By comparing of the 1999 leaders against the five-year averages, it appears that the firm occupying the top spot has changed in seven of eight industry grouping. Only IBM (computers) continues to be the head of its class. Incyte Pharmaceuticals (biotech / biopharmaceuticals), AT&T (telecommunications) and GM (automotive) show a very interesting evolution in their business strategies. 

The virus reported in the book at this regard is the human herpes virus-6 [HHV-6, the sixth herpes virus that had been isolated (1987)]. RNA was detected in the serum as a marker of the breakdown occurring in the normal genetic functioning of the individual.

April

Regulation of carbamoyl phosphate synthetase by MPA kinase

by Lee M. Graves et al (2000) Nature 403, 328-332

see the comment by A.J. Whitmarsh and R.J. Davis "A central control for cell growth" (2000), Nature 403, 255 - 256

The de novo synthesis of pyrimidine nucleotides is required for the proliferation of the mammalian cells. The rate-limiting step in this pathway is catalysed by carbamoyl phosphate synthetase (CPSII), part of the multifunctional enzyme CAD. CAD contains three enzymatic activities: carbamoyl phosphate synthetase, aspartate transcarbamoylase and dihydroorotase. CPSII is related to the mitocondrial enzyme carbamoyl phosphate synthetase (CPSI), a component of the urea metabolic cycle. The biosynthesis of pyrimidines is essential for cell proliferation, and CPSII activity is correlated with increased growth in normal and tumor cell lines. The mitogen-activated protein kinase (MAPK) cascade is a ubiquitous protein phosphorylation pathway that is required for cell proliferation and is activated by many growth-promoting stimuli. [Three types of MAP kinases, the extracellular signal regulated protein kinases (ERKs), C-jun amino-terminal kinase (JNK) and the p38 have been found in the mammalian cells].  Graves et al. investigated the regulation of CAD in response to MAPK activation in vitro and in vivo.The activity of CPSII is increased after cells are exposed to the epidermal growth factor or if the CPSII is incubated with ERK MAP kinase in vitro. Under these conditions, ERK MAP kinase catalyses the attachment of phosphate groups to CPSII at a particular amino acid (threonine 456). As a consequence, the conformation of CPSII is altered with two consequences: (i) increased activation of CPSII by the regulatory molecule phosphoribosyl pyrophosphate and  (ii) block of the feedback inhibition of CPSII activity by uridine triphosphate, a product of pyrimidine-nucleotide synthesis.  To show that ERK MAP kinase is directly responsible for these effects, Graves et al. inhibited the the activation of ERK MAP kinase or mutated the ERK MAP kinase phosphorilation site. In both cases, the increase in CPSII activity was blocked, suggesting that ERK MAP kinase regulates the activity of CPSII.The contribution of these signals to the biosynthesis of pyrimidines ( and then to cell growth) merits further investigation.

Whitmarsh and Davis summarize also other mechanisms by which ERK MAP kinase can mediate the process of cell growth: (i) effect at the level of gene expression (transcription factors enhancing gene expression), (ii) effect on protein synthesis (recruitment of ribosomes), (iii) effect on growth-promoting genes.

Construction of a genetic toggie switch in Escherichia coli

by T.S. Gardner, C.R. Cantor and J.J. Collins (2000) Nature 403, 339 - 342

This paper is mentioned in the article "Biological Computing" by S.L. Garfinkel, in: Technology Review, May - June 2000, pages 70 - 77

"The toggle switch is composed of two repressors and two constitutive promoters. Each promoter is inhibited by the repressor that is transcribed by the opposing promoter. The described approach to the construction of a genetic toggle switch represents a significant departure from traditional genetic enginnering in that we rely primarily on the manipulation of network architecture, rather than the engineering of proteins and other regulatory elements to obtain desired behaviours. The toggle switch may find applications in gene therapy and biotechnology. As a cellular memory unit, the toggle forms the basis for "genetic applets" able to control cell functions."

