How the Brain Works (UCLA) (4 parts)

ORIGINAL: UCLA Health

These brief videos provide an introductory appreciation of how we learn skills and information, move, think, feel, speak and remember. They are brought to you by the UCLA Brain Research Institute and by Bruce H. Dobkin, MD, who directs the neurorehabilitation program in the Department of Neurology at UCLA. The videos especially aim to reach out to students in grade school to stir their interest, and to people with disabilities in walking, using an affected upper extremity, and loss of memory from neurological diseases such as stroke, brain trauma, tumors, multiple sclerosis, cerebral palsy, Parkinsons, and Alzheimers disease.

Video 1:
General organization of a real human brain.

Video 2:
The pathology of brain injuries and diseases. Rat versus human brain complexity. How do we reach for a ball? How do we walk?

Video 3:
How does practice enable us to learn and retain skills and information?

Video 4:

How can we drive the nervous system to adapt in ways that help restore lost skills after injury from disease? Can we reorganize the brains connections?

Harvard's Wyss Institute and Sony DADC Announce Collaboration on Organs-on-Chips

ORIGINAL: Wyss Institute

Date: Mar 18, 2013

Boston, MA -- Today the Wyss Institute for Biologically Inspired Engineering at Harvard University and Sony DADC announced a collaboration that will harness Sony DADC's global manufacturing expertise to further advance the Institute's Organs-on-Chips technologies. 

Human Organs-on-Chips are composed of a clear, flexible polymer about the size of a computer memory stick, and contain hollow microfluidic channels lined by living human cells -- allowing researchers to recapitulate the physiological and mechanical functions of the organs, and to observe what happens in real time. The goal is to provide more predictive and useful measures of the efficacy and safety of new drugs in humans -- and at a fraction of the time and costs associated with traditional animal testing.

"We are excited to apply Sony DADC's deep manufacturing expertise to confront one of the major challenges in the life sciences by helping to accelerate the translation of the Wyss Institute's Organ-on-Chips from the benchtop to the marketplace," said Christoph Mauracher, Senior Vice President of the BioSciences division of Sony DADC. "The Organs-on-Chips have the potential to revolutionize testing of drugs, chemicals, toxins and cosmetics."

Organs on a Chip from Wyss Institute on Vimeo.

This collaboration builds on the momentum the Wyss Institute team has gained recently on its Organs-on-Chips research program. With support from Defense Advanced Research Projects Agency (DARPA)*, National Institutes of Health (NIH), Food and Drug Administration (FDA), and pharmaceutical partners, more than ten Organs-on-Chips are currently under development at the Wyss Institute, including a lung, heart, liver, kidney, bone marrow, and gut-on-a-chip; there is also a major effort to integrate these organ chips into "human body on-chips" that mimic whole body physiology.

In February, Wyss Founding Director Don Ingber, M.D., Ph.D., who leads the Organs-on-Chips research program, received the prestigious 3Rs Prize from the UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research for the lung-on-a-chip. This month, the Society of Toxicology awarded him the Leading Edge in Basic Science Award for his "seminal scientific contributions and advances to understanding fundamental mechanisms of toxicity."

"Our work with Sony is a wonderful example of the Wyss Institute model in action," said Ingber. "We collaborate with industry to help de-risk the technologies we develop, both technically and commercially, and therefore expedite their translation into real world applications."

###

*Part of this research was sponsored by the U.S. Army Research Office (ARO) and DARPA; the views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of ARO, DARPA or the U.S. Government.

Contacts

Wyss Institute for Biologically Inspired Engineering 

Kristen M. Kusek

+1 617-432-8266

Kristen.kusek@wyss.harvard.edu 

Sony DADC

Manfred Koranda

+43 6246 880 8143

manfred.koranda@sonydadc.com

Secrets of Human Speech Uncovered

ORIGINAL: UCSF

By Jason Bardi
February 20, 2013

Work at UCSF Shows Brain Exerts Symphony-Like Control of Vocal Tract During the Act of Speaking

A team of researchers at UC San Francisco has uncovered the neurological basis of speech motor control, the complex coordinated activity of tiny brain regions that controls our lips, jaw, tongue and larynx as we speak.

Edward Chang, MD

Described this week in the journal Nature, the work has potential implications for developing computer-brain interfaces for artificial speech communication and for the treatment of speech disorders. It also sheds light on an ability that is unique to humans among living creatures but poorly understood.

