Tag Archives: basic research

Don’t let medical progress go over the cliff, contact your representative today!

In this blog we frequently discuss threats to medical research, ranging from harassment of individual scientists by animal right extremists, to spurious complaints by animal rights groups, to legislative proposals that may harm medical research.  The threat we wish to draw your attention to today is somewhat different, as it impacts not only on medical research but on all areas of scientific research in the US, but it is one which demands urgent action.

As the end-of-year deadline for agreement on a new federal budget looms ever closer, and discussions in the US Congress continue, the danger of going over the “fiscal cliff” is increasing, an event that would trigger  sequestration — automatic spending cuts scheduled to take effect in January 2013.  These cuts, amounting to about 600 billion in non-defence spending would reduce funding for research agencies by $3.9 billion in 2013 alone. These agencies include those charged with protecting the health of US citizens and developing innovative new therapies to treat disease, the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Science Foundation (NSF), and provide funding for many of the exciting research projects that we have discussed on this blog over the past few years.

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The impact of such cuts, coming after almost a decade of stagnant funding levels – in reality funding decreases in most agencies once you adjust for inflation and a sharp increase in administrative costs over the same period – would be devastating for biomedical research in the USA, as the report “Sequestration: Health Research at the Breaking Point” from Research! America makes all too clear. The leadership of Research!America, a not-for-profit public education and advocacy alliance whose members include many research institutions, charities and scientific associations, noted that this would:

  • Result in the loss of 33,000 NIH-funded jobs and a $4.5 billion decline in economic activity.
  • Eliminate NSF funding for more than 19,300 researchers, students and technical support personnel.
  • Eliminate 2,500 specialized disease detectives in state and local health departments funded by the CDC, severely limiting efforts to identify and stop food borne outbreaks.
  • Mean the loss of $111 million in FDA user fees that are vital for its evaluation activities, delaying patient access to new medical treatments.

What is not so easy to calculate is the longer-term impact when promising young researchers leave science due to career insecurity, when great new ideas go unstudied, when fewer opportunities exist to capitalize on scientific and technical advances, and when new therapeutic ideas don’t get developed to the point where they can be tested in the clinic. The Federal Government provides about 60% of funding for basic research, so it is clear that Research! America’s use of the term “devastating” to describe the impact of the cuts is fully justified. Indeed, investments in science and engineering have produced more than half of U.S. economic growth since WWII, with government funding fostering new knowledge, industrial innovation, and the training of future scientists and engineers, which explains why a recent Pew Research centre poll found that a clear majority of Americans oppose cuts in funding for scientific research.

Unfortunately there are those who see this crisis as an opportunity to renew their ongoing attacks on science. In particular the animal rights group PeTA – using the kind of misleading propaganda we have grown very used to -  is urging it’s supporters to write to their senators and congressional representatives to ask then to cut all funding for animal research (Warning: PeTA Website). Such campaigns make it even more crucial for scientists and those who support science to make their voices heard by the politicians who are currently debating the budget.

So what can we all do about this?

Well, you can head over to the Advocacy and Action page at Research! America, where they have loads of information on how you can contact your Senator, Congressional Representative and President to let them know that while reducing the deficit is important it must not come at the cost of scientific advancement, future economic prosperity, health or human lives. They even have an online tool to help you compose messages to tell our politicians that we need cures, not cuts!

A new campaign SaveResearch.org has united dozens of research charities and scientific organizations to campaign against the cuts, and has lots of suggestions for action, including this research advocacy toolkit that offers lots of helpful advice and tips.

And if you are a scientist the American Association for the Advancement of science has a great resource where you can leave a message or video  that they will take to Capitol Hill and the White House.

You might even take up the suggestion made by the editors of Nature to put on your lab coat and march on Capitol Hill.

Whatever you decide to do, doing nothing is not an option. We in the scientific community – and all those who support scientific research – need to make sure that our political representatives hear our voices, and act now before the damage is done!

Speaking of Research

 

 

Animal rights activists protest Curiosity driven research

The last couple of days was nothing but jubilation at NASA/JPL after the landing of the rover Curiosity on Mars.  President Obama congratulated scientists on the occasion by stating:

The successful landing of Curiosity — the most sophisticated roving laboratory ever to land on another planet — marks an unprecedented feat of technology that will stand as a point of national pride far into the future.”

However, the atmosphere changed dramatically this morning. As JPL scientists came to work, they were perplexed to be greeted by a group of noisy animal rights protestors at the entrance to the Jet Propulsion Labs in Pasadena, California.

