KAMPALA: Dr. Monica Musanza Musenero, the Minister of Science Technology and Innovations, has been in the news following accusations of misappropriating about Shs 30 billion given to her line ministry to develop and manufacture Covid-19 vaccines. Last week, she faced a parliamentary investigation launched after Ntungamo Municipality MP Yona Musinguzi accused the minister on the floor of parliament of misappropriating the money. She was accompanied by a team of scientists; Prof Pontiano Kaleebu, the executive director of the Uganda Virus Research Institute (UVRI), Dr. Jennifer Sserwanga, Dr. Sheila Balinda (UVRI), Dr. Cissy Kityo (Joint Clinical Research Council), Prof. Charles Ibingira (Makerere University) and Dr. Enoch Matovu from Busitema University. During her appearance, she revealed that a single mouse needed for clinical trials during vaccine development costs Shs 8 million, stunning the MPs. Ugandans took it a notch higher and swarmed social media spaces wondering how a mere rat can cost the nation 8 million shillings. But what are the facts? What is the Science involved? TOP INTELLIGENCE brings you the details from our fact finding mission. Please, READ ON:-
This week, Uganda’s Social Media spaces got crammed with thousands of posts mocking the Ministry of Science Technology and Innovations, about a mouse costing 8 million Uganda shillings. This followed a revelation by Minister Dr. Monica Musenero before parliament where she is seeking a supplementary budget to equip the vaccine research efforts currently going on in the country. One of the key components of this process is the purchase of these ‘special’ rodents. Some Ugandans asked, and genuinely, “How can a mere mouse that lives in the backyard of my home cost so much?”
Based on pieces of information we have put together from our interaction with scientists at the ministry, and also from sifting through volumes of data, evidence of which shall be provided at the end of this briefing, there is no fuss about a mere mouse in vaccine research. It is not only expensive, it is logistically and technically quite difficult to obtain. It is also not your ordinary mouse, the kind we find menacing our homes, especially kitchens.
“Mice in their natural form share similar genes with humans the same way it is with other animals like Chimpanzes, guerillas among others. To understand the progression of disease in humans, reaction to the introduction of a drug or vaccine in the body, we need to ‘further humanise’ the mice to allow for investigations on potential efficacy of drugs or vaccines,” one of the scientists on the vaccine research programme wrote back to us preferring to remain anonymous.
The scientist calls this type of mice‘trasigenic mice.’ These are the mice that Dr. Musenero was talking about. Which then begs the question that our TOP INTELLIGENCE team has put to these scientists for the benefit of the wider public who may not understand how vaccine/drug research moves:
What are transgenic mice and why are they important?
Transgenic mice are genetically modified mice or genetically engineered mice models that have had their genomes (or DNA) altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. When this process involves the human genomes, it breeds the term “humanise mice” for scientific studies, for example biological and medical research for human therapeutics, drugs and vaccines.
A humanized mouse is one that carries functioning human genes, cells, tissues or organs. To achieve this, mice have genes or DNA from another source put into their DNA through a process called microinjection (transferring genetic materials into a living cell using glass micropipettes or metal microinjection needles) thus becoming transgenic in nature. Put in other terms, they are animal models used as a type of surrogates of various parts of human biology, such as the human immune system.
By transgenic, mean having DNA (genes) from a different organism put into a genome of another. This foreign DNA is put into the nucleus of a mouse. The foreign DNA becomes part of every cell and tissue of the mouse thus transforming the mouse into a whole new organism. In this case we refer to that mouse as being transgenic. These mice differ from the common mice (or rats) because of the alterations and manipulations made to them.
These mice are used in the laboratory for research purposes to study diseases that affect both humans and animals. Researchers usually need mouse models to study the severity of the illness to a disease of interest for example, COVID-19, HIV, Malaria, Tuberculosis, Foot and mouth disease, East Coast Fever Disease, Ebola, cancer and many others.
How Mice help Clinical Trials
TOP INTELLIGENCE can reveal that before a new drug or vaccine is approved for human consumption, it has to go through various stages of clinical trials. These stages include; Preclinical studies which involve both invitro(or test tube or cell culture) and in vivo studies (animal trials) and Human Clinical Trials which include : Phase I trials that test the safety of a possible new treatment in a small group; Phase II trials expand the study to test the effectiveness of the possible new treatment in a larger group of people; Phase III trials expand the study to an even larger group of people and Phase IV is the post marketing trial or drug monitoring trial to assure long-term safety and effectiveness of the drug, vaccine, device or diagnostic test.
Animal studies are conducted in the “Humanized Mice”. During preclinical trials for a new drug, the mice are infected with the germ or virus in question and allowed time to develop the specific disease. Then, the study drug is administered to the mice in a wide range of doses in order to evaluate the efficacy. The point here to establish is the drug or vaccine is effective, toxicity (if it is poisonous) and pharmacokinetics which provides the basis for development as a new investigational drug candidate.
On the other hand, TOP INTELLIGENCE notes that if a new vaccine is being investigated, the mice are vaccinated with the investigational vaccine and allowed time to build immunity and later infected with the germ or virus of the disease in study.
This is done using different doses at different points in time using different mice under the same conditions to determine and study efficacy, toxicity and pharmacokinetics and other side effects. These animal studies involve the use of mice of different gender, age and physiological conditions such as pregnancy in order to study the effects of the vaccine or drug in the various conditions which reflect what would happen in humans in similar states or with similar characteristics.
This implies that for one to carry out a preclinical study for just one investigational drug or vaccine, one requires several mice (or rats) so that tests can be done in different mice with varying characteristics.
How ‘Rats’ are humanized for Vaccine/drug research
If human DNA is input into a mouse, the mouse cells mimic behaviour as when they are in humans thus taking on the term humanized mice. One of the ways to humanise a mouse is microinject human DNA into the cell nucleus of a pregnant mouse. It should be noted that, the success rate of the microinjection procedure results is not guaranteed.
Nevertheless, when achieved, the average success rate of a live-born animal is at only 30% which is really small hence the high cost of production. The other ways to humanise mice is by human immune system engraftment into an immuno-deficient host. Scientists can also do a transfer of fecal microbiota into a human donor into a germ-free mouse.
“All these procedures are costly,” says the scientist on Dr. Musenero’s team.
“An ideal animal model should be permissive to infection and must reproduce the clinical course and pathology observed in humans and this should be customized to the study. Disease models should mimic the type of human disease as closely as possible in immunocompetent animals with a challenge dose and a suitable exposure route as in humans,” he emphasized.
EDITOR’s NOTE: In the next installment, TOP INTELLIGENCE brings you the process by which mice are humanized and why it is a costly venture for a poor country like Uganda.