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Francisco, California 94080, USA‡Eos Biotechnology, Inc., 225A Gateway Boulevard,South San Francisco, California 94080, USA§Division of Immunology, Beckmann ResearchInstitute of the City of Hope, 1500 East Duarte Road,Duarte, California 91010, USA¶MetaXen, 280 East Grand Avenue, South SanFrancisco, California 94080, USA#HESKA, Gruengenstrasse 19, CH-4416 Bubendorf,Switzerland1. Marshall, E. Science 284, 883–886 (1999).

2. Goeddel, D. V. et al. Nature 281, 544–548 (1979).

Statement fromPeter Seeburg

Sir — I, as an inventor of a patent held by theUniversity of California on cloned humangrowth hormone complementary DNA, wasa witness in a trial involving a patent disputebetween the university and Genentech (seepage 289 of this issue and ref. 1).

My testimony concerned events thatoccurred 20 years ago, my work at theUniversity of California, San Francisco(UCSF) and early work at Genentech,which collectively resulted in the expressionof human growth hormone (hGH) inbacteria. This pioneering work with mycolleagues at Genentech was theculmination of three years of previousefforts at UCSF by which I and mycolleague John Shine had succeeded incloning the main part of the codingsequence for human growth hormone. Ithad been a difficult personal time as thisproject had often involved working nights,owing to efforts by my lab head to stop myresearch on growth hormone, asdocumented in the 1987 book InvisibleFrontiers: The Race to Synthesize a HumanGene by Stephen S. Hall (Tempus Books ofMicrosoft Press).

As I testified during the trial, the Naturepaper2 reporting the landmark study byGenentech regrettably contains a technicalinaccuracy. This inaccuracy concerns aplasmid, pHGH31, which represents one ofthe intermediate steps in the constructionof the expression vector for hGH. In thisplasmid, the coding region for amino acids24–191 plus 3' noncoding sequence, allcontained on a 551-base-pair HaeIIIcomplementary DNA fragment, is insertedby ‘GC tailing’ into the PstI site of pBR322.Not this plasmid, but an equivalent onecarrying the same 551-base-pair HaeIIIfragment inserted by linkers in the HindIIIsite of pBR322 and previously constructedby me and Shine at UCSF, was used assource of the natural coding region foramino acids 24–191 in the construction ofthe final hGH expression vector.

The existence of pHGH31 is questioned

by the fact, acknowledged by Genentech,that there never was a sequence recordshowing hGH DNA sequence attached to aG or a C tail, even though such a recordshould have existed, according to theNature paper. Several attempts atGenentech by a colleague and me to obtainpHGH31 were unsuccessful, primarily dueto the poor quality of the RNA startingmaterial available to us at the time. Withincreasing pressure to complete theexpression work, my colleague and I agreedto use the University of California’s cDNAclone for part of the work.

To be absolutely clear, I, like mycoauthors, view it as mandatory thatpublications are correct in all aspects,including all technical and methodologicaldetails. Hence, I deeply regret that, contraryto my own principles and the principles ofscientific endeavour, the Nature papercontains a technical inaccuracy.

As I emphasized during the trial, allscientific results and conclusions of theNature paper are unambiguous and correct.The expression vector is exactly asdescribed and the bacteria make the correcthormone at the levels described in thepublication. The study reported in thepaper forms the basis for the first humangrowth hormone preparation free ofneurodegenerative agents3, and the firstrecombinant therapeutic to be marketed byGenentech, from which 100,000 childrenbenefit worldwide. Peter H. Seeburg Department of Molecular Neuroscience,Max-Planck Institute for Medical Research,Jahnstrasse 29, 69120 Heidelberg, Germany 1. Marshall, E. Science 284, 883–886 (1999).

2. Goeddel, D. V. et al. Nature 281, 544–548 (1979).

3. Seeburg, P. H. “Human growth hormone: from clone to clinic”

Cold Spring Harbor Symposia on Quantitative Biology 51,

669–679 (1986).

Innocents suffer asrogue regime rapped

Sir — Christian Seelos’s Commentary,“Lessons from Iraq on bioweapons”,discussed only active warfare, where theweapons themselves contain infectiousmaterials or biological toxins (Nature 398,187–188; 1999). He failed to mention anequally nefarious kind of biological warfare,of the passive variety.

The bombing of Iraq during the GulfWar targeted infrastructure, with drasticeffects on public health. One of the manyresults was a lack of water free of infectiousparticles, which led to a resurgence ofbacterial infections, especially infantilediarrhoea, cholera and many otherinfectious diseases. The mortality rate forinfants soared, with excess mortality of

close to a million children, exacerbated nodoubt by the severe malnutrition that theUnited Nations embargo has imposed.

One factor that exacerbated this problemwas the lack of chlorine, which the UNSpecial Commission (UNSCOM) hasdecreed to be, in Seelos’s sanitized phrase,“dual use”. Eventually another UN agency,the children’s fund UNICEF, campaigned toallow chlorine back, but the amount recentlyallowed is probably enough for only two orthree cities. This kind of biological warfare issimilar to poisoning wells or rivers upstreamof besieged cities, which has its own long andnotorious history.

Yet these issues are not discussed,perhaps because the personal viewpoint ofSeelos, or the official one of UNSCOM, isthat only when you lob the carcass of aninfected animal into a besieged city do youcommit the horrible crime of biologicalwarfare. Or else, they might simply state, inthe words made famous 50 years ago, thatthey were only following orders.

How many more people have to diebefore we decide that the price of ourpolicies towards the rogue regime of theday is unsupportable?Qais Al-AwqatiDepartment of Medicine, Columbia University,630 West 168th Street, New York 10032, USA

Science powerhouseof Central America

Sir — Small is beautiful, but when you aresmall nobody sees you. Democratization ofLatin America is our chance to progress as aregion, as your supplement on Science inLatin America demonstrates (Nature 398(Suppl. 1 April); 1999). The articles onrecent developments in Mexico, Chile,Argentina, Brazil and Cuba are inspiring.But only the largest countries of the regionwere considered. There are also smallcountries that have scientists who are tryingto make a difference.

Costa Rica has a population of 3.5million and a research budget much smallerthan the US$108 million indicated in thefigure on page A5 of the supplement. Yet itproduces more scientific papers than muchlarger and richer countries. It has been anuphill challenge for us, however. Thegovernment is unsupportive of science, andwe suffer all the maladies described in thesupplement.

Even so, Costa Rica has managed to bethe science powerhouse of CentralAmerica, and we will continue our fight toadvance science in this minuscule country.Jorge CortésCIMAR, Universidad de Costa Rica,San Pedro, Costa Rica

correspondence

298 NATURE | VOL 399 | 27 MAY 1999 | www.nature.com