Zero Order


Censorship of science: security at what price?

Posted in Uncategorized by Amy Ross on December 28, 2011

There’s been a lot of debate about the recent announcement that the  U.S. government advisory boards asked Science and Nature to censor information about the alteration of a bird flu virus.

The virus in question, subtype A H5N1 caused a scare in mid 2000s because of its high human fatality rate (60%).  Remember when people feared bird flu would kill  millions? ABC even aired a mediocre movie about what might happen in a worldwide flu epidemic.The virus’ damage was limited in that it could not be transmitted from one human to another; the few hundred affected individuals contracted the virus from birds.  Researchers at University of Wisconsin-Madison and the Erasmus Institute in the Netherlands created a strain of H5N1 that was easily transmissible-and fatal-among ferrets.  The US National Science Advisory Board for Biosecurity recommended the methods sections of the papers be withheld to prevent use of this  information in bioterrorism.

I understand the rationale for not wanting this information to fall into the wrong hands, but I don’t like the idea of censoring research.  I really don’t. I worry about sacrificing liberties in the name of national security. There’s been a lot of criticism of the board’s decision, arguing that censorship of research is not in the spirit of scientific inquiry. The board has stated they will make the methods available on a need to know basis. How they determine need to know, and how long will the process take? We don’t know.   Also,  the board’s recommendation can’t prevent the methods from being published in other ways. The reseachers could easily publish their technique in a European journal.

I also find it ironic that the news about the papers being censored brought a lot more attention to the story than if the paper had been quietly published. Perhaps the board’s decision will have the opposite of its intended effect!

Those are just my thoughts. More later if there are further developments.

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The Cure for Biotechnology (Mis)adventures

Posted in Uncategorized by Amy Ross on December 22, 2011

I recently read  The Cure, Geeta Anand’s account of John Crowley’s effort to develop a treatment for the rare debilitating disease affecting his children. The story was the basis for the 2010 movie Extraordinary Measures.

Crowley’s children Megan and Patrick were diagnosed with Pompe disease, a genetic metabolic disorder that causes muscle weakening, heart enlargement, and severe respiratory difficulties. Both children are ventilator dependent by the age of two.  In Pompe disease, alpha-glucosidase,  an enzyme that breaks down glycogen is deficient or absent. Glycogen is a complex carbohydrate molecule that stores energy for use in the body.  Alpha glucosidase is found in the lysosomes of cells. Lysosomes are the “garbage bins” of cells, primarily responsible for processing cellular waste. Anyway, since the enzyme is deficient, glycogen builds up in cells and causes muscle weakening.

Megan and Patrick have a life expectancy of about five years. Crowley, desperate to save his kids, begins meeting with Pompe researchers. He eventually becomes CEO of Novazyme, a company formed to manufacture the missing enzyme. He eventually negotiates the sale of Novazyme to Genzyme and continues to work with the Pompe team to get the enzyme in clinical trials.

Crowley is stubborn, charismatic, and absolutely determined to get his kids in clinical trials before they succumb to the disease.  I’d like to address a couple issues I had with his behavior in the book.

1. Indiscriminate research grants. Crowley’s initial tactic is to form a nonprofit, the Children’s Pompe Foundation, and raise research funds. The foundation impressively raises $750,000 in eight months. However, he makes all the decisions about awarding grant money himself, and solely based on what the researchers say about their expediency to be approved for clinical trials.  Crowley, a director of marketing at Bristol-Myers Squibb, acknowledged science is not his strong suit.  I certainly didn’t expect Crowley to retrain as a biochemist, but he should have had a scientific advisor in the Foundation to assess research feasibility. The Komen Foundation and the Tourette’s Syndrome Association award research grants, and both have scientific advisory boards.

Granted, the field of Pompe researchers is small, but his ignorance about the research specifics cause problems for Crowley when he becomes CEO of Novazyme. He takes the job fully believing the company is his best chance into getting a Pompe treatment into clinical trials. At a meeting with venture capitalists, the potential investors point out the planned manufacturing process would never be approved by the FDA-something Crowley didn’t realize.

2. Conflict of Interest.  In order to motivate the Novazyme staff, Crowley brings in Pompe patients and hosts lunchtime seminars on the disease. A number of venture capitalists question Novazyme’s ability to practice good science since Crowley is far from objective in the outcome of Novazyme’s drug development.  Being in the senior management of Novazyme (and later Genzyme) actually is detrimental in getting Megan and Patrick in clinical trials, and I have mixed feelings on Crowley getting involved as intimately as he does getting his children treated.  He wasn’t well qualified to be a CEO and had a steep learning curve. Taking the Novazyme job undoubtedly gave him a sense of control.  I did like the lunchtime seminars. I think it gives a sense of urgency to the research being done. It’s easy to focus on the small details of a project on a day to day basis-this technique isn’t working, the cells are contaminated-that it’s easy to forget the end goal, and that people’s lives are depending on what you are able to accomplish.

