Author Archives: darioringach

Of what use?

Posted on March 23, 2012 | 5 Comments

By Isaac Asimov

One may detest nature and despise science, but it becomes more and more difficult to ignore them.  Science in the modern world is not an entertainment for some devotees.  It is on its way to becoming every-body’s business.  — Theodosius Dobzhansky, in The Biology of Ultimate Concern.

It is the fate of the scientist to face the constant demand that he show his learning to have some “practical use.”  Yet it may not be of interest to him to have such a “practical use” exist; he may feel that the delight of learning, of understanding, of probing the universe, is its own reward.  In that case, he might even allow himself the indulgence of contempt for anyone who asks more.

There is a famous story of a student who asked the Greek philosopher Plato, about 370 B.C., of what use were the elaborate and abstract theorems he was being taught.  Plato at once ordered a slave to give the student a small coin that he might not think he had gained knowledge for nothing, then had him dismissed from the school.

The student need not have asked and Plato need not have scorned.  Who would today doubt that mathematics has its uses? Mathematical theorems, which seem unbearably refined and remote from anything a sensible man can have any interest in, turn out to be absolutely necessary to such highly essential part of our modern life as, for instance, the telephone network that knits the world together.

This story of Plato, famous for two thousand years, has not made matters plainer to most people.  Unless the application of a new discovery is clear and present, most are dubious of its value.

A story about the English scientist Michael Faraday illustrates the point.  In his time, he was an enormously popular lecturer, as well as a physicist and chemist of the first rank.  In one of his lectures in the 1840s, he illustrated the peculiar behavior of a magnet in connection with a spiral coil of wire which was connected to a galvanometer that would record the presence of an electric current.

There was no current in the wire to begin with, but when the magnet was thrust into the hollow center of the spiral coil, the needle of the galvanometer moved to one side of the scale, showing that a current was flowing.  When the magnet was withdrawn from the coil , the needle flipped in the other direction, showing that the current was now flowing the other way.  When the magnet was held motionless in any position within the coil, there was no current at all, and the needle was motionless.

At the conclusion of the lecture, one member of the audience approached Faraday and said, “Mr. Faraday, the behavior of the magnet and the coil of wire was interesting, but of what possible use can it be?”  Faraday answered politely, “Sir, of what use is a newborn baby?”

It was precisely the phenomenon whose use was questioned so peremptorily by one of the audience that Faraday made use to develop the electric generator, which, for the first time, made it possible to produce electricity cheaply and in quantity.  That, in turn, made it possible to build the electrified technology that surrounds us today and without which life, in the modern sense, is inconceivable.  Faraday’s demonstration was a new-born baby that grew into a giant.

Even the shrewdest of men cannot always judge what is useful and what is not.  There never was a man so ingeniously practical in judging the useful as Thomas Alva Edison, surely the greatest inventor who ever lived, and we can take him as our example.

In 1868, he patented his first invention.  It was a device to record votes mechanically.  By using it, congressmen could press a button and all their votes would be recorded and totaled instantly.  There was no question that the invention worked; it remained only to sell it.  A congressman whom Edison consulted, however, told him, with mingled amusement and horror, that there wasn’t a chance of the invention being accepted, however unfailingly it might work.  A slow vote, it seemed, was sometimes a political necessity.  Some congressmen might have their opinions changed in the course of a slow vote, whereas a quick vote might, in a moment of emotion, commit the Congress to something undesirable.

Edison, chagrined, learned his lesson.  After that, he decided never to invent anything unless he was sure it would be needed and wanted and not merely because it worked.

He stuck to that.  Before he died, he had obtained nearly 1,300 patents — 300 of them over a four-year stretch, or one every five days, on the average.  Always he was guided by his notion of the useful and the practical.

On October 21, 1879, he produced the first practical electric light, perhaps the most astonishing of all his inventions. (We need only sit by candlelight for a while during a power breakdown to discover how much we accept and take for granted the electric light.)

