Interview with an expert

Because of the sensitivity of my blog topic about preclinical testing, I was only since today allowed to put the read out of my interview with an expert online. First, Prometheus had to give their approval.

For my interview I asked professor Marina Maréchal to tell us about her experiences with animal testing. I wrote out a text that can serve as a complete summarization of my posts and I think it will give you all a clear view on the system and organs behind preclinical and to a lesser extent clinical tests.

Interview with Marina Maréchal

Introduction

Marina Maréchal graduated in 1983 as a dentist and in 1987 she became a specialist in Periodontology. In this period she already did some clinical trials using students as a guinea pig. After her specialization she started a private practice in the periodontology for about 13 years. Her passion for scientific research let her apply for a PhD funded by an IDO project in cooperation with the departments of periodontology, rheumatology, MTM, Biomechanics and prosthodontics. In this collaboration Marina did in vivo experiments with rabbits as animal testing in preclinical trials. After her PhD she started working at Tigenix where she became head of Preclinical in cartilage repair. When the R&D department was shut down, she made a come-back to KU Leuven in preclinical research at Onderwijs&Navorsing, Gasthuisberg.

First steps towards animal testing

The main goals of performing preclinical trials (animal testing) is collecting data about feasibility, iterative testing and safety to define the ultimate safety profile of a new product before clinical trials start. To collect valuable data out of these preclinical experiments, it very important to design these animal experiments as if they are human clinical trials.   As logical as this statement is, the acceptation of doing an animal testing is already provided. An animal is to be treated as humanely as possible. Surgical procedures should be performed using sterile material and under aseptic conditions and using general anaesthesia. During postoperative check-ups the recovery of the animal will be followed checking the experience of pain, monitoring the body temperature, evaluation of the food intake or the occurrence of infections. This implies that the animal may not experience pain or suffer from a severe infection. If this is the case and some medical treatments (e.g. antibiotics, painkillers) do not solve the problem, humane endpoints determine if and when the animal will be sacrificed. Since sacrificing animals before the endpoint of the experiment decrease the number of data collected during the experiments, the animals will be treated as good as possible and also cage enrichment (some toys in the cage) will improve their well-being. Just like with humans, if an animal is feeling happy in general it will be healthier and the delivered data will be more useful.

Ethical commission

In vivo experiments cannot start before the ethics committee approves the experimental template of the study. An ethical commission form has to be prepared and submitted, and without any approval the study is not allowed and no test animals will be available for the study. The number of test animals and the type of animals that will be used in the study will be compared to the preliminary results and the expected results. Mostly in preclinical trials animal testing will involve two different species. One will start using some small animals such as mouse or rats, … followed by a larger animal based on which animal will give the best correlation with a human trial, such as a rabbit, pig, a goat, a sheep, a horse, … The choice of using mice, rabbits, horses or another animal for example is not only one of having the best correlation with a human setting, but safety, efficacy, ethics and money will also be important factors.

To the clinical trials

Before any treatment or product will be commercially available, three clinical test phases are necessary after the preclinical experiments. Phase I clinical trial is conducted in a small group of healthy volunteers (mostly male) to check mainly safety issues that could not yet be answered in the preclinical trials. Phase II clinical trial evaluates the efficacy and also safety issues in a selected population of patients (the target group) and includes a large patient group (around 100-500). Phase III clinical trial is performed in a real-life population (500-5000 patients) when efficacy and safety have already been established and therefor the goal will be to generate additional data on efficacy and safety in relatively large number of patients. Before clinical trials can be done, an enormous amount of preclinical data is needed to convince the ethics committee and the FAGG (in Belgium), put down in a clear document where all issues are mentioned. When one of these two authorities gives negative advice, the clinical trial is not approved. The importance of these extensive controls and the growing importance of preclinical data are demonstrated by some terrible incidents: http://en.wikipedia.org/wiki/Thalidomidehttp://en.wikipedia.org/wiki/TGN1412

Marina Maréchal

I asked her the question if she was still emotional at the moment she had to sacrifice an animal used in a preclinical trial and her reply was clear: “Doing preclinical experiments will include surgical procedures, postoperative care and sacrifice. If at a certain point  I would not feel any difficulty anymore to sacrifice an animal, I will not perform preclinical experiments anymore”.

 

I want to thank Marina for giving me this inside view on the whole mechanism around animal testing and especially by giving me her own perspective on this subject.

 

I hope you now all have a view on why animal testing is done and also how that it has to be performed. I want to thank you all for blogging together those months and for giving me your personal contribution to my topic.

 

Thank you,

Jeroen

Boeing’s hydrogen-powered Drone

Image

Once operational, the Phantom Eye, boasting a wingspan of 150 feet (46 m), will reach altitudes of up to 65,000 feet and carry payloads weighing up to 450 pounds (204 kg). Its liquid-hydrogen propulsion system, whose only byproduct is water, is designed to allow the aircraft to stay aloft for up to four days.

 

 

Another interesting fact  is shown by the graph below, it again shows the great potential of hydrogen!

Energy_density

Source: http://www.gizmag.com/boeing-phantom-eye-taxi-testing/26157/

Robots and dinosaurs

11/04/2013 1 comment

After giving up the idea of cloning dinosaurus, Clive Palmer built a Jurassic Pak with 117 animatronic dinosaurs at the Palmer Coolum Resort at north of Brisbane.

dino

Palmer started his collection by putting two animatronic behemoths. Those are Tyrannosaurus rex called Jeff and an Omeisaurus named Bones.

The creatures in the park will soar up to 6m and have a weight over a ton. That’s not all, they’ll be able to move their tails and blink.