“Speaking is so fundamental to who we are as humans – nearly all of us learn to speak,” said senior author Edward Chang, MD, a neurosurgeon at the UCSF Epilepsy Center and a faculty member in the UCSF Center for Integrative Neuroscience. “But it’s probably the most complex motor activity we do.”

The complexity comes from the fact that spoken words require the coordinated efforts of numerous “articulators” in the vocal tract – the lips, tongue, jaw and larynx – but scientists have not understood how the movements of these distinct articulators are precisely coordinated in the brain.

To understand how speech articulation works, Chang and his colleagues recorded electrical activity directly from the brains of three people undergoing brain surgery at UCSF, and used this information to determine the spatial organization of the “speech sensorimotor cortex,” which controls the lips, tongue, jaw, larynx as a person speaks. This gave them a map of which parts of the brain control which parts of the vocal tract.

They then applied a sophisticated new method called “state-space” analysis to observe the complex spatial and temporal patterns of neural activity in the speech sensorimotor cortex that play out as someone speaks. This revealed a surprising sophistication in how the brain's speech sensorimotor cortex works.

They found that this cortical area has a hierarchical and cyclical structure that exerts a split-second, symphony-like control over the tongue, jaw, larynx and lips.

“These properties may reflect cortical strategies to greatly simplify the complex coordination of articulators in fluent speech,” said Kristofer Bouchard, PhD, a postdoctoral fellow in the Chang lab who was the first author on the paper.

In the same way that a symphony relies upon all the players to coordinate their plucks, beats or blows to make music, speaking demands well-timed action of several various brain regions within the speech sensorimotor cortex.

Brain Mapping in Epilepsy Surgery 

The patients involved in the study were all at UCSF undergoing surgery for severe, untreatable epilepsy. Brain surgery is a powerful way to halt epilepsy in its tracks, potentially completely stopping seizures overnight, and its success is directly related to the accuracy with which a medical team can map the brain, identifying the exact pieces of tissue responsible for an individual's seizures and removing them.

The UCSF Comprehensive Epilepsy Center is a leader in the use of advanced intracranial monitoring to map out elusive seizure-causing brain regions. The mapping is done by surgically implanting an electrode array under the skull on the brain’s outer surface or cortex and recording the brain’s activity in order to pinpoint the parts of the brain responsible for disabling seizures. In a second surgery a few weeks later, the electrodes are removed and the unhealthy brain tissue that causes the seizures is removed.

This setting also permits a rare opportunity to ask basic questions about how the human brain works, such as how it controls speaking. The neurological basis of speech motor control has remained unknown until now because scientists cannot study speech mechanisms in animals and because non-invasive imaging methods lack the ability to resolve the very rapid time course of articulator movements, which change in hundredths of seconds.

But surgical brain mapping can record neural activity directly and faster than other noninvasive methods, showing changes in electrical activity on the order of a few milliseconds.

Prior to this work, the majority of what scientists knew about this brain region was based on studies from the 1940’s, which used electrical stimulation of single spots on the brain, causing a twitch in muscles of the face or throat. This approach using focal stimulation, however, could never evoke a meaningful speech sound. 

Chang and colleagues used an entirely different approach to studying the brain activity during natural speaking brain using the implanted electrodes arrays. The patients read from a list of English syllables – like bah, dee, goo. The researchers recorded the electrical activity within their speech-motor cortex and showed how distinct brain patterning accounts for different vowels and consonants in our speech.

“Even though we used English, we found the key patterns observed were ones that linguists have observed in languages around the world – perhaps suggesting universal principles for speaking across all cultures,” said Chang.

The article, “Functional organization of human sensorimotor cortex for speech articulation” is authored by Kristofer E. Bouchard, Nima Mesgarani, Keith Johnson and Edward F. Chang. It appears in the February 20, 2012 issue of the journal Nature. After this date, the article can be accessed at: http://dx.doi.org/10.1038/nature11911

This work was funded by the National Institutes of Health via grant #R00-NS065120, #DP2-OD00862 and #R01-DC012379 and by the Ester A. and Joseph Klingenstein Foundation.

