII-Electronic Library Service TheTheJapaneseSociety Japanese Society for Chemical Regulation of Plants (JSCRP){JSCRP)

262 ditzokftMzaVo].39, .No. 2, 2004

chemical basis and allowed the structure of the then known ICI in 1956 for the acceleration ofthc germinution of barley

fungal gibberellins, and subsequently isolated gibberellins, grain, the first important commercial use, in the brewing

to be determined by correlating their structures to gibberet- industry, ofgibberellic acid. But perhaps the most notable

lin A3 by defined chemical reactions. scientific result of this perlod was the observed effect, on

The main sclentists involved in the study of the chemistry dwarf plants by Brian und Hemming (1955). They showed

of gibberellic acid were B.E. Cross, J.F. Grove and T.P.C. that suitable doses of gibberellic acid eliminated the Mulholland. My contribution was modest. I had been difference in growth rate between talt .and dwarf varieties. appointed in 1949, immediately after obtaining my Ph.D., to In other words gibberellic acid conve[ts a dwarf phenotype 'based insecticides, upon but without into a similar to a tall This result directly prepare gammexane plant phenotype. chLorine, for even then the toxicity of organic chlorides was initiated the work by Phinney (1956) on single gene dwarf

an issue. When the first head of the Chemistry greup, J.C, mutants of maize and eventually to the explanation of the

McGowan, was replaced by J,F. Grove, I became involved orjginal genetic work by Mende] on pea plants (Martin et in determining the structure of the anti-mycotic fungal al. 1997). In a review ofhis early work Brian (1957) made metabolite, griseofulvin and its dechloro- and bromo-ana- several prophetic comments, I quote two of them:

My fu11 time involvement on the gibberellins came later an internal growth regu]ator jn addition to the system

from the studies by Brian and his group on the plant and that dwarfLrecessive ptants are the resu]t of metabolic

growth-promoting properties of gibberellic acid. blocks in the chajn of synthesis leading to this hypothetical "GA Related to the studies on the chemistry of gibberellic acid, growth regulator.,,,"; and (b) and the hypotheti-

chemists at the Frythe, notably B.E. Cross, J.R. Hanson and cal GA-like natural growth promoter are inhibitors of

R,H.B, Ga]t a]so made detailed studies of new metabolites inhibitors". Both predictions were proven to be correct as of Gibberetla fiij'ikuroi, related to gibberellic acid. Each noted later, continued this work for a time after the closure of the Akers }x. Studies on the Occurrence of Gibberellins in Plants Research Laboratories, Cross at the University of Leeds, geLX),at the Frythe Galt briefly at the Pharmaceuticals Division of ICI and Brian's suggestion that gibberellLc acid was a naturaL

Hanson at the University of Sussex. Thus, they isolated the regulator of plant growth stimulated the search in many

minor fungal gibberel]ins A2 and A,, known from the laboratories in many countries for evidence of the presence

previous work of Takahashi et al. (1955, 1957) and the of gibberellin-like substances in hi:gher plants. Since my

previously unknown GA7, GAg and GATo to GAi6, They brief is to present a history of research in the U.K. ]

also iso]ated and determined the structures of a range of confine my description of the isolation of gibberellins from

tetracyclic diterpenes, such as ent-kaurene and relatives, higher plants to the work at the Frythe. By the summer of

which led to studies on the intermediates in the biosynthetic 1956 it was already known tbe immature seed of runner

pathway of the gibberell{ns in GibbereUa fL{iikuroi as de- bean (Phaseolus coeeineus) was a .rich source of gibberel- sciibed ]ater. lin-like activity although this work was not pub]ished until ",x., 'K,nv Studies on the Physiological Effects of Gibberellic later

leagues were studying the plant growth stimu[ating prop- many hands, about 100 kg ofimmat'ure seeds were collected

erties of gibberel]jc acid and its derivatives. Some of the and extracted in batches to provide pure crysta11ine samples

early results were presented at an international meeting of GA, (2 mg. per kg. fresh wt. seed), GA, (1 mg. per kg,

