Induced pluripotent stem cell

Eye Stem Cell Therapy Moves Ahead

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Scientists in Korea have injected human embryonic stem cell (hESC)-derived retinal support cells into the eyes of four men with macular degeneration, according to a study published today (April 30) inStem Cell Reports. Three of the men experienced vision improvements in their treated eyes in the year following the procedure, while the fourth man’s vision remained largely the same. The trial adds to growing evidence that injecting hESC-derived cells is feasible, feeding hopes for their future therapeutic use.

This latest study follows on two papers published inThe Lancet in 2012 and 2014, which similarly demonstrated that hESC-derived cells could be safely injected into the space behind the retina in macular degeneration patients. These studies, sponsored by the Massachusetts-based company Advanced Cell Technology (now Ocata Therapeutics), were the first published accounts describing the application of hESC-based therapies in humans.

Korean company CHA Biotech carried out the new trial. Ocata provided the hESCs and some methodological instruction. “Together with the results here in the US, I think this bodes well for the future of stem cell therapies,” said study coauthor Robert Lanza, chief scientific officer at Ocata.

Jeanne Loring, a stem cell researcher at the Scripps Research Institute in La Jolla, California, agreed that the apparent safety of the therapy in the subjects tested is encouraging. However, she added, it would be difficult to draw firm conclusions about efficacy based on such a small study. “I think it’s still anecdotal that some people seem to improve,” said Loring.

“At least it shows safety,” said Magdalene Seiler, a project scientist at the University of California, Irvine. “Whether it works in the long term is up for debate.”

Like many other teams working to develop stem cell-based therapies, the Ocata-led team sought to treat a disease of the eyes in part because the organs are accessible. For the current study, the researchers treated two men with dry age-related macular degeneration, aged 65 and 79, as well as a 40-year-old man and a 45-year-old man, both with Stargardt macular dystrophy, an earlier-onset inherited disease. Both forms of macular degeneration lead to vision loss resulting from the destruction of retinal pigment epithelium (RPE) cells. RPE cells support retinal photoreceptor cells by nourishing them and cleaning up their waste. Without functional RPEs, retinal photoreceptors die.

The researchers differentiated hESCs into RPE cells and injected them into one eye of each patient, hoping that the transplanted RPE cells would take root and replace those that had been lost, preventing further loss of photoreceptors. Lanza explained that “the goal of the therapy was not to improve vision.”

Even so, the vision of three of the men improved by two to four lines of letters on a standard vision test. The vision of the fourth patient, the older man with age-related macular dystrophy, improved by just one letter —a negligible change.

Because of the study size, it is too early to conclude whether the treatment systematically improves vision in patients, said Lanza. However, he hypothesized that patients could have experienced vision improvements because the infusion of new RPE cells revived photoreceptors that had gone dormant but were not yet dead.

Lanza was also encouraged to see that the transplanted cells did not form tumors or differentiate into cells other than RPEs, a major concern among researchers in the field. Regulators “don’t really want to see a tooth in the eye or they don’t want to see beating heart cells in the wrong place,” Lanza said. By carefully screening all cells transplanted into patients, researchers were able to avoid transplanting cells that were not fully differentiated and could, therefore, have formed unwanted tissues.

The scientists were also relieved to see that the patients’ immune systems did not reject the transplanted cells. Like the brain, the eye is immune privileged, meaning that it is largely inaccessible to immune cells. To be safe, the researchers still gave the patients immunosuppressive drugs for a limited period before and following the surgery. It is unclear whether this was necessary.

Finally, by focusing on men of Asian descent, the study added to the diversity of the small group of patients who have received transplanted hESC-derived cells. The previous Lancet studies largely focused on Caucasian patients. Asian and Caucasian patients have different alleles that contribute to risk for age-related macular degeneration.

CHA Biotech is hopeful to get the go-ahead from Korean regulators to proceed with Phase 2 trials using hESC-derived cells to treat Stargardt macular dystrophy this year.

Ocata, meanwhile, will start Phase 2 trials for both Stargardt macular dystrophy and age-related macular degeneration in the “next several months,” according to Lanza. Meanwhile, researchers at the RIKEN Center for Developmental Biology in Japan last year began a trial to test induced pluripotent stem cell (iPSC)-derived RPE cells for the treatment of macular degeneration.