In succeeding years, Edison labored to improve the electric light and, mainly, to find ways of making the glowing filament last longer before breaking.  As was usual with him, he tried everything he could think of.  One of his hit-or-miss efforts was to seal a metal wire into the evacuated electric light bulb, near the filament but not touching it, the two separated by a small gap of vacuum.

Edison then turned on the electric current to see if the presence of the metal wire would somehow preserve the life of the glowing filament.  It didn’t, and he abandoned the approach.  However, he could not help noticing that an electric current seem to flow from the filament to the wire across  the vacuum gap.

Nothing in Edison’s vast practical knowledge of electricity explained that phenomenon, and all Edison could do was to observe it, write it up in his notebooks, and, in 1884 (being Edison), patent it.  The phenomenon was called the “Edison effect,” and it was the inventor’s only discovery in pure science.  Edison could see no use for it.  He therefore pursued the matter no further and let it go, while he continued the chase for what he considered the useful and the practical.

In 1880s and 1890s, however, scientists who pursued “useless” knowledge for its own sake, discovered that subatomic particles (eventually called “electrons”) existed, and that electric current was accompanied by a flow of electrons.  The Edison effect was the result of the ability of electrons, under certain conditions, to travel unimpeded through as vacuum.

In 1904, the English electrical engineer John Ambrose Fleming (who had worked win Edison’s London office in the 1880s in connection with the developing electric-light industry) made use of the Edison effect and of the new understanding that the electron theory had brought.  He devised an evacuated glass bulb with a filament and a wire which would let the current through in one direction but not in the other.  The result was a “current rectifier.”

In 1906, the American inventor Lee De Forest made a further elaboration of Fleming’s device, introducing a metal plate that enabled it to amplify electric current as well as to rectify it.  The result is called a “radio tube” by Americans.

It is called that because only such as device could handle an electric current with sufficient rapidity and delicacy to make the radio a practical instrument for receiving and transmitting sound carried by the fluctuating amplitude of radio waves.  In fact, the radio tube made all of our modern electronic equipment possible — including television.

The Edison effect, then, which the practical Edison shrugged off as interesting but useless, turned out to have more astonishing results than any of his practical devices.  In a power breakdown, candles and kerosene lamps can substitute (however poorly) for the electric light, but what substitute is there for a television screen?  We can live without it (if we consider it only as an entertainment device, which does it wrong), but not many people seem to want to.

In fact, the problem isn’t a matter of showing that pure science can be useful.  It is much more difficult problem to find some branch of science that isn’t useful. Between 1900 and 1930, for instance, theoretical physics underwent a revolution.  The theory of relativity and the development of quantum mechanism led to a new and more subtle understanding of the basic laws of the universe and of the behavior of the inner components of the atom.

None of it seemed it seemed to have the slightest use for mankind, and the scientists involved — a brilliant group of young men — apparently had found an ivory tower for themselves that nothing could disturb.  Those who survived into later decades looked back on that happy time of abstraction and impracticality as a Garden of Eden out of which they had been evicted.  For out of that abstract work there unexpectedly came the nuclear bomb, and a world that now lives in terror of a possible war that could destroy mankind in a day.

But it did not bring only terror.  Out of that research also came radio-isotopes, which have made it possible to  probe the workings of living tissue with a delicacy otherwise quite impossible, and whose findings have revolutionized medicine in thousand ways.  There are also nuclear power stations, which, at present and in the future, offer mankind the brightest hope of ample energy during all his future existence on earth.

There is nothing, it turns out, that is more practical, more downright important to the average man, whether for good or for evil, than the ivory-tower researches of the young men of the early twentieth century who could see no use in what they were doing and were glad of it, for they wanted only to revel in knowledge of its own sake.

