Category Archives: Science News

Stem cell therapy allows blind to see again, thanks to animal research

A team of scientists led by stem cell pioneer Professor Robert Lanza has reported today in the Lancet (1) the first evidence for the long-term safety of  retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) in patients who took part in a trial undertaken in four centres in the US. substantial improvements in vision were also recorded in almost half the treated patients, compared to no improvement in untreated patients.

This is the first time that clinical benefits have been demonstrated in the medium to long term in patients with any disese treated with hESC-derived cells, and is a major milestone in the development of the field of regenerative medicine. It’s an achievement that is due to many years of animal research.

Image:UCL/PA

Image:UCL/PA

The trial focused on 18 patients with two different types of macular degeneration,  Stargardt’s macular dystrophy and nine with dry atrophic age-related macular degeneration, that are common causes of blindness in adults and children and for which no effective treatments are currently available.

Nine patients with Stargardt’s macular dystrophy and nine with dry atrophic age-related macular degeneration received injections of 50,000 to 150,000 RPE cells behind the retina of their worst-affected eye. Robert Lanza, adjunct Professor at the Institute for Regenerative Medicine, Wake Forest University School of Medicine and Chief Scientific Officer at Advanced Cell Technology who funded the trial, describes the results:

The vision of most patients improved after transplantation of the cells. Overall, the vision of the patients improved by about three lines on the standard visual acuity chart, whereas the untreated fellow eyes did not show similar improvements in visual acuity. The patients also reported notable improvements in their general and peripheral vision, as well as in near and distance activities”

Professor Steven Shwartz, who led the team at the Jules Stein Eye Institute that took part in this trial, noted how important this result is to both the patients in this trial and the field of hESC-derived stem cell medicine.

Our results suggest the safety and promise of hESCs to alter progressive vision loss in people with degenerative diseases and mark an exciting step towards using hESC-derived stem cells as a safe source of cells for the treatment of various medical disorders requiring tissue repair or replacement,

You can listen to interviews with Steven Schwartz and several of the participants in this clinical trial in an NPR broadcast here.

In 2011 we discussed the launch of trials of these hESC-derived RPE cells, including some of those whose results are reported today,  at Moorfields Eye Hospital in London and the Jules Stein Eye Institute at UCLA. A paper published in the Journal Stem Cells in 2009 showed how studies in rodent models retinal degerneration paved the way for these trials by demonstrating that RPE cells derived from hESCs were safe and could restore vision:

Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases.”

This work – and earlier studies of RPE cells derived from ESCs – built on decades of basic stem cell research, starting with the pioneering work of Gail Martin, Matthew Kaufman and Martin Evans in mice, and the subsequent derivation of ESCs in macaques and then humans by James Thompson and colleagues at the university of Wisconsin- Madison.

Laboratory Mice are the most common species used in research

The humble mouse has played a key role in the development of stem cell medicine.

Today’s announcement is a major milestone in regenerative medicine, and one that id justifiably being celebrated, but we should also remember the many years of careful research that has led up to this moment. As with many medical advances much of the early research on embryonic stem cells was undertaken without any immediate clinical application in mind, but it nevertheless created the knowledge that is now driving an important emerging field of medicine. This is a lesson we need to remember when we donate to charities, when we discuss the importance of research with others, and most of all when we go to the ballot box!

Paul Browne

1) Schwartz SD et al. “Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies” Lancet published onlin3 15 October 2014. Link.

2) Lu B et al. “Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration.”
Stem Cells. 2009 Sep;27(9):2126-35. doi: 10.1002/stem.149.

Nobel Prizewinner John O’Keefe warns of threat to science from overly restrictive animal research and immigration rules

In an interview with the BBC yesterday 2014 Nobel laureate  John O Keefe has warned of the dangers posed by regulations that restrict animal research and the free movement of scientists across borders.

“It is an incontrovertible fact that if we want to make progress in basic areas of medicine and biology we are going to have to use animals.

“There is a worry that the whole regulatory system might begin to be too difficult, it might be constrictive.”

Professof John O'Keefe, 2014 Nobel Laureate in Medicine or Physiology. Image: David Bishop, UCL.