Michael Bunkie, from Stop Alien Exploitation Now, told a group of reporters gathered at the scene that:

 These experiments have been done before and nothing came out of them. How many times do we have to land on Mars to just look at rocks?  I mean, all of them look the same! We already have space junk on Mars.  Why do we need more? This is clearly duplicative research done at the taxpayer expense and it must stop.”

Mr. Bunkie said he will FOIA every employee at NASA to obtain more information on what he called “an outrageous waste of resources.”

Dr. Maximus Ego, a retired physician and long-time scientific advisor to Bunkie, added:

“There is really nothing we can learn on Mars that will help humans.  Chaos theory and the Heisenberg uncertainty principle guarantee that even if life originated first on Mars, nothing we learn about its evolutionary history will be applicable to us.  I have published a 300-page long proof of this obvious statement (available from Amazon for $12).  After all, they are Martians and we are humans. Isn’t this obvious to NASA and its so-called scientists?”

When asked about the potential benefits of the research claimed by the space agency Dr. Ego added:

Gimme a break! This is clearly curiosity-driven research.  Nothing else, nothing more. They even named the rover ‘Curiosity’!  It is unacceptable for them to keep misleading the public by saying the questions at hand have any significance for advancing well-being on Earth. This type of research is worse than the discovery of the Higgs Boson!”

As JPL scientists quickly walked past, Dr. Ego ran after them screaming “I challenge you to a debate! Come on, I challenge you to a debate!  Do you know what a hypothesis is? Do you?!” 

Meanwhile, Rick Bungled, of the Alliance for Microbial Ethics, stood by silently holding a sign that read “How like us are they?”  When asked about its meaning Mr. Bungled explained:

How can we be invading Mars when we know there is a chance there might be life there? We must give these hypothetical organisms the benefit of the doubt, and assume they are sentient and conscious life forms just like us. For humans to gratuitously invade other planets is nothing more than a sign of our decadence. We have already destroyed Earth and now we are going to destroy the rest of the Universe. Humans are nothing but evil monsters (except me, of course). The Universe would be a better place if we all killed ourselves (I mean, if you killed yourselves).”

Nearby, Dr. Andrew Smoothtalk, from the Humane Planetary Society, said his organization held a much more moderate position.

“Of course we support science.  But we are now in the 21st century and have developed advanced computers, such as IBM’s Watson which can defeat you at Jeopardy. Clearly, we have the technology to simulate the origin of the solar system. We could send a virtual rover to a simulated Mars and explore simulated life in this simulated planet. We could even give scientists 100 bonus points for a good landing!  Given these new methods, which these NASA scientists are completely unaware of, we think time has come for NASA to switch these type of space exploration with more cost-effective methods than studying the real thing”  Waving out a piece of paper he pulled form his pocket he exclaimed “Here, I have with me a pledge that NASA can sign which already counts with the support of about 800 Raelians.”

NASA/JPL reacted to the criticism by circulating an email to the press this morning stating that they have serious and important work to do and are not planning on wasting precious time in responding to the activist’s allegations.

A masked activist, after being told of the NASA statement, said the activist will continue their relentless work to make space exploration stop “by all means necessary” — and walked away with a Molotov cocktail under his arm.  “To educate the neighbors” — he clarified.  Mr. Bungled, standing next to him, sighed deeply and explained that “the continued refusal by scientists to engage with activists can only lead to violent actions by the underground. Don’t tell us we didn’t warn you.”

Disclaimer: Although this may look like a real story you might have read over the past year or two,  it is in fact satire. Any resemblance to actual living persons is…err…purely coincidental and not to be taken (too) seriously.

Speaking of Research

So, what can a growing fly teach us about skin cancer?

Back in April we welcomed launch of the Golden Goose Awards , an annual prize awarded to honor federally funded research  “whose work may once have been viewed as unusual, odd, or obscure, but has produced important discoveries benefiting society in significant ways.”.

The Golden Goose award was developed in response to attacks on basic research by politicians who fail to appreciate the value of basic research, and it is not difficult to imagine that a research project begun back in the 1980’s which sought to determine the role of a gene named “hedgehog” during embryonic development in fruit flies would have been greeted with derision by the usual suspects .

D. melanogaster, an organism whose small size belies its huge contribution to medical science. Image courtesy of André Karwath.