The point is that we cannot foresee the consequences in detail.  Plato, in demonstrating the theorems of geometry, did not envisage a computerized society.  Faraday knew that his magnet-induced electric current was a new-born baby, but he surely did not foresee our electrified technology.  Edison certainly didn’t foresee a television set when he puzzled over the electric current that leaped the vacuum, and Einstein, when he worked out the equation E = mc2 from purely theoretical considerations in 1905, did not sense the mushroom cloud as he did so.

We can only make the general rule that, though all of history, an increased understanding of the universe, however out-of-the-way a particular bit of new knowledge may seem, however ethereal, however abstract, however useless, has always ended in some practical application (even if sometimes only indirectly).

The application cannot be predicted, but we can be sure that it will have both its beneficial and its uncomfortable aspects.  (The discovery of the germ theory of disease by Louis Pasteur in the 1860s was the greatest single advance ever made in medicine and led to the saving of countless millions of lives.  Who can quarrel with that?  Yet it also has led , in great measure, to the dangerous population explosion of today.)

It remains for the wisdom of mankind to make the decisions by which advancing knowledge will be used well or not ill, but all the wisdom of mankind will never improve the material lot of man unless advancing knowledge presents it with the matters over which it can make those decisions.  And when, despite the most careful decisions, there come dangerous side-effects of the new knowledge, only still-further advances in knowledge will offer hope for correction.

And now we stand in the closing decades of the twentieth century, with science advancing as never before in all sorts of odd, and sometimes apparently useless, ways.  We’ve discovered quasars and pulsars in the distant heavens.  Of what use are they to the average man? Astronauts have brought back rocks from the moon at great expense.  So what? Scientists discover new compounds, develop new theories, work out new mathematical complexities.  What for?  What’s in it for you?

No one knows what’s in it for you right now, any more than Plato knew in his time, or Faraday knew, or Edison knew, or Einstein knew.

But you will know if you live long enough; and if not, your children or grandchildren will know.  And they will smile at those who say, “But what is the use of sending rockets into space?” just as we know smile at the person who asked Faraday the use of his demonstration.

In fact, 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.

—

From the introduction to “The greatest adventure: basic research that shapes our lives”, Eds. E. H. Kone and H. J. Jordan, Rockefeller University Press, 1974.

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A Brief History of Deep Brain Stimulation

Posted on March 15, 2012 | 11 Comments

An on-going campaign against the use non-human primates to study Parkinson’s disease (PD) at the University of British Columbia prompted me to summarize some basic facts about the work and the history of a successful therapy was developed.

Why is the work done?

In the U.S. alone there are between 500,000 and 1 million people living with PD, with about 50 to 60 thousand new diagnoses every year.  The National Institutes of Neurological Disorders and Stroke (NINDS) estimates the cost to our society is at least $5.6 billion, including both direct medical expenses and indirect costs from lost income, disability payments and so on.  Moreover, the emotional toll of Parkinson’s on patients and families is enormous.

One of the most successful therapies developed for PD  involves the electrical stimulation of deep structures within the human brain — so called deep brain stimulation (DBS).  The technique works remarkably well for some patients.

How was the method developed?

Back in 1983 Langston and colleagues reported on a clinical case study of four patients that developed Parkinsonism after illicit drug use.  Analyses of the drugs they had taken via mass spectroscopy revealed primarily MPTP, but there were also traces of MPPP. They suggested MPTP might be the most likely culprit and suggested that:

“Given the pathologically studied case, the relative purity of the clinical syndrome seen in our patients, and its remarkable clinical resemblance to Parkinson’s disease, the drug [MPTP] may be of value in producing an animal model of Parkinson’s disease.”

In other words, a group of clinicians studied a handful of human patient cases, identified a potential link between MPTP toxicity and the development of PD, and proposed to follow up with animals studies.