The new work adds to the climate of hope for stem cell therapies. “It’s inspiring other scientists,” said Loring, whose team is working to eventually treat people with Parkinson’s disease with iPSC-based therapies. “It makes us feel like we’ll be able to do similar things in whatever diseases we’re studying.”

W.K. Song et al., “Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients,” Stem Cell Reports,doi:10.1016/j.stemcr.2015.04.005, 2015.

Human stem cells converted to functional lung cells.

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For the first time, scientists have succeeded in transforming human stem cells into functional lung and airway cells. The advance, reported by Columbia University Medical Center (CUMC) researchers, has significant potential for modeling lung disease, screening drugs, studying human lung development, and, ultimately, generating lung tissue for transplantation. The study was published today in the journal Nature Biotechnology.

“Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells, intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine,” said study leader Hans-Willem Snoeck, MD, PhD, professor of medicine (in microbiology & immunology) and affiliated with the Columbia Center for Translational Immunology and the Columbia Stem Cell Initiative. “Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplants — that is, transplants that use a patient’s own skin cells to generate functional lung tissue.”

The research builds on Dr. Snoeck’s 2011 discovery of a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells into anterior foregut endoderm — precursors of lung and airway cells. (Human iPS cells closely resemble human ES cells but are generated from skin cells, by coaxing them into taking a developmental step backwards. Human iPS cells can then be stimulated to differentiate into specialized cells — offering researchers an alternative to human ES cells.)

In the current study, Dr. Snoeck and his colleagues found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells (cells that cover the lung surface). The resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells. Type 2 cells are important because they produce surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

The findings have implications for the study of a number of lung diseases, including idiopathic pulmonary fibrosis (IPF), in which type 2 alveolar epithelial cells are thought to play a central role. “No one knows what causes the disease, and there’s no way to treat it,” says Dr. Snoeck. “Using this technology, researchers will finally be able to create laboratory models of IPF, study the disease at the molecular level, and screen drugs for possible treatments or cures.”

“In the longer term, we hope to use this technology to make an autologous lung graft,” Dr. Snoeck said. “This would entail taking a lung from a donor; removing all the lung cells, leaving only the lung scaffold; and seeding the scaffold with new lung cells derived from the patient. In this way, rejection problems could be avoided.” Dr. Snoeck is investigating this approach in collaboration with researchers in the Columbia University Department of Biomedical Engineering.

“I am excited about this collaboration with Hans Snoeck, integrating stem cell science with bioengineering in the search for new treatments for lung disease,” said Gordana Vunjak-Novakovic, PhD, co-author of the paper and Mikati Foundation Professor of Biomedical Engineering at Columbia’s Engineering School and professor of medical sciences at Columbia University College of Physicians and Surgeons.

 

Stem Cells Converted Into Lung Tissue.

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Lung transplant recipients have a relatively low 10 year survival rate of about 28%. Cellular rejection of the donor organ occurs about 90% of the time, which brings additional obstacles for the patient and doctors. This might be about to change, as functional lung tissue has been created from human stem cells. The research comes from Hans-Willem Snoeck from the Columbia Center for Translational Immunology and was published in the current edition of Nature Biotechnology.

A couple of years ago, Dr. Snoeck was able to convert stem cells into the precursor endoderm cells that can eventually differentiate into lung cells. This was done with human embryonic stem cells as well as human induced pluripotent stem cells, which involve a bit more work but are easier to come by. Those precursor cells were shown to actually differentiate into six different respiratory tissues, including the coveted type II alveolar cells. which facilitate gas exchange and produce surfactant.

Type 2 alveolar cells, also called pneumocytes, are responsible for producing surfactant, the compound that allows the lungs to remain inflated with air. These type II cells also aid in gas exchange and lung repair.

The lung tissue produced by stem cells could give researchers a unique perspective to study the tissue and learn more about how lung diseases originate. This could lead to better treatment options for lung diseases.