Professof John O’Keefe, 2014 Nobel Laureate in Medicine or Physiology. Image: David Bishop, UCL.

His concerns are well founded. Our post yesterday discussed the key role of recordings of single neuron activity in rats to the discoveries made by John O’Keefe, May-Britt Moser and Edvard Moser. The post also discusses two other advances made through basic research in animals whose impact in medicine has been recognized by awards, deep brain stimulation in Parkinson’s disease, and infant massage in preterm babies. Nevertheless in many countries around the world there is increasing pressure from animal rights groups on politicians to restrict, and even ban, animal research. Scientists have a key role to play in ensuring that important basic and translational research, and we welcome John O’Keefe’s statement,  it’s an example that scientists around the world should follow.

The issue of immigration is another important one for science, and John O’Keefe knows this better than most. Born in New York, he completed his PhD at the University on Montreal under the supervision of renowned Psychologist Ronald Melzack, before moving to the UK to undertake a postdoctoral fellowship, and credits the research environment in the UK and at UCL for giving him the opportunity to make his discoveries, and later May-Britt and Edvard Moser spent time as postdoctoral researchers at his laboratory.  For science to flourish scientists must be free to travel to centres of excellence in other countries, to learn skills and establish collaborations that are key to success in many fields of research in the 21st century. This freedom is under threat from narrow-minded isolationism in many countries, for example earlier this year Switzerland found its position as a leading scientific nation undermined by a new immigration law that threatens its ability to recruit talented scientists from abroad, and has disrupted its participation in a key EU research programmes.

John O’Keefe’s warning is a reminder that the threats to scientific research can come from many directions, and of the need for supporters of science to be ready to take action to defend the freedoms on which science is built.

Speaking of Research

Nobel Prize 2014: Fortune favours the prepared mind

Speaking of Research congratulates John O’Keefe, May-Britt Moser and Edvard I. Moser on being awarded the 2014 Nobel Prize in Physiology or Medicine “for their discoveries of cells that constitute a positioning system in the brain”.

Noble_med_medal_intro

By recording the activity of individual nerve cells within the brains of rats that were moving freely through their environment, they have shown how specialised nerve cells work together to execute higher cognitive processes.

In 1971 John O’Keefe identified the first component of the system, by identifying cells in the hippocampus that were only activated when a rat was in a certain position in its environment. These cells were activated when the rat visited the same location, but different nerve cells were activated when the rat visited a new location, these “place cells” were not merely registering visual input, but were building up an inner map of the environment. John O’Keefe is now a professor at University College London, where he studies the neural basis of cognition and memory in humans and animals.

Professor John O'Keefe UCL Institute of Cognitive Neuroscience. Image: David bishop, UCL

Professor John O’Keefe, UCL Institute of Cognitive Neuroscience. Image: David Bishop, UCL

In 2005 May-Britt Moser and Edvard I. Moser identified a second part of the system, a group of nerve cells in the an area of the brain adjacent to the hippocampus named the entorhinal cortex which were activated when a rat passed multiple locations arranged in a hexagonal grid. Each of these “grid cells” was activated in a unique spatial pattern and together they allow the rat form mental representation of a coordinate system that allows the rat to navigate through space. If you would like to learn more about their work at the Norwegian University of Science and Technology in Trondheim, Alison Abbott has written an excellent article in Nature News on the studies that led to the discovery of grid cells and their ongoing research in this field.

May-Britt Moser, Edvard Moser, and the rats that they use in their groundbreaking neuroscience research. Image Geir Mogan/ NTNU

May-Britt Moser, Edvard Moser, and the rats that they use in their groundbreaking neuroscience research. Image Geir Mogan/ NTNU

These place and grid cells have since been found to be present in all mammals, including humans, and equivalents are present in other vertebrates. In humans, the hippocampus and entorhinal cortex are frequently affected in the early stages of Alzheimer’s Disease, and it is hoped that understanding how the positioning system discovered by this year’s Nobel laureates in Physiology or Medicine will help us to understand the mechanism underpinning the loss of spatial memory that often leaves patients unable to recognize and navigate through familiar environments.

