Beyond the Hype

I have been meaning to write a little about all the hype & media surrounding the recent articles in Cell and Science about turning skin cells into Embryonic-like, pluripotent stem cells. There is a small company in Walkersville called LifeLine Cell Technology, which is a subsidiary of International Stem Cells. I found this on Yahoo! and thought y’all should know that a local, Frederick County company made a similar and possibly better discovery years ago:

International Stem Cell Corporation CEO Issues Statement on De-Differentiation Research and Parthenogenesis
Sunday November 25, 3:11 pm ET

OCEANSIDE, Calif.–(BUSINESS WIRE)–Jeff Krstich, Chief Executive Officer of International Stem Cell Corporation (OTCBB:ISCO - News), today issued a statement on the recent announcement that two groups of scientists have succeeded in turning human skin cells into cells that are very similar, though not identical, to embryonic stem cells.
In his full statement, “A Message from the CEO”, which appears on the company’s website, www.internationalstemcell.com, Mr. Krstich applauds this latest advancement, called de-differentiation, and provides explanation of the differences in methodologies between de-differentiation and ISCO’s Parthenogenetic Stem Cell Lines (phESC), which were announced in a peer review paper published in Cloning & Stem Cells Journal on June 26, 2007. http://www.liebertonline.com/doi/pdfplus/10.1089/clo.2007.0033

The explanation affirms that ISCO’s Parthenotes are pluripotent and have thus far shown the same differentiation capability as stem cells derived from human embryos—except that they were created without using fertilized eggs and no fertilized human embryos were destroyed. ISCO Parthenotes have already been differentiated into several specific cell types, including two types of nerve cells scheduled for human trials shortly.

Mr Krstich’s message further noted that unlike the de-differentiation process, the stem cell lines produced by ISCO’s Parthenogenesis process do not employ the use of any cancer causing genes or the use of viruses that may cause disease in humans. In addition, ISCO Parthenotes are developed with either no use or minimal use of animal serums or animal by-product. Further, ISCO’s Parthenotes hold the promise for human therapeutic use with the distinct advantage of requiring little or no immunosuppressant drugs.

ABOUT INTERNATIONAL STEM CELL CORPORATION:

International Stem Cell is a biotechnology company currently focused on developing therapeutic and research products. In the area of therapeutic product development, ISCO’s objective is to create an unlimited source of human cells for use in the treatment of several diseases, including diabetes, liver disease and retinal disease through cell transplant therapy. In furtherance of this objective, ISCO has developed pluripotent human stem cells from unfertilized human eggs, and techniques to cause those stem cells to be “differentiated” into the specific cell types required for transplant. It has developed manufacturing protocols to produce the cells minimizing contamination with animal by-products, a characteristic likely to be important in meeting U.S. Food and Drug Administration requirements. ISCO also provides the specialized cells and growth media needed for therapeutic cell transplantation research to academic and commercial researchers in related fields. For more information, visit the ISCO website at: www.internationalstemcell.com.

DynPort Wins another $201M

From the Gazette papers:

DynPort Vaccine Co. has won a $201.2 million contract modification with Baxter International Inc. from the U.S. Department of Health and Human Services. The funding completes a May 2006 contract award of $242 million.

DynPort will develop Baxter’s influenza vaccine candidate. The first volunteers in a phase 3 trial were vaccinated Monday.

Might be a good time to check their Job Board!

Atlantic Biomass

Another nice write up in the FNP today about Atlantic Biomass

I hope, in the future, I can stop lifting stories off the FNP and come up somethings on my own, just our own Biodiesel testing business is starting to take off and I have been busy playing in the lab.

On a different topic, I added a couple new Biotech blogs to the blogroll via The Regeneration Station. I found this one through PIMM.  I like it because it is industry focused with a bend towards regenerative medicine and stem cell stuff. I copied a few other links off his blogroll, a couple sites I hadn’t seen before. Please check it out.

Veracity Pays Off

There was a nice write up featuring the ventures of Victor Buckwold and his company, Veracity Biotechnology LLC, in the FNP yesterday.

Apparently, they have outgrown their space at FITCI@Hood and followed Akonni by acquiring space downtown on South Wisner.