The term "appled" is borrowed from computer science: it is a small application program (usually written in the Java programming language), that can be called up for use while working in another application.

It is possible to create appropriate "genetic applets" and use them "to program cells to perform new functions (for example to control the glucose level in a diabetic's blood stream and to regulate the synthesis of insulin) .

May

Building innovation factory

by Andrew Hargadon and Robert I. Sutton (2000) Harvard Business Review , May - June, pages 157 - 166

The Authors describe the "The knowledge-Brokering Cycle", that consists essentially in four steps: (i) Capturing good ideas, (ii) Keeping ideas alive, (iii) Imagining new uses for old ideas (the basis for innovation), (iv) Putting promising concepts to the test. "Business leaders must change how they think about innovation and must change how their company cultures reflect that thinking. ...Innovation and creativity are far less mysterious than that image implies. They are a matter of taking developed ideas and applying them in new situations. If your company has the right connections and the right attitude, it works."

Wall St Focuses on Biotech Trials

by Justine Pope (2000) Wall Street Journal, May 14

The question is reported on who has the right to produce Epogen (= erytrhopoietin), an extraordinary lucrative substance. Amgen (CA, USA) <www.amgen.com> holds patents on the protein, but a small company, Transkaryotic Therapies Inc. (MA, USA) < www.tktx> has found another way to make the protein. And the winner will be.....

Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord trasplantation

by Su Liu, Yun Qu, Todd J. Steward, Michael J. Howard, Shushovan Chakrabortty, Terrence F. Holekamp, and John W. McDonald (2000), Proc. Natl. Acad. Sci. USA 97, 6126 - 6131

A nerve tissue that is usually damaged in spinal injuries was restored in laboratory animals (adult rats and myelin-deficient shiverer (shi/shi) muant mice) using embryonic stem cells. These rersults may eventually lead to a new treatment for people paralyzed by injury or disease. For a reference on stem cells, follow this link: :"Stem Cells: A Primer" at <www.nih.gov/news/stemcell/primer.htm>.

Note: As reported by Gretchen Vogel on the magazine Science  287 , 948 - 949 (2000), The University of Wisconsin (UW, Madison, U.S.A.) will distribute embryonic cell lines. derived by UW researcher James Thomson. An agreement exist with Geron Corp. (Menlo Park, CA, U.S.A.). Thomson's work was supported by Geron, Corp. and by the Wisconsin Alumni Research Foundation (WARF).  WARF has now created the WiCell Research Institute for distributing cells to academic and industrial scientists late this spring. WiCell's first customers could come from Japan [Dennis Normile,  in Science  287, 949 (2000); David Cyrano, in Nature 403, 470 (2000)]

Using human embryonic stem cells in research is controversial becuse the cells must originate from humam embryos or aborted fetuses. The final guidelines from The National Institutes of Health are still under review.

Aastrom Biosciences, Inc. (Ann Arbor, MI, U.S.A.) has developed a new large-scale procedure that improves upon its own technology to grow human stem cells ex vivo (see the press release on the web page of Aastrom Biosciences)

June

Code Breakers: Scientists are altering bacteria in a most fundamental way

by Tina Hesman (2000), in: Science News 157  360 - 362

Scientists are engineering E. coli with an altered genetic code for translating DNA information into proteins.  "The researchers are trying to move beyond the hundrum set of 20 aminoacids that make up the building blocks for life today. They plan to add protein-building materials not found naturally in any living organism.