If treatments do not work and transplant becomes inevitable, physicians can use the patient’s own cells to provide a new disease-free organ. This eliminates both the potential for cellular rejection as well as the stress of waiting on the transplant list. To make a replacement lung, researchers would first remove the patient’s lung and decellularize it, leaving only a cartilaginous scaffold. The stem cells would then be used to coat the scaffold and regrow functional tissue to be put back into the patient.

Though it is a long way from getting implanted into a human body, these results are exciting. A patent has been filed by Columbia University for their technique of converting induced pluripotent stem cells into the functional tissue.

Stem cell transplant repairs damaged gut in mouse model of inflammatory bowel disease.

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A source of gut stem cells that can repair a type of inflammatory bowel disease when transplanted into mice has been identified by researchers at the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge and at BRIC, the University of Copenhagen, Denmark.

The findings pave the way for patient-specific regenerative therapies for inflammatory bowel diseases such as ulcerative colitis.

All tissues in our body contain specialised stem cells, which are responsible for the lifelong maintenance of the individual tissue and organ. Stem cells found in adults are restricted to their tissue of origin, for example, stem cells found in the  will be able to contribute to the replenishment of the gut whereas stem cells in the skin will only contribute to maintenance of the skin.

The team first looked at developing intestinal tissue in a mouse embryo and found a population of stem cells that were quite different to the  that have been described in the gut. The cells were very actively dividing and could be grown in the laboratory over a long period without becoming specialised into the adult counterpart. Under the correct growth conditions, however, the team could induce the cells to form mature intestinal tissue.

When the team transplanted these cells into mice with a form of , within three hours the stem cells had attached to the damaged areas of the mouse intestine and integrated with the gut cells, contributing to the repair of the damaged tissue.

Dr Kim Jensen, a Wellcome Trust researcher and Lundbeckfoundation fellow, who led the study, said: “We found that the cells formed a living plaster over the damaged gut. They seemed to respond to the environment they had been placed in and matured accordingly to repair the damage.

“One of the risks of  like this is that the cells will continue to expand and form a tumour, but we didn’t see any evidence of that with this immature stem cell population from the gut.”

Cells with similar characteristics were isolated from both mice and humans and the team were also able to generate similar cells by reprogramming adult human cells, so called induced Pluripotent Stem Cells (iPSCs), and growing them in the appropriate conditions.

“We’ve identified a source of gut  that can be easily expanded in the laboratory, which could have huge implications for treating human inflammatory bowel diseases. The next step will be to see whether the human cells behave in the same way in the mouse transplant system and then we can consider investigating their use in patients,” added Dr Jensen.

‘INDIVIDUALIZED’ THERAPY FOR THE BRAIN TARGETS SPECIFIC GENE MUTATIONS CAUSING DEMENTIA AND ALS.

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Stem cell-based approach manipulates brain cells in test tube studies

Johns Hopkins scientists have developed new drugs that — at least in a laboratory dish — appear to halt the brain-destroying impact of a genetic mutation at work in some forms of two incurable diseases, amyotrophic lateral sclerosis (ALS) and dementia.

They made the finding by using neurons they created from stem cells known as induced pluripotent stem cells (iPS cells), which are derived from the skin of people with ALS who have a gene mutation that interferes with the process of making proteins needed for normal neuron function.

“Efforts to treat neurodegenerative diseases have the highest failure rate for all clinical trials,” saysJeffrey D. Rothstein, M.D., Ph.D., a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine and leader of the research described online in the journal Neuron. “But with this iPS technology, we think we can target an exact subset of patients with a specific mutation and succeed. It’s individualized brain therapy, just the sort of thing that has been done in cancer, but not yet in neurology.”

Scientists in 2011 discovered that more than 40 percent of patients with an inherited form of ALS and at least 10 percent of patients with the non-inherited sporadic form have a mutation in the C9ORF72 gene. The mutation also occurs very often in people with frontotemporal dementia, the second-most-common form of dementia after Alzheimer’s disease. The same research appeared to explain why some people develop both ALS and the dementia simultaneously and that, in some families, one sibling might develop ALS while another might develop dementia.

