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BTI in the News

Tech Can Solve Stem Cell Sector’s Manufacturing Challenges, Genetic Engineering & Biotechnology
05-Jan-2021

Transplanted stem cells have been used as regenerative therapies for decades. But stem cells have wider therapeutic potential. Despite this potential, to date only one stem cell therapy—the ocular burns treatment Holoclar—has been approved by a major regulator. Manufacture is a major challenge that holds back the sector, according to Steve Oh, director of stem cell bioprocessing at Singapore’s Agency for Science, Technology and Research (A*STAR). To try and address the scalability issue Oh and colleagues developed a micro-carrier-based culturing process—in which the cells grow on the surface of beads in solution—to increase productivity. In addition, Oh notes, protein coatings such as laminin, vitronectin, and fibronectin can be added to the surfaces of the carriers to cater to different cell types. The approach also reduces manual steps, while reducing the overall costs of goods for biomanufacturing. The A*STAR technology was recently licensed to Singapore-based contract development and manufacturing organization (CDMO) SingCell, which is offering it as a service to cell therapy companies.

New Protocol Advances Toward Lab-Made Universal Red Blood Cells, The Scientist
17-Dec-2020

The COVID-19 pandemic has led to a steep drop in blood donations, leading blood centers in the US to raise the alarm about critical shortages, laying bare the fragility of the current blood supply. For years, scientists anticipating disruptions to the blood supply have been working on developing ways to produce blood in factories in order to provide an alternative source of the vital substance. In a study published on December 10 in Stem Cell Reports, Steve Oh, the director of the Stem Cell Bioprocessing group at the Agency for Science, Technology and Research (A*STAR) in Singapore, and his colleagues report a new method to generate large quantities of red blood cells (RBCs) from induced pluripotent stem cells (iPSCs), cells that have been reprogrammed from a differentiated state back to an embryonic-like state.

Blood test kit rolled out to detect gastric cancer early, The Sunday Times
25-Oct-2020

A blood test kit that can accurately detect gastric cancer in its early stages is being rolled out in local hospitals and evaluated for use in primary care settings such as polyclinics, said the National University Health System (NUHS) on Friday. The test kit, known as Gastroclear, is the first of its kind in the world. It has been progressively rolled out in public hospitals such as National University Hospital (NUH) and Tan Tock Seng Hospital, some private general practitioner clinics and specialist clinics for pre-screening of gastric cancer. The project to develop the new blood test began in 2012. The research team included clinicians and scientists from NUHS, the Bioprocessing Technology Institute (BTI) of the Agency for Science, Technology and Research (A*STAR), national platform Diagnostics Development (DxD) Hub, and MiRXES, a molecular diagnostic company which was spun off from A*STAR. The test takes around three hours to process in a clinical lab, and patients can expect results to be delivered to their doctor in a week.

Interview with Dr Kelvin Ng, Head, Strategic Innovation & Enterprise, Bioprocessing Technology Institute on cultured meat, Hao 96.3FM
02-Oct-2020

A*STAR's Dr Kelvin Ng was interviewed on the advanced technology used for producing cultured meat. Dr Ng is the head of Strategic Innovation & Enterprise at Bioprocessing Technology Institute. Dr Ng said the stem cells are extracted from animals and cultured in bioreactors, which undergo tissue engineering to make cultured meat. Dr Ng outlined the challenges for cultured meat in the market, including the quality and taste of meat, price of products, regulations, and food safety of the process. Dr Ng and his team help scientists to understand the needs of different industries and how technologies could be combined to achieve specific goals. Dr Ng said cultured meat is a very innovative product and it is crucial to foster consumers acceptance. As such, it is important to raise consumers' awareness on the benefits of cultured meat and for the industry to improve its price point, to make it affordable for all.

Digitalized Twin Model of the Workhorse, Genetic Engineering & Biotechnology News
30-Jun-2020

In the biotherapeutic industry, many experts would agree that Chinese hamster ovary (CHO) cells are the workhorse. “CHO cells are the preferred choice because of their human-like post-translational modifications that are more compatible with humans and are less immunogenic than other host cells,” says Dong-Yup Lee, PhD, associate professor in the School of Chemical Engineering at Sungkyunkwan University in the Republic of Korea. “Therefore, almost all biopharma companies use CHO cells to produce biotherapeutics, such as recombinant proteins and monoclonal antibodies, and thus have made significant progress in improving the performance of CHO cells and their cultures via cell-line and process development.”