Veracity offers a number of in vitro services based upon Hepatitis C infection of liver cells. Knowing Victor and what he is doing, I wish him the best of luck in his new facility. I’ll have to get over there and check it out some time.

Give me a Break

So, this is a blog. This is not the Frederick News Post, a press release for my company or a philanthropic endeavor. This is a blog about biotech in Frederick, intended to facilitate the growth of biotech in Frederick. Exchange ideas, learn, live, pursue happiness. Let me rant (you are also invited to rant along).

I saw an article about a small number of discontent deviants raging about blocking the expansion at Ft Detrick which will infuse the local economy with about 2.5 BILLION dollars and some 1,500 jobs over the next 5-8 years. They are primarily biotech-based jobs, but also administrative, facilities, regulatory jobs. High paying, desirable jobs. Putting our tax money back into the local economy.

I don’t blame the vocal minority trying to prevent all this “progress” because they’re obviously ignorant of the facts. If they understood what a BL4 facility is, what the organisms in a BL4 facility are, the level of regulatory compliance dictated by “The Man”, the mechanism of infection, pathology, etc., then they’d be better served monitoring snot levels or prevalence of STDs at the whatever private school they send their kids to to be educated.

Give me a break. Let the people who know what they’re doing handle it. I have met a lot of the people involved in managing Ft Detrick. They are people of integrity, honor, skilled in their profession and would never do something to harm another innocent, vunerable person intentionally.

To sum it up, I back this statement from the Axis of Evil Fort 110%:

We have already provided numerous opportunities for the public to comment and provide input during the EIS process, we see no need to participate in another public meeting,” Sarah Maxwell, the post’s spokeswoman wrote in an e-mail. “We openly and fully complied with the National Environmental Policy Act and any other law or regulation that governs the environmental process.”

Having attended previous public forums, I would rather gouge my own eye out, rub infectious Ebola virus into the lesion and wait for the inevitable desanguination than listen to that drivel again.

Akonni Ribbon Cutting

I went to the ribbon cutting ceremony at Akonni Biosystems Friday afternoon. They have a beautiful new facility, converting an old Warehouse on Sagner Ave, across from McCutheon’s (who are also planning a major expansion) and along the Carroll Creek Promenade.

There were a number of dignitaries form across the county, with a keynote address by Dr Roscoe Bartlett. The facility itself appears to be a modest storefront from street level. Through the double entry doors is a large, open foyer with glass lined offices against the wall and a “cube farm” for the the staff towards the back wall leading into the labs. They have a number of clean suites for production because their technology is PCR-based an needs to avoid adulteration by contaminating DNA.

Their product is a slick, smaller than a credit card, plastic micro array and a bench top reader. Samples are collected using a liquid sample medium, and pipetted onto the sample card, insertred in the reader and a result is provided. They have a number of different cards with different platforms for infectious diseases to biowarfare bugs.

I also had a chance to talk to a number of the people working for Akonni and found them all excited and enthusiastic about their product and technology platform.

I wish them the best of luck. I am so thrilled to see actual Manufacturing (I know this is s dirty word in the Biotech world, but that’s what it is) moving back into Downtown Frederick.

Here is a link to a nice article in the FNP today about the event

BioTechniques Techniques

I have been meaning to add some links for Protocols, Methods and SOPS. One useful web resource I encountered is to the BioTechniques Molecular Biology Techniques forum. There is just a ton of information, protocols and the like. I haven’t had a chance to play around with it too much, but this looks like a good resource to book mark.

For example:

Welcome to the BioTechniques® Molecular Biology Forums, a science-based bulletin board for techniques, tips, and questions concerning molecular biology, cell biology, microscopy, and bioinformatics.

BioTechniques® Molecular Biology Techniques Forums
Reasons for or against putting a hist tag at both ends?

Post new topic Reply to topic BioTechniques® Molecular Biology Techniques Forums Index -> Protein

PostPosted: Nov 16 2007 7:37 am Post subject: Reasons for or against putting a hist tag at both ends? Reply with quote
I ordered a custom made NusA fusion vector from Addgene recently and originally thought that the vector had only a C-terminal histidine tag. Upon closer inspection I noticed that there is also a N-terminal histidige tag. The C-tag is naturally optional so that by including a stop codon in your insert you can choose not to have it. My question is that is there especially something for or against using both tags? We can assume that the tag sequence does not affect the specifity of my assay and doesn’t need to be removed. The tag(s) are there for purification.