De los músculos al computador

ORIGINAL: UdeA

por Elizabeth Cañas - Vicerrectoría de Investigación 

10 de august de 2012

Investigadores de la Alma Máter trabajan en un modelo computacional de la liberación y recaptura de calcio en los músculos. Los resultados servirán para el desarrollo de soluciones farmacológicas para problemas de fatiga y afecciones deportivas. 

Célula aislada del músculo extensor digitorum longus, de ratón.
Cortesía: Juan C. Calderón. Modelación fisicomatemática

La posibilidad de que un músculo esquelético se contraiga o no, depende de que las células musculares liberen iones calcio desde un compartimiento llamado retículo sarcoplásmico. La contracción muscular es un acortamiento que cuando el músculo está unido, por ejemplo, a un hueso, genera el movimiento.

“Lo que estamos modelando es ese proceso, mediante el cual sale el calcio y se une a los componentes de la célula. Para lograrlo, se apela a teorías físicas o modelos matemáticos para poder describir los procesos que hay entre los elementos y establecer un modelo computacional que facilite la reproducción de este proceso que se da al interior de las células”.

Así lo explicó Daniel Mejía Raigosa, estudiante del Instituto de Física de la Universidad de Antioquia, al señalar que se trata de un desarrollo innovador en Colombia en el que se combina la biofísica, es decir la unión de la biología y la física; así como los desarrollos de la fisiología muscular.

La investigación es su proyecto de grado que, además, se destaca por tratar de avanzar en la modelación de un proceso que ocurre en pocos milisegundos.

Según el estudiante, este proceso tiene como precedente la modelación y propagación del potencial de acción realizada después de la Segunda Guerra Mundial. En ese momento un Premio Nobel, Alan Lloyd Hodgkin, relacionó los impulsos eléctricos necesarios para conducir las señales nerviosas.

Próximamente se compartirán publicaciones científicas de esta investigación, que se adelanta gracias a la orientación de los profesores Marco Giraldo Cadavid, del Grupo de Biofísica, y Juan Camilo Calderón, del Grupo de Investigación en Fisiología y Bioquímica-PHYSIS, de la Facultad de Medicina, y expertos como el científico Carlo Caputo, del Instituto Venezolano de Investigaciones Científicas, IVIC.

Insumos científicos

La modelación para definir parámetros de relaciones entre los iones y proteínas, entre otros factores relacionales, combina las matemáticas, las leyes físicas y cálculos obtenidos de la toma de datos.

"Con ellos se busca reproducir los fenómenos que fueron medidos experimentalmente y los cambios que pueden generar el aumento o la disminución de la velocidad del proceso, la interacción que se presente el mismo y otras fluctuaciones. Se trata de avanzar en los estudios de movimientos moleculares, básicos para el desarrollo de opciones terapéuticas y para generar soluciones que modulen la salida del calcio", explicó Mejía.

Así comentó el profesor Giraldo Cadavid, al explicar que para lograr dicha reproducción se han realizado, previamente, por parte del profesor Calderón, una serie de mediciones de los cambios de fluorescencia inducidos por la liberación de calcio dentro de la célula muscular, y lo que se quiere es convertir las señales de fluorescencia a calcio y luego reproducir toda esa liberación de calcio en un computador.

Eso demanda que en forma computacional se tomen todos los elementos, se modele con ecuaciones y principios físicos que son traducirlos al lenguaje de computador, variando parámetros para entender bien el proceso, definir cuantos iones intervienen, su importancia y qué pasa si se varía la liberación de calcio, entre otros factores.

La investigación apela a la biología de sistemas, que consiste en describir o modelar un organismo o sistemas de organismos biológicos, no a nivel de componentes sino de sus interacciones.

Los sistemas que se estudian son fibras musculares de ratón, porque es más cómodo instrumentalmente y es un mamífero del que se pueden manipular fácilmente los músculos. Además, los ratones empleados hacen parte de cepas de laboratorio estandarizadas, para garantizar la reproductibilidad del experimento.

Wyss Institute to Receive up to $37 Million from DARPA to Integrate Multiple Organ-on-Chip Systems to Mimic the Whole Human Body

ORIGINAL: Wyss Institute (Harvard)

Date: Jul 24, 2012

New instrument would accelerate assessment of drug safety and efficacy, and inform regulatory decision-making

Wyss Institute researchers and a multidisciplinary team of collaborators seek to build and link 10 human organs-on-chips to mimic whole body physiology. The system will incorporate the Institute's Human Lung-on-a-Chip (top) and Human Gut-on-a-Chip (bottom).