In 1983, Burns and colleagues follow up on this idea by trying to replicate the disease in monkeys.  Indeed, intravenous administration of MPTP caused the animals to develop rigidity, postural tremor, eyelid closure, and many other symptoms of Parkinsonism.  Moreover, their symptoms could be relieved by the administration of L-dopa, exactly as it was the case with the Langston et al patients. The animal model also allowed them to characterize the selective destruction of dopaminergic neurons in the subtantia nigra and a marked reduction in the dopamine content of the striatum.  They offered MPTP treated monkeys as a model to explore therapies for PD.  How many animals were used?  Twelve.

Although these anatomical studies shed light into the brain areas that might be involved in PD it was unclear what functionally was causing the observed symptoms.  Subsequent work by Mitchell et al (1989) using single unit recordings and lesion studies in monkeys pointed to increased activity in the subthalamic nucleus (STN) as generating motor abnormalities.  How many monkeys were used?  Eight.

A natural question arose from these studies.  Would suppressing the activity of these hyperactive neurons help in alleviating the symptoms of the disease?

Two studies showed that lesions of the STN could reverse the effect of Parkinson symptoms in the monkey MPTP model, with studies by Bergman et al (1990) and Aziz et al (1991).  These studies not only began to dissect the functional connectivity within the basal ganglia-thalamocortical circuit, but also offered evidence that inactivation of the STN could work as a potential therapy for Parkinson’s.   How many monkeys were used in these two studies?  Four.

Shortly after, Benazzouz et al (1993) showed that instead of lessoning the STN one could use high frequency stimulation of the STN to alleviate the symptoms in MPTP treated monkeys.  Supposedly, the high frequency stimulation suppresses the activity of these cells acting as a “virtual lesion”.  How many monkeys were used here?  Two.

Indeed, Limousin et al (1995) successfully applied this method in three patients and concluded:

“In this study, bilateral subthalamic nucleus stimulation improved akinesia and rigidity in three patients with Parkinson’s disease.  This is in agreement with the results obtained in monkeys with MPTP-induced parkinsonism by lesions or stimulation of the sub-thalamic nucleus.”

Number of humans used?  Three.

And to dispel any remaining doubts he writes in a recent review that:

“The knowledge of the functional changes of basal ganglia activity in the parkinsonian state as it emerged from extensive experimental studies on animal models has provided the theoretical basis for surgical therapy in PD. The 6-hydroxydopamine (6-ODHA) rat model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD provided powerful research tools for uncovering the pathophysiology of changes in functional basal ganglia activity in PD.” 

And finally one may ask, ho many human patients have benefited from this type of work?

The answer is 80,000 and counting.

What do these patients think of such studies?

Here is one — please listen to him carefully.

And if you truly want to learn more here are some extra resources:

SfN brain briefing on PD discoveries.
The Michael J. Fox Foundation
Information from National Institutes of Neurological Disorders and Stroke.
Information from Understanding Animal Research.

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Posted in Science News, Animal Rights News

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The Morality of Inaction: Reframing the Debate

Posted on March 9, 2012 | 2 Comments

Opponents of the use of animals in research challenge scientists and society as a whole to answer a simple question – How can we possible justify harming other living beings in the course of scientific studies?

In framing the moral debate with this question there is an implicit assumption that needs to be clarified. That is, opponents of the research assume that they do not need to provide a moral justification for their own position since they are not the ones harming animals.

However, there are many circumstances where choosing not to act turns out to be untenable.

If we were to find a toddler drowning in a bathtub, we would feel morally obliged to act and to save her life, particularly because doing so would not require us to assume any significant risk to ourselves.  Inaction in this case would be morally wrong and unjustifiable.  This illustrates the fact that inaction is not morally neutral; it requires justification.

In this regard opponents of animal research are avoiding an important question. What would be the consequence of inaction?  That is, what would be the cost to mankind of not doing medical research with animals?  And if the answer is that there is substantial cost in terms of lives and suffering, how can one justify not doing the work?