Question 2: Do you know if there is an actual difference in leakage between using TAA versus TGA as the stop codon in bacterial expression?
PostPosted: Nov 16 2007 10:42 am Post subject: Reply with quote
There is no reason to use both tags. I think the vector is designed that way, so someone can have a choice of putting the tag at the N-terminus or the C-terminus, depending on the protein being expressed. There may be restriction enzyme site upstream of the N-terminus His-tag to let you delete the tag sequence, if you so chose.

It is better to avoid TGA stop codon when you express protein in E. coli to avoid read through. Here is an example.

http://www.biochemj.org/bj/309/0411/3090411.pdf

Just like human, they go through STOP sign. Laughing

Incompetent Managers

As I alluded to in a previous post, Biosciences struggles to set themselves apart from other industries because we think our technology makes us that much different and special.

One of the unique problems with Biotech and academic research I have encountered over the years is that we seem to give more leverage to degree than to managerial competence. Time and time again I have seen a person with an advanced degree moved straight from academia into a Leadership position with no management skills.

I ran across this article today, from a web site called fastcompany.com.  Sound familiar?

Ten Habits of Incompetent Managers

by Margaret Heffernan

How do you identify the members of your team that could sink it? Get an expert’s tips on the signs you should look for.

Bias against action:There are always plenty of reasons not to take a decision, reasons to wait for more information, more options, more opinions. But real leaders display a consistent bias for action. People who don’t make mistakes generally don’t make anything. Legendary ad man David Ogilvy argued that a good decision today is worth far more than a perfect decision next month. Beware prevaricators.Secrecy: “We can’t tell the staff,” is something I hear managers say repeatedly. They defend this position with the argument that staff will be distracted, confused or simply unable to comprehend what is happening in the business. If you treat employees like children, they will behave that way — which means trouble. If you treat them like adults, they may just respond likewise. Very few matters in business must remain confidential and good managers can identify those easily. The lover of secrecy has trouble being honest and is afraid of letting peers have the information they need to challenge him. He would rather defend his position than advance the mission. Secrets make companies political, anxious and full of distrust.

Over-sensitivity: “I know she’s always late, but if I raise the subject, she’ll be hurt.” An inability to be direct and honest with staff is a critical warning sign. Can your manager see a problem, address it headlong and move on? If not, problems won’t get resolved, they’ll grow. When managers say staff is too sensitive, they are usually describing themselves. Wilting violets don’t make great leaders. Weed them out. Interestingly, secrecy and over-sensitivity almost always travel together. They are a bias against honesty.

Love of procedure: Managers who cleave to the rule book, to points of order and who refer to colleagues by their titles have forgotten that rules and processes exist to expedite business, not ritualize it. Love of procedure often masks a fatal inability to prioritize — a tendency to polish the silver while the house is burning.

Preference for weak candidates: We interviewed three job candidates for a new position. One was clearly too junior, the other rubbed everyone up the wrong way and the third stood head and shoulders above the rest. Who did our manager want to hire? The junior. She felt threatened by the super-competent manager and hadn’t the confidence to know that you must always hire people smarter than yourself.

Focus on small tasks: Another senior salesperson I hired always produced the most perfect charts, forecasts and spreadsheets. She was always on time, her data completely up-to-date. She would always volunteer for projects in which she had no core expertise — marketing plans, financial forecasts, meetings with bank managers, the office move. It was all displacement activity to hide the fact that she could not do her real job.

Allergy to deadlines: A deadline is a commitment. The manager who cannot set, and stick to deadlines, cannot honor commitments. A failure to set and meet deadlines also means that no one can ever feel a true sense of achievement. You can’t celebrate milestones if there aren’t any.

Inability to hire former employees: I hired a head of sales once with (apparently) a luminous reputation. But, as we staffed up, he never attracted any candidates from his old company. He’d worked in sales for twenty years — hadn’t he mentored anyone who’d want to work with him again? Every good manager has alumni, eager to join the team again; if they don’t, smell a rat.