In the C9ORF72 gene of a normal person, there are up to 30 repeats of a series of six DNA letters (GGGGCC); but in people with the genetic glitch, the string can be repeated thousands of times. Rothstein, who is also director of the Johns Hopkins Brain Science Institute and the Robert Packard Center for ALS Research, used his large bank of iPS cell lines from ALS patients to identify several with the C9ORF72 mutation, then experimented with them to figure out the mechanism by which the “repeats” were causing the brain cell death characteristic of ALS.

In a series of experiments, Rothstein says, they discovered that in iPS neurons with the mutation, the process of using the DNA blueprint to make RNA and then produce protein is disrupted. Normally, RNA-binding proteins facilitate the production of RNA. Instead, in the iPS neurons with the C9ORF72 mutation, the RNA made from the repeating GGGGCC strings was bunching up, gumming up the works by acting like flypaper and grabbing hold of the extremely important RNA binding proteins, including one known as ADARB2,  needed for the proper production of many other cellular RNAs. Overall, the C9ORF72 mutation made the cell produce abnormal amounts of many other normal RNAs and made the cells very sensitive to stress.

To counter this effect, the researchers developed a number of chemical compounds targeting the problem. This compound behaved like a coating that matches up to the GGGGCC repeats like velcro, keeping the flypaper-like repeats from attracting the bait, allowing the RNA-binding protein to properly do its job.

Rothstein says Isis Pharmaceuticals helped develop many of the studied compounds and, by working closely with the Johns Hopkins teams, could begin testing it in human ALS patients with the C9ORF72 mutation in the next several years. In collaboration with the National Institutes of Health, plans are already underway to begin to identify a group of patients with the C9ORF72 mutation for future research.

Rita Sattler, Ph.D., an assistant professor of neurology at Johns Hopkins and the co-investigator of the study, says without iPS technology, the team would have had a difficult time studying the C9ORF72 mutation. “Typically, researchers engineer rodents with mutations that mimic the human glitches they are trying to research and then study them,” she says. “But the nature of the multiple repeats made that nearly impossible.” The iPS cells did the job just as well or even better than an animal model, Sattler says, in part because the experiments could be done using human cells.

“An iPS cell line can be used effectively and rapidly to understand disease mechanisms and as a tool for therapy development,” Rothstein adds. “Now we need to see if our findings translate into a valuable treatment for humans.”

The researchers also analyzed brain tissue from people with the C9ORF72 mutation who died of ALS. They saw evidence of this bunching up and found that the many genes that were altered as a consequence of this mutation in the iPS cells were also abnormal in the brain tissue, thereby showing that iPS cells can be a faithful tool to study the human disease and discover effective therapies.

In the future, the scientists will look at cerebral spinal fluid from ALS patients with the C9ORF72 mutation, searching for proteins that were found both in the fluid and the iPS cells. These may pave the way to develop markers that can be studied by clinicians to see if the treatment is working once the drug therapy is moved to clinical trials.

ALS, sometimes known as Lou Gehrig’s disease, named for the Yankee baseball great who died from it, destroys nerve cells in the brain and spinal cord that control voluntary muscle movement. The nerve cells waste away or die, and can no longer send messages to muscles, eventually leading to muscle weakening, twitching and an inability to move the arms, legs and body. Onset is typically around age 50 and death often occurs within three to five years of diagnosis. Some 10 percent of cases are hereditary. There is no cure for ALS and there is only one FDA-approved drug treatment, which has just a small effect in slowing disease progression and increasing survival, Rothstein notes.

Pioneering adult stem cell trial approved by Japan.

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The first trial of stem cells produced from a patient’s own body has been approved by the Japanese government.

Stem cells can become any other part of the body – from nerve to bone to skin – and are touted as the future of medicine.

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Researchers in Japan will use the cells to attempt to treat a form of blindness – age-related macular degeneration.

The announcement was described as “a major step forward” for research in the field.

There are already trials taking place using stem cells taken from embryos. But this is ethically controversial and the cells will not match a patient’s own tissues, so there is a risk of rejection.

Induced pluripotent stem cells, however, are made by coaxing a sample of the patient’s skin to become stem cells, so there should be no risk of rejection.

Sight saving?