Some research opponents prefer to avoid the question altogether by denying that the research is relevant to human or animal health, implying that harm is done to animals without producing any benefits. However, no matter how many times animal activists attempt to rewrite medical history the facts are clear. Animal research contributed to the development of vaccines for polio, smallpox, diphtheria, tetanus, whooping cough, measles, rubella, mumps, hepatitis A/B, influenza, rotavirus, chickenpox, meningitis, human papillomavirus, all of which combined saved billions of human lives. Animal research also played an important role in the development of antibiotics, blood transfusion, lung surfactants for neonatal care, insulin, antidepressants, anti-retroviral therapy, and so on. The scientific consensus indicates that animal research is critical at the present time to advance medical research and human health.  Arguments along these lines fail.

A Nature poll shows that 92% of scientists agree or strongly agree that "animal research is essential to the advancement of biomedical research"

On the other hand, if one accepts the immense benefits of the work to the health of animals and humans alike, then the only way to oppose it is by arguing the case that all living beings have the same basic rights. Certainly, if a mouse has the same rights to life and freedom as a human being, we would not experiment on the mouse for the same reasons we do not experiment on healthy humans. But the overwhelming majority of opponents of research are reluctant to argue the case for animal rights, retreating to the anti-science argument described above instead of explaining clearly to the public why is that a mouse has the same rights to life and freedom as you and me.

If society is being asked to stop doing the research, the least we can expect is a clear and strong moral argument why all living beings deserve same rights to life and freedom accorded to human beings. It is evident that, so far, animal rights philosophers and activists have failed to persuade the public. For those who are frustrated by this failure, we also note that harassment, threats and intimidation do not count as moral arguments either.

When one walks through the halls of a hospital and sees the myriad of patients and the suffering that they and their families experience; and when we further recognize that we have the scientific ability to reduce and eliminate suffering from the world with our work, it adds a dimension to this debate.  Suddenly it is the opposition who has the burden of explaining why it would be morally permissible to stop the work that has produced, and will continue to produce, immeasurable benefit to both animals and humans alike.

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Follow the Law or Your Extremist Convictions?

Posted on March 8, 2012 | 3 Comments

This is the question that animal rights activist Camille Marino must be pondering as she heads back to Florida with an order by Wayne Circuit Court Judge Susan L. Hubbard to remove threatening statements from her web site against a Wayne State Professor, for which she will face trial on May 2nd.

Marino’s lawyer, John F. Royal failed to convince the judge that the court had no jurisdiction over the case. He remained convinced that “Our position is that everything that was posted so far is protected by the First Amendment”.  This is a view that other animal activists have expressed before.

Mr. Royal argued that O’Leary can’t prove his client wrote the threatening postings on the blog, including statements such as the professor is a “serial torture-murderer” and “a piece of human excrement.” Yet earlier Wednesday, Ms. Marino was once again expressing her view that researchers are “torturing” animals and that her job is to “use a sledgehammer and expose what they are doing.”  The judge rejected this argument as well.

The judge’s decision is not surprising.  Because of her hateful and threatening language, Ms. Marino has been recently featured in the Hate Watch column of the Southern Poverty Law Center. In that interview, she apparently acknowledged writing the statements Mr. Royal now seems to deny.

“I simply published information about a man who tortures dogs to death for money. He’s euphemistically called a researcher,” she said of the Wayne State professor. On NIO’s (Negotiation is Over) website, she described the researcher as a “Serial Torture-Murderer” while encouraging “[l]ocal NIO activists” to “show up at his home and snap pictures of his blood-money mansion and his miscreant spawn for publication.”

But, as we know now, O’Leary’s lab was inspected by the U.S. Department of Agriculture, the U.S. Department of Health and Human Services Office of Laboratory Animal Welfare and an internal group. There was “no evidence of noncompliance in Dr. O’Leary’s lab with the federal policy on humane care and use of laboratory animals” in his important work to study cardiac diseases. In other words, despite Marino’s inflammatory words, Dr. O’Leary was doing the research society has charged him to do, according to the mandates of the Animal Welfare Act and the PHS Policy on Humane Care and Use of Laboratory Animals.