Any such derision would have been badly misplaced. An article posted last week on the Cancer Research UK Science Update blog reveals how studying the hedgehog gene in the fly Drosophila melanogaster ultimately led to the development ofVismodegib, a drug recently approved for the treatment of advanced basal-cell carcinoma by the FDA, noting that:

 For us, the hedgehog’s tale is a testament to the beauty and potential of basic biology. It’s certainly not the first time that our basic research has helped set the stage for a new drug that can help cancer patients, and – given the progress we’re continuing to make in our research centres across the country – we doubt it will be the last.”

I encourage you to read the full CRUK Science Update Blog post “High-impact science: Hedgehogs, flies and skin cancer – the story of vismodegib” , it’s an excellent example of how research on flies, rodents and a range of other organisms combined with studies of cancer genetics in humans to enabled the development of an innovative therapy.

Paul Browne

The Golden Goose Awards

Politicians sometimes deride research based on the what they perceive as being “silly” titles of federal funded grants.  If they spot a title that deals with “games”, for example, they may assume it deals with some sort of amusement of little value to society, instead of a deep, powerful branch of mathematics that describes the behavior of competing rational agents with much relevance to voting, economics, cooperation, and so on.  Animal rights activists also enjoy the hobby.  The latest example is IDA’s list of “ridiculous research” ,whose claims were sadly repeated by far too many news journalists who were clearly too lazy check if they were accurate.  There were some honorable exceptions, notably an excellent editorial entitled “When the facts ruin a good spin” in the Times Union, which discusses a project on the role of music as a conditioning stimulus for drug use ends with a statement with which we heartily agree:

What’s “ridiculous,” to borrow the press release’s language, is that we fall for it, over and over, egged on by politicians eager to score easy points. And what’s “wasteful” is the time and energy that could be so much better spent on something other than a cheap shot.”

Back in 1976 the House Committee on Appropriations asked the National Science Foundation “Why does the Foundation persist in supporting research whose results have no apparent value to the American people?”  The NSF responded in part that:

Basic research seeks an understanding  of the laws of nature  without  initial  regard  for specific  utilitarian  value. Ultimately, however, it  is of the  most important  practical significance, because in a broad sense it is the foundation upon  which rests  all technological development.  Applied research builds on the results of basic research, seeking detailed  information  about  a specific situation  whose general laws have  been  discovered by  basic  research.  The  final step  toward  utilization  of research-development is  the systematic  application  of knowledge to  the  design  of  end products. [...]

As we  increase  our  knowledge  of nature  and  mankind,  in order  to adjust  nature  to our survival, safety,  comfort and convenience, we must  depend  upon  scientific research  to clarify the  relationships  of many, many things.  Thus,  we study  atoms,  even  though  they  will never  be seen  by an  unaided  human  eye.  We study  stars  too  faint  to  be  seen without  a  telescope  and  with  wavelengths  which  can  only be  detected  with  radio  receivers  or  photographic  plates. To  understand  geology, we must  look  at  geologic formations  and processes in many  parts  of the world where different  conditions have existed.  To understand  more about the  phenomena  of life, we must  study  the  behavior  of viruses,  single  cells,  plants,  and  animals  of  many  species.

A book was compiled covering various areas of research with Isaac Asimov writing an essay defending the value of basic research.

Thus, it was with some surprise and delight that we read in the news about Rep. Jim Cooper (D-Tenn) understanding the value of basic research.  The Washington Post reports that:

On Wednesday afternoon, Cooper rose to the defense of taxpayer-funded research into dog urine, guinea pig eardrums and, yes, the reproductive habits of the parasitic flies known as screwworms–all federally supported studies that have inspired major scientific breakthroughs.

Together with two colleagues he created the Annual Golden Goose Awards to honor federally funded research  “whose work may once have been viewed as unusual, odd, or obscure, but has produced important discoveries benefiting society in significant ways.”

Studying dog urine, among other stuff deem crazy by animal rights cranks, led to major medical discoveries

The article goes on to describe how research on dog urine led to an understanding of the effects of hormones on the human kidney, how studies in the guinea pig led to a treatment for hearing loss in infants, and how studies on the screwworm led to the effective control of the a deadly parasite that targets cattle.  All these provide additional examples refuting the notion that learning about life processes from animals cannot yield knowledge applicable to human health.

The Golden Goose Award has the backing of the American Association for the Advancement of ScienceAssociation of American Universities (who in 2011 published a series of “Scientific Inquirer” articles skewering dubious politically-motivated attacks on basic science) and the Progressive Policy Institute, who are to be congratulated for this excellent initiative to highlight the importance of basic research.

