Yi Yu, a research assistant in the Melton lab, holds flasks containing human embryonic stem cells. Researchers have developed a recipe to turn them into beta cells, which secrete insulin in the pancreas. In what they call the Foundry, they hope to produce 200 flasks of beta cells this year. (All images by Chlo Hecketsweiler)
Pluripotent stem cells have the potential to generate any human cell type and researchers have shown that they may be used to repair damaged tissues and organs in the body. But what looks good in the lab doesnt always translate to the clinic. In laboratories around the world, thousands of scientists are trying to close the gap between promise and real-world therapies.
For a month and a half, starting in January, I was embedded in the daily life of one such group of scientists Douglas A. Meltons laboratory at the Harvard Stem Cell Institute. I watched their experiments, learned about the complex science of stem cells, and talked with the researchers about their work and hopes. I was allowed to take pictures, and for this photo essay I tried to pick out moments and details that I found revealing, although scientists may see them as business as usual.
Meltons lab focuses on diabetes, a disease that affects almost one in 10 Americans. In the lifelong form of the disease (known as type 1), the bodys immune system attacks and destroys the beta cells that produce insulin in the pancreas. Diabetic patients must rely on daily injections of insulin to control the level of sugar in their blood.
Meltons team has invented aprotocolto turn embryonic stem cells into beta cellsand has shown that they effectively secrete insulin when transplanted into diabetic mice. To push the research forward, Melton has co-founded a biotech company, Semma Therapeutics, and hopes to start a clinical trial in the next three or four years.
He is not alone in the race. Timothy Kieffers lab, in Vancouver, British Columbia, has developedanother protocolto turn stem cells into beta cells that reverse diabetes in mice, and theapproach is being tested by California biotech company ViaCyte. Big pharmaceutical companies are on the lookout too. AstraZeneca collaborates with Meltons lab, and the Danish company Novo Nordisk, the worldwide leader in diabetes drugs, is working on its own project.
All have major challenges to overcome before any stem cell therapy hits the market. How results in mice translate into humans is not clear, and finding ways to trick the bodys defense system will be a huge step. New tools such as the gene-editing technology CRISPR-Cas 9 and the ability to handle huge sets of data will help, but they also raise many new questions. The idea that we can have some mastery and control of the cells is a fantastic thing, Melton told me, adding that while in the 20th century humans gained control over much of their physical environment, we are now entering a century when we are going to get control over the human body.
Chlo Hecketsweiler, a 2016-17 Knight Science Journalism fellow, is a Paris-based journalist with Le Monde, specializing in the pharmaceutical and life sciences industries.
You Have to Keep the Cells Happy Precision is critical in the lab, lest cells become damaged or experiments rendered uncertain.
Elise Engquist, a research assistant, looks at the sizes and shapes of stem cell clusters. They have to be monitored closely, as they multiply quickly and take about one month to turn into beta cells. The differentiation is done in six steps and is guided by a cocktail of growth factors added according to precise timing. Scientists always follow the same recipe, but there are still some differences between batches.
Maria Keramari, a postdoc from Greece, delicately handles a dish with human embryonic stem cells. She uses the gene-editing tool CRISPR-Cas9 to create a line of cells that will be fluorescent when they express insulin. Scientists must feed the cells at regular intervals and be careful not to hurt them during the experiment. You have to keep the cells happy before you keep yourself happy, Keramari says.
Jos Rivera-Feliciano, a postdoc from Puerto Rico, prepares samples for DNA analysis. Rivera-Feliciano works on a new family of proteins that play important roles in the development of the pancreas, and he hopes to have his own lab in the future. Its very competitive, he says. For every faculty position you have 100 to 300 candidates.
Here, Rivera-Feliciano prepares the gel for electrophoresis, a technique for separating DNA fragments based on their size. If the result is positive, he can turn to more sophisticated and expensive DNA sequencing techniques to get more information.
They Are Like Our Babies Sophisticated experiments still require some day-to-day innovation inside the lab.
Nadav Sharon, a postdoc from Israel, adds small segments of DNA, called plasmids, into petri dishes containing E. coli bacteria. Some of these bacteria will take up the foreign DNA and clone it as they replicate. Researchers routinely use these bacterial factories to build genetic tools that will be used to modify stem cells or create transgenic animal models. To design their experiments, scientists can dig into huge databases of bacteria, enzymes, and genes with well-known properties. Most of them can be ordered online from specialized companies and are delivered by mail.
Sharon handles vials of bacteria and puts them on ice. The heat shock causes some of them to take up the plasmids that have just been added to the vial. Sophisticated experiments often start with this kind of handmade biological tool. The recipes are well known, but there is always a measure of uncertainty in the results. Researchers can lose weeks of work without knowing what exactly went wrong.
Ornella Barrandon, a postdoc, tests 3,000 compounds to find out which ones boost the replication of beta cells in the pancreas. Beta cells derived from human embryonic stem cells could accelerate the discovery of new drugs, as research is hindered by the limited supply of beta cells extracted from cadavers. We spend so much time on our projects, they are like our babies, she says.
