Category Archives: Science News

Does talcum powder cause ovarian cancer? Weighing up the human and animal studies

In this article, Justin Varholick, investigates the evidence on whether talcum powder can cause ovarian cancer. Over the years, several courts have ruled that talcum powder can cause ovarian cancer, while the scientific evidence suggests otherwise. In light of Ovarian Cancer Month, it is important to highlight how animal and human studies can improve our understanding of the disease, and prevent misinformation spread from the media. This article outlines that both animal and human studies are not perfect. Animal studies sometimes do not have proper controls and human studies suffer from bias. The current research suggests no direct link between talc and cancer, but more research is certainly necessary.

Ovarian cancer is a serious disease affecting around 22,000 women in the United States and contributing to around 14,000 deaths each year. Since the 1960s the American public has questioned whether the use of talcum powder – for soothing dry skin, absorbing sweat, and preventing chafing of the thighs — increases women’s’ risk for ovarian cancer. This speculation began after acknowledging the risks of asbestos and public theories that asbestos was in talc products; however, cosmetic grade talc undergoes strict quality control and does not contain asbestos.

Image by Austin Kirk

Multiple studies on rodents, non-human primates, and humans have investigated the link between talc and cancer since the 1960s. Overall the results are inconsistent; some studies suggest talc is associated with ovarian cancer while others suggest talc is not carcinogenic. Recently, despite these inconsistencies, a Los Angeles jury ordered Johnson & Johnson to pay $417 million to a woman who blamed her terminal ovarian cancer on the use of baby powder — this is just one of many lawsuits against Johnson & Johnson over their talc powder. In light of this recent event I would like to delve into the animal and human studies investigating the link between talcum powder and ovarian cancer.

Is talcum powder a carcinogen?

Empirical studies first began on rodents such as hamsters, rats, and mice; however, these studies only focused on whether talc was a carcinogen in general. Researchers chose rodents because it is relatively easy to systematically administer talc to rodents via inhalation. Furthermore, rodents — especially the laboratory rat — are particularly sensitive to forming malignant tumors in the lungs when exposed to chemicals via inhalation regardless of the chemical itself. Therefore, by using rodents there is an increased chance of detecting an effect of cancer following exposure to talc via inhalation — if one is present. It is important to note here that although humans are exposed to talc by inhalation or via topical application, the specific method of applying talc is not important when determining general carcinogenicity.

For one of the first studies investigating talc exposure and cancer in rodents, researchers first gathered information on how much baby powder human infants were regularly exposed to – although infants are usually exposed via topical application and rodents are exposed via inhalation. Using this information they designed an experiment using hamsters and exceeded the amount of talc human infants are normally exposed to by 30 to 1700 times — depending on the experimental treatment group. The scientists also formed a control group that was exposed to a negative dust control; titanium dioxide. This control is important because increased levels of dust in the air can lead to chronic inflammation of the lungs, which increases the risk of malignant tumors — independent of particle type (e.g. talc powder, titanium dioxide, toner, carbon black, etc.). Controlling for dust and exceeding levels of normal exposure, the study reported no difference between the groups in body weight, survival, or signs of cancer in the larynx, trachea, lungs, liver, kidney, stomach, uterus, ovaries, or testes of these hamsters.

Further studies were conducted on rodents — specifically mice and rats — that did find an effect linking cancer to talc; however, these studies were confounded. One study in particular found that female rats and mice exposed to high levels of talc via inhalation for 4 months had a higher risk of lung cancer. Unfortunately, this study did not use a titanium dioxide control group, thus the finding could be an artefact of chronic inflammation from air particles — as discussed above. Furthermore, this study was unable to identify another biological mechanism beyond chronic inflammation responsible for the onset of cancer.

In summary, these rodent studies allowed scientists to exceed normal exposure levels and use an animal with increased sensitivity to the treatment in question. However, proper control groups must be used to help elucidate whether the effect is an artefact. Importantly, these studies were only interested in whether talc is a possible carcinogen, not whether ovaries exposed to talc have increased risk of cancer specifically. Overall, these studies were unable to find a link between talc and risk of cancer, beyond chronic inflammation from increased levels of air particulates.

Can talcum powder be found in the ovaries?

