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Prion research wish list

Although the sensitivity of current post-mortem diagnostics for transmissiblespongiform encephalopathies (TSEs),or prion diseases, could be improved,the most critical need is a live-animal,antemortem TSE blood test, accordingto a November report by the NationalAcademies’ Institute of Medicine (IOM).Various applications, such as screeningblood bank samples and testing animalherds and military personnel, wouldall benefit from a live-animal TSE test,says Richard Johnson, chair of the IOMCommittee on TSEs and professor ofneurology at the Johns Hopkins Uni-versity School of Medicine.

The number of TSE tests currentlybeing conducted and slated to be con-ducted is overwhelming. According toan October 2003 Kalorama Informationstudy about prion diagnostic technolo-gies and markets worldwide, 12 millionpostmortem TSE tests are conductedannually on cows, deer, goats, andsheep. That number is likely to grow,particularly following the detection ofthe first case of bovine spongiform en-cephalopathy, or mad cow disease, in

the United States in late December.In addition, there are 75 million

blood bank samples worldwide, manyof which will need to be screened forTSEs. Johnson reports that there is cur-rently a blood shortage in the UnitedStates, so knocking out donors whohave merely lived in parts of Europeduring the mad cow disease epidemicis a real problem. Johnson emphasizesthat releasing the restrictive regulationswill be difficult because of politics. “But,if a sensitive and specific test were avail-able, then regulations could be relaxed.”

“Blood bank screening, however,presents huge ethical problems,” saysDean O. Cliver, another member of theIOM committee and professor of foodsafety at the University of California–Davis School of Veterinary Medicine.Cliver explains the caution: “Even a testthat has a low probability of yieldingfalse positive results, applied in a situa-tion where the probability of a truepositive result is infinitesimal, will yieldmostly false positives.” He continues,“It is one thing to take a suspect unitof blood out of the pool, but quite an-other thing to tell the donor that he orshe is going to die.”

Johnson expects that “something asnovel as PCR, but for proteins,” is neededto meet the accuracy and sensitivity de-mands of a live-animal test. He hypoth-esizes that an error rate of 1/100,000 isunacceptable, and a live-animal test needsto be 1000-fold more sensitive than anycurrent postmortem assays.

According to the report, definingwhat is a single infectious unit of a prionwill be critical for live-animal test devel-opment. Having TSE repositories thatcontain a collection of reference materi-als, genetically engineered animals, andreagents for diagnostic development andbasic research is also important.

According to Cliver, the recom-mendations in the report are used as aguideline for funding the U.S. Depart-ment of Defense’s National Prion Re-search Program. In 2002, Congress ap-propriated $42 million to be spent in2003. Johnson comments that Europespends ten times more money on prionresearch because of the mad cow dis-ease epidemic. The Europeans thinkthat the United States is “sitting on achronic wasting disease [prion diseasethat affects deer and elk] time bomb.” a

—Laura Ruth

Analytical chemist winsISFG forensic award

John Butler, a research chemist at theNational Institute of Standards and Tech-nology (NIST), received an award fromthe International Society for Forensic Ge-netics (ISFG) for his work on the forensicanalysis of DNA, in particular for improv-ing the analysis of single-nucleotide poly-morphisms. Although Butler was notifiedSeptember 11, 2003, he has to wait untilthe ISFG meeting in 2005 to officiallyaccept his award. He is only the fifth re-cipient of the prestigious award. Alongwith the kudos of winning, Butler willreceive a cash award of ¤3000.

While a postdoc at NIST, Butlercreated the short tandem repeat (STR)Internet database that is now com-monly used among forensic scientistsworldwide. He is also the author ofForensic DNA Typing: Biology andTechnology behind STR Markers, a lead-ing text in the field. In addition, hisgroup developed technology that wasinstrumental in the analysis of DNAsamples from the World Trade Centerterrorist attacks. The catalyst for thiswork, he says, stemmed from the needto improve methods for analyzingsmall pieces of damaged DNA andfinding a better way to prevent signalloss from samples.

Butler is fund-ed by the Nation-al Institute ofJustice and leadsa six-memberproject team atNIST to improveforensic DNAtyping methods.

Now that he has won the ISFG award,what is next for the analytical chemist?Along with cataloging and mapping theexact positions of the 13 STR markersprimarily used in the forensic commu-nity, he plans to tackle a new methodfor analyzing multiple DNA markerssimultaneously.

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