This year’s Nobel Prize highlights once again the continuing importance of animal research in pushing the frontiers of Neuroscience, and in particular the critical importance of techniques that use implanted electrodes to record the activities of individual nerve cells.

In an interview following the Nobel Prize announcement John O’Keefe stressed the continuing importance of animal research and warned of the danger to science from excessively strict animal research regulations.

Lasker Awards recognize pioneers of Deep Brain stimulation

The Nobel Prize is of course not the only award that recognizes excellence in scientific and medical research, and since the 1940’s the Lasker Foundation has granted awards to recognize excellence in basic and clinical medical research. In 2014 the Foundation has awarded its Lasker-DeBakey Clinical Medical Research Award to Alim Louis Benabid and Mahlon R. DeLong for “the development of deep brain stimulation of the subthalamic nucleus, a surgical technique that reduces tremors and restores motor function in patients with advanced Parkinson’s disease.”.

Lasker_2014_illustration_clinical_1

The development of deep brain stimulation of the subthalamic nucleus is a classic example of the intellectual cross fertilization between laboratory and clinical research that drives medicine forward, as Dario Ringach described on this blog a couple of years ago in “A Brief History of Deep Brain Stimulation”.

In the award description the Lasker Foundation again highlights the synergy between animal and clinical research.

First it looks at how Mahlon DeLong recognized the significance of the accidental discovery that a chemical called MPTP could induce Parkinson’s disease like symptoms, a discovery that would allow him to resolve long-standing questions concerning the role of different regions of a part of the brain known as the basel ganglia in Parkinson’s disease.

DeLong seized upon the opportunity. A part of the basal ganglia called the subthalamic nucleus drives the inhibitory output signal, and in 1987, DeLong reported that MPTP triggers neurons in the subthalamic nucleus of monkeys to fire excessively. Perhaps, DeLong reasoned, the overexuberant signals quash motor activity in PD. If so, inactivating the subthalamic nucleus might ameliorate some of the illness’s worst symptoms.

Next, he did an experiment that would transform PD treatment. He administered MPTP to two monkeys; as usual, they gradually slowed down until they sat motionless, their muscles stiffened, and they developed tremors. DeLong then injected a second toxic chemical that inactivated the subthalamic nucleus. Within one minute, the animals began to move. Gradually, their muscles loosened and the tremors ceased. These findings strongly supported the hypothesis that hyperactivity in the subthalamic nucleus underlies PD symptoms.”

On the other side of the Atlantic in Grenoble, Alim-Louis Benabid realized that DeLong’s findings could used to greatly improve a new therapy for Parkinson’s disease that he had pioneered.

Although the technique quelled tremors, Benabid knew that this symptom was not the one that most debilitated people with PD. Perhaps high-frequency stimulation of brain areas other than the thalamus (i.e., the subthalamic nucleus) would alleviate the more troublesome aspects of the illness such as slowness of movement and rigidity, he reasoned.

In this state of mind, Benabid read DeLong’s report that damage to the subthalamic nucleus wipes out multiple symptoms of PD in animals. This site was not an attractive target: Lesioning procedures and spontaneous lesions had established decades earlier that, when things went wrong, violent flailing could result. By that time, however, Benabid had performed high-frequency stimulation of the thalamus and other brain regions’ in more than 150 patients. He was confident that he would cause no harm in the subthalamic nucleus; if necessary, he could remove the electrode.

In 1995, Benabid reported results from the first humans who received bilateral, high-frequency stimulation of the subthalamic nucleus—three people with severe PD. The treatment suppressed slowness of movement and muscle rigidity.”

While DBS of the subthalamic nucleus is not a cure for Parkinson’s disease, it can relieve many of the major symptoms, and has benefited tens of thousands of patients around the world whose symptoms are not adequately controlled by first-line therapies. Currently DBS is also being explored as a therapy for several other neurological conditions, including depression and chronic pain.

From Golden Gongs to Golden Geese

What would you think if you read that scientists had received tens of thousands of taxpayer dollars to massage newborn rat pups?