Some studies in animals and humans have been particularly focused on finding a link between talc use and ovarian cancer — not just whether talc is a carcinogen. To understand the plausibility of this link, these studies first needed to establish whether it is possible for particles of talc to migrate into the genital tract after being applied topically to the perineal region (area between vagina/scrotum and anus). A simple understanding of biophysics led many to conclude that it was impossible for the particles to travel up the vagina, cross the cervix, travel through the uterus, and then “swim” upstream through the oviducts; without being assisted by some form of locomotion. Nonetheless, some studies using animals investigated whether it was a possibility. Specifically, one study using female cynomolgus monkeys (Macaca fascicularis) — an animal model anatomically and physiologically comparable to human female — investigated whether carbon black particles could reach the oviducts or ovaries. This study was unable to conclude that carbon black particles could indeed travel up to the oviducts or ovaries.

Image by Noveprim

Further studies were done with human females that applied talcum powder to their underwear or perineal region daily that also had ovarian or pelvic cancer; which required surgical removal of the ovaries.  After removing the ovaries, scientists used microscopy techniques to scan the ovaries and identified low numbers of particles that were relatively small in size in about 50–75% of cases (multiple studies). Thus, although talc can be found in or around ovarian tissue the amount found was considered too small to cause ovarian cancer. It has also been noted that findings from these studies were widely inconsistent and were confounded by women lying in a supine or Trendelenburg position — which may aid in the surgery of the pelvic region but is also used to aid in vitro fertilization.

Thus, studies in both animals and humans cannot definitively suggest talc can translocate from the perineal region to the ovaries, which may be necessary for the talc to affect the ovaries. Nonetheless, both animal and human studies have been limiting; studies with monkeys only used a particle similar to talc and human studies involved a lying position that aided in the migration of talc up the genital tract.

How many women using talcum powder get ovarian cancer?

Two types of human studies have investigated, and continue to investigate, the link between talc and ovarian cancer; case-control and cohort studies. The case-control studies gather a group of women diagnosed with ovarian cancer and a group of women with no ovarian cancer. They then ask all women to retrospectively discuss their use of talc on the genital area throughout their life — noting frequency and average amount. The obvious downside to this type of study is that it is open to reporting bias. Some women may forget when or how often they used talc, while others may overestimate their use and further bias may occur if there is an expectancy that talc may have contributed to the onset of ovarian cancer. In contrast, the cohort studies gather a group of women early in life and then have them report in real-time throughout their life how often they use multiple products — including products with talc. After several decades they then compare how many women are diagnosed with ovarian cancer and used talc products, diagnosed with ovarian cancer and did not use talc products, etc. Cohort studies, however, are often limiting because few women are actually diagnosed with ovarian cancer compared to those that are not.

A recent meta-analysis, published this year, gathered 24 case-control and 3 cohort studies investigating the use of talc on the perineal region and its relation to ovarian cancer. Gathering all of these studies into a single analysis, they found that talc powder use on the perineal region is associated with a small increased risk of developing ovarian cancer; however, case-control studies largely contributed to this association — which have obvious disadvantages as outlined above. This positive association was also limited to a single type of ovarian cancer; identified as serous carcinoma — the most common type of ovarian cancer (types of ovarian cancer). Importantly, if reporting bias is affecting the case-control studies, then the association between talc use and ovarian cancer should not be limited to a single type of ovarian cancer. The authors also note that publication bias may also be affecting the case-control studies, meaning that some hospitals may gather information about talc use and ovarian cancer but do not publish their findings because they do not find a link between the two.

In summary, studies with humans do suggest that there is a small positive association between talc use and ovarian cancer; however, these studies are largely limited to case-control studies which have disadvantages of reporting and publication biases. Furthermore, these studies can only tell us about the relative risk of ovarian cancer when using talc. They cannot tell us about the biological basis linking talcum powder use to cancer.

Talcum powder does not cause ovarian cancer

The current evidence from both animal and human studies does not suggest that talc can be directly linked to ovarian cancer. However, both animal and human studies are not perfect. Studies using animals sometimes lack important controls and are not able to properly investigate the specific question at hand without proper animal models (i.e. cynomolgus monkeys). However, animals can be utilized in investigating whether talc is a carcinogen in general because some are especially sensitive to different types of treatments. Studies with humans also have disadvantages due to limitations of subject pools and biases. Despite this, studies with humans somewhat consistently find a link between talc and ovarian cancer, thus humans may be particularly sensitive to talc beyond other animals — although this is highly unlikely given that studies on other mammals suggest no direct relationship.