Addiction to consultants: A common — but expensive — way to put off making decisions is to hire consultants who can recommend several alternatives. While they’re figuring these out, managers don’t have to do anything. And when the consultant’s choices are presented, the ensuing debates can often absorb hours, days, months. Meanwhile, your organization is poorer but it isn’t any smarter. When the consultant leaves, he takes your money and his increased expertise out the door with him.

Long hours: In my experience, bad managers work very long hours. They think this is a brand of heroism but it is probably the single biggest hallmark of incompetence. To work effectively, you must prioritize and you must pace yourself. The manager who boasts of late nights, early mornings and no time off cannot manage himself so you’d better not let him manage anyone else.

Any one of these behaviours should sound a warning bell. More than two — sound the alarm!

Research Tool Sites for Molecular Biology

I’ve added a new link to the Web Links page which contains a large number of links to other useful Molecular Biology web sites.  I would suggest you bookmark it for future reference

Research Tool Sites for the Molecular Biology

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[ What's New | Home | My Favorite | Yeast | Web | LINKS | Database | Protocol | Journal | Others | Software | General ]

My Favorite Sites

• Essential Research Tools
  • Tools for the Molecular Biology - Quick Access Table
  • EMBOSS - a graphical user interface to the EMBOSS suite of bioinformatics tools. : EMBOSS (European Molecular Biology Open Software Suite) is a suite of free software tools for nucleotide and protein sequence analysis
  • All-IN-ONE SEQ-ANALYZER - by Naohiro Inohara
  • The CMS Molecular Biology Resource - by Christopher M. Smith at SDSC
  • DNA & Protein Analysis Toolkit - Computing Services at The Rockefeller University (USA)
  • JaMBW - Java based Molecular Biologist’s Workbench
    • List of Java-based Molecular Biology Work Bench sites
  • ExPASy Proteomics tools - at Swiss Institute of Bioinformatics (SIB)
  • Research Tools: [FRAME] - by Jun Ishikawa at National Institute of Health (Japan) : You can select [NONFRAME]: [JAPANESE-NONFRAME]
• DataBases
  • GenomeNET: Institute for Chemical Research, Kyoto University Human Genome Center: Kyoto, Institute of Medical Science, University of Tokyo: Tokyo (Japan)
  • Restriction Enzyme Database - New England Biolabs, Inc.
• Table
  • Amino Acid Information
  • Codon_usage
  • Periodic table
• Reference Sites
  • Entrez - NCBI Entrez Browser (USA)
  • The Molecular Biologist’s Desk Reference: at NIH: National Institutes of Health (USA)
  • NCBI PubMed - A search tool for accessing literature citations and linking to their full-text versions at publishers’ Web sites - An experimental service of the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM)
  • PaperChase - PaperChase provides 9,337,834 references - MEDLINE | HealthSTAR | AIDSLINE | CANCERLIT
  • ingenta - Reference search and document delivery service
  • Chemfinder - Chemical Searching and Information Integration
• Others
  • Frontiers in Bioscience: [ THE VIRTUAL LIBRARY ] [ THE JOURNAL ] - The most informative Web-space
  • Schizosaccharomyces pombe & Yeast Sites

[ What's New | Home | My Favorite | Yeast | Web | LINKS | Database | Protocol | Journal | Others | Software | General ]