BOSTON -- The Wyss Institute for Biologically Inspired Engineering at Harvard University today announced that it has entered into a Cooperative Agreement worth up to $37 million with the Defense Advanced Research Projects Agency (DARPA) to develop an automated instrument that integrates 10 human organs-on-chips to study complex human physiology outside the body. This effort builds on the Institute's past breakthroughs in which Institute researchers engineered microchips that recapitulate the microarchitecture and functions of living organs, such as the lung, heart, and intestine. Each individual organ-on-chip is composed of a clear flexible polymer -about the size of a computer memory stick- that contains hollow microfluidic channels lined by living human cells. Because the microdevices are translucent, they provide a window into the inner-workings of human organs without having to invade a living body.

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented "human-on-a-chip" will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

Several U.S. agencies are working together to help safeguard Americans from deliberate chemical, biological, radiological, and nuclear threats, as well as from emerging infectious diseases, by drastically accelerating the drug development process. As an example, DARPA, the National Institutes of Health (NIH), and the U.S. Food and Drug Administration (FDA) are actively collaborating to develop cutting edge technologies to predict drug safety. The Wyss project was selected under the DARPA Defense Sciences Office (DSO) Microphysiological Systems Program and will be administered through a Cooperative Agreement by the Army Research Office (ARO) and DARPA.

The Lung-on-a-Chip, which makes use of living human cells, mimics the lung's tissue-tissue interface and breathing motions. Watch video to learn more...

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed "has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development."

Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member, Kevin Kit Parker, Ph.D., will co-lead this five-year project. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences (SEAS). Parker is the Tarr Family Professor of Bioengineering and Applied Physics at SEAS. The organ-on-chip program will also draw on the Institute's leading scientists and engineers, including Geraldine Hamilton, Ph.D., Anthony Bahinski, Ph.D., and Daniel Levner, Ph.D., who have extensive industrial experience in drug development, safety pharmacology, and systems engineering, to accelerate translation of this technology from the lab into the marketplace where it can best help the people who need it most. Other key collaborators participating in the project include John Wikswo, Ph.D., University Professor of Physics at Vanderbilt University, and Andrzej Przekwas, Ph.D., from CFD Research Corporation.

For more information, contact Twig Mowatt

Twig.mowatt@wyss.harvard.edu

###

About the Wyss Institute for Biologically Inspired Engineering at Harvard University 

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard's Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, , Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature's principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

50 Deadly Consequences of Lab Animal Experiments

ORIGINAL: Vivisection Information

February 28, 2012

From US Doctors Group Americans for Medical Advancement
Click here for a 33 fact summary of why animal testing does not work

 

  