Importantly, there are many more studies on animals and humans that investigate the link between talc and cancer that I did not include in this brief discussion. Therefore, it is important to note that in a recent review in 2015, the Cosmetic Ingredient Review Expert Panel reported that talc is safe to use in standard practices with normal concentrations. They also note that there is:

  • Absence of persuasive evidence that talc can migrate from the perineum to the ovaries
  • Lack of consistent statistically significant positive associations across studies
  • Failure to rule out plausible alternative explanations of statistically significant results, including biases, risk factors, and exposure to misclassifications
  • Absence of a plausible biological mechanism
  • Lack of credible, defensible evidence of carcinogenicity from results of epidemiological studies of occupational exposures and animal bioassays

Thus, more research is necessary to determine whether talc is linked to ovarian cancer, despite what the Los Angeles courts might say.

Justin Varholick

 

References

Berge, W., Mundt, K., Luu, H. and Boffetta, P. 2017. Genital use of talc and risk of ovarian cancer: a meta-analysis. European Journal of Cancer Prevention.

Fiume, M.M., Boyer, I., Bergfeld, W.F., Belsito, D.V., Hill, R.A., Klaassen, C.D., Liebler, D.C., Marks, J.G., Shank, R.C., Slaga, T.J., Snyder, P.W. and Andersen, F.A. 2015. Safety assessment of talc as used in cosmetics. International journal of toxicology 34(1 Suppl), p. 66S–129S.

Reid, B.M., Permuth, J.B. and Sellers, T.A. 2017. Epidemiology of ovarian cancer: a review. Cancer biology & medicine 14(1), pp. 9–32.

Wehner, A.P. 2002. Cosmetic talc should not be listed as a carcinogen: comments on NTP’s deliberations to list talc as a carcinogen. Regulatory Toxicology and Pharmacology 36(1), pp. 40–50.

Research with dogs develops an artificial pancreas to treat diabetes

White Coat Waste is a conservative animal rights organization devoted to the elimination of animal research. Its first target is biomedical research conducted using dogs at the US Department of Veterans Affairs (VA). Unfortunately, this campaign is gaining traction. While White Coat Waste is supported mainly by Republicans, some Democrat representatives like Dina Titus (Nevada) and Ted Lieu (California) have expressed their support. In view of that, it is important to highlight the remarkable achievements of dog research at the VA and the tremendous loss that its cancellation would be for Veterans and the general public. 

Diabetes is a nasty disease that affects millions of people worldwide and continues to increase. It is a metabolic disorder in which the body becomes incapable of controlling the blood levels of glucose, either because the pancreas fails to produce enough insulin (type 1) or because cells in the body fail to respond to insulin (type 2). Untreated, diabetes can lead to cardiovascular disease, stroke, kidney disease, neuropathic pain, gangrene of the extremities, amputations, blindness, and death. In 2014, 422 million people had diabetes worldwide (8.5% of the population). These numbers have more than tripled since 1980 (108 million; 4.7% of the population) and continue to increase due to poor dietary habits and lack of exercise. The annual number of deaths worldwide was estimated at 4.9 million in 2014. The incidence of diabetes is particularly high in the USA and other developed countries, but it is increasing fast in Asia and Africa. In the USA, diabetes has a high impact in Veterans: one in four patients receiving care at the US Department of Veterans Affairs (VA) has diabetes. This makes it a high priority for medical research at the VA.

People with serious cases of diabetes need multiple daily injections of insulin. Failure to administer the insulin appropriately can lead to kidney failure, amputations, blindness, coma, and even death. However, the dose of insulin has to be tuned to the needs of the body. To do this, patients measure the glucose level in their blood by drawing blood from their fingers using needle sticks. This has to be done several times a day in order to calculate and inject insulin according to the blood glucose levels. An artificial pancreas has been developed at the VA to help improve the outcomes for diabetic patients. This device measures glucose in the blood in real time and automatically administers the right dose of insulin. This technology will dramatically improve the patient’s quality of life and reduce life-threatening complications. It would also tremendously reduce diabetes-related healthcare costs.

The artificial pancreas uses a reconfigured smart phone as part of its system. Image by UVA

This research project was initiated decades ago by Dr. Seymour Levin, a VA endocrinologist who specialized in diabetes and was horrified by the large number of VA patients who needed amputations because of problems with properly administering insulin to treat their diabetes. He obtained funds from the Mann Foundation. In the early 1980s, the Mann Foundation created a company called MiniMed Technologies to design an insulin pump that patients could wear throughout the day. MiniMed Technologies used dogs at the VA diabetes laboratory to test prototypes of this pump. In the early 2000s the company was acquired by Medtronic, which has been fully supporting this research project ever since. No taxpayer money has been used for it, a detail that seems to be important for White Coat Waste.