World-Wide-Web Sites

• All the Virology - by the Garry Laboratory in the Department of Microbiology and Immunology in the School of Medicine at Tulane University (USA)
• The Biotechnology Information Center - One of ten information centers at the National Agricultural Library of the US Department of Agriculture: ARS
• Computional Biology and Informatics Laboratory - at Pennsylvenia University
• Computational Molecular Biology: by the Computational Molecular Biology Section (CMBS) at NIH (USA)
• DNA Information and Stock Center: DISC - National Institute of Agrobiological Resources (Japan)
• EMBnet: The European Molecular biology network: [ http://ben.vub.ac.be/ | ftp://dbmdec5.ulb.ac.be/ | ]
• European Bioinformation Institute (UK)
• The ExPASy Molecular Biology Server - by Amos Bairoch at the Geneva University Hospital and the University of Geneva (Switzerland)
• GenomeNET: Institute for Chemical Research, Kyoto University Human Genome Center: Kyoto, Institute of Medical Science, University of Tokyo: Tokyo (Japan)
• Health Sciences Topics - Molecular Biology: Medical Center at Vanderbilt University (USA)
• Human Genome Center: Institute of Medical Science at The University of Tokyo (Japan)
• Image Library of Biological Macromolecules - featured as website of the day on February 19, 1997 by the ‘webzine’ HMS Beagle.
• MRC - Human Genetics Unit - WWW Server(UK)
• National Institute for Basic Biology: NIBB (Japan)
• Sheffield ChemDex - at University of Sheffield (UK)
• Theoretical Biophysics Group - NIH Resource for Concurrent Biological Computing at Beckman Institute for Advanced Science and Technology
• UK MRC HGMP Resource Centre - Human Genome Mapping Project Resource Centre (UK)
• Weizmann Institute Genome and Bioinformatics: (Israel)

[ What's New | Home | My Favorite | Yeast | Web | LINKS | Database | Protocol | Journal | Others | Software | General ]

Useful Database Sites

• ATCC - American Type Culture Collection
• Databases for Molecular Biology - NIH (USA)
• DNA Data Bank of Japan: DDBJ - Center for Information Biology of Genetics - SAKURA On-Line Gene Submission (Japan)
• DSHB: Developmental Studies Hybridoma Bank under the auspices of the National Institute of Child Health & Human Development (USA)
• EMBL DataBase
• Escherichia coli Databank - at The Graduate School of Biological Sciences: NAIST (Japan)
• E.coli Genetic Stock Center: CGSC - E. coli Stock Center Database at Yale University (USA)
• E. coli Genome Project: The purpose of this server is to provide a front-end graphical interface to our FTP site - at University of Wisconsin-Madison (USA)
• GenBank Database
• A Gene Map of the Human Genome - The Gene Map web site is hosted by the National Center for Biotechnology Information: NCBI (USA)
• GenLink - at Washington University (USA)
• Online Research Resources - The National Center for Human Genome Research: Genome and Genetic Data at The National Center for Human Genome Research (NCHGR): The Human Genome Project for the National Institutes of Health (NIH)
• MPDB: The Molecular Probe Data Base - The Molecular Probe Data Base (MPDB) contains information on ca. 4000 synthetic oligonucleotides with a sequence of up to 100 nucleotides - at The Interlab Project (Italy)
• National Collection of Yeast Cultures - at Genetics and Microbiology Department, Institute of Food (UK)
• NDB: Nucleic Acid Database - The goal of the Nucleic Acid Database Project is to assemble and distribute structural information about nucleic acids at The State University of New Jersey (USA)
• REBASE: Restriction Enzyme Database - by Richard J. Roberts
• Restriction Enzyme Information Resources - by Mary Hoenecke and Carolyn Stock at Promega Corporation (USA)
• SEQNET - The U.K. academic communitiesSEQuence NETwork computer for molecular biologists at Daresbury Laboratory (UK)
• TIGR Database- TDB: a collection of molecular biology databases (USA)
• TIGR Human Genome Sequencing Projects - at The Institute for Genomic Research: TIGR (USA)

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• Protein Database and Resources
  • ENTREZ: Protein and nucleotide database (NCBI)
  • ENZYME: Enzyme nomenclature database
  • Molecules R US: Web interface for accessing molecular structure data in PDB
  • ProDom: The ProDom protein domain database consists of an automatic compilation of homologous domains detected in the SWISS-PROT database - The ProDom team in Toulouse (France)
  • PRO-SITE: Dictionary of protein sites and patterns
  • Protein Data Bank: Brookhaven National Laboratory
  • PROLYSIS: A protease and protease inhibitor Web server by Thierry MOREAU (France)
  • SCOP: Structural Classification of Proteins. Release 1.32. 4432 PDB Entries (all through May 96). 8330 Domains. 169 Literature References. - at MRC Laboratory (UK)
  • SWISS-PROT: Annotated protein sequence database

[ What's New | Home | My Favorite | Yeast | Web | LINKS | Database | Protocol | Journal | Others | Software | General ]

