The Age of the Genome: Commercial DNA Sequencing, Familial Searching and What We Are Learning

Crowd of people at the street, city center

All of these people are 99% the same at the genomic level. The individuals of the human species are far more alike than different.

There are 3 billion (3,000,000,000) bases in my genome—in each of the cells of my body. Likewise, Johanna, the writer who sits next to me at work also has 3 billion bases in her genome. Furthermore, our genomes are 99% the same. Still, that’s a lot of places where my genome can differ from hers, certainly enough to distinguish her DNA from mine if we were both suspected of stealing cookies from the cookie jar. The power of discrimination is what makes genetic identity using DNA markers such a powerful crime solving tool.

The completion of the human genome project in 2003 ushered in a tremendously fast-paced era of genomics research and technology. Just like computers shrank from expensive, building-filling mainframes to powerful hand-held devices we now call mobile phones, genome sequencing has progressed from floor-to-ceiling capillary electrophoresis units filling an entire building to bench top sequencers sitting in a corner of a lab. The $99 genome is a reality, and it’s in the hands of every consumer willing to spit into a tube.

Commercial DNA sequencing services are promising everything from revealing your true ancestry to determining your likelihood to develop dementia or various cancers. Is this progress and promise or is it something more sinister?

As it turns out, that isn’t an easy question to answer. What is probably true is that whole genome sequencing technologies are being put into the hands of the consumer faster than society understands the ethical implications of making all of this genomic information so readily available. Continue reading

Letter from Uganda: A Promega International Internship Scholarship Recipient Shares her Experiences

Sydney Roberts, left, at work at a rural community outreach health clinic outside of Kabale, Uganda where she helped conduct basic health screenings. Here she is measuring a woman’s MUAC (midupper arm circumference).

Sydney Roberts, left, at work at a rural community outreach health clinic outside of Kabale, Uganda where she helped conduct basic health screenings. Here she is measuring a woman’s MUAC (midupper arm circumference).

We were inspired by a letter we recently received from one of the recipients of the Promega International Scientific Internship Scholarship. The scholarship supports undergraduate students at the University of Wisconsin – Madison. who are undertaking an international internship aimed at using science to improve the quality of life in the world. Students from all scientific fields are eligible but preference is given to those whose internships use molecular biology techniques. Students must be based in a country other than their own for at least six weeks and cannot be in a country where the recipient has already spent significant time.

Sydney Roberts, a junior at UW Madison majoring in Community and Nonprofit Leadership with a certificate in Global Health, was awarded the Spring 2018 Promega scholarship. As a result, she’s spending her spring a long way from her hometown of Cedarburg, WI. Sydney is currently working in Kabale, Uganda, a town in the southwestern part of the country near the border of Rwanda, as an intern with the Kigezi Healthcare Foundation (KIHEFO).

KIHEFO operates a primary care clinic, HIV/AIDS clinic, Nutrition and Rehabilitation center, and works with rural community groups. Sydney is supporting local staff members as they treat clients, provide counseling sessions for families affected by disease, and work on global health initiatives that support prevention of these diseases and health complications. She has only been in Uganda for a few weeks, but she says her experiences have already been life-changing. Continue reading

The Free Scientific Resource: Evaluating the Accuracy of Wikipedia

Several weeks ago, I came across an article on ScienceNews.org about how Wikipedia is becoming a scientific resource, whether we like it or not. Scientists are reading Wikipedia, the article said, and it’s affecting how they write. The article cited a study by researchers from MIT and Pitt that found statistical evidence of language in peer-reviewed articles being influenced by Wikipedia articles relevant to the topic. They concluded that journal articles referenced in Wikipedia are subsequently cited more than other similar articles, and that on a semantic level, Wikipedia is influencing the language of scientific journal articles at an astounding rate.

I was intrigued by the idea that reading Wikipedia affects how we later write about a subject. When I start writing about a new topic, the first thing I do is head to Wikipedia to gather a basic understanding before I dive into journal articles. I’ll skim through the overview and most relevant subsections, then check out the references to see what I should continue reading. However, the findings of the study imply that even though I don’t directly use information or language from Wikipedia in my work, it’s still subtly influencing how I write. Continue reading

Get Out and Count: The Great Backyard Bird Count of 2018

2018 has been designated “The Year of the Bird”, and beginning today, Friday, February 16, 2018, bird lovers around the world will grab their binoculars, fill their bird feeders, update their eBird app, and look toward the skies. The 21st Annual Great Backyard Bird Count, one of the largest and longest running citizen science projects, begins today, and you can be part of this grand event of data collection.