Taking advantage of new computer technology, the device being developed incorporates not only an insulin pump but also a glucose sensor and software to calculate the amount of insulin to be injected into the blood according to the glucose level. This makes it a true artificial pancreas. Working with dogs allows researchers to do the pre-clinical testing of the artificial pancreas required for approval by the USA Food and Drug Administration (FDA) at the same time that the hardware and the software are refined and improved.

Why use dogs for this research project? Animals like mice, rats or guinea pigs are too small for the devices being tested and their blood volume is not large enough to allow for frequent blood sampling without causing them harm. On the other hand, dogs have been an important model for metabolic studies and can replicate human diabetes quite well (much early research into diabetes and insulin relied on research in dogs). They can also be used for long-term studies lasting years, which are not possible in rodents. The sensors and catheters implanted in the dogs are the same ones to be used in humans, and the dogs adapt very well to wearing them. Dogs also like interacting with humans and can be trained to go along with these painless procedures without needing to be anesthetized or restrained. Other large animals like pigs and sheep were tried and were found to be far less suitable than dogs for this work.

The standard procedure consists of having the dog rest on a soft bed, unrestrained. Glucose sensors are inserted under the skin and an insulin pump is attached via a subcutaneous catheter (similar to a human patient using these devices). The procedures are painless and the dog soon becomes habituated to them. The dog is given a small amount of glucose solution to raise its blood-glucose level in order to see how the experimental sensor, software, and pump respond. Blood samples are then tested on a large and expensive glucose analyzer to see how well the sensor is working.

The dogs in the VA diabetes research project are very well cared for, and the diabetic ones are maintained on insulin pumps. Pet dogs sometimes develop diabetes as they age. Just like humans, they develop cataracts, kidney problems and all the other complications of diabetes. Even when they are given insulin injections under a veterinarian’s care, they all die within 1-2 years. In contrast, the diabetic dogs in this research program are maintained free of symptoms by the insulin pumps and live at least a decade with no cataracts or other diabetes complications. Non-diabetic dogs are adopted out at the end of the study period whenever feasible.

dog, animal testing, animal experiment

Beagle in research

On September 28, 2016, the FDA approved the first artificial pancreas, the Medtronic’s MiniMed 670G System, intended to automatically monitor blood-glucose levels and adjust basal insulin doses in people with type 1 diabetes. The pre-clinical testing of this device was all done on dogs at the VA diabetes research laboratory. However, the research project is ongoing and much work remains to be done. If it is canceled due to political pressure from White Coat Waste, it would be a huge loss for Veterans and the millions of people worldwide who need more reliable ways to treat their diabetes.

Juan Carlos Marvizon, Ph.D.

References:

  1. Grosman B, Voskanyan G, Loutseiko M, Roy A, Mehta A, Kurtz N, Parikh N, Kaufman FR, Mastrototaro JJ, Keenan B. Model-based sensor-augmented pump therapy. J Diabetes Sci Technol. 2013 Mar 1;7(2):465-77.
  2. Loutseiko M, Voskanyan G, Keenan DB, Steil GM. Closed-loop insulin delivery utilizing pole placement to compensate for delays in subcutaneous insulin delivery. J Diabetes Sci Technol. 2011 Nov 1;5(6):1342-51.
  3. Panteleon AE, Loutseiko M, Steil GM, Rebrin K. Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system. Diabetes. 2006 Jul;55(7):1995-2000.

Research Roundup: Cholesterol vaccine in mice, zebrafish & osteoporosis, new cytomegalovirus treatment, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Human trials of cholesterol-lowering vaccine are underway after success in mice. This vaccination is designed to stop fatty deposits from clogging arteries — reducing the effects of a form of cardiovascular diseases known as atherosclerosis. This vaccination targets a protein called PCSK9 that allows low density lipoprotein (LDL; “bad cholesterol”) to accumulate in the arteries. In mice, this treatment reduced LDL levels up to 50% over 12 months. This vaccination provides promise of a simpler way “to target high cholesterol and ultimately reduce people’s risk of heart disease.” An editorial on this research was published in the European Heart Journal.

Blocked arteries impede blood flow. Source: Getty.