At the press conference to launch the award Rep. Robert Dold told reporters that “When we invest in science, we also invest in jobs. Research and development is a key part to any healthy economy,” while  Rep. Charlie Dent (R-Penn.) added “It’s critical, and the federal government has an important role to play,” who went on to describe how injecting horses with snake venom might “seem peculiar” but led to the discovery of the first anti-venom.

Taking us, once again, to the concluding words of Asimov’s essay:

Unless we continue with science and gather knowledge, whether or not it seems useful on the spot, we will be buried under our problems and find no way out.  Today’s science is tomorrow’s solution — and tomorrow’s problems , too — and, most of all, it is mankind’s greatest adventure, now and forever.

How nerve cells reach their niche.

Developmental biology, the study of the processes through which organisms grow and develop, is an area of biomedical research where modal organisms – ranging from the slime mold Dictyostelium  discoideum to the chicken – play a crucial role, and one that has been honoured with several  Nobel Prizes in recent years.  For example, the 1995 prize for “discoveries concerning the genetic control of early embryonic development” was awarded for studies of the fruit fly  Drosophila melanogaster , and the  2002 prize for “discoveries concerning ‘genetic regulation of organ development and programmed cell death”, was awarded for research undertaken with the nematode worm Caenorhabditis elegans, while the 2007 prize for  “discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells”” depended on studies of stem cells in the developing mouse embryo undertaken by Martin Evans.

Today on the Neurophilosophy blog Mo Costandi has another great example of how our knowledge of developmental biology is being advanced through animal research. In a post entitled “Astrocytes build blood vessel scaffolds for long distance neuron migrations” he discusses how a research team led by Dr Armen Saghatelyan  used  Green Fluorescent Protein labeling and genetic modification to track the processes that control the migration of nerve cells to their correct location in the developing mouse brain.

It’s fascinating work, and you can read about it on the Neurophilosophy blog here.

 

 

So what does this basic research in developmental biology mean to medicine?

Scientists have known for some time that the brain has a limited ability to repair itself following injury, for example after a stroke, and more recent studies have identified a critical role for adult neuronal precursor cells in this recovery.  But the process by these adult neuronal precursor cells migrate to the site of injury and integrate into the damaged brain circuitry is very inefficient, with only a small number of cells reaching the correct location, so scientists are working on a variety of approaches to boost the brain’s ability to repair itself.

One approach to doing this is the use of exogenous stem cells, such as the human embryonic stem cell derived neuronal precursor cells developed by the UK-based company ReNeuron that entered clinical trials for stroke in 2011.

Another avenue being pursued by several research groups around the world is to improve the efficiency with which the endogenous neuronal precursor cells migrate to and repair damaged regions of the brain. In order to develop therapies that improve endogenous brain repair scientists first need to understand the processes that drive – and limit – neuronal precursor production, migration and integration in the developing and adult brain, so that they can modify and enhance those processes to safely  optimize repair.  The work of Dr Saghatelyan and his colleagues has provided medical science with another important piece of a puzzle that when solved will benefit many thousands of stroke victims around the world.

Paul Browne

A breakthrough against Chronic Lymphocytic Leukemia…thank the mice!

A challenge that science communicators frequently face when discussing the process whereby a scientific discovery eventually leads to a medical breakthrough is the time that this often takes, indeed by the time that the reports of exciting clinical trial outcomes start to appear in the press the role of the scientists who made the initial discoveries is often relegated to a passing comment…if it is mentioned at all. An example of this comes from the Weizmann Wave blog, produced by the Weizmann Institute of Science.

You may remember reports last month on the very promising results of a small clinical trial where a new immunotherapy technique was used to eradicate cancer cells in patients with Chronic Lymphocytic Leukemia (CLL), a blood cancer for which currently available treatments are often inadequate.  That trial, conducted by scientists at the University of Pennsylvania led by Professor Carl June, involved removing T-cells from the patient, treating the cells with a lentiviral vector that encodes for a Chimeric Antigen Receptor which recognises a protein named CD19 that is found on B-cells, including the cancer cells responsible for CLL, and then infusing the transformed T-cells back into the patients.  As the reported in the Los Angeles Times the results were dramatic, within a few weeks of the infusion the modified T-cells expanded rapidly and targeted the cancer cells in all three paients, so that a year later two of the three patients were still in complete remission.