Overall, I enjoyed the book. Anand tells the story well, and it took large amounts of willpower to not skip to the end and find out if Megan and Patrick were treated.  I also learned a lot about venture capital investment!

Although it’s a couple days since Solstice and the start of Haunakkah,  I hope you all have a great holiday!

Hydrogels in action: artificial intestines

Posted in Uncategorized by Amy Ross on December 19, 2011

Discovery News reported last week on an artificial intestine intended to treat short bowel syndrome in children.  I thought this was pretty snazzy and looked up the original publication on PubMed.

Tissue engineering, while an exciting field with sexy goals, is fraught with challenges, starting with the scaffold. What scaffold materials can be used that can be implanted in a patient without adverse affects and encourage functional tissue development? What characteristics should the scaffolds have?  Hydrogels are useful scaffolds because their physical and mechanical properties resemble soft tissue. A hydrogel also allow water and small molecules to diffuse throughout its structure, allowing nutrients to reach growing tissues. Cells can be encapsulated either within the hydrogel at the time of polymerization, or added to the surface after polymerization; the choice depends on a variety of factors including the application and the type of cells.

The researchers who have developed this artificial intestine employed the principle that replicating the cells’ environment as closely as possible will provide the most functional engineered tissue.  One of the challenges in replicating small intestinal structure was to be able to create villi, or fingerlike protrusions from the surface of the intestine. The presence of villi increases the small intestine’s surface area and allows a greater amount of nutrients to be absorbed. The villi are small structures-on the order of millimeters in a human-and conventional molds would either not be able to make the villi small enough or  allow the hydrogel to emerge intact from the mold. The researchers solved the problem by making two molds. The first is made of PDMS, a hard polymer with the villi projections. A mold of calcium alginate was cast on the PDMS. The sodium alginate mold is filled with the hydrogel. Once the hydrogel is polymerized, the calcium alginate is dissolved, leaving just the hydrogel with the  projections for villi. The villi formed were 400-500 microns (millionths of meters) in height, or 0.4-0.5 millimeters.

Using collagen as their hydrogel of choice, the researchers were able to grow Caco-2 (colon cancer cells) on the hydrogel. The cells were able to grow on the scaffold, and the cells that grew on the projections resembled villi.

Although this model of a human intestine is pretty awesome, I wouldn’t consider artificial intestines to be “near reality”. The Discovery News article states their next step is to grow a larger intestine model (the published data was on a very small scale), and then to implant the intestine in mice. Will the engineered intestine function absorb enough nutrients to sustain a living being? Is it possible to vascularize the newly developed tissue?  Will cells from the patient be able to grow as well in the hydrogel as the Caco-2 cells?  There are a lot of steps between these experiments and a working intestine for humans.

Reference:

J.H. Sung et. al. “Microscale 3-D Hydrogel Scaffold for Biomimetic Gastrointestinal (GI) Model” Lab Chip, 2011, 11, 389

One more time

Posted in Uncategorized by Amy Ross on December 15, 2011

Hello there:

I haven’t written anything since the beginning of March, although it appears I’m still getting some traffic.  Here’s what I’ve been up to:

  • I graduated! I finished the bulk of my research by the end of June, and defended my thesis in mid-August.  My thesis took about four months to write, off and on, and ended up running nearly 150 pages.  This is a bit long for a Master’s, but I did have a lot of figures.  The thesis defense went very well. I expected my committee would ask me a lot of tough questions, but it wasn’t as bad as I thought it would be. I got the bound copies back last month, and gave one to my parents. Mom got to page one and asked if there was an audio version 🙂
  • I became an experienced presenter of scientific data.  I presented my research at multiple regional conferences, and actually won second place at the Midwest Biomedical Engineering Career Conference in April. I presented at my first national meeting at  the AAPS National Biotechnology Conference last May. The poster presentations were great preparation for both my thesis defense and discussing my research with potential employers for two reasons. One, I gained experience explaining my research to people who weren’t in my field. Two, I had practice thinking on my feet when questions were asked.
  • I have two publications in progress. I wrote a paper on my thesis that has been submitted to a pharmaceutical journal. The other is a previous M.S. student’s project whose paper I helped rewrite.

Now I’m looking for a job. I’ve had several interviews this fall, but no offers yet. I’ve also been doing volunteer work and doing lots of reading. A few nonfiction titles of interest:

  • Vaccinated! by Paul Offit-some history of vaccines and the development of multiple vaccines at Merck
  • The Xeno Chronicles by G. Wayne Miller-about xenotransplanation research at Harvard
  •  Every Second Counts: The Race to Transplant the First Human Heart by Donald McRae-Christiaan Barnard, who performed the first successful human heart transplant, was actually the underdog among four competing physicians.
  • Ether Day by Julie Fenster- about the discovery of ether as a surgical anesthetic.

Since I’m not actively doing research, I’d like to rebirth this blog into my take on current events in science, thoughts on reading, and adventures in job hunting! Stay tuned.