Biology Has Taken a Turn But even with sophisticated genome editing tools such as CRISPR-Cas 9, this is not an exact science.
Adrian Veres, a graduate student from Canada, prepares samples for single-cell analysis, a cutting-edge technique that allows scientists to look at all the cells that constitute an organ and better understand which genes are expressed in each of them. It requires them to deal with unprecedented quantities of data: Biology has taken a turn, and biologists must learn to deal with statistics, Veres says. You cant just give the data to a statistician and look at the results.
Chi Yang Chen, a research assistant, with a lab notebook. Each scientist has one, and must record every step of every experiment. Its the memory and the legacy of the research done in the lab. Its also a legal document that will be closely scrutinized in case the lab applies for a patent or is ever sued for fraud.
Jennifer Kenty, a research assistant, feeds mice with pellets. The Melton labs mouse house hosts about 1,200 mice. Beta cells derived from human stem cells are transplanted into mice that are both immunodeficient and diabetic. The goal is to determine how much insulin they secrete in response to glucose injections. Genetically modified mice are also used to test the role of different genes in the development of the pancreas and endocrine cells.
Pancreases of mouse embryos float in vials. Many questions regarding pancreas development are still open. By analyzing the type of cells that compose it at different stages of fetal development, scientists hope to create a kind of movie that will help them understand what may go wrong along the way. In other experiments, transgenic mice models are used to study the role of specific genes. Even with sophisticated genome editing tools such as CRISPR-Cas 9, this is not an exact science. I tried once to create a CRISPR mouse, says Nadav Sharon. When you read the papers, it looks like magic but that is not that simple.
Read the rest here:
A Month in the Life of a Stem Cell Lab - Undark Magazine
- Politics of Stem Cell Research - May 7th, 2011 [May 7th, 2011]
- Obama Ends Funding Ban for Stem Cell Research - May 8th, 2011 [May 8th, 2011]
- Stem Cell Research: A Father's Fight - May 10th, 2011 [May 10th, 2011]
- Human Embryonic stem cell research - May 11th, 2011 [May 11th, 2011]
- Frost Over The World - Stem Cell Research and Turkey -26 Oct - May 20th, 2011 [May 20th, 2011]
- McCain Favors Embryonic Stem Cell Research - May 20th, 2011 [May 20th, 2011]
- US divided over stem cell research reversal - 09 Mar 09 - May 21st, 2011 [May 21st, 2011]
- The Politics and Promise of Stem Cell Research - May 22nd, 2011 [May 22nd, 2011]
- Inside Story - Obama to end stem cell research ban - March 9 - Part1 - May 30th, 2011 [May 30th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Douglas Boyd - June 3rd, 2011 [June 3rd, 2011]
- The Human Embryo and Embryonic Stem Cell Biology: Spotlight on Stem Cell Research - June 3rd, 2011 [June 3rd, 2011]
- US appeals court lifts stem cell research ban - June 7th, 2011 [June 7th, 2011]
- Trailer for Mapping Stem Cell Research: Terra Incognita - June 9th, 2011 [June 9th, 2011]
- Politics: President Obama on Stem Cell Research - June 10th, 2011 [June 10th, 2011]
- Stem Cell Research Documentary - June 11th, 2011 [June 11th, 2011]
- TEDxSingapore - Susan Lim - Hype and hope of stem cell research - June 13th, 2011 [June 13th, 2011]
- Lou Gehrig's Disease (ALS): Spotlight on Stem Cell Research - Wrapup - June 14th, 2011 [June 14th, 2011]
- The Next Frontier in Stem Cell Research - June 17th, 2011 [June 17th, 2011]
- Robert Klein: Stem Cell Research - June 22nd, 2011 [June 22nd, 2011]
- Fibrocell Stem-Cell Wrinkle Smoother Wins FDA Clearance - June 23rd, 2011 [June 23rd, 2011]
- The Politics of Stem Cell Research - June 23rd, 2011 [June 23rd, 2011]
- A Dose of Reality on Alternative Stem Cell Treatments: What you don't know can hurt you - June 28th, 2011 [June 28th, 2011]
- Governor Tim Pawlenty Discusses Stem Cell Research - June 30th, 2011 [June 30th, 2011]
- The EU and stem cell research - July 5th, 2011 [July 5th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Jeff Bronstein - July 6th, 2011 [July 6th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Yung-Wei Chi - July 7th, 2011 [July 7th, 2011]
- Spotlight on Cancer Stem Cell Research - July 11th, 2011 [July 11th, 2011]
- A Stem Cell Story - July 12th, 2011 [July 12th, 2011]
- Bishop Blair bars support for Komen breast cancer group - July 13th, 2011 [July 13th, 2011]
- Stem Cell Research In Toronto - July 14th, 2011 [July 14th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Introduction - July 14th, 2011 [July 14th, 2011]