References

robot park

dinos park

The zero energy solution

I found this article about a solution when excess solar energy is used to create hydrogen gas.
A schedule to show the working principle:

A SOLAR-HYDROGEN SYSTEM.
A barn-size array of solar panels collects energy from the sun and converts it to electricity. An electrolyzer runs any excess electricity through water to produce hydrogen gas, which can then be stored for later use. The gas can fuel an experimental hydrogen car. Or it can be converted back to electricity whenever extra power is needed to light or heat the family home.

I believe there are possibilities with techologies like this one. Do you guys agree?

You can read the entire article here:

http://www.nytimes.com/2007/05/20/magazine/20solar-t.html?_r=2&oref=slogin&

 

Biological Hydrogen Production

New technology from researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University greatly improves the efficiency with which hydrogen can be produced in one type of microbe — potentially bringing biological production of this clean fuel source one step closer to economic feasibility. Their discovery, the findings for which appear in the Proceedings of the National Academy of Sciences, resulted in a 500-fold increase in the amount of hydrogen produced in the bacterium used in this research.

For more than a decade, hydrogen has been touted as a clean alternative to fossil fuels because it releases a significant amount of energy relative to its weight and also produces nothing but water when it burns. It can also be produced cleanly, using biological methods, such as photosynthesis. However, the high costs incurred in production have proved too big an obstacle to allow for its wide-spread use.

BioHydGen

In this cross-section illustration of a cyanobacteria, incoming sunlight is captured and used to generate a cellular electron pool that researchers were able to tap to produce hydrogen.

Silver’s team, which included Wyss Institute postdoctoral fellow, Daniel Ducat, and Gairik Sachdeva of Harvard’s School of Engineering and Applied Sciences, has made headway toward one such gain. They focused their attention on one possible — yet problematic — biological production method involving an enzyme known as hydrogenase.

Certain types of hydrogenase can produce a constant flow of hydrogen using only sunlight and water, but most cannot. The difference lies in the particular enzyme’s ability to tolerate oxygen. Most variations are so intolerant of oxygen that its presence will shut down hydrogen production process within a matter of minutes. Yet, creating a way to keep oxygen from entering the production environment would be both costly and impractical — issues that have effectively kept this method off the table.

The researchers developed a technology that could serve as a platform from which to engineer oxygen-tolerant enzymes. Their approach could help lead the way to a cost-effective process for producing significant amounts of hydrogen.

I think that it is great technology, although I am not sure if this technology can provide us with a high and steady flow of hydrogen. What do you think?

Source: http://wyss.harvard.edu/viewpage/238/

Festo

05/04/2013 2 comments

Festo is a German automation company. But beyond industrial automation they also do a lot of research in the field of robotics. While they have some nice parts of humanoid designs, the most interesting designs are their designs based on the locomotion of animals. They base their designs on animals because evolution has “developed” animals in an energy deficient environment. Thus, development based on animals will lead to lightweight and energy efficient designs.

Their first robotic animal experiment was in 2006. They made a robotic fish that could swim.

They continued in the same line in 2007 when they made a manta ray that would swim. They also made a flying version of it.

They continue their aquatic designs with a jelly fish.

Festo Aqua Jelly

Festo Aqua Jelly

And they also build a flying version of it. Which is my personal favourite project of theirs.

In 2009 they build a penguin. Again both in swimming and in flying version.

Festo Aqua Pengiun

Festo Aqua Penguin

In 2010 they stop with their aquatic based designs and make an elephant trunk like arm what they call their Bionic Handling Assistant.

In 2011, they make a robot based on a real flying animal, their smartbird. The wings not only go up and down, but also twist at specific angles.

2012 brings a gripper based on the head of a bird. Because of its design, a very light gripper with a large stroke and force can be achieved.

Festo Powergripper

Festo Powergripper

And this year they released a dragonfly like robot. The Bionicopter. The Bionicopter has 13 degrees of freedom, so this is really a nice example of miniaturisation as all sensors, actuators and control components have to be put in a very small space.

I think they have a very nice research and development atmosphere at Festo and wouldn’t mind working for such a company.

Sources:

Festo : http://www.festo.com/cms/en_corp/13165.htm

Testing on non-human primates

On the occasion of the protest that occurred in front of the royal palace yesterday, I wanted to know what you people think about animal testing on non-human primates. The link to the article at ‘de redactie’ about the demonstration you can find here. Yesterday there was a protest by some members of the anti animal testing organization with the slogan: “Monkeys are no utensils!”. Testing on primates is already been forbidden also in Belgium, but non-human primates are still used for scientific animal testing. The organization wants our government and even our king to stop this testing and to stop the discrimination between different apes.

monkey_1958030c

Associations against animal testing and in particular against testing on (non-human) primates are numerous. I found a website where they are suggesting alternative ways for this scientific tests. Some of these are:

– Embryonic stem cell test: using mouse-derived cells to assess potential toxicity to developing embryos, has been validated as a partial replacement for birth-defect testing in rats and rabbits.

– Human skin model tests: such as the validated EpiDerm™ test, which has been accepted almost universally as a total replacement for skin corrosion studies in rabbits.

– Use of human skin leftover from surgical procedures: or donated cadavers can be used to measure the rate at which a chemical is able to penetrate the skin.

Of coarse if testing is possible without the use of primates and with the use of such alternatives, I would think nobody would understand why it is still done. End even more when you use such pictures like I used in this post. But that is just the reason why these experiments are still done: it is not possible yet. In vivo experiments, especially experiments with drug release and drug absorption involve the totality of the complexity of a living being. No in vitro tests can already cope with this, but the amount of data of these tests is increasing at rapid speed.

Maybe, in future an almost completely digital version of life will be available. What do you think? And should we already stop with testing on non-human primates?

Another interesting article that appeared in the ‘daily telegraph’ in 2011 can be found here. It is about the reasoning, efficiency and the justification of scientific testing on monkeys.