`[The entitled Chemistry and Mode of Action of Plant fresh wt. seed), GA6 (1 mg. per kg. f'resh wt. seed) and GAs

Growth Substances'] held at Wye College in 1956-a precur- (16mg. per kg, fresh wt. seed), The structures of these

sor ofthe IPGSA Conferences. Brian's presentation creat- gibberellins, were determined by relELting them chemLcally to

ed great interest and added to the growing intense and gibberellic acid. After a delay while ICI considered the

widespread interest in the gibberellins, One early conse- possiblc commercial implications of the identification of quence of Brian's studies was the granting ofputent rights to GAi in a higher plant, this result was reported in prelimi-

NII-Electronic Library Service TheTheJapaneseSociety Japanese Society for Chemical Regulation of Plants{JSCRP)Plants (JSCRP)

ditzothftueenVo]. ]9, No. 2,2004 263

nary form for GA, (MacMillan and Suter t958) and for tor of the research on the gibberellins at the Frythe. Much

GA, (MacMillan et al, 1959), Fu]1 reports ofthe isolation of' my final days Were spent arranging the take-over of the

Of the four gibberellins fo11owed a few years later (MacMil- Frythe･by the Unilever company. 1 felt- too young to

lan et al. 1960,1962), The work was also reported at a becorne a fu11-tLme administrator.and 1 missed research so

Symposium on GLbberellins at the 138th Meeting of the much that l began to look for a University lectureship.

Arnerican Chemical Society in New York in September With great luck the Chemistry Department at Bristol Uni-

1960 where 1 gave two successive talks on the Gibberellins versity took u chance with a person in his Iate 30s without

from Higher Plants (see MacMillan et al, 1961) and The teaching experience and appointed me in 1963, Structures of Fungal Gibbere]]ins (see Cross et al, L961). idnelldeedUt'5'stop

During these talksI had the strange and unique experience getGill\eE:lllnoi]POhSatd-FaiYmtohset research on of listening to myself talking us though I was in the audi- the gibberellins, My decision to continue came from inter- "]ost" ence, Perhaps this was a sign that Ihad my audi- act{on with a new colleague, R. Binks, who was interested in

ence! gas chromatography and mass spectrometry. Following

Although th{s is u review of gibbere]lin research in the the publjcation by Ikegawu et a], (1963) on the GC of the

U.K.,it must be noted that the suggestion by Brian that methy] esters of GA, to GAs, we used the methy] ester

gibberellin-like substances might occur in higher ptants had trimethyl ethers and provided the first examples of･ the

prompted many groups outside the UK to search for evi- identification of GAs in crude plant extructs by combined

dence for their occurrence, lt was no surprise therefore gas chromatography-mass spectrometry (GC-MS) at･the that, about the same time, West and Phinney (1959) report- Sixth lnternariona] Conference on Plant Growth

ed the identification-ofGA, from seed of Phaseotus vuigaris in Ottawa in i967. It was at that Conference that Nobuta-

and Kawarada and Sumiki (19S9) isolated GA, from ka Takahashi and I met fbr the first time and proposed bamboo shoots. (MacMMan and Takahashi 1968) the system for assigning

Gibberellin Research after the closure of the Akers tr[via[ GA numbers to GAs as they are isolated and in Research Laberatories identified, irrespective of their source-a' system which has 'By the early 1960s jt became clear that the future of the stood the fest of time for there are, at the latest,count, t36

Akers Research Laboratories･at the Frythe was in doubt. gibberellins, systematically ordered from GAi to GAi36 (for

There were many reasons which need not be discussed here. their st･ructures and occurrence in higher p[ants, fungi and

There were also many consequences, not least of which was bacteria see http[/lwww,plant-hormones,infb/gainfo,asp).

that staff began to drift away. A major blow was the loss Our initial work ,using GC-MS was done on instruments in

of P.W. Brian. By then the Director of the Akers Research laboratories in Sweden, Glasgow and BristoL often over-