All it takes is a mobile device (or computer) to log your results, an account at gbbc.birdcount.org , and 15 minutes of your time during the four-day event.

Can’t tell a red-tailed hawk from a red-winged black bird? That’s okay. The GBBC web site provides a handy online bird guide.  The web site also provides a guide for tricky bird IDs, including: Which Red Finch is it, Identifying Some Common Sparrows, and Identifying Doves.

I recently spent some time talking to Brian Schneider, one of the educators at the Aldo Leopold Nature Center in Monona, WI, to get some tips for first-time birders. Continue reading

Evaluating the Costs of Endotoxin Testing

http://www.eniscuola.net/en/mediateca/king-crab/

Recently, I had the opportunity to attend a fascinating symposium held at Promega featuring conservationist Steward Brand, where he described some of the projects developed by his foundation, Revive & Restore.

The organization’s mission is to apply emerging biotechnology techniques to endangered and extinct species with the intent to increase genetic diversity, provide disease resistance and facilitate adaptation to changing climates. Although the overall message of enhancing biodiversity through the application of new genetic technology was inspiring, the project that resonated most for me was related to the plight of horseshoe crabs.

Horseshoe crabs, often referred to as living fossils, include four extant species with origins dating back about 450 million years. Although they look like crabs, they belong to their own subphylum and are more closely related to spiders. When horseshoe crabs spawn, they leave their usual habitat on the ocean floor and migrate to shore in large numbers. As a result, they have been exploited for bait and fertilizer for decades.

Enter endotoxins, an indicator for bacterial contamination in biologicals, drugs and medical devices. U.S. Food & Drug Administration regulations dictate that finished products be tested for the presence of endotoxins. These pyrogenic compounds, found in the cell wall of Gram-negative bacteria, can cause fever and affect a wide range of biological activity, possibly leading to aseptic shock and death. The most common method for testing is the gel clot and Limulus Amebocyte Lysate (LAL) Test.

I first learned about the LAL test during graduate school, where it was presented as a ubiquitous and standard requirement for testing bacterial contamination in injectable drugs. I remember being fascinated that horseshoe crabs (Limulus sp.), contain a substance that could be used to detect endotoxins. Although the instructors mentioned the need to collect blood from horseshoe crabs in order to produce the test, the method or scale of this harvest wasn’t discussed, nor were the true costs of using this method of endotoxin testing.

The LAL test has served as a faster, more inexpensive replacement for the rabbit pyrogens test for the past 35 years. Every year during mating season horseshoe crabs move to shallow water, where they are removed in huge numbers. (To get an idea of scale for the harvest and read a much more comprehensive investigation of the issue, check out this article in The Atlantic, which features an archive photo of Delaware Bay horseshoe crab harvest from 1928—for fertilizer, not pharmaceutical testing.)

After collection, the crabs end up in a lab where up to 30% of their blood is drained from a needle stuck in tissue around their heart. The LAL is extracted from the blood and can yield a product worth up to $15,000/quart. In order to avoid recollection, the crabs are returned to the ocean far from the shore where they were collected a few days before. Although it’s estimated that only 10-30% of these crabs die as a result of the process, there are indications that the horseshoe crab population and their ecosystems are impacted in other ways.

Researchers at the University of New Hampshire and Plymouth State University used accelerometers attached to recently bled female horseshoe crabs to test the hypothesis that harvesting for LAL was affecting their ability to spawn. While the research supported previous estimates with a death rate of 18%, females were found to be less likely to mate after being bled.

During his talk, Brand shared results from a study still in review that confirm the effect of over-harvesting Limulus on the survival of long distance migratory shorebirds. These birds synchronize their migration with horseshoe crab spawning, which provides a needed feast of eggs before the homestretch of their journey. Along with other ecosystem threats from climate change, the accelerated decline in the horseshoe crab population and dependency of migratory birds will likely to lead to a devastating ecological domino effect.