It’s exciting stuff but as the Weizmann Wave reports the Press Release issued by Penn Medicine noted that this was a “cancer treatment breakthrough 20 years in the making” but “didn’t, however, explain those “20 years in the making.””. The Weizmann Wave goes on to discuss the pioneering basic scientific research undertaken by Professor Zelig Eshhar at theWeizman Institute of Science in the late 1980’s, which you can read about here.

Of course between the basic research undertaken by Prof. Eshhar and his colleagues in the 1980’s and the clinical trial whose outcome was announced last month there was a lot of work to be done. It would be impractical to describe all the different discoveries that made this immunotherapy possible, but one discovery in particular highlights the importance of animal research to this breakthrough.

There have been previous attempts to use Chimeric Antigen Receptors to target T-cells to attack cancer, but these had disappointing results in clinical trials.  A major improvement made by the University of Pennsylvania team was to include an additional motif – named the CD137 co-stimulatory molecule- which greatly enhances the cancer killing ability of the infused T-cells.  In a recent paper published in the Journal of Cancer the University of Pennsylvania team point out that the decision to include CD137 (called 4-1BB in mice) in their Chimeric Antigen Receptor construct was based on promising results in studies undertaken in mice:

 Our group has tested a CAR directed against CD19 linked to the CD137 (4-1BB) co-stimulatory molecule signaling domain to enhance activation and signaling after recognition of CD19. By inclusion of the 4-1BB signaling domain, in vitro tumor cell killing, and in-vivo anti-tumor activity and persistence of CART-19 cells in a murine xenograft model of human ALL (acute lymphocytic leukemia) is greatly enhanced”

Indeed, in a paper published by Professor June and colleagues in the journal Molecular Therapy in 2009 they describe this work in much more detail, highlighting just how groundbreaking the results were:

Previous in vitro studies have characterized the incorporation of CD137 domains into CARs.10,11,29 Our results represent the first in vivo characterization of these CARs and uncover several important advantages of CARs that express CD137 that were not revealed by the previous in vitro studies. We demonstrated that CARs expressing the CD137 signaling domain could survive for at least 6 months in mice bearing tumor xenografts. This may have significant implications for immunosurveillance, as well as for tumor eradication. For example, in a mouse prostate cancer xenograft model, survival of CAR+ T cells for at least a week was required for tumor eradication.30

Long-term survival of the CARs did not require administration of exogenous cytokines, and these results significantly extend the duration of survival of human T cells expressing CARs shown in previous studies.17,31 To our knowledge, this is the first report demonstrating elimination of primary leukemia xenografts in a preclinical model using CAR+ T cells. Furthermore, complete eradication was achieved in some animals in the absence of further in vivo therapy, including prior chemotherapy or subsequent cytokine support.

The long-term control of well-established tumors by immunotherapy has rarely been reported. Most preclinical models in a therapeutic setting have tested tumors that have been implanted for a week or less before initiation of therapy.32 After establishing leukemia 2–3 weeks before T cell transfer, we found that many animals had long-term control of leukemia for at least 6 months. The efficacy of targeted, adoptive immunotherapy in this xenograft model of primary human ALL compares favorably to our prior experience testing the antileukemic efficacy of single cytotoxic (ref. 27 and data not shown) or targeted agents,26 where we have observed extension of survival but not cure of disease. Additionally, we have not previously observed the ability to control xenografted ALL for a period of as long as 6 months.”

These results led directly to the clinical trial reported last month.

So there you have it, behind the headlines are years of graft by hard-working and innovative scientists, who utilised a wide range of experimental approaches – among which animal studies figure prominently – to develop a novel therapy for CLL. As Professor Bruce Levine points out in the video above, the key to success is often keeping one hand in the basic research lab and the other in the clinic.

Paul Browne

Addendum: Scienceblogger Erv has written an excellent commentary on this study

Taming the Wolf: a new treatment for Lupus

Earlier today we posted a commentary on PeTA’s misleading propaganda by Professor Anthony Garro of UMass Dartmouth.   At the time I mentioned that it was a pity that Prof. Garro was not able to write more about the role of animal research in 21st century medicine, but a recent story in Nature News provides an excellent example, showing how research on mice and monkeys was crucial to the development of a new drug for lupus.