As Ms Marino heads home the judge’s advice to her was simple: “If you continue to engage in posting where you are threatening him and he’s in fear, you are violating the law.” But we know how she feels about the rule of law. In her recent interview with SPLC Ms. Marino offered that: “ [...] the law does not exist to protect the innocent. The law exists to regulate and enforce the agenda of the corporate industrial complex. Their job is to make money, to make money off the animal holocaust. When we talk about laws, it’s all relative [...]”

There is no doubt that Ms. Marino has been faithful to her deepest held convictions and principles in the past. We will have to wait and see if she decides to remove the threats from her web site, as ordered by a Judge whose job is merely to “enforce the agenda of the corporate industrial complex”, or if she will stick by her principles, challenge the order, and exercise what she and her lawyer are convinced are her first amendment rights.

In the meantime, society and hate-watch groups – the Southern Poverty Law Center has just published a new and more detailed report on NIO and its activities - will continue to view the actions of Marino and her accomplices for what they are: the organized harassment, intimidation and threats from animal rights thugs who cannot accept their failure to convince the public of their ideas by means of reasoned debate, and have decided that it is now time to force them unto others by means of threats and violence.

Speaking of Research 

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A welcome end to random-source dog and cat dealers

Posted on February 15, 2012 | 2 Comments

The National Institutes of Health has announced that starting October 1, 2012, NIH funds may no longer be used to buy cats from Class B dealers. A similar prohibition in the purchase of dogs from Class B dealers takes effect in 2015.

Although dogs and cats constitute only small percentage of research animals, they have been used in American biomedical research for over a century for studies of cardiovascular and neurological diseases, and for other areas of research including recent studies that led to a gene therapy for the eye disease Leber’s congenital amaurosis, whose success was reported widely last week.  The use of these animals is tightly regulated by the Animal Welfare Act, and they are only employed for studies where lower species do not provide adequate models.

Class B dealers are individuals licensed by the USDA under the Animal Welfare Act to resell animals they did not breed themselves. Class A dealers are breeders who do raise the animals themselves. Class B dealers may purchase dogs and cats from sources such as municipal pounds, from individuals who bred and raised the animals, and from other licensed dealers. They are required to keep records on where they got each animal and to hold pound animals for a minimum period so that if an unwanted animal was actually a stray, the owner has time to reclaim it.

Animal statistics in 2010 (US data) - Dogs account of 0.25% and cats 0.08% of the total number of animals used.

Class B dealers used to provide a large number of cats and dogs for research because they were virtually the only source for older animals and for some breeds. Regrettably, some Class B dealers used practices that violated the Animal Welfare Act both in terms of how they acquired animals and how they treated them.  The National Academies of Science studied the specific areas of science where Class B dogs and cats were being used and concluded that NIH could develop alternate supply mechanisms to replace them. NIH decided the best way to facilitate the transition was to provide an initial outlay of funds so that Class A dealers could begin raising older dogs of the breeds required for scientific research. It is expected that these breeders will be able to produce the necessary animals by 2015.

After October 1, 2012, NIH-grant supported research can only use cats from the following sources: Class A dealers, privately owned research colonies, or client owned animals, such as animals that participate in veterinary clinical trials.  The same policy will apply to dogs in 2015 when the Class A breeding program is in full swing.

The transition of NIH-funded research away from the use of Class B dogs and cats is an example of how measures can be taken to correct ethical problems regarding the treatment of animals.  When ethical concerns exist, thoughtful and deliberate steps can address those concerns, while preserving important biomedical research projects.

Bill Yates and Alice Ra’anan.