Fortunately, a synthetic alternative to LAL, recombinant factor C (rFC), has been available for nearly 20 years. Alas, there has been no significant shift by pharmaceutical companies away from the test based on horseshoe crab blood. rFC was patented and licensed to one company, Lonza, which Brand posited as one reason for the reluctance of drug companies to adopt its use.

Obviously, relying on one source for an essential testing reagent with no competition to temper cost is quite unattractive. But that argument has less bearing now that the patent is scheduled to expire in a few months, opening the door for additional manufacturers and creating an economic incentive for switching to the synthetic test.

Another reason may be that implementing a new test would require additional resources to validate the synthetic test for products that are already being tested with the LAL. Since the LAL has been specified in FDA guidance documents on endotoxin testing for decades, quality standards for existing products are based on the LAL, limiting momentum to change.

If both tests offered the same benefits, these arguments would make sense; however, research by one of the discoverers of rFC, Jeak Ling Ding of the National University of Singapore, shows that in many respects rFC is more efficacious than LAL. Since the raw material for the LAL test depends on an organism, there is seasonal variation in the components of the processed blood that must be taken into account. The reaction of the LAL also depends on a cascade of multiple compounds that can be affected by temperature, pH and proteins—leaving the test vulnerable to false positive results.

Although Eli Lilly is the only pharmaceutical company to date to use rFC in place of LAL, It seems the tide may be turning. According to Brand, others are interested in making the transition. It seems foolish not to, given the source for LAL shows signs of dwindling due to overexploitation. Perhaps pharmaceutical companies are beginning to see the value of a “slower/better” philosophy (the cornerstone of the Long Now Foundation, another brainchild of Brand’s), rather than “faster/cheaper.” I have certainly gained a new perspective on endotoxin testing and a deep appreciation for the work of Brand and his foundation.

Does your organization use the LAL test? What is preventing you from switching to the synthetic alternative? Let us know!

Announcing the 13th Annual Wisconsin Stem Cell Symposium

20 Years of Human Pluripotent Stem Cells: Current Clinical Trials and Regulatory Framework

April 18, 2018 | Madison, WI

Picture of Stem Cell Booth display from last year's meetingOver the years, the BTC Institute has partnered with the Stem Cell & Regenerative Medicine Center, at the University of Wisconsin-Madison to offer this packed day of excellent talks and opportunities to interact with renowned speakers, poster session presenters, sponsor representatives and other attendees.

Our UW-Madison committee members define each year’s content and pull together a strong group of presenters.  This year, we’re working with Timothy J. Kamp, M.D. (Professor, Medicine, Cell and Regenerative Biology; Co-director, Stem Cell and Regenerative Medicine Center), William L. Murphy, Ph.D. (Professor, Biomedical Engineering, Orthopedics & Rehabilitation; Co-director, Stem Cell & Regenerative Medicine Center) and James Thomson, Ph.D. (John D. MacArthur Professor, Director, Regenerative Biology, Morgridge Institute for Research; Professor, Department of Molecular, Cellular, & Developmental Biology, University of California – Santa Barbara).

Attendees at last year's stem cell symposiumOur 2018 symposium brings together leading researchers advancing human pluripotent stem cell products to clinical applications for a range of degenerative diseases. Progress in clinical trials, as well as major barriers for developing these revolutionary new therapies will be discussed.

As Dr. Kamp notes, “This will be a remarkable meeting highlighting the emerging field of regenerative medicine which has grown from the pioneering discovery of human embryonic stem cells 20 years ago.” Continue reading

Encouraging, Supporting, and Advocating for Diversity in Science

On December 27, 2017, the life sciences community lost a pioneer in neurobiology and an advocate for equality in science. Dr. Ben A. Barres passed away at the age of 63. His work focused on the critical role of glia (non-neuronal cells) in the brain and how they interface with neurons to maintain cognitive function.

Equally remarkable was the more personal side of his life. In 1997, Dr. Barbara Barres transitioned from female to male and lived the remainder of his life as Ben Barres. I read a number of the articles that Dr. Barres wrote and came across one that particularly caught my attention. Continue reading

FutureQuest17: Dynamic Career Exploration for Middle School Students

Isabel Agasie speaks with middle school students at FutureQuest 17.

Isabel Agasie speaks with middle school students at FutureQuest 17.