- Huntington's Disease: Spotlight on Stem Cell Research 2007 - Han Keirstead - July 15th, 2011 [July 15th, 2011]
- TMconfUK2011-08 - Stem Cell Research in the UK - Prof Charles Ffrench-Constant - July 16th, 2011 [July 16th, 2011]
- UCSF opens stem cell research building - July 16th, 2011 [July 16th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - July 17th, 2011 [July 17th, 2011]
- Deafness: Spotlight on Stem Cell Research - Ebenezer Yamoah - July 22nd, 2011 [July 22nd, 2011]
- Spotlight on Basic Stem Cell Research - Irv Weissman - July 25th, 2011 [July 25th, 2011]
- Diabetes: Spotlight on Stem Cell Research - Peter Butler - July 27th, 2011 [July 27th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - July 27th, 2011 [July 27th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - July 27th, 2011 [July 27th, 2011]
- Alzheimer's Disease: Spotlight on Stem Cell Research - Leeza Gibbons - August 2nd, 2011 [August 2nd, 2011]
- Geron's Embryonic Stem Cell Clinical Trial for Spinal Cord Injury - August 3rd, 2011 [August 3rd, 2011]
- The Skin Gun stem cell research - August 10th, 2011 [August 10th, 2011]
- Deafness: Spotlight on Stem Cell Research - Karen Doyle - August 10th, 2011 [August 10th, 2011]
- Stem Cell Research: Huntington's Disease - August 14th, 2011 [August 14th, 2011]
- Adult and Non-Embryonic Stem Cell Research Conference at Notre Dame - August 20th, 2011 [August 20th, 2011]
- Stemcell Research and Aging - Panel 1 - August 22nd, 2011 [August 22nd, 2011]
- Texans for Stem Cell Research Learn for Life: KXAN Coverage Aired August 16th, 2011 - August 24th, 2011 [August 24th, 2011]
- Stem Cell Research: Macular Degeneration - September 18th, 2011 [September 18th, 2011]
- Brilliant Minds - Stem Cell Research | Tomorrow Today - September 25th, 2011 [September 25th, 2011]
- Ethics of Stem Cell Research (1) - September 29th, 2011 [September 29th, 2011]
- Legal and Public Policy Dimensions of Stem Cell Research - September 29th, 2011 [September 29th, 2011]
- Stem cell symposium - October 2nd, 2011 [October 2nd, 2011]
- StemCONN 2011, The Latest in Stem Cell Research - October 6th, 2011 [October 6th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Mark Genovese - October 7th, 2011 [October 7th, 2011]
- Judy Roberson: Patient advocates drive stem cell scientists - October 8th, 2011 [October 8th, 2011]
- Sam Harris - Stem Cells and Morality - October 8th, 2011 [October 8th, 2011]
- Stem Cell Research, Ethics and Religion - October 9th, 2011 [October 9th, 2011]
- Stem Cells: Fulfilling the Promise - 2011 CIRM Grantee Meeting - October 10th, 2011 [October 10th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) - October 13th, 2011 [October 13th, 2011]
- Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease - Video - October 18th, 2011 [October 18th, 2011]
- Life in the Balance: Perspectives on Stem Cell Research - Video - October 18th, 2011 [October 18th, 2011]
- Stem Cell Research Funding Halt - Video - October 19th, 2011 [October 19th, 2011]
- Vatican lending hand in adult stem cell research - Video - October 20th, 2011 [October 20th, 2011]
- First Spinal-Cord Surgery With Stem Cells - Video - October 21st, 2011 [October 21st, 2011]
- Michael J. Fox Embryonic Stem Cell Research - Video - October 22nd, 2011 [October 22nd, 2011]
- stem cell research - Video - October 22nd, 2011 [October 22nd, 2011]
- Gayle Atteberry - Cloning - November 5th, 2011 [November 5th, 2011]
- It Takes Nerve: UC Irvine - Sue - November 6th, 2011 [November 6th, 2011]
- Embryonic Stem Cell Research - Video - November 9th, 2011 [November 9th, 2011]
- Adult Stem Cell Research Far Ahead of Embryonic - Video - November 10th, 2011 [November 10th, 2011]
- Is stem cell research a growing concern .flv - Video - November 10th, 2011 [November 10th, 2011]
- Forbes Discusses Stem Cell Research - Video - November 14th, 2011 [November 14th, 2011]
- Stem Cell Research Presentation - Video - November 16th, 2011 [November 16th, 2011]
- Benedict XVI: No embryonic stem cell research - Video - November 28th, 2011 [November 28th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - Video - November 30th, 2011 [November 30th, 2011]
- CIS 111 Digital Media Project - Stem Cell Research - Video - December 13th, 2011 [December 13th, 2011]
- Regenerative Medicine and Applications of Stem Cell Research - Video - December 20th, 2011 [December 20th, 2011]
- Stem Cell Research Today: Larry Goldstein - CIRM Science Writer's Seminar - Video - December 22nd, 2011 [December 22nd, 2011]
- CIRM Bridges Award: Building California's Stem Cell Research Workforce - Video - December 22nd, 2011 [December 22nd, 2011]