The autoimmune disease lupus, or to give it its full name Systemic Lupus Erythematosus (SLE), affects over 100,000 people in the United States, causing damage to a variety of tissues in the body and a wide range of symptoms ranging from fever, headache and  joint pains to anemia and renal failure. While there is no cure for lupus it can be treated successfully, though current treatments do not work well for all patients. Continue reading

Magic Bullets and Monoclonals: A Breakthrough in Bioscience

The Federation of American Societies for Experimental Biology (FASEB) is one of the world’s largest and most influential scientific organizations, representing as it does 23 independent scientific societies and over 90,000 individual scientists.  As a coalition that represents tens of thousands of US medical researchers FASEB has policies and positions on all kinds of issues which affect scientific research, from federal funding of research to the legal status of embryonic stem cells and human cloning, and you will probably not be altogether surprised to learn that FASEB has taken a very strong position in support of animal research and the scientists who undertake it.

FASEB also takes its responsibility to educate and inform members of the public about the role of biomedical research very seriously and has produced the excellent Breakthroughs in Bioscience, a series of essays written with the help of leading scientists on the research that led to important advances in medicine. While these essays do not of course focus solely on the role of animals in research, key discoveries have after all been made through approaches as disparate as clinical observations and X-ray crystallography,  they do illustrate how important animal research has been as an integral and frequently vital part of the research process.

The most recent essay entitled Magic Bullets and Monoclonals: An Antibody Tale is a great example of this;  I would encourage anyone who is interested in finding out how the role of antibodies in the immune system was first uncovered and how this eventually lead to the development of these “magic bullets” to read it.

A couple of years ago I wrote on the Pro-Test blog about the role of animal research in the development of the monoclonal antibody drug Lucentis that is used to treat the wet form of age-related macular degeneration, a common form of blindness , but it is only one example out of many.  The Breakthroughs in Bioscience essay focuses on the development other monoclonal antibody drugs including Rituximab, a treatment for cancers of the immune system such as non-Hodgkin lymphoma, infliximab, a treatment for autoimmune diseases such as rheumatoid arthritis, and trastuzumab, better known as Herceptin and used to treat breast cancer. While the essay discusses how animals were vital to the production of these monoclonal antibody drugs, the contribution of animal research to the development of these treatments went far beyond just that, as the following two examples illustrate.

Herceptin (1) targets the HER2/neu receptor, a protein whose normal function is to regulate the growth of cells but which is produced in excess in some breast cancers where it promotes tumor growth. HER2 was first discovered to have a role in cancer through studies of cancer in rats and mice, and scientists following up on this discovery then found that it was over-produced in some breast cancers.  Subsequently research in transgenic mice enabled scientists to understand how HER2 promoted tumor growth, while xenograft models where  immunodeficient mice wre injected with  of HER2 positive human breast cancer cells were used to screen candidate monoclonal antibodies, eventually identifying the antibody that was taken into successful human trials as trastuzumab.

The story was similar for infliximab, which works by blocking the action of a chemical messenger called Tumour Necrosis Factor-alpha (TNF-alpha) that promotes inflammation and is a key factor in the development of several autoimmune disorders.  Studies in rodents and dogs played a key role in the isolation and identification of TNF-alpha, and in subsequently animal research that demonstrated its role in both the normal immune system and in inflammatory and autoimmune diseases. This work included studies in transgenic mice which provided the definitive evidence that TNF-alpha plays a crucial role in the development of rheumatoid arthritis , which formed the basis for studies which demonstrated that a chimeric human/mouse monoclonal antibody against TNF-alpha could protect transgenic mice which produced human TNF-alpha from inflammation-induced cachexia (2). Follow up studies in transgenic mice expressing human TNF-alpha provided important pre-clinical information about the safety of infleximab (3).

The examples above show just how important animal research is to both basic research which seeks to understand what is going on in normal physiology and disease, and translational research which seeks to take that knowledge and apply it to developing treatments that can be used effectively in the clinic.  We’re delighted by the work that FASEB is doing to ensure that the public is aware of how all types of research contribute to medical progress, and hope that they continue these efforts for many years to come.

Paul Browne

1)      Pegram M. and Ngo D. “Application and potential limitations of animal models utilized in the development of trastuzumab (HerceptinR): A case study”  Advanced Drug Delivery Reviews Volume 58, Pages 723-734 (2006) DOI:10.1016/j.addr.2006.05.003

2)      Siegel S.A. et al. “The Mouse/Human Chimeric Monoclonal Antibody cA2 Neutralizes TNF In Vitro and Protects Transgenic Mice from Cachexia and TNF Lethality In Vivo” Cytokine Volume 7(1), Pages 15-25 (1995) DOI:10.1006/cyto.1995.1003

3)      European Medicines Agency report http://www.ema.europa.eu/humandocs/PDFs/EPAR/Remicade/190199en6.pdf