The Dane County School Consortium and the Madison Metropolitan School District’s Career and Technical Education Division collaborated to offer FutureQuest17 on December 6th at the Alliant Energy Center.  Designed as a hands-on experience for Dane County middle school students to explore areas of potential interest within a 16 career cluster, over 70 companies provided information and activities for 5300+ attendees.

BTC Institute staff members (Isabel Agasie, Amy Prevost and Karin Borgh) and volunteer Promega production scientists (Molly Nyholm and Kay Rashka) created a lively table area that focused on bioluminescence. Our space included opportunities to see an illustration of the range of careers in a biotechnology company like Promega, practice with different sizes of pipettes, view glowing recombinant luciferase, watch a scrolling slide show illustrating bioluminescence both in nature and in the lab and consider why a scientist might be interested in bioluminescence as a research tool.

Most importantly, we were able to engage in many wonderful conversations, and for this we needed all five of us since the schedule for the day included 14 periods of 20 minutes each—our estimate is that we were able to speak with ~40–50 students during each of these cycles!

As Molly noted:

The questions students asked were fantastic!!  “What is the chemical composition of this luciferin solution?”  “How much money do you make?”  “Do all glowing creatures have the same luciferase enzyme or are they different?”  “Are there any bioluminescent fish in Wisconsin?”  “Do I have to go to school for as long as you did if I want to be a scientist?”  “What pH is this solution?”  “Does this have potassium or sodium iodide?”  “Can I do an internship?”  “Can I be on the culinary team at Promega?”  “Does my glow paint have luciferase in it?”  “Do you have to take luciferase and luciferin out of those creatures or is there a way to make it in the lab?”

Kay Rashka works with students at FutureQuest17.

Kay Rashka works with students at FutureQuest17.

And, Isabel added:

It was really great to connect with students and also with teachers. Lots of fun being surrounded by kids and fantastic adults. Some kids were surprised to learn that a biotechnology company hires people in other areas besides science. They asked about diversity and were very glad to hear that there are many different kinds of jobs in biotech companies.

Some of the other presenters in the STEM area of the event that we were in close proximity to included: the City of Madison Engineering Division (where students could construct marble runs that represented water flow), Saris (where students could ride bikes set up to display a training program), Laser Tag (try it out!), very active construction companies’ hammering stations and the MG&E’s electric car. In other words, the level of activity was high, and it was wonderful to contribute to this event—we’ll be back next year!

Where Science and Art Meet: The 2017 Holiday Card

The Promega Holiday Card

The Promega Holiday Card

University of Wisconsin-Madison undergraduate Celia Glime didn’t think she was creating a design for the 2017 Promega holiday card while doing lab work last winter for her introductory Chemistry 104 class. She was simply doing her homework.

Celia explains she was studying the progression of three chemical reactions in test tubes when she decided to take out her smartphone and snap some photos to use for her lab report. (Bonus points if you can tell from the photo what’s causing each reaction. Answers below.)

“I ended up creating an art project instead,” she says.

Celia, who at the time was considering a major in genetics and a minor in visual art, had been keeping an eye out for instances of science in real life. Her mentor on campus, Professor Ahna Skop, a geneticist and artist herself, had recently told Celia about the annual University of Wisconsin Cool Science Image Contest, sponsored by Promega. The contest aims to bring together the worlds of science and art by recognizing the technical and creative skills required to capture images or video that document science or nature.

Celia did exactly that. Continue reading

Biotechnology in Space: Partnering with the Wisconsin Space Grant Consortium

The BioPharmaceutical Technology Center Institute (BTC Institute) has been a member of the Wisconsin Space Grant Consortium (WSGC) since 2002. As an educational arm of NASA, the mission of WSGC “is to use the excitement and vision of space and aerospace science to equip the citizens of Wisconsin with the math, science and technology tools they need to thrive in the 21st century.”

Also as noted on WSGC’s website, “The mission of NASA’s Space Grant Program is to contribute to the nation’s science enterprise by funding education, research, and informal education projects through a national network of university-based Space Grant consortia.” Members of these consortia include academic institutions, government agencies, businesses and other educational organizations, such as the BTC Institute.
Of particular relevance to the WSGC/BTC Institute partnership, Space Grant Program goals include working to:

  • Recruit and train professionals, especially women, and underrepresented minorities, and persons with disabilities, for careers in aerospace related fields.
  • Develop a strong science, mathematics, and technology education base from elementary through university levels.

Continue reading