You might think that it is exactly the sort of research that opponents of basic science like to parade as examples when accusing the NIH of wastefulness. However, as usual the truth turns out to be quite different.

In September the 18th Saul Schanberg, Tiffany Martini Field, Cynthia Kuhn and Gary Evoniuk ,  were among the 8 recipients of the Golden Goose Award at a ceremony at the Library of Congress in Washington, D.C., an award established “to demonstrate the human and economic benefits of federally funded research by highlighting examples of seemingly obscure studies that have led to major breakthroughs and resulted in significant societal impact”.

The work began in 1979 with a problem. Cynthia Kuhn and Gary Evoniuk needed to separate newborn rat pups from their mothers as part of their NIH funded research project to investigate the factors influencing two key growth markers, ornithine decarboxylase and growth hormone , but they found that despite being kept fed and warn the pups failed to thrive. What happened next was a classsic example of how careful observation and outside-the –box thinking advances science:

A series of experiments ruled out factors such as nutrition, body temperature and maternal pheromones. The researchers then made the key observation: the rat mothers spent a great deal of time grooming and vigorously licking their pups. Wondering whether the act of stimulation through licking was making the difference, the researchers simulated the mother’s tongue with a small brush and stroked up and down the rats’ tiny backbone. This was the missing link. Enzyme and growth hormone levels rose and the rat pups thrived again.

Field, a psychologist at the University of Miami Medical School who was conducting her own research on how to help premature infants survive and grow, learned of Schanberg’s groundbreaking work and wondered whether it had implications for human infants. In 1986, Field published her own landmark study drawing from Schanberg, Kuhn and Evoniuk’s work with rat pups. Funded by the National Institute of Mental Health (part of NIH), Field’s study demonstrated that using similar tactile stimulation in preterm human infants had immediate positive effects. Premature infants who were massaged for 15 minutes three times a day gained weight 47 percent faster than others left alone in their incubators (standard practice at the time), were more alert and responsive, and were released from the hospital an average of six days sooner than the premature babies who were not massaged.”

Since their discovery tactile stimulation of preterm babies, in the form of infant massage, has become standard practice in many neonatal intensive care units around the world. It has been demonstrated to greatly improve the outcome for babies born prematurely millions of lives around the world, and saved billions of dollars in healthcare costs in the United States alone.

It’s yet another example of how “Off the wall” scientific research can deliver the goods!  Spending on basic scientific research is a crucial long-term investment, one whose precise outcomes are never certain, but which will pay off in both advancing knowledge and improving our future health, well-being and prosperity!

Paul Browne

Crash course in medical history

Opponents of animal research often portray two of the pioneers of experimental physiology, François Magendie (1783-1855) and his student Claude Bernard (1813-1878), as deranged, vicious, and sadistic individuals who derived pleasure in harming animals. Moral philosophers Peter Singer and Lori Gruen convey this sort of message in their book “Animal Liberation: A graphic guide”.

Portrayal of Claude Bernard in Singer and Gruen's book

Portrayal of Claude Bernard in Singer and Gruen’s book

A quick look at how Claude Bernard’s face is portrayed in their book is sufficient to get a sense of Singer and Gruen’s feelings towards scientists who engage in animal research. The peculiar use of quotes around ‘experiment’ in the caption suggests they believe the work did not qualify as legitimate scientific research, nor that it could contribute any benefits to mankind. Such view fails to consider the historical context of their experiments.  In particular, one could ask how were human patients treated by their physicians of the time.

Here is a brief summary of 19th century medicine —

The theory of counter-irritation was in vogue. To counter-irritate basically meant causing additional wounds to the patient as a form of treatment. One technique involved inserting inflamed limbs were into giant anthills. More convenient was produce large blisters by means of a fire iron or acid. In 1824, an article in the Lancet by Dr. Abernathy suggested that a 1 foot square blister was probably a bit too large — several small blisters were indicated instead.  A third method of counter-irritation involved making a saw-shaped wound and inserting dried peas or beans into it. The doctor would then ensure the wound remained open, keeping it from healing, from weeks to months, replacing the peas and/or beans as necessary.