  • Zebrafish, genetics and osteoporosis. The zebrafish’s ability to regenerate body parts, including scales and fins, has led to their involvement in the study of bone physiology and repair, as well as the identification of treatments for human bone diseases. Researchers at the University of Malta are working with zebrafish as a model to investigate osteoporosis, specifically the genetic factors that may contribute to the disease.  Dr Melissa Marie Formosa, a researcher involved in the project ‘Genetics of Osteoporosis’, writes, “The ultimate aim of genetic research remains that of elucidating the best treatment options based on the person’s genetic make-up and predicting disease outcome in susceptible individuals.”

Healthy bone, left, and osteoporosis, right. Source here.

  • An alternative explanation for loss of consciousness during anaesthesia was published this week in PLOS Computational Biology. Scientists typically speculate that when animals and humans are given anaesthesia, communication between brain areas is disrupted thus leading to loss of consciousness. Although such speculations have been previously tested and suggested to be true, the logic behind such speculation is questionable. Specifically, communication only seems to decrease when less information is available to exchange, thus loss of information should “reduce” rather than “disrupt” communication between brain areas. With these thoughts in mind, German neuroscientists measured brain activity in two ferrets over 3 trials of anaesthesia and recovery — increasing the amount of anaesthesia each time. Their measurements suggested that the ferrets’ brain activity was more subdued when anesthetized, but it didn’t seem communication was disrupted. Rather, the brain areas that send communication signals were less active, and the brain areas that receive communication signals were just as active as normal. This brings into question our current understanding of the mechanisms behind anaesthesia, and will be a starting point for future research in this area.

Lab-housed ferrets. Source: NC3Rs.

Image of mice courtesy of Understanding Animal Research

  • Drug used to treat anxiety found to be effective against the effects of cytomegalovirus (human herpes 5), which can cause major birth defects such as microcephaly, seizures, developmental disabilities, and deafness. Approximately 50% of all humans over the age of 40 harbour the cytomegalovirus and approximately four in 1000 babies suffer massive defects as a consequence. Mice treated during the first three weeks of life with valnoctamide — a drug used in the treatment of anxiety — were found to have reduced levels of the virus available for entry to the brain, to have restored timely acquisition of neurological milestones, and to display rescued motor and behavioral outcomes. Given the pervasiveness of this virus and its debilitating effects, and also that there is no vaccine against this virus, this work is extremely timely and promising. This study was published the Journal of Neuroscience.

Cytomegalovirus (CMV) virus. Source: J. Cavallini.

Research Roundup: Monkeys and face recognition, animals advance AI, sugar to treat heart disease, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • New study challenges our current understanding of how the brain recognizes faces. We can often pick out a face or a person in a crowd (e.g., finding Wally/Waldo), but the cellular mechanism via which this occurs has remained poorly understood. Using rhesus macaques, these researchers investigated which neuronal cells are responsible for facial recognition. By varying aspects of the face systematically (e.g., shape, distance between the eyes) and measuring 205 neurons in 2 animals, researchers found that each neuron responded to a specific combination of facial parameters rather than the face itself, using fMRI. In other words “the neuron is not a face detector, it’s a face analyser”, says Leopold. The brain “is able to realize that there are key dimensions that allow one to say that this is Person A and this is Person B.” Subsequent replication and extension using more subjects is warranted, but these findings provide an exciting new avenue of research with regards to face processing. This research was published in the journal Cell.

    Macaque. Source: Kathy West. CNPRC.

  • Researchers are using animal cognition to make advances in artificial intelligence.  Harvard assistant professor David Cox and his team are studying the rat visual cortex by training rats to play a complex object discrimination video game. While the rats are learning the video game, a 2 photon excitation microscope images neural activity in the visual cortex. These images are then used in conjunction with microscopic images of brain tissue slices to make digital maps of of the visual cortex. The hope is that these neural circuits could become maps for artificial neural networks and next generation artificial intelligence. Check out this video on “How to Digitize a Rat Brain”!
  • Artificial intelligence system detects pain levels in sheep. Researchers at the University of Cambridge have developed an artificial intelligence (AI) system which uses five different facial expressions to recognize whether a sheep is in pain, and to estimate pain severity. Building on earlier work which teaches computers to recognize emotions and expressions in human faces, Dr. Krista McLennan developed the Sheep Pain Facial Expression Scale (SPFES) in 2016, which can recognize pain with high accuracy. In the current study, Dr. Peter Robinson and colleagues developed machine learning techniques to reduce the time required for humans to learn to use SPFES, as well as the confounds of human bias in interpreting facial expressions. Researchers trained the AI model with a small dataset of about 500 photographs of sheep, and early tests showed that the model could estimate pain levels with about 80% degree of accuracy, indicating the system is learning. The next steps for the researchers will be to train the system to detect and recognize sheep faces from moving images, and to train it to work when the sheep are in profile. Ultimately, this research will lead to better pain detection and faster medical attention. The research was presented June 1 at the IEEE International Conference on Automatic Face and Gesture Recognition in Washington, DC.