Laboratories he left to become the Regius Professor of night in the latter case, using light-sensitive paper to reco'rd

Botany at 61asgow University where he did little more work the GC and MS traces. Then, with the crucial help ofJ,S,

on the gibberellins. When it was finally decided'to close Littler and R.L. Clettver, an on-line data processing system

the site and move the organic chemists and biotogists to the was developed (Binks et al. 197t) fbr low resolution mass

Pharmaceutical Division of' ICI at Alderley Park in Cheshi- spectrometry, Examptes of the use of this system were

re, jt had become clear that the basic, interdiscipljnary described for the first time in Kyoro (MacMillan 197])

gibberellin research within ICI was over and the group during my first visit to Japan in' 1970 on my way to the 7th

dispersed. I have previousty mentioned the movements of IPGSA Conference in Canberra. At that time paeked and

Cross, Galt and Hanson, Margaret Radley moved to SCOT columns were used for GC and it was not unti]･1981

Rothamsted Research Statjon. MuLholland transferred to that we acquired a dedicated commercial･ system using 'capillary the Pharmaceuticals Division and Grove teft ICI, both to GC co]umns. With this capability of identifying

work on non-gibberellin research, GAs in plant extracts, and with the expertise of P. Gaskin

l was appointed to succeed Brian as Djrector and spent (see Gaskin and MacMi[tan t991), gibberetlin research at

the next two years,as an administrator in a large oMce ln the Bristol Universlty fiourished, New gibbereLLins fi'om the

main house at the Frythe, and frequenily travelling between fungus and higher plants were identified and their structures ･avaitable the Frythe and Alderley Park to consult on the details ofthe were confirmed by their partial synthesis from

relocation of stafi' liasing ironically with Sexton, the origina- gibberellins. Gibbereilins, labelled with radio-active and

NII-Electronic Library Service TheTheJapaneseSociety Japanese Society for Chemical Regulation of Plants (JSCRP){JSCRP)

264 reMOkftsuMVol. 39,No,2, 2004

stable isotopes, were prepared and used in biosynthetic and career. It was situated a few miles f'rom Bristol and or{gi-

metabolic studies in higher plants and in the fungus. nally established to study apple horticulture for the locaL

This work fostered internation.al coltaborations with cider industry. Soon ufter my arrivaL at Bristol I contacted

many scientists from many countries. For example we L.C. Luckw"1 who was studying the role of gibberellins in

contributed to the biosynthetic work ofJ,E, Graebe:s group the biennial fruiting of the apple, Cox's Orange Pippin.

at the University of Gottingen on biosynthesis using celL- This led to a close association between my group and the

free enzymc preparations from maxitna seeds. Station which was financed by the (then) Agricultural

tn the course of that work we re-discovered that the specific Resea-rch CounciL (ARC), now the Biotechnology and

radioactivity of [i`C]-labelled compounds could be deter- Biological Research Council (BBSRC). A consequence of mined by mass spectrometry (Bowen et a], 1972). Another this collaboration was my inyolvement in the decision by

example was with B.O,Phinney and his group at the the AFRC in the early 1980s to consolidate its basic

University of California, Los Angeles, initial]y on the research on natural plant hormones at Long Ashton. This biosynthesis in fi{fikuroi using a single gene decision brought together three strands of the history of

mutant, Bl-41a, and subsequentLy in vegetative tissue using gibberelLin rcsearch in the UK. Thus, J.R. Lenton was

GA-responding, single-gene mutants of maize. The col- transferred from Rothamsted Experiniental Research Station

laboration on the fungal mutant has an interesting Japanese where he had been an associate of rv{[argaret Radley ex-ICI

connection since it was initiated by the visit to Bristol by from the Frythe. P, Hedden, a graduate student of mine Machj Fukuyama (now Dilworth), then a graduate student and subsequently a post-doctoral fe11ow with J.E. Graebe

of B,O. Phinney. Both of these collaborations contributed and B.O.Phinney was transferred from East Malling

significantly in defining the biosynthetic steps in gibberellin Research Station and eventually M,H. Beale, P, Gaskin and

biosynthesis as shown in a recent reyiew by MacMillan myself when I formally retired in 1990 from the University