Bill Yates is the Chair of American Physiological Society Animal Care and Experimentation Committee. Alice Ra’anan is Director of Science Policy for the American Physiological Society. The views expressed above are exclusively those of Bill Yates and Alice Ra’anan and do not necessarily represent those of their employers.

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Posted in Animal Rights News, Science News

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Pop Quiz!

Posted on February 3, 2012 | 11 Comments

Take out a piece of paper and a sharpened #2 pencil.

Please read carefully the following story and answer all the questions.

You have 15 min.

One Saturday morning Dr. X was walking her dog thinking about some recent results in her field when it dawned on her that she might actually have the key to explaining all those findings.  If she was correct, she could go on to develop a new therapy for a terrible disease.

Being a scientist, Dr. X rapidly turned that idea into a specific hypothesis with testable predictions.  She ran back to her laboratory, gathered her students, told them the idea, and got to work.  They were excited when their first test (T1) yielded a positive result.  This simply meant that the implications of her hypothesis were corroborated by the experiment.  Good job everyone!

The next day her students were up all night running the second test (T2).  Dr. X arrived at the laboratory after dropping her kids in school to find very tired students, but with big smiles on their faces.  The second test, she correctly guessed, gave them another positive result.  Hurrah!

That night, at the dinner table, she shared the excitement with her family. Even the dog appeared to notice something important was going on. Next morning, one of her postdoctoral students came up with, what appeared to be, a direct test of the central idea.  It was agreed at the Lab meeting that this would be the next experiment (T3).

It was a difficult experiment.  Dr. X’s husband agreed to pick up the kids instead and let her finish her work.  Close to midnight the results came in.  Everyone in the lab ran to see the results.   They stared at each other in disappointment.  The result was clearly negative — what this meant is that the outcome contradicted a key prediction of the hypothesis.

Dr. X’s Lab had a difficult month.  They went over the data over and over again — nothing was obviously wrong; but they decided not to give up.  Instead, they brainstormed about how they could come up with a new hypothesis that may explain the data they had collected so far.  And yes, Dr. X explained, this must include a reason for the outcome of the negative experiment as well.

One night, Dr. X was awoken by the sound of the phone. She was startled, it was unusual that anyone would call at 3 am to her home. Understandably, Dr. X answered the phone with some apprehension.  She was relieved to hear one of her students, which after calming himself down and apologizing for the time, described to her a new idea that, he said, came to him out of nowhere in the middle of his sleep.  She grumbles, but listened…  her sleepy eyes slowly widening as the student went on.  When he was done Dr. X immediately knew that there was no doubt her student could explain the diverse findings.

Everyone gathered in the laboratory next morning and started to test again based on the new concept over the week.  T4… positive!  T5….positive!  T6… negative…  Negative?!  Oh no…  Again?!

Yes, again.  But Dr. X gathered her students and explain to them that this is how science works.  New ideas emerge from old ones in an effort to account for all the data their community gathered so far.  And that negative findings were important for science too. They all felt a bit better as they went home… just a little bit.  But more than Dr. X’s words, it was a group feeling that they were getting closer to the truth.

It took her Lab a few more iterations of this difficult game called science, but one day they knew they had nailed it.  They had a new idea that not only explained all past results but stood many additional tests, including replications by her colleagues.  Their work delivered a medical breakthrough that allowed them to develop a new medical treatment that saved uncountable human lives.

Questions:

Assume that in this story, from beginning to end, including her experiments those of her colleagues, scientists performed 20 experimental tests that yielded positive results, 15 experimental tests that yielded negative results, and that each test required the use of exactly one mouse.

Q1. How many mice were scientifically necessary to develop this medical breakthrough?

Q2. Which experimental tests were more important in developing this breakthrough?  The tests yielding positive results or the ones yielding negative results?  Explain.

Q3. Given the end result was that uncountable human lives are being saved.  Which test was morally justifiable and which was not?  Were positive tests in any way more justifiable than negative ones?  Were experiments used in replicating Dr. X’s findings necessary