1. Smoking was thought non-carcinogenic because smoking-related cancer is difficult to reproduce in lab animals. Many people continued to smoke and to die from cancer.[2]
2. Benzene was not withdrawn from use as an industrial chemical despite clinical and epidemological evidence that exposure caused leukemia in humans, because manufacturer-supported tests failed to reproduce leukemia in mice.[1]
3. Animal experiments on rats, hamsters, guinea pigs, mice, monkeys, and baboons revealed no link between glass fibers and cancer. Not until 1991, due to human studies, did OSHA label it carcinogenic.[3][4][5]
4. Though arsenic was a known human carcinogen for decades, scientists still found little evidence in animals to support the conclusion as late as 1977.[6] This was the accepted view until it was produced in lab animals.[7][8][9]
5. Many continued to be exposed to asbestos and die because scientists could not reproduce the cancer in lab animals.
6. Pacemakers and heart valves were delayed in development because of physiological differences between animals they were designed on and humans.
7. Animal models of heart disease failed to show that a high cholesterol/high fat diet increases the risk of coronary artery disease. Instead of changing their eating habits to prevent the disease, people continued their lifestyles with a false sense of security.
8. Patients received medications that were harmful and/or ineffective due to animal models of stroke.
9. Animal studies predicted that beta-blockers would not lower blood pressure. This withheld their development. [10][11][12] Even animal experimenters admitted the failure of animal models of hypertension in this regard, but in the meantime, there were thousands more stroke victims.
10. Surgeons thought they had perfected radial keratotomy, surgery performed to enable better vision without glasses, on rabbits, but the procedure blinded the first human patients. The rabbit cornea is able to regenerate on the underside, whereas the human cornea can only regenerate on the surface. Surgery is now performed only on the surface.
11. Combined heart lung transplants were also “perfected” on animals, but the first 3 patients all died within 23 days.[13] Of 28 patients operated on between 1981 and 1985, 8 died peri-operatively, and 10 developed obliterative bronchiolitis, a lung complication that the experimental dogs did not get. Of those 10, 4 died and 3 never breathed again without the aid of a respirator. Obliterative bronchiolitis turned out to be the most important risk of the peration.[14]
12. Cyclosporin A inhibits organ rejection, and its development was watershed in the success of transplant operations. Had human evidence not overwhelmed unpromising evidence from animals, it would never have been released.[15]
13. Animal experiments failed to predict the kidney toxicity of the general anesthetic methoxyflurane. Many people lost all kidney function.
14. Animal experiments delayed the use of muscle relaxants during general anesthesia.
15. Research on animals failed to reveal bacteria as a cause of ulcers and delayed treating ulcers with antibiotics.
16. More than half of the 198 new medications released between 1976 and 1985 were either withdrawn or relabeled secondary to severe unpredicted side effects.[16] These side effects included complications like lethal dysrhythmias, heart attacks, kidney failure, seizures, respiratory arrest, liver failure, and stroke, among others.
17. Flosint, an arthritis medication, was tested on rats, monkeys and dogs; all tolerated the medication well. In humans, however it caused deaths.
18. Zelmid, an antidepressant, was tested on rats and dogs without incident. It caused severe neurological problems in humans.
19. Nomifensine, another antidepressant, was linked to kidney and liver failure, anemia, and death in humans. Animal testing had given it a clean, side effect-free bill of health.
20. Amrinone, a medication used for heart failure, was tested on numerous animals and was released without trepidation. Humans developed thrombocytopenia, a lack of the type of blood cells that are needed for clotting.
21. Fialuridine, an antiviral medication, caused liver damage in 7 out of 15 people. 5 eventually died and 2 more needed liver transplants.[17] It worked well in woodchucks.[18][19]
22. Clioquinol, an antidiarrheal, passed tests in rats, cats, dogs and rabbits. It was pulled off the shelves all over the world in 1982 after it was found to cause blindness and paralysis in humans.
23. Eraldin, a medication for heart disease, caused 23 deaths despite the fact that no untoward effects could be shown in animals. When introduced, scientists said it noted for the thoroughness of the toxicity studies on animals. It caused blindness and deaths in humans. Afterwards, scientists were unable to reproduce these results in animals.[20]
24. Opren, an arthritis medication, killed 61 people. Over 3500 cases of severe reactions have been documented. Opren had been tested on monkeys and other animals without problems.
25. Zomax, another arthritis drug, killed 14 people and caused many more to suffer.
26. The dose of isoproterenol, a medication used to treat asthma, was worked out in animals. Unfortunately, it was much too toxic for humans. 3500 asthmatics died in Great Britain alone due to overdose. It is still difficult to reproduce these results in animals.[21][22][23][24][25][26]
27. Methysergide, a medication used to treat headaches, led to retroperitoneal fibrosis, or severe scarring of the heart, kidneys, and blood vessels in the abdomen.[27] Scientists have been unable to reproduce this in animals.[28]
28. Suprofen, an arthritis drug, was withdrawn from the market when patients suffered kidney toxicity. Prior to its release researchers had this to say about the animal tests:[29][30] “…excellent safety profile. No …cardiac, renal, or CNS [central nervous system] effects in any species.”