(I997). In another collaboration with J,B.Reid, Univer- of Bristol. Another important player in the powerful group

sity of Tasmania, a quantitative rellationship between level that was assembled at Long Ashton was A.L. Phillips who

ofGA, and stem elongatfon of pea seedlings was established came from Rotham sted Research Station. This team of

(Ross et aL 1989). organic chemists, molecu]ar biologists, biochemists and AI[ of gibberellin research at Bristol University was only physiologists made notable contributions to the develop-

possible by the dedication and skill of rnany graduate ment of gibberellin research in the fo11owing two decades.

students and post-doctoral researchers. Their names are These achievements have been sum[narised by Lenton and

acknowledged in MacMillan (1996). Some ofthese names Hoad (2003). The interdisciplinary studies inc[uded the

will be recognised from their subsequent contributions to characterisation of the dioxygenases that control the feed-

gibberel]inology. back of GA biosynthesis and the feed-forward of GA

As noted ea[lier concurrent with work at Bristol, gibbere]- catabolism and demonstating the manipulation ofGA levels

lin research was also being continued in the U.K. by B.E. and plant growth development by ectopic expression of

Cross at the University of Leeds and by J,R. Hanson at the these genes. Of historical interest was the demonstration

University of Sussex. Both groups built upon the initial that Mendel's dwarfing gene in pea encodes a GA 3-oxidase

dernonstration by Birch et al. (1959) of the diterpenoid catalys.ing the final step in forming bio-active GA and that origin･ of GA, from [2-""C]-mevalonic acid in GthbereUa the te dwarf mutatjon contains a single amino-acid substitu-

with assistance the Frythe tion c]ose to the active site of the 3-oxjdase reducing .fiijikuroi the technical of group.

Inter atia Cross and his colleagues isolated ent-kaurene binding of the GA substrate (Martin et aL. 1997). Of from the fungus and showed that it was a precursor ofGA3. evolutionary interest was the genetic evidence that the They also prepared ['`C]-GAi!-aldehyde and showed it to biosynthesjs of gibberellins after the intermediate, GAi2- be an intermediate in the biosynthesis of GAs. The essen- aldehyde, is catalysed by cyto/:hrorne' P450 mono-

tials of this b{osynthetic work by Cross and by Hanson are oxygenases in GibbereUa fZijikuroi and by solubte diox-

put into context in the previously mentioned review ygenases in higher plants. Thus gibberellin biosynthesis (MacMMan 1997>. Historically, the nextcentre ofgibber- must have evolved independently in higher plants and

ellin research was at et al. and references in the U.K. Long Ashton Research Gibbereaa .flijikuroi (Tudzynski 2003

Station where, coincjdentally, P.W, Brian began his research therein). Upon the c]osure of Long Ashton Res,earch

' NII-Electronic Library Service TheTheJapaneseSociety Japanese Society for Chemical Regulation of Plants (JSCRP){JSCRP)