    Face detection in sheep. Source: Liu et al., 2017, University of Cambridge

  • Lifelong protection from allergies a possibility? When your body comes into contact with a foreign particle, for example, pollen, your immune system kicks into play, producing antibodies (Immunoglobulin E). These antibodies travel to these foreign cells, attempt to “neutralize” them and in this process – triggers an allergic reaction. In order to quickly identify and mount a response to foreign particles that your body has encountered before, the body uses “memory” T cells. However, in some cases, this “memory” may be an “overreaction” of the system and once this “memory” is formed it is virtually impossible to be removed. In the present study using
    mice
    , researchers tackled this issue and were able to desensitize these memory cells which overreact to allergens using therapeutic gene transfer. Approximately 50 million American suffer from some form of allergic disease and this research, which is in pre-clinical trials, provides some hope of treatment. This study was published in the journal JCI Insight.

  • Type of sugar may treat atherosclerosis, mouse study shows. Researchers at the Washington University School of Medicine in St. Louis worked with mice prone to atherosclerosis, clogged arteries due to the buildup of plaque, and found that when injecting trehalose, a natural sugar, the immune system “cleans up” this plaque.  Babak Razani, MD, PhD, an assistant professor of medicine, and his colleagues showed that trehalose activates TFEB, a molecule that then.goes into the nucleus of macrophages and binds to DNA. This turns on specific genes and leads to additional organelles that act as “housekeeping machinery.”  Babak says, “Trehalose is not just enhancing the housekeeping machinery that’s already there,” Razani said. “It’s triggering the cell to make new machinery..”  Trehalose is a mild sweetener and FDA approved for human consumption.  Plaque degradation is not seen when administered orally.  Researchers hope to study trehalose as a potential therapy for atherosclerosis in hopes to find a way to protect its  housekeeping properties when given orally.

    Cross section of mouse aorta with a large plaque. Source: Ismail Sergin

 

 

 

Last surviving member of Pittsburgh polio vaccine team dies at 96

Dr. Julius S. Youngner, the last surviving member of the team that developed the Salk polio vaccine in the 1950s, died in his home on April 27 at the age of 96.

Yougner - Image by University of Pittsburgh

Dr. Julius Youngner. Photo courtesy of University of Pittsburgh

Dr. Youngner, like many scientists, pursued a passion to help people via his love of the scientific method.  His own experiences as a child recovering from numerous infectious diseases, including severe pneumonia that almost killed him at age 7, inspired him to pursue a career in science — specifically, virology.

His interest in infectious disease led him to join Dr. Jonas Salk’s vaccine team at the University of Pittsburgh in the quest to fight polio. Polio crippled an average of 1,000 children every day in more than 125 countries during its peak.  The polio vaccine ended this serious illness that plagued the United States from the late 1800s to the mid-20th century.

Dr. Youngner made three critical advances in the polio vaccine research, much of which relied on research with animals. He first devised a way to break down monkey cells so the team could grow large quantities of poliovirus in the lab. He then developed a way to inactivate the virus so it could be safely injected as a vaccine, and finally, he developed tests to determine the vaccine’s effectiveness in the first human patients. The number of polio cases went from an average of 35,000 a year before the vaccine to fewer than 2,500 two years later. Today, polio is virtually eradicated in the United States and much of the world.

Since his polio work, Dr. Youngner made other major advances in virology and immunology, continuing to rely on animal models. Youngner was the first to demonstrate that non-viral agents could trigger interferon infection in animals, and his research team devised a novel approach to antiviral therapy. By demonstrating that the live, attenuated virus vaccine for influenza A interacts with wild-type influenza to confer protection, rather than inducing a protective immune response, Youngner and his team demonstrated that this type of vaccine, tested in animal models, has the potential for significantly reducing morbidity and mortality associated with influenza.