Research Protocol & Tool Sites

• To Get More Software: TRY This Page !!
• BioPD - at Interdepartmental Biological Building - University of Padova (Italy) 05.5.21
• BOXSHADE 3.21 - Pretty Printing and Shading of Multiple-Alignment files - by the Bioinformatics Group at the ISREC (Swiss Institute for Experimental Cancer Research) in Epalinges s/Lausanne
• Computational Biochemistry Research - at ETH: Eidgenossische Technische Hochschule Zurich
• FramePlot.pl: v.0.5 - coding region prediction of high G+C-content bacteria by Jun Ishikawa at National Institute of Health (Japan)
• Genome Information Research Center: Home Page in Japanese - at Osaka University (Japan)
• A Guide to Structure Prediction (version 2)
• IDEAS - Integrated Database and Extended Analysis System for Nucleic Acids and Proteins - at GenomeNET (Japan)
• Molecular Biology Club - Biology Courses|Protocoles|Data Analysis|Software for Science|Other Sotware…
• Molecular Phylogenetic Tree - Making Molecular Phylogenetic Tree at Kyoto University (Japan)
• Multiple Alignment Resource - VSNS BioComputing Division (Germany)
• NIH Image Home Page - The most powerful “Image” soft
• PCR Methods
  • Long PCR Protocol
  • PCR Jump Station - The ultimate Web page for information and links on all aspects of the Polymerase Chain Reaction (PCR)
  • Primer3: Pick PCR primers from nucleotide sequence by Steve Rozen and Helen J. Skaletsky at Whitehead Institute for Biomedical Research (USA)
• Molecular Biology Protocols
• Search the Genentech Web Site - Genentech, Inc.
• SOSUI - Secondary Structure Prediction of Membrane Proteins at GenomeNET (Japan)

How to Fix the Life Sciences

I read an interesting couple of blogs/articles today comparing the Semiconductor Idustryof the 80/90’s with the Bioscience/Drug Discovery process of today. The latter arguing something is vastly wrong, namely that Drug Discovery is not moving forward fast enough, and one taking the point that Biosciences can’t advance as rapidly as the semiconductor industry because we simply don’t understand it well enough.

I tend to agree with Andrew Grove, Former Intel CEO. People in Bioscience hide behind the unknown and use the Regulatory environment as a crutch against taking risks required to advance science at a velocity we’re capable of.

Specifically, these excerpts from his Rant interview by Newsweek are spot on:

How do the two industries deal with failure?
When I started Intel we couldn’t make a device twice in a row in the same way. I earned my reputation by being part of a team that figured out why a thing was not reproducible, what you need to do to make results come out the same way twice in a row. The attitude [in high-tech] is, something went wrong for a reason, let’s find the gold nugget. In 1970, Dov Frohman [at Intel] was investigating insulator leakage, and it led him to invent a brand-new device that is now a fundamental building block of cellphones, cameras, MP3 players and computers. But in pharma, if a clinical trial doesn’t work–which means the average of all the patient responses is not better than the average of a placebo treatment–they just throw [the drug] away, when in fact the averages may hide stuff that did work, and something that made patients different [such as genetics]. I’ve never heard anyone talk about the opportunity costs of a good drug being thrown away. But a good drug wrongfully convicted means the loss of benefits goes on forever.

What stands in the way of more and faster success in getting cures to patients?

The peer review system in grant making and in academic advancement has the major disadvantage of creating conformity of thoughts and values. It’s a modern equivalent of a Middle Ages guild, where you have to sing a particular way to get grants, promotions and tenure. The pressure to conform [to prevailing ideas of what causes diseases and how best to find treatments for them] means you lose the people who want to get up and go in a different direction. There is no place for the wild ducks. The result is more sameness and less innovation. What we need is a cultural revolution in the research community, academic and non-academic. We need to give wild ducks the opportunity to emerge and quack their way to success. But cultural change can be driven only by action at the top.

I wish I had a nickel for every time I’ve heard a highly trained Scientist blame a failed experiment or process on “Science” because we work within the confines of the dreaded and ambiguous “Biological System”. As if things don’t go wrong for a reason?