Biosana and A*STAR in continuous bioprocessing laboratory project, Bio Pharma
10-Dec-2019

BiosanaPharma and A*STAR’s Bioprocess Technology Institute (BTI) announced a research collaboration to set up a laboratory in Biopolis following the incorporation of a local entity by Biosana. According to Biosana, the collaboration aims to address the current challenges of diverse product pipelines, as well as rising competition due to the development of biosimilars, which lead companies to need highly flexible and cost-effective manufacturing.

Bioelectricity's promise for therapeutic targets in cancer, Phys Org
9-Oct-2019

Bioelectricity of Cancer, a special issue of the peer-reviewed journal Bioelectricity, has just been published. A study by the Lee Kong Chian School of Medicine, the Nanyang Technological University, the Agency for Science Technology and Research (A*STAR), and the University of California, titled "Extracellular K+ Dampens T-Cell Functions: Implications for Immune Suppression in the Tumor Microenvironment”, was also published in the journal. This study demonstrated that the high K+, taken up by the anti-tumor T-cells (lymphocytes), significantly inhibited their proliferation as well as their production of cytokines whilst up-regulating the expression of the immune checkpoint protein PD-1.

Blood test for stomach cancer first step to ending all cancer deaths by 2048, says its Singapore-based co-inventor, Business Insider India
19-Sep-2019

MiRXES, a biotech company behind the GastroClear test, aims to boost patients’ prognosis for survival while reducing the health care burden of treating the disease. Company co-founders, Dr Zhou Lihan, Too Heng-Phon and Dr Zou Ruiyang, developed technology that could accurately detect microRNAs – ribonucleic acids found in plant and animal cells. The three were previously working in A*STAR and started their company in 2014. 

Blood test for stomach cancer first step to ending all cancer deaths by 2048, says its Singapore-based co-inventor, South China Morning Post Online
18-Sep-2019

MiRXES, a biotech company behind the GastroClear test, aims to boost patients’ prognosis for survival while reducing the health care burden of treating the disease. Company co-founders, Dr Zhou Lihan, Too Heng-Phon and Dr Zou Ruiyang, developed technology that could accurately detect microRNAs – ribonucleic acids found in plant and animal cells. The three were previously working in A*STAR and started their company in 2014.

How consumers' food preferences are changing, CNBC
16-Aug-2019

CNBC's Oriel Morrison speaks to scientists and restaurant owners about the future of food and the business opportunities that lie ahead. Concerns over climate change and animal welfare are driving companies to explore alternatives to meat production such as cultured meat or plant-based products. The Agency for Science Technology and Research (A*STAR) is running trials on producing cleaner meat with a low carbon footprint, without the need to kill animals. Dr Kelvin Ng from A*STAR’s Bioprocessing Technology Institute (BTI) shared that once this concept reaches consumers’ minds, scientists can educate the public on why producing cultured meat is a different version of producing cells in the body. It is a more controlled version of producing meat with very similar nutritional benefits.

Frontline: Interview with Prof Lam Kong Peng, ED of BTI on cultured meat, Channel 8
31-May-2019

More than 50 F&B businesses are selling plant-based meat burgers from Impossible Foods since its venture into the Singapore market in March. In addition to plant-based meat, there are institutions here, such as A*STAR’s Bioprocessing Technology Institute, researching on cultured meat from animal cells. Professor Lam Kong Peng, Executive Director of BTI said cultured meat would be cleaner, have relatively stable nutrients, and have more customisable flavours. He expects cultured chicken meat is expected to be available in two to three years’ time.

Study finds new way to starve cancer cells, The Straits Times
29-May-2019

Researchers from A*STAR and the National Cancer Centre Singapore (NCCS) discovered that cancer stem cells can use an amino acid called methionine as fuel and are especially dependent on it. The team found that starving lung cancer cells of methionine for 48 hours resulted in a “dramatic” 94 per cent reduction in tumour size compared with a control sample. Dr Tam Wai Leong, Group Leader for Precision Oncology at the Genome Institute of Singapore under A*STAR, said that it may be possible to prevent the cancer stem cells from using methionine by inhibiting an enzyme called MAT2A, and that it will be important for clinicians to select patients who are most likely to benefit from such a drug. The study also involved researchers from A*STAR’s Bioprocessing Technology Institute (BTI) and the team is working on developing a drug for clinical trials that inhibits MAT2A. 