Japan’s health minister, Norihisa Tamura, has ruled that the cells can now be tested in patients.

The trial will by run by the Riken Center for Developmental Biology and the Institute of Biomedical Research and Innovation Hospital in Kobe.

Initially, six patients will receive transplants of cells to see if the procedure can restore their damaged vision.

Prof Chris Mason, an expert on regenerative medicine at University College London said: “This was expected, but it’s obviously a major step forward.

“They are beneficial for two main reasons. One, they are from the patients themselves so the chance of rejection is greatly reduced and there are the ethical considerations – they do not have the baggage which comes with embryonic stem cells.

“On the down side we are a decade behind on the science. Induced pluripotent stem cells were discovered much later, so we’re behind on the safety.”

In 2012, Prof Shinya Yamanaka shared the Nobel prize for medicine or physiology for his discovery that adult human tissue could be coaxed back into a stem cell state.

Source: BBC

Hans-Peter Kiem genetically manipulates stem cells to treat HIV, genetic diseases and cancers.

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Fred Hutch oncologist, stem cell and gene therapy researcher

Imagine if we could treat deadly diseases by generating healthier versions of the very building blocks of our bodies—blood stem cells. That’s the vision of Dr. Hans-Peter Kiem, whose Hutchinson Center laboratory is working to make such therapies a reality.

“Not long ago, this was science fiction,” he said.

Kiem’s cutting edge research reflects his longstanding interest in blood stem cell transplantation, now one of the standard treatments for many blood cancers, in which the patient receives an infusion of blood stem cells, either from a donor or from the patient’s own multiplied cells. The idea is that the new stem cells will grow into disease-free blood cells—a concept that Kiem’s research takes a step further.

“Stem cells can do everything,” said Kiem, who first came to the Hutchinson Center as a fellow in 1992 and joined the faculty five years later. “If we can correct defective stem cells, we can cure diseases.”

Kiem and his colleagues investigate how stem cells can be extracted from sick patients, manipulated at a genetic level and then delivered back to them to treat a range of diseases, from infections like HIV to genetic diseases to aggressive cancers.

One ongoing research effort confronts a major challenge in cancer treatment: Patients can receive only so much chemotherapy at a time, or else their blood cell counts may drop to a level that invites infections, anemia, excessive bleeding and other serious health complications. In such a scenario, the patient must stop receiving chemotherapy until the cell counts recover to healthy levels—but meanwhile, the cancer can worsen.

Kiem’s lab has developed a way to extract a patient’s blood stem cells and insert a special “resistance” gene that is designed to protect the cells from damage by common chemotherapy drugs such as temozolomide and BCNU. An infusion of these enhanced cells could give new hope to patients with the most aggressive form of brain cancer—glioblastoma—which is very difficult to treat. A small study for glioblastoma patients that Kiem started in fall 2009 is showing promising initial results and continuing to expand.

Kiem is also planning a study of patients with AIDS and lymphoma, who would receive blood stem cells with two inserted genes: one that counteracts the HIV infection and one that protects the patient from chemotherapy’s effects.

More recently Kiem has extended his work to derive blood stem cells from a new class of stem cells called induced pluripotent stem cells. What makes pluripotent stem cells promising for new treatments is that they can be derived from readily accessible adult tissues, such as skin cells, and can mature into many other types of tissues and cells, including blood stem cells. These blood stem cells could in turn be expanded and used for blood stem cell transplantations, offering a new treatment option for patients with defective marrow or immune function.

Kiem’s groundbreaking work led to his selection in 2009 as the recipient of the first José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. The award is named for internationally known tenor and leukemia survivor Carreras and Thomas, who developed bone marrow transplantation.

“Don Thomas was pursuing something that was at that time viewed as very difficult,” Kiem said. “It’s a bit of the same thing right now for gene therapy in stem cells. I hope that in 10 or 20 years it will be like what Don has achieved.”

Source: Fred Hutchinson Cancer Research Center

 

 

 

Stem-cell pioneer banks on future therapies.

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Japanese researcher plans cache of induced stem cells to supply clinical trials.