People working on this topic:

Andrew Ellington and coworkers, University of Texas, Austin, TX, USA ("Uncoli"", growing on fluorotryptophan)

David R. Liu, Harvard University, Cambridge, MA, USA

Peter G. Schultz and coworkers - The Scripps Research Institute, La Jolla, CA, USA

Masahiko Sisido and coworkers, Okayama University, Okayama, JapanI

Recent references:

• Progress toward the evolution of an organism with an expanded genetic code (1999) , by D. R. Liu and P.G. Schultz,  PNAS 96, 4780 - 4785
• Incorporation of two different nonnatural aminoacids independently into a single protein through extension of the genetic code (1999) by Takahiro Hohsaka et al. , J. Am. Chem Soc 121, 12194 - 12195.
• A new functional suppressor tRNA/aminoacyl-tRNA synthetase pair for the in vivo incorporation of unnatural amino acids into proteins (2000) by Lei wang, Thomas J. Magliery, David R. Liu, and Peter G. Schultz, J. Am Chem Soc. 122, 5010 -5011

An interesting example of "virtual drug company"

This is referred to the investment made by the Cystic Fibrosis (CF) Foundation (Bethesda, Maryland) in a small biotech firm Aurora Biosciences (San Diego, CA).  A "virtual drug company" ( a hybrid profit - non profit venture) has been created, as reported by Eliot  Marshall on Science 288, 1716 - 1717 (2000)

Crime laboratory investigations

Crime laboratory investigators can identify criminals by analyzing hairs and fibers collected at the crime scenes [read the aticles on:"Forensic Science Communications" 2   (3) (July 2000) at the FBI web site]

July

Verso i farmaci personalizzati

Progetto Genoma: verso i farmaci personalizzati di Pier Carlo Montecucchi da "Il Sole 24 Ore"

Un draft del codice genetico umano è stato realizzato separatamente da due gruppi di ricercatori, dopo 10 anni di studi con un costo di miliardi di dollari. Sicuramente si tratta di un risultato legato all'alta tecnologia impiegata, ma soprattutto del frutto di tenacia e di volontà. È stato "a day for the ages", come definito dal presidente Clinton, il quale però ha aggiunto che la mappa genetica umana non dovrà mai essere usata per segregare, discriminare o invadere la vita privata dei singoli cittadini. Ora inizia un lungo lavoro di identificazione dei vari geni e della loro espressione, e di studio delle varie interazioni. Sicuramente si potranno correlare geni a specifiche situazioni patologiche e stabilire la loro esatta collocazione cromosomica, studiare il polimorfismo genico e arrivare a un proprio "personal genomics", magari scritto su un CD.
Tuttavia la sequenza del DNA del genoma umano ci racconta solo una piccola frazione di quello che una specifica cellula vivente (definita anche una "nanotechnological factory") sta facendo in un dato momento (C. Ezzell, Sci Am. 283, 64-69, 2000). Pertanto non credo che sarà molto facile trovare una immediata soluzione alle malattie geniche, pur conoscendo la sequenza del gene stesso e potendo caratterizzare il prodotto della sua espressione in un sistema estraneo al corpo umano.
Infatti, il prodotto dell'espressione genica (la proteina) che può essere ottenuto attraverso un processo di clonazione del gene isolato, non sempre corrisponde alla proteina che è responsabile di uno stato patologico nell'essere umano. In natura infatti un gene può codificare per più di una proteina ed esiste un network proteico che può esercitare il suo influsso sullo sviluppo di una situazione patologica. Non è poi da sottovalutare la quantificazione dell'espressione della proteina coinvolta in una data malattia. Inoltre esistono nell'organismo molteplici sistemi omeostatici che, sotto l'influenza di forze ambientali, possono interagire a livello di espressione genica senza modificare il DNA.
Sotto questo profilo, è molto promettente l'attenzione rivolta direttamente allo studio del prodotto ('proteomics / dynamic proteomics") dell'espressione genica così come si realizza nel corpo umano. La caratterizzazione di tali proteine con il loro polimorfismo permetterà la realizzazione di modelli molecolari utili alla costruzione dei cosiddetti "farmaci personalizzati".