European Medicines Agency grants Marketing Authorisation Application for Prestige BioPharma's Herceptin biosimilar, BioSpectrum Asia
29-May-2019

The Marketing Authorisation Application (MAA) for Prestige BioPharma's trastuzumab (Herceptin) biosimilar ̶ Tuznue/HD201 ̶ has been accepted for review by the European Medicines Agency (EMA). This brings Prestige's lead development candidate one step closer to being indicated for the treatment of adult patients with HER2-overexpressing breast, gastric, and gastroesophageal cancers. This review would put Tuznue in the race along with other biosimilars to seize the EU market, which is currently dominated by Herceptin. This acceptance was also recently boosted by the announcement of positive top-line results from a Phase III global clinical trial (Troika) of Tuznue, demonstrating its exceptional similarity to Herceptin in terms of clinical response, pharmacokinetics, and safety profile. Prestige BioPharma is a Singapore-based biopharmaceutical company focusing on the development of biosimilars and new antibody therapeutics. Its R&D laboratory is situated in the Bioprocessing Technology Institute (BTI), A*STAR.

How Bacteria Influence Host Immunity, Science & Technology Research News
28-May-2019

Researchers from A*STAR’s Institute of Molecular and Cell Biology (IMCB), Bioprocessing Technology Institute (BTI) and Singapore Immunology Network (SIgN) in collaboration with colleagues in China and Netherlands have sought to understand the influence that bacteria exert on the overall, or systemic, immune response of the body. They homed in on the molecule peptidoglycan (PGN), a major component of the bacterial cell wall. They observed that microbiota-colonised mice had significantly higher PGN levels compared to antibiotic-treated and germ-free mice.

Local researchers found the source of nutrients for cancer cells, Lianhe Zaobao
27-May-2019

我国跨机构科研人员成功破解癌症“始作俑者”的营养来源，日后若研发出能阻断癌细胞如何“消化”这个营养的新药，有望对付目前传统化疗无法治愈的癌症。 找出这个对抗癌症关键环节的是一组来自新加坡科技研究局属下两个研究院－－新加坡基因研究院和生物处理科技研究院的科研人员，以及来自新加坡国立癌症中心的肿瘤学家。

A Nutrition Pathway to Stamp out the Start of Cancer, Bio Spectrum
27-May-2019

In a landmark study, scientists at the Agency of Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS), Bioprocessing Technology Institute (BTI) and oncologists at the National Cancer Centre Singapore (NCCC), have discovered that cancer stem cells, the founder cells of a tumour, have unique nutrient requirements. Unlike the rest of the tumour cells, cancer stem cells are addicted to a type of dietary amino acid -methionine- which is linked to its ability to form a tumour. The breakthrough innovation was announced by Dr Daniel S.W. Tan, Senior Clinician-Scientist, GIS and Dr Tam Wai Leong, Group leader, Precision Oncology, GIS on 27th May 2019 at A*STAR in Singapore.

Interview with Prof Lam Kong Peng, Executive Director of BTI on cultured meat, Channel 8
14-May-2019

Professor Lam Kong Peng, Executive Director of A*STAR’s Bioprocessing Technology Institute (BTI) shared about the process of culturing meat, which will be grown in large scale bioreactors. Regarding the nutritional value and safety of cultured meat, he said that meat cells should provide the same nutritional content as conventional meat and to ensure healthy cell growth, the bioreactor must be monitored stringently for contamination. BTI started culturing chicken cells due to the availability of chicken farms in Singapore and their next goal will be beef, pork, duck and seafood. 

Journey of local seafood from lab to farm to table, The Sunday Times
12-May-2019

Singapore is taking various steps in order to become more self-sufficient in food production. For instance, A*STAR's Bioprocessing Technology Institute (BTI) has started trials on culturing meat, which will be grown on a large scale in bioreactors. Three technical groups comprising 10 scientists each have been formed to look at feed nutrition, disease and husbandry, as well as genetics and breeding.