retzotsftsuenVoL39, No.2,2004 265

Station on jts 100th birt]iday in 2003 gibberellin research Chemistry of Organie Naturat Products, Ed. Zechmeister, L, pp. 351-343, Springer-Verlag, Wien. was transfeFred to Rothamsted Experimental Research Sta- Chem Abs (.l950) 44, columns le814-10817, tion where it continues. Cress, BE (1954) J Chem Soc 4670-4676. Cross, BE, Groye, JF, MacM;]lan, J, Moffatt, JS, MuLholland, Genealogy of Gibberellin Research in the UK TPC, Seaton, JC and Sheppard, N (t9S9a) Proc Chem The Akers Research Laboratomes of in (Butterworth) Sec 302-303. Cross, BE, JF, McCloskey, P, Mulholland, TPC and ICI Ltd. at the Frythe were a delightful place to conduct Grove, Klyne, W (1959b) Chem and lnd/ 1345-1346. research for several reasons. The average age of scientists Cross, BE, Groye, JF, McCloskey, P, MacMillan, J, Moffatt, was ]ow and the majority lived on site either ln the large JS andMulholland,TPC (]961) Adv in Chem Series 28 : 3-17, house or in dormitories built in the grounds, So interac- Curtis, PJ and Cross, BE ([9S4) Chem and. Ind 1066. tion was high. No wonder therefore that the approach to Gask;n,PandMacMitlan,J (1991) GC-MSoftheGibberel- lins and Related Compounds: Methodology and a Library research was interdisciplinary. The administration was of Spectra. Bristol / Cantoeks Enterprises. enlightened and staff were a]lowed to develop their own Groye, JF {1961) Quart Rev 15/ 56-70. and strengths and interests irrespective of their backgrounds. Crove, JF, MacMil]an, J, MuLholtand, TPC Rogers, MAT (l952) J Chem Soc 3977-3987. Two examp]es were Margaret Radley, originally a librarian Harberd, NP, King, KE, Carol, P, Cowling, RJ, Peng, J and who became a plant physiologist and G,W, Elson, originally Richards, DE (]998) Bioessays 20/ 100t-IO08. Ikekawa, N, Kagawa, T and Sumiki, Y (]963) Proc Japan a merchant seaman who went on to co-ordinate the expLoi- Acad 39 : 507-512. tation of the use of gibberellins in horticulture and agricul- Kawarada, A and Sum{ki Y (1959) Bull Agric Chem Soc

Jdpan 23/ 343-344. ture at ICI PIant Protection Ltd. The Frythe was also the Knaggs, J. http/lfhomepage.ntlworld.comfjeffery,knaggsf and of the main of parent grandparent groups gjbberel]jn Frythe.htrn1 research in the UK, It directly spawned the groups at the Lenton, JR and Hoad, GV (2003) Hormones and plant devel- opment tn Long Ashton Research Statipn: one hundred Universities of Leeds, Sussex and Bristol and indirectly the years of science in support of agriculture, Eds. Anderson Long Ashton group,. Tn other studies in the UK glimpses HM, Lenton, JR and Shewry. PR, pp. 291-331. Iles Ltdt) Bristol, UK. of the infiuences of the Frythe are seen. For example the McCapra, F, McPhail, AT, Scott, AT, Sims, GA and Young, ear]y suggestion by Brian that GAs might act as inhibitors DW (1966) J Chem Soc C 1577-158S. l697-[702. of an inhibitor has been justified by genetic studies on GA- MacMillan, J (1953) J Chem Soc MacMiLlan, J (1954) J Chem Soc 2S85-2S87. signaliing mutants (see Harberd et al. 1998). The charac- MacMMan, J (l959) J Chem Soc ]823-l830, teristic interdisciplinary aspect of the research at the Frythe MacMilla", J (1971) Che'micat Reguiation of Plants 6, 150-IS6 Japanese). was continued by the research groups at the University of (in MacMillan, J (1996) Annu Rev Plant Physiol Plartt Mol Bristol and Long Ashton ]eading to international collabora- Biol 47/ ]-21.

MacMillan, J Natt Prod Rep 14: 221-243. tions, particularly in Japan, Germany and the United States, (1997) MacMillan, J and Suter, PJ (1958) Naturwissensehqf}en. 45 /

I am confident that this finetradition wi[[ be continued at f 46-47. Rothamsted Research Station where future gibberellin MacMiLlan, J and Taka･hashi, N (1968) Nketure 217: t7e- 17LMaeMillan, research in the U.K. [s in good hunds, J, Seaton, JC and Suter, PJ (1959) Proc Chem Soe 325, References MacM;]Lan,J,Seaton,JCandSuter,PJ (]960) Tletrahedron 11i 60-66.