Progress toward stem-cell therapies has been frustratingly slow, delayed by research challenges, ethical and legal barriers and corporate jitters. Now, stem-cell pioneer Shinya Yamanaka of Kyoto University in Japan plans to jump-start the field by building up a bank of stem cells for therapeutic use. The bank would store dozens of lines of induced pluripotent stem (iPS) cells, putting Japan in an unfamiliar position: at the forefront of efforts to introduce a pioneering biomedical technology.

A long-held dream of Yamanaka’s, the iPS Cell Stock project received a boost last month, when a Japanese health-ministry committee decided to allow the creation of cell lines from the thousands of samples of fetal umbilical-cord blood held around the country. Yamanaka’s plan to store the cells for use in medicine is “a bold move”, says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. But some researchers question whether iPS cells are ready for the clinic.

Yamanaka was the first researcher to show, in 2006, that mature mouse skin cells could be prodded into reverting to stem cells1 capable of forming all bodily tissues. The experiment, which he repeated2 with human cells in 2007, could bypass ethical issues associated with stem cells derived from embryos, and the cells could be tailor-made to match each patient, thereby avoiding rejection by the immune system.

Japan is pumping tens of millions of dollars every year into eight long-term projects to translate iPS cell therapies to the clinic, including a US$2.5-million-per-year effort to relieve Parkinson’s disease at Kyoto University’s Center for iPS Cell Research and Application (CiRA), which Yamanaka directs. That programme is at least three years away from clinical trials. The first human clinical trials using iPS cells, an effort to repair diseased retinas, are planned for next year at the RIKEN Center for Developmental Biology in Kobe.

Those trials will not use cells from Yamanaka’s Stock. But if they or any other iPS cell trials succeed, demand for the cells will explode, creating a supply challenge. Deriving and testing iPS cells tailored to individual patients could take six months for each cell line and cost tens of thousands of dollars.

Yamanaka’s plan is to create, by 2020, a standard array of 75 iPS cell lines that are a good enough match to be tolerated by 80% of the population. To do that, Yamanaka needs to find donors who have two identical copies of each of three key genes that code for immune-related cell-surface proteins called human leukocyte antigens (HLAs). He calculates that he will have to sift through samples from some 64,000 people to find 75 suitable donors.

Using blood from Japan’s eight cord-blood banks will make that easier. The banks hold some 29,000 samples, all HLA-characterized, and Yamanaka is negotiating to gain access to those that prove unusable for other medical procedures. One issue remains unresolved: whether the banks need to seek further informed consent from donors, most of whom gave the blood under the understanding that it would be used for treating or studying leukaemia. Each bank will determine for itself whether further consent is needed.

Yamanaka has already built a cell-processing facility on the second floor of CiRA and is now applying for ethics approval from Kyoto University to create the stock. Takafumi Kimura, a CiRA biologist and head of the project’s HLA analysis unit, says that the team hopes to derive the first line, carrying a set of HLA proteins that matches that of 8% of Japan’s population, by next March.

Yamanaka’s project has an advantage in that genetic diversity in Japan is relatively low; elsewhere, therapeutic banks would have to be larger and costlier. Most iPS banks outside Japan specialize in cells from people with diseases, for use in research rather than treatment. The California Institute for Regenerative Medicine (CIRM) in San Francisco, for example, plans to bank some 3,000 cell lines for distribution to researchers.

Alan Trounson, president of CIRM, says that unresolved research questions about iPS cells make it “premature” to begin therapeutic trials. “We don’t have complete pictures of how good they would be,” he says, noting that such cells accumulate mutations and other defects as they are produced from differentiated cells. Irving Weissman, a stem-cell biologist at Stanford University in California, warns that iPS cells derived from blood cells have been shown to form tumours3.

Kimura says that the answer is to carefully avoid the white blood cells that cause tumours when deriving the cell lines, and he stresses that all safety concerns will be addressed. “We’re building a national resource. It has to be safe and have the confidence of the people.”

Daley, who last month toured CiRA’s facility, calls it “nothing short of spectacular, pristine, perfect”. He agrees that proving the safety of the cells will be tough, but he is enthusiastic about the effort. “It’s clear they’re readying themselves for a big project,” he says.

Source: Nature.