From lab to table, The Edge Singapore
6-May-2019

Singapore is set to accelerate the growth of cultured meat research, led by the Agency for Science, Technology and Research (A*STAR) and its three-decade expertise in bioprocessing technology. Dr Kelvin Ng, head of strategic innovation at A*STAR’s Bioprocessing Technology Institute (BTI) shared that the proponents of these meat-replacement products assert that the alternatives are even better than the original. For one, lab-grown meats are just like genuine meat since they are grown from stem cells and A*STAR is researching alternatives to pharmaceutical-grade nutrient mixes amid the advances in global technology. 

Singapore increases efforts in producing food, Berita Minggu
21-Apr-2019

As a small country with limited land area, Singapore needs to depend on a variety of foreign sources for its food supply. In fact, the country imports more than 90 percent of its food supplies from abroad. According to statistics from the Food and Agriculture Authority (AVA), only 9 percent of fish eaten in Singapore last year was produced in local livestock. In addition, A*STAR's Bioprocess Technology Institute (BTI) is utilising technology in bio-producers and bio-engineering to produce meat in the lab. 

Lab-grown and plant-based meat can help us move towards a more sustainable food system, TODAY Online
18-Apr-2019

With the March launch of Impossible Foods’ plant-based meat in Singapore and this month’s announcement of S$144 million research funding in food innovation under the Government's Research, Innovation and Enterprise 2020 plan, Singapore has further established itself as a leader in shaping the food system of the future. This new research plan includes funding for cell-based meat, also known as clean meat, and is in line with Singapore’s previous investments in alternative proteins. Meanwhile, Dr Kelvin Ng, head of strategic innovation at A*STAR’s Bioprocessing Technology Institute (BTI) which has started trials on producing clean meat, had told Straits Times in a recent interview that clean meat will be cost-competitive with grass-fed meats within the next three to five years, compete with all meat products in about a decade, and eventually become less expensive than conventionally-produced meats. 

Singapore backs lab-grown meat under billion dollar innovation programme, Berita Harian Online
29-Mar-2019

Cultured meat is a key protein alternative of the future and could be making its way to dinner plates here, as Singapore ramps up production of home-grown food. To make meat, stem cells extracted from chickens, cows, fish and pigs will be grown and multiplied in bioreactors, and eventually undergo tissue engineering to make whole meat cuts, say researchers. Singapore's Bioprocessing Technology Institute (BTI) has already started trials on culturing meat, which will be grown in bioreactors. Cells will comprise most of the culture meat, with bulking agents making up the rest. However, its nutritional value will be similar to traditional meat, according to Dr Kelvin Ng, the head of strategic innovation at BTI. 

Singapore backs lab-grown meat under billion dollar innovation programme, Just-Food
29-Mar-2019

Cultured meat is a key protein alternative of the future and could be making its way to dinner plates here, as Singapore ramps up production of home-grown food. To make meat, stem cells extracted from chickens, cows, fish and pigs will be grown and multiplied in bioreactors, and eventually undergo tissue engineering to make whole meat cuts, say researchers. Singapore's Bioprocessing Technology Institute (BTI) has already started trials on culturing meat, which will be grown in bioreactors. Cells will comprise most of the culture meat, with bulking agents making up the rest. However, its nutritional value will be similar to traditional meat, according to Dr Kelvin Ng, the head of strategic innovation at BTI. 

Lab-grown meat getting boost from Government, The New Paper Online
28-Mar-2019

Lab-grown meat is a key protein alternative of the future and could be making its way to dinner plates here, as Singapore ramps up production of home-grown food. The effort is getting a boost from the Government's Research, Innovation and Enterprise 2020 plan, under which $144 million is going into food-related research, including sustainable urban food production, future foods and food safety science and innovation. To make meat, stem cells extracted from chickens, cows, fish and pigs will be grown and multiplied in bioreactors, and eventually undergo tissue engineering to make whole meat cuts, said researchers. 