29. Surgam, another arthritis drug, was designed to have a stomach protection factor that would prevent stomach ulcers, a common side effect of many arthritis drugs. Although promising in lab animal tests, ulcers occurred in human trials.[31][32]
30. Selacryn, a diuretic, was thoroughly tested on animals. It was withdrawn in 1979 after 24 people died from drug induced liver failure.[33][34]
31. Perhexiline, a heart medication, was withdrawn when it produced liver failure that had not been predicted by animal studies. Even when they knew they were looking for a particular type of liver failure, they could not induce it in animals.[35]
32. Domperidone, designed as a treatment for nausea and vomiting, made human hearts beat irregularly and had to be withdrawn. Scientists were unable to reproduce this in dogs even with 70 times the normal dose.[36][37]
33. Mitoxantrone, a treatment for cancer produced heart failure in humans. It was extensively tested on dogs, which did not manifest this effect.[38][39]
34. Carbenoxalone was supposed to prevent formation of gastric ulcers but caused people to retain water to the point of heart failure. After scientists knew what it did to humans they tested it on rats, mice, monkeys, rabbits, without reproducing this effect. [40][41]
35. Clindamycin, an antibiotic, causes a bowel condition called pseudomenbraneous colitis. It was tested in rats and dogs every day for one year. They tolerate doses 10 times greater than humans.[42][43][44]
36. Animal experiments did not support the efficacy of valium-type drugs during development or after.[45][46]
37. Pharmacia & Upjohn discontinued clinical tests of its Linomide (roquinimex) tablets for the treatment of multiple sclerosis after several patients suffered heart attacks. Of 1,200 patients, 8 suffered heart attacks as a result of taking the medication. Animal experiments had not predicted this.
38. Cylert (pemoline), a medication used to treat Attention Deficit Hyperactive Disorder, caused liver failure in 13 children. Eleven either died or needed a liver transplant.
39. Eldepryl (selegiline), a medication used to treat Parkinson’s disease, was found to induce very high blood pressure. This side effect has not been seen in animals, where it is used to treat senile dementia and endocrine disorders.
40. The diet drug combination of fenfluramine and dexfenfluramine was linked to heart valve abnormalities and taken off the market although animal studies had never revealed heart abnormalities.”[47]
41. The diabetes medication troglitazone, better known as Rezulin, was tested on animals without significant problems, but caused liver damage in humans. The company admitted that at least one patient had died and another had to undergo a liver transplant as a result.[48]
42. The plant digitalis has been used for centuries to treat heart disorders. However, clinical trials of the digitalis-derived drug were delayed because it caused high blood pressure in animals. Human evidence overrode. As a result, digoxin, an analogue of digitalis, has saved countless lives. Many more could it have survived had digitalis been released sooner.[49][50][51][52]
43. FK 506, now called Tacrolimus, is an anti-rejection agent that was almost shelved before proceeding to clinical trials due to severe toxicity in animals.[53][54] Animal studies suggested that the combination of FK 506 with cyclosporin might prove more useful.[55] In fact, just the opposite proved true in humans.[56]
44. Animal experiments suggested that corticosteroids would help septic shock, a severe bacterial infection of the blood.[57][58] Unfortunately, humans reacted differently. This treatment increased the death rate in cases of septic shock.[59]
45. Despite the ineffectiveness of penicillin in his rabbits, Alexander Fleming used the antibiotic on a very sick patient since he had nothing else to try. Luckily, Fleming’s initial tests were not on guinea pigs or hamsters, it kills them. Howard Florey, the Nobel Prize winner credited with co-discovering and manufacturing penicillin, stated: “How fortunate we didn’t have these animal tests in the 1940s, for penicillin would probably never been granted a license, and possibly the whole field of antibiotics might never have been realized.”
46. Fluoride was withheld as a cavity preventative initially because it caused cancer in rats.[60][61][62]
47. The notoriously dangerous drugs thalidomide and DES were tested in animals and released. Tens of thousands suffered and died as a result.
48. Animal experiments misinformed researchers about how rapidly HIV replicates. Based on this false information, patients did not receive prompt therapies and their lives were shortened.
49. Animal-based research delayed the development of the polio vaccine, according to Dr. Albert Sabin, its inventor. The first rabies and polio vaccines worked well on animals but crippled or killed the people who tried them.
50. Researchers who work with animals have succumbed to illness and death due to exposure to diseases that though harmless to the animal host (such as Hepatitis B) but kill humans.

Time, money, and resources devoted to these experiments could have gone to human-based research. Clinical studies, in vitro research, autopsies, post-marketing drug surveillance, computer modeling, epidemiology, and genetic research pose no hazard to humans and provide accurate results. Importantly, animal experiments have exhausted resources that could have been dedicated to educating the public about health hazards and health maintenance, therein diminishing the incidence of disease that require treatment.

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