A comprehensive obituary of Dr. Youngner, including his work on the Manhattan Project and his feud with Dr. Jonas Salk, was published on April 28 by the Pittsburgh Post-Gazette.

Research Roundup: An artificial womb for preemie lambs, umbilical cord protein enhances cognition, smartphones to control diabetes, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • An artificial womb has successfully kept premature lambs alive. Extreme prematurity — infants born at 22 to 23 weeks gestation — is a leading cause of infant mortality, and infants who do survive often have serious disabilities like cerebral palsy or major cognitive deficits. Researchers at the Children’s Hospital of Pennsylvania have developed a first-of-its kind artificial womb that mimics the uterine environment, and have found in studies of lambs that this womb allows the premature lambs to grow normally inside the womb for 3-4 weeks. The thought is that treating the preemies more like fetuses than newborns by extending normal gestation may give them a better chance of survival. The artificial womb, pictured below, is a fluid-filled transparent container that simulates how fetuses float in amniotic fluid inside the mother’s uterus. The womb is attached to a mechanical placenta that keeps blood oxygenated for the fetus. Over the four weeks of study, the lamb fetuses grew to open their eyes, grow wool, breathe, and swim. Human trials are still several years away, though the research team is already in discussions with the Food and Drug Administration. The study was published in Nature Communications and is freely available for download.

  • New research finds that at least one third of all gut nerve cells are replaced weekly. The gut contains the second largest nervous system in the body, the enteric nervous system. Similarly to the number of viable eggs that a woman is born with, it was a once held scientific belief that the gut nerve cells we’re born with are the same ones that we die with. Using healthy adult you mice, and a variety of modern techniques, this study confirmed previous research findings of ongoing neuronal cell loss because of apoptosis (cell death) — although total neuronal numbers remain constant. This observed neuronal homeostasis was found to be maintained from dividing precursor cells that are located within myenteric ganglia. Mutation of these adult precursors led to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Since gut nerve cells were thought to remain unchanged across time, it has limited our understanding and treatment of diseases which affect the gut. These results “enable a new understanding of the pathogenesis of enteric neuromuscular diseases as well as the development of novel regenerative therapies.” This study was published in the Proceedings of the National Academy of Sciences.

  • A new study finds that protein found in human blood makes mice smarter. Previous research investigating the effects of young blood on aging animals has generally focused on within (same) species comparisons. In this study, researchers investigated the role of a human umbilical cord plasma and its effects on aged mice — in particular with respect to hippocampus and behavioral measures of cognition. These particular measures were investigated as impairment is observed in older individuals. They found that human plasma, injected in mice, was associated with revitalization of the hippocampus with increased levels of gene expression there. Additionally, they found that behavioral measures of cognition were also improved. The protein tissue inhibitor of metalloproteinases 2 (TIMP2), was found to be implicated with these positive changes. This study has been published in Nature.

    hippocampus

    Schematic of the hippocampus. Source.

  • The European Ombudsman rejected a complaint by the “Stop Vivisection” European Citizens Initiative that they had not received adequate reasoning behind the decision by the European Commission to reject the initiative in July 2015. “Stop Vivisection” wanted to repeal the European animal research regulation, Directive 2010/63/EU and replace it with a proposal to speed a ban on such practices. The ombudsman noted that the Commission has complied with its duty to explain, in a clear, comprehensible and detailed manner, its position and political choices regarding the objectives of the ECI “Stop Vivisection””.
  • A new study uses your smartphone to control symptoms of diabetes. In a good example of multi-disciplinary translational medicine, and using “a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology” researchers based at the Shanghai Key Laboratory of Regulatory Biology “engineered a technological infrastructure enabling smartphone-assisted semiautomatic treatment of diabetes in mice.” Hydrogel capsules, containing cells that could produce “mouse insulin” in vivo and which contained wirelessly powered infrared LEDs were implanted in mice. Smartphones were then used to control this implant causing it to secrete “mouse insulin” as needed. Researchers were able to maintain glucose homeostasis over several weeks in the diabetic mice. This study provides a step toward translating cell-based therapies into the clinic. It also highlights that even though this technique was developed in vitro, safety and efficacy trials in animals are needed before they can be used in humans. This study was published in the journal Science.
Apr27_2017_ShanghaiKeyLabOfRegulatoryBiology_DiabeticMouseSmartPhone2447847722.jpg

Photo courtesy of Shanghai Key Laboratory of Regulatory Biology