Using live chicken cells to cultivate chicken meat food products, Lianhe Wanbao
28-Mar-2019

Cultured meat is a key protein alternative of the future and could be making its way to dinner plates here, as Singapore ramps up production of home-grown food. To make meat, stem cells extracted from chickens, cows, fish and pigs will be grown and multiplied in bioreactors, and eventually undergo tissue engineering to make whole meat cuts, say researchers. Leveraging its existing technology in bioproduction and stem cell bioengineering, A*STAR's Bioprocessing Technology Institute (BTI) has started trials on culturing meat, which will be grown in large scale bioreactors. Eventually, for both cultured meat cuts and minced meat, the cells will comprise only 20 to 50 per cent of the meat, but its nutritional value will be similar to that of traditional meat, said Dr Kelvin Ng, Head of Strategic Innovation at BTI. 

Beefing up efforts to grow meat in labs, The Straits Times
28-Mar-2019

Cultured meat is a key protein alternative of the future and could be making its way to dinner plates here, as Singapore ramps up production of home-grown food. The effort is getting a boost from the Government's Research, Innovation and Enterprise 2020 plan, under which $144 million is going into food-related research, including sustainable urban food production, future foods and food safety science and innovation. To make meat, stem cells extracted from chickens, cows, fish and pigs will be grown and multiplied in bioreactors, and eventually undergo tissue engineering to make whole meat cuts, say A*STAR researchers. 

Tapeworm Drug Could Be an Effective Treatment for Certain Cancers, Bio Space
19-Feb-2019

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have discovered that niclosamide, an FDA-approved anti-parasitic drug, can effectively kill p53-defective cancer cells, potentially increasing the specificity for cancer targeting and sparing normal cells that carry wildtype p53. The p53 gene is a tumour suppressor gene that inhibits the growth of tumours, and if this gene is mutated, cancer cells are able to thrive. Working in collaboration with researchers from A*STAR’s Bioprocessing Technology Institute (BTI) and p53 Laboratory, the Skin Research Institute of Singapore, Duke-NUS Medical School, the Cancer Science Institute of Singapore, KK Women’s and Children’s Hospital, National Cancer Centre Singapore, and National University of Singapore, the IMCB research team found that niclosamide, a drug conventionally used in the treatment of intestinal tapeworm infections, induces metabolic stress in colon cancer cells without p53, thereby effectively causing death of these cancer cells.

Singapore researchers reveal role of anti-parasitic drug in treating cancer, Bio Spectrum
15-Feb-2019

Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have discovered that niclosamide, an FDA-approved anti-parasitic drug, can effectively kill p53-defective cancer cells, potentially increasing the specificity for cancer targeting and sparing normal cells that carry wildtype p53. The p53 gene is a tumour suppressor gene that inhibits the growth of tumours, and if this gene is mutated, cancer cells are able to thrive. Working in collaboration with researchers from A*STAR’s Bioprocessing Technology Institute (BTI) and p53 Laboratory, the Skin Research Institute of Singapore, Duke-NUS Medical School, the Cancer Science Institute of Singapore, KK Women’s and Children’s Hospital, National Cancer Centre Singapore, and National University of Singapore, the IMCB research team found that niclosamide, a drug conventionally used in the treatment of intestinal tapeworm infections, induces metabolic stress in colon cancer cells without p53, thereby effectively causing death of these cancer cells.

Esco Aster, A*STAR to advance BioProcessing technologies for cell and gene therapies, Bio Spectrum Asia
30-Jan-2019

Esco Aster, a contract development and manufacturing organisation (CDMO) of Esco Group, has announced the official opening of the BTI–ESCO ASTER Centre of Excellence in Bioprocessing in Biopolis, Singapore. The company has entered into an agreement with A*STAR’s Bioprocessing Technology Institute (BTI) to adopt an Industry 4.0 integrated bioprocessing platform. This COE marks a significant milestone to advance the development of safe and effective cell and gene therapies. Prof. Lam Kong-Peng, Executive Director of A*STAR’s Bioprocessing Technology Institute (BTI) said that BTI is pleased to be a partner in setting up this Centre of Excellence. It will leverage BTI’s expertise in bioprocessing science and engineering and affirms our commitment to work with local enterprises to develop innovative biomanufacturing solutions and meet the demands of the high-value cell and gene therapy space. 

Esco Aster and A*STAR’S Bioprocessing Technology Institute to Advance Bioprocessing Technologies for Cell and Gene Therapies
24-Jan-2019

Esco Aster, a contract development and manufacturing organisation (CDMO) of Esco Group, today announced the official opening of the BTI–ESCO ASTER Centre of Excellence in Bioprocessing in Biopolis, Singapore. The company has entered into an agreement with A*STAR’s Bioprocessing Technology Institute (BTI) to adopt an Industry 4.0 integrated bioprocessing platform.