Leeches were used in vast quantities and for many purposes.  Physicians would lower leeches down patient’s throats.  Hundreds of them would be used to bleed a man’s testicle over days. Leeches were also applied to the vagina to relieve “sexual excitement” and, not to discard other orifices, doctors would push them up the anus. It was noted that during these procedures there was always a possibility that some of the leeches would get lost inside the patient body which, according to the physicians of the time, resulted in  “very annoying accidents”.

What about mental disease? A common treatment involved psychiatrists spinning patients in centrifuge-like machines a hundred of times per minute. This is how unruly patients came to understand the authority of the doctor, with one of them asserting that the more lively his intimidation towards the apparatus the more charitable the effects of the therapy.”  

rush

Benjamin Rush’s tranquilizer chair

Benjamin Rush, one of the founding fathers and signatories of the Declaration of Independence, adopted some of these same methods and developed them further.  He would pour acid on his patients backs and cut them with knives to allow the discharge “form the neighborhood of the brain”.  Rush also developed the famous “tranquilizer chair” where patients were restrained for up to entire days — the chair had a convenient hole for defecation at the bottom.

Bloodletting was used to treat a number of ailments.  It also often led to death.  One famous incident involves George Washington, who in 1799 suffered from a bad sore throat and died shortly after a visit by three different doctors who, altogether, took about half of his blood volume. The famous medical journal The Lancet derives its name from the tool used in these procedures.

Given Singer and Gruen’s depiction of animal research one must also ask — How did human surgeries look back then?  By all accounts they were the most excruciating, traumatic and dangerous experience for patients.  As an example, the novelist Fanny Burney recounted part of her experience with a mastectomy as follows:

I mounted, therefore, unbidden, the Bed stead & M. Dubois placed me upon the Mattress, & spread a cambric handkerchief upon my face. It was transparent, however, & I saw, through it, that the Bed stead was instantly surrounded by the 7 men & my nurse. I refused to be held; but when, Bright through the cambric, I saw the glitter of polished Steel I closed my Eyes. I would not trust to convulsive fear the sight of the terrible incision. Yet — when the dreadful steel was plunged into the breast cutting through veins arteries flesh nerves I needed no injunctions not to restrain my cries. I began a scream that lasted unintermittingly during the whole time of the incision & I almost marvel that it rings not in my Ears still? so excruciating was the agony. When the wound was made, & the instrument was withdrawn, the pain seemed undiminished, for the air that suddenly rushed into those delicate parts felt like a mass of minute but sharp & forked poniards, that were tearing the edges of the wound. I concluded the operation was over Oh no! presently the terrible cutting was renewed & worse than ever, to separate the bottom, the foundation of this dreadful gland from the parts to which it adhered Again all description would be baffled yet again all was not over, Dr. Larry rested but his own hand, & — Oh heaven! I then felt the knife (rack)ling against the breast bone scraping it!

Ms Burney was lucky to have survived to describe her experiences.  Most surgeries taking place in surgical theaters simply ended up in death.

The above were some of the common practices of medicine a mere 200 years ago. Magendie was one among the main critics of the dominant medical theories (humorism and vitalism) and the use of unproven methods on human patients. On the use of animals in research he said at a meeting [] I beg my honorable colleague to observe that I experiment on animals precisely because I do not wish to experiment on men.  That is what he felt about medicine — it was nothing short of human experimentation.

In the introductory pages of his Journal de Physiologie Expérimentale Magandie, he added:

“What subject is indeed more fertile in gross errors and absurd beliefs than that of health and disease? Consider the painful disquietude you would produce in the minds of the majority of men if you said to them:There are no such things as rheumatismal humour, gouty humour, scabby virus, venereal virus, and so forth.  Those things which are so designated are imaginary things, which the human mind has created to hide from itself its own ignorance.’   The chances are that you would be taken for a lunatic just as it but recently befell those who maintained that the sun was immovable and the earth turned.”

Any honest reading of medical history has to give credit to the experimental physiologists who put medicine in the right track to become what it is today. The handful of physicians and psychiatrists that speak against animal research should remember that from Hippocrates to the early 19th century, their profession caused more harm than good to their patients.  They ought to be reminded that it was the work of the experimental physiologists that turn this around.  Charles Darwin acknowledged this fact when he wrote:

[] I know that physiology cannot possibly progress except by means of experiments on living animals, and I feel the deepest conviction that he who retards the progress of physiology commits a crime against mankind.