MacMMan, J, Seaton, JC and Suter, PJ Mdv in Binks, R, Cleayer, RL, Littler, JS and MacMillan, J (t971) (t961) Chem Series 28: 18-25. Chemtstry in Britain 7 / 8-]2. MacMillan,J,Seaton,JCandSuter,PJ 71etrahedron B;rch, AJ, Richards, RW, Smith, H, Harris, A and Whalley, (1962) l8: 349.35S. WB (]959) 7letrahedron 7: 24t-2Sl. Mftrtin, DN, Proebsting, WM and Hedden, P Proc Borrow, AC, Brian, PW, ChesterT VE, Curtis, PJ, Hemming, ('1997)

HG, Henehan, Catherine, Jefferys, EG, Lloyd, PB, Nixon, AiattAcad Sci USA 94 : 8907-891]. Ph;nney, BO Proc tVatl Acad Sci USA 42: 185-189. IS, Norris, GLF and RadLey, Margaret (l955) J Sci (1956) Physiology of food Agric 6, 340-348. Ph;nney, BO ([983) In The B{ochemistry ancl Ed. Crozier, A, New Bowen, DH, MacMillan, J and Graebe, JE (1972) Phyto- Gibberellins-Volumer, pp.I9-52. chemisttv 11: 2253-2257. York / Praeger, Boyce, F and Everett, DH (2003) SOE/ the seientij7c seerets Radley, M (1956) Nature 178: 1070-1071. Stroud, Sutton. Radley, M (1958) Ann Bot XXII, 297-307. Ross, Reid P and MacMillan, J Brian, PW and Hemming, HG (195S) Physiot Plant8/ 669- JJ, JB, Gask;n, (1989) 68].Brian, Physiol Plant 76: 173-176. PW {19S7) SJ?mp Soc Exp Biol 11 / ]66-182. Stodola, FH (195g) Source Book on Gibberellins 1828-1957. Brian, PW, Grove, JF and MacMillan, J (1960) ln The Agricultural Research Service, U.S. Department of Agricul-

NII-ElectronicNII-ElectronicMbraryService Library Service The JapaneseSocietyJapanese Society for Chemical Regulation of Plants (JSCRP){JSCRP)

266 ditzOtsftxepm Vo].]9, No.2, 2004

ture, Gaskin, P and Hedden, P (2003) J Biol Chem 278/ Stodola, FH, Raper, KB, Fennel, D, Conway, HF, Johns, VE, 28635.28643, Langford, CT and Jackson RW (1955) Arch Biochem Vass, RC and Jefferys, EG (t979) Gibberellic acid. In Eco- Biophys 54: 240-245. nomic Microbiology, Vol.3 Ed. Rose AH, pp,42]-435, Stovve,BB,andYamaki,T (1957) AnnuRevPlantPhysiol8: Academic Press, New York. 181.216. West CA and Phinney BO (1959) J Amer Chem Sec 81: Takahashi, N, Kitamura, H, KawarEda, A, Seta, Y, Takai, M, 2424-242･7. Tamura, S and Sumiki, Y (1955) Bult Agrc Chem Soc Japan 19/ 267-277. Corresponding address : Jake MacMillan Takahashi, N, Seta, Y, Kitamura, H, and Sumikl, Y (1957) School of Chemist[y, University ef Bua Agrc Chem Soc Japan 21 : 396-398. Bristol, Cantock's Close, Bristol, BS9 TamurE, S (1969) In Gibberellins, Chemistry, Biochemistry and Physiology, Ecl. Tamura. S1: 3-27. Tokyo/ Tokyo ITS, UK

Taigakushuppankai. (in Japanese), Tei: Ol17-3317162 Tamura, S In Ptant Hormones, I8-50, Dai nippon (]977) pp. E-mail : [email protected], tosho Co. Ltd., Tokyo, (in Japanese), uk Tudzynski, B, MihLan, M, Rojas, MC, Linnemannstons, P,

NII-Electronic Library Service