New Stem Cell Antibody Targets Cancer, Science & Technology Research News
21-Jan-2019

Researchers from A*STAR’s Bioprocessing Technology Institute (BTI) have developed an antibody that targets and is taken up only by certain types of cancer cells. Combining this antibody with an anticancer drug could lead to a new treatment for some types of breast and ovarian cancers. The team wanted to develop monoclonal antibodies that could specifically target and kill cancer cells through one of a variety of potential mechanisms. Pluripotent stem cells and many cancer cells share some of the same proteins, called oncofetal antigens, on their surfaces. They utilised this to develop monoclonal antibodies by injecting human embryonic stem cells (hESCs) into mice, spurring their immune system into producing antibodies.

Making Heart Tissue ‘Beat’, Science & Technology Research News
21-Jan-2019

Researchers from A*STAR’s Bioprocessing Technology Institute (BTI) have shown that the key to efficient cardiac cell production lies in syncing the induction of differentiation with the cell cycle of the starting pluripotent material. Although a widely used protocol for making heart muscle seems to work better with some stem cell lines than others, the team found this same standard method can be made to work with all stem cells with high efficiency if the cells are first cultured at optimal densities and stages of the cell cycle ahead of cardiac induction.

Antibody that targets a protein on the surface of stem cells also targets same protein on cancer cells, Medical Xpress
15-Jan-2019

Researchers from A*STAR’s Bioprocessing Technology Institute (BTI) have developed an antibody that targets and is taken up only by certain types of cancer cells. Combining this antibody with an anticancer drug could lead to a new treatment for some types of breast and ovarian cancers. The team wanted to develop monoclonal antibodies that could specifically target and kill cancer cells through one of a variety of potential mechanisms. Pluripotent stem cells and many cancer cells share some of the same proteins, called oncofetal antigens, on their surfaces. They utilised this to develop monoclonal antibodies by injecting human embryonic stem cells (hESCs) into mice, spurring their immune system into producing antibodies.

Researchers report key to efficient production of heart muscle from pluripotent stem cells, Medical Xpress
15-Jan-2019

Researchers from A*STAR’s Bioprocessing Technology Institute (BTI) have shown that the key to efficient cardiac cell production lies in syncing the induction of differentiation with the cell cycle of the starting pluripotent material. Although a widely used protocol for making heart muscle seems to work better with some stem cell lines than others, the team found this same standard method can be made to work with all stem cells with high efficiency if the cells are first cultured at optimal densities and stages of the cell cycle ahead of cardiac induction.

Unlocking New Antibiotics, Science & Technology Research News
3-Jan-2019

A*STAR researchers from ICES, BTI, MERL and MEL have unearthed a new antibiotic, auroramycin, from a silent biosynthetic gene cluster discovered in the S. roseosporus genome, and believe there are many more just waiting to be found. Dr Yee Hwee Lim from ICES said that this strain of bacteria is very well studied and it was interesting that, even after so many molecules have been discovered, they now have a new antibiotic simply because they had the tools to access it. The team used CRISPR-Cas9 to introduce a potent gene transcription activator - the kasO* promoter - into the bacterial genome to activate expression of an entire cryptic biosynthetic gene cluster. The gene cluster was found to encode auroramycin, an antibiotic with potent antibacterial activity against Gram-positive bacteria, including MRSA and vancomycin-resistant Enterococcus faecalis (VRE).

Uncapping a New Therapy, Science & Technology Research News
3-Jan-2019

Scientists from A*STAR have found that switching off the enzyme that adds protective caps to chromosome ends could help fight many types of cancer. The team from GIS, IMB, IMCB and BTI demonstrated the treatment's potential by using it to thwart tumour growth in mice. The team found that a master regulator of development, HOXC5, and the microRNA mir-615-3p, which is nested inside the HOXC5 gene, act together to suppress telomerase through these distant switches. Further study showed that the switches are present in many long-lived mammals, including humans and chimpanzees, but not in short-lived mammals, like mice and rats, as an extra barrier against the increased tumour risk that accompanies a longer lifespan.