As experimental medicine advanced, so did our ability to treat the potential pain and suffering animals may experience in research.  Animal welfare laws were established. Today, the vast majority of animals participating in research benefit from the use of modern anesthetics and analgesics. The public and our representatives recognize that responsible, regulated animal research has continued to produce new therapies and cures through the years — benefiting humans and non-human animals alike. Stopping the work and depriving future generations of new advances would be immoral.

Responsible Antibody Production

Antibodies Part 2 (read Part 1 here)

As noted in our previous post, there are many promising uses for antibodies. Therefore, it is no wonder that antibody production is big business. The Scientist reported that revenues from antibody sales were over $1.6 billion in 2011. In the United States, antibody producers that use regulated species of animals must comply with the Animal Welfare Act, just as research institutions that use animals must do.

Earlier this year, we reported that one large antibody producer, Santa Cruz Biotechnology (SCB), was accused by the United States Department of Agriculture (USDA) of numerous animal welfare violations. The company originally planned to address these allegations at a USDA administrative law hearing scheduled for the week of July 14, 2014. That hearing has since been postponed while SCB and the USDA try to reach a negotiated settlement on the alleged violations. We would welcome such a settlement if the end result is better animal welfare practices at SCB.

Mice in a Cage

“We would welcome such a settlement if the end result is better animal welfare practices at SCB.”

Meanwhile, the USDA recently announced a settlement with another antibody producer: Rockland Immunochemicals, Inc.  Rockland paid a $32,071 fine for multiple Animal Welfare Act violations in 2012 and 2013. It is noteworthy that all inspections of Rockland Immunochemicals by the USDA thus far in 2014 have indicated that the company was compliant with the Animal Welfare Act. Hopefully, Rockland has learned an important lesson: animal welfare matters

Neither Rockland Immunochemicals nor Santa Cruz Biotechnology discusses corporate responsibility or their commitment to animal welfare on their websites, but other antibody producers do. For example, the Aves Labs website plainly states its commitment to animal welfare and heralds the fact that the company voluntarily sought accreditation of its animal use program by the Association for the Assessment and Accreditation of Laboratory Animal Welfare (AAALAC).   Protocols describing the company’s use of animals for antibody production are also provided on its website.

Other examples of antibody producers with strong commitments to animal welfare and transparency in animal use include ImmunoPrecise, Pocono Rabbit Farm and Laboratory, EMD-Millipore, and Bethyl Laboratories.

We urge all antibody producers to establish corporate responsibility practices and transparency regarding their animal use programs. We also urge scientists and pharmaceutical companies to weigh the producers’ commitment to these important values in selecting which antibodies to use.

Alice Ra’anan and Bill Yates

Pregnancy Kits to Ebola Treatment: Medical Tests & Disease Treatments Depend on Animal Products

Antibodies Part 1

There has been considerable discussion on this website about the use of animal studies to develop new medical treatments. But some animal-derived products such as antibodies also play a crucial role in diagnostic tests for some diseases and targeted treatments for others. In the last week, antibodies hit the front pages of newspapers and websites with the news that the ZMapp serum given to 2 Americans aid workers stricken with the deadly Ebola virus was a cocktail of antibodies. Developed through research in mice, the two components of this experimental serum – ZMab and  MB-003 – had only previously been tried in monkeys, but the results were very promising. As of this writing, both aid workers’ conditions had improved.

Mice played a critical role in developing the antibodies used to treat aid workers with Ebola. Tweet this!

Antibodies are proteins the immune system produces to identify and neutralize foreign objects such as bacteria and viruses. Antibodies “recognize” specific proteins, a property that makes them highly useful for a variety of purposes. For instance, antibodies can be used in diagnostic tests to determine whether a protein associated with a particular disease or medical condition is present in a patient’s blood, urine, saliva, or tissues. The home pregnancy test is an example of a diagnostic test that relies on antibodies. These tests detect the hormone human chorionic gonadotropin, a protein that is only present during pregnancy.  Many other medical tests also utilize antibodies; a few examples are:

  1. Tests to look for heart proteins in the blood such as troponin that indicate that a heart attack has occurred.
  2. Tests for the presence of the HIV (AIDS) virus in the blood.
  3. Tests for proteins present in the blood of patients with Lupus, an autoimmune disease where the immune system attacks the body’s own tissues.

A diagram showing the characteristic Y shape of an antibody molecule. It is able to grab two of its target molecules with the ends of the two arms of the Y.

Antibodies can also be used to treat disease. Certain antibodies can neutralize toxins such as snake venom.  Other antibodies are coupled to a toxin or other chemical, such that it is delivered only to cells carrying the protein that antibody recognizes.  For example, some cancer cells generate unique proteins so antibody-coupled drugs can be used to deliver a toxic agent to the cancer cells without harming other cells in the body. Antibody therapies have been effective in treating a number of types of cancer, including Hodgkin lymphoma and non-Hodgkin lymphoma, some forms of skin cancer, and some forms of breast cancer. Now we learn that antibodies may also be effective in treating Ebola.

Unique cell surface proteins on a cancer cell, which can be detected using antibodies.

Unique cell surface proteins on a cancer cell, which can be detected using antibodies.

There are two types of antibodies used for medical diagnostics and treatments: polyclonal antibodies and monoclonal antibodies. Both require animals in their production.

Polyclonal antibodies are produced by injecting the protein of interest (or part of it, called an antigen) into an animal.   Since this is a foreign substance, the animal’s immune system reacts to it by generating antibodies to fight off the intruder. Later, samples of the animal’s blood are removed and the antibodies isolated. Larger animals such as sheep, goats, and rabbits are often used for antibody production because they have enough blood in their bodies that large blood samples can be removed without harming them. Antibodies generated using this method are called “polyclonal,” because they came from many different immune cells known as B cells or B-lymphocytes.

Process for producing polyclonal antibodies

Process for producing polyclonal antibodies

To produce monoclonal antibodies, an animal (often a mouse) is injected with the partial protein or antigen of interest. Antibody-producing cells are later isolated from the animal, often from its spleen. Fast-growing but harmless tumor cells are cultivated in the lab and fused with the isolated antibody-producing cells. This produces a new cell type called a hybridoma that can be grown in the lab. Once it is confirmed that the hybridomas are generating antibodies against the right antigen, these hybrid cells can serve as factories to grow large numbers of pure monoclonal antibodies in the lab.

From: FASEB’s Breakthroughs in Bioscience Series.  Used by permission.

Monoclonal antibody production process

Alice Ra’anan and Bill Yates

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Behaviourists Defend Basic Science

The August issue of the journal Animal Behaviour contained a commentary “Time to step up: defending basic science and animal behaviour.” The authors, Dr. Patricia Brennan, Dr. Rulon Clark and Dr. Douglas Mock begin by providing a history of how it became politically fashionable to ridicule basic scientific research. The Golden Fleece Awards were started in 1975 by Senator William Proxmire to provide examples of frivolous spending. Unfortunately, several federally funded research projects fell under Proxmire’s scrutiny and had small pieces of information exaggerated or distorted to seem completely ridiculous. The practice continues to this day and was last written about here in 2010. The mocking of basic science provided some people short-term political gains with unknown long-term national costs.

The bitter partisanship existing within the USA and challenges over budget appropriations the authors discuss strategies for how scientists can defend their work if they are the focus of unwarranted political or media attention.   The commentary outlines what researchers can do before or after one is targeted. Who should be informed, what to say and nine talking points to drive home the importance of basic science.

Talking points

  1. Basic science is the foundation of all applied science. Because we cannot predict which basic science projects will turn into an application, we must cast a wide net.
  2. The connection between basic and applied science is seldom a straight line; more often, it involves a network that connects novel ideas, methods and data in a new way, leading to innovations.
  3. The government must fund basic science because its potential economic gains are unpredictable and generally long term. No private investing company can invest under those conditions.
  4. Government investment in science guarantees that at least some of our discoveries are free of special interests, and therefore it protects the integrity of the scientific process. Federal investment in research and development was only 24% of all U.S. science investment in 2008 .
  5. Funding decisions at NSF, NIH and other agencies are made by panels of scientists who judge projects on the basis of their intellectual merit and impact to society.
  6. These agencies are severely underfunded and, as a result, many high-priority projects do not get funded.
  7. The return on investment estimated from government funding of science is enormous. Not all projects turn a profit, but when they do, they can transform society: think Google, Taq polymerase and green fluorescent protein (GFP).
  8. Federally funded basic science projects are the engine of many research universities. Without these projects, universities could not train the next generation of scientists. Involvement in basic research is often the highlight of a student’s undergraduate experience and provides training that cannot be replicated through coursework.
  9. Organisms are exquisitely adapted to their environment and the study of these adaptations has allowed us to make great strides in medicine and technology.

“Not responding to politically motivated attacks is likely to be the wrong strategy. Silence may further erode public confidence in science, as it may be interpreted as implicit acceptance that there is something wrong with your project.”

They also include several examples of fundamental behaviour research that have had unanticipated significant impacts. For example:

The Sexual Behaviour of the Screwworm Fly

One of the recipients of a Golden Fleece Award was E. F. Knipling for his research into the sex life of parasitic screwworm flies. Knipling developed the sterile male technique to eradicate this cattle pest, based on observations during the 1930s that male screwworm flies will mate with many females, while females will mate only once. He used this information to devise a male sterilization strategy using X-rays. He released sterile males into the population and in a few generations completely eradicated this parasite. Knipling’s $250,000 grant from the Department of Agriculture led directly to a program estimated to have saved at least $20 billion for U.S. cattle producers. The sterile male technique is currently used as a standard eradication technique on many agricultural pests.

Screwworm Fly

Neuroplasticity and Neurogenesis in the Brain

The discovery that humans can grow functional neurons in the brain during adulthood is revolutionizing the understanding of learning and memory, recovery from brain injury and disease, and the effects of addiction and neurodegenerative diseases. Several of the most influential early studies that discovered adult neurogenesis in the brain were conducted by Fernando Nottebohm, who showed that seasonal changes in the song nuclei of male canaries, Serinus canaria, were explained by recruitment of new neurons and death of old ones. Nottebohm also showed that black-capped chickadees, Poecile atricapillus, grow neurons associated with spatial memory in the brain during the autumn, perhaps to facilitate finding their food caches during the winter months, further supporting a role of learning on neurogenesis. Nottebohm was an avid birder from childhood and his interests were centred on understanding how and why birds sing. When Nottebohm published his first papers on neurogenesis in the avian brain, the central dogma of neurobiology was that no new neurons grew in adult brains, but his careful and continued work served as a platform to develop new ideas on neurogenesis and neuroplasticity.

Atlantic Canary

Host Manipulation by Parasites

Studies of host manipulation by parasites were not begun by behavioural ecologists, but they have embraced this field in the last two decades, rapidly advancing the grasp of how parasites change host behaviour. The study of parasite manipulations has important applications to conservation, agricultural production and medicine. One of the iconic examples involves infection of carpenter ants by the trematode Dicrocoelium denditricum, which affects wild and domestic ruminants. Ants are the intermediate host of this trematode, and the larvae form cysts that make the ants climb grass blades and grasp the top securely until a grazer comes by and eats it, thereby completing the parasites’ life cycle. In humans, toxoplasmosis infection has been linked to a variety of mental disorders, and this link has been particularly well studied in schizophrenia. Many studies have shown that schizophrenic individuals are more likely to be seropositive for antitoxoplasma antibodies. Moreover, Toxoplasma gondii appears to have major effects on human behaviour, including several personality traits.

The authors finish their commentary by stressing the need to educate the public, engage the younger generation, increase social media presence, train scientist to communicate science to the general public and support them actively communicating their findings. The recommendations to defend the need for basic science presented in the current edition of Animal Behaviour are relevant not only to this field but all scientific diciplines across the world.

Michael Brunt