September

Strategic plan to address bioterrorism

by Ted Agres (2000), in: Drug Discovery & Development (June / July) 15 - 16

"A strategic plan has been developed by the Centers for Disease Control and Prevention (CDC) focused on five areas to reduce US vulnerability to biological and chemical terrorism. They are: (i) preparedness planning, (ii) detection and surveillance, (iii) laboratory analysis, (iv) emergency response, (v) communications systems. The first indications would conceivably be seen at the local level by physicians and other primary health-care providers in hospital emergency rooms and clinics. Only a brief window of opportunity will exist between the time the first cases are identified and a second wave of the population becomes ill through contagion. During this short period of time (probably a week or two) health officials must (i) determine that a terroristic attack has occurred, (ii) identify the organism, and (iii) prevent more casualties through mass vaccinations or other treatments...... The CDC has identified three categories of biological agents and organisms based on factors, such as ease of dissemination and potential for mortality. Category A agents (that includes those having the greatest threat), Category B agents, Category C agents.

For details:

Biological and Chemical Terrorism: strategic plan for preparedness and response. April 21 (200), 49 (RR04); 1 - 14

"What would happen if terrorists released deadly organisms... into a crowd? Find out why Donald. A. Henderson... calls for a new national strategy to fight biological terrorism" at The National Academies

Search for "Bioterrorism" at The National Academies WebSearch 

October

Gene therapy in orthopaedic medicine: possibility of using genes for delivery of therapeutic agents directly into somatic tissue cells. This somatic gene therapy can be performed locally or systematically. For orthopaedic injuries or diseases, a local gene delivery into the diseased or injured tissue is desirable.

Growth factors have believed to be the key to accelerated healing and tissue regeneration.

Somatic gene therapy provides an excellent technique to deliver growth factors locally into the site of injury

The gene for a specific growth factor can be introduced into the injured tissue directly (in vivo) or indirectly (ex vivo). The direct method involves injection of the vector (viral and nonviral) at the appropriate site, whereas the ex vivo method involves the genetic modification of cells in culture (the vector, viral or non-viral)  in nature, is given onto the cell culture) followed by injection at the diseaded.site.

The process is referred to as transfection when nonviral vectors are used

The process is referred to as transduction when viral vectors are used.

Transfection and transduction include the attachment of the vector to the cell membrane and insertion of the encoded gene into the cellular genome.

Does the immortality exist for bacteria?

Vreeland et al. claim to have isolated bacteria from 250-million-year-old, buried salt crystals

"Development of a protocol to retrieve microorganisms from ancient salt crystals" by William D. Rosenzweig, Jennifer Peterson, Jennifer Woish, Russell H. Vreeland, (2000) in: Geomicrobiology Journal, 17, 185 - 192

"Isolation of a 250 million-year-old halotolerant bacterium from a primary salt crystal" by Russell H. Vreeland, William D. Rosenzweig and Dennis W. Powers (2000) in: Nature, 407, 897 - 900 [quoted by John Parkes (2000) on the same journal: "A Case of bacterial immortality?" : Nature, 407, 844 - 845]

The Authors report the isolation and growth of a previously unrecognized spore-forming bacterium (Bacillus species, designated 2-9-3) from a brine inclusion within a 250 million-year-old salt crystal from the Permian Salado Formation (Utah, U.S.A.). Complete gene sequences of the 16S ribosomal DNA show that the organism is part of the lineage of Bacillus marismortui and Virgibacillus pantothenticus.

November

Biometrics creates human passwords

Sam Costello and James Niccolai, IDG News Service (November 17, 2000) - PCWORLD.COM

Skin, eyes, and voice can be used to verify identity in emerging security market. Biometrics devices are becoming popular in the insurance and financial industries.

See also the following article on the same topic: "Are the password's days numbered?" by Matthew Newton, PCWorld.com (June 28, 2000)

In-House Microarrays

 "In-House Microarrays Put Researchers in Control" by Julia Boguslavsky,in: Drug Discovery & Development (October, 2000), 30 - 36

"Optical Biosensor Tools for Biotechnology" by Neil McKenna in : Genetic Engineering News (2000) 20 (19), 8

"Biosensors - Sense and Sensitivity" by Anthony P.F. Turner in: Science (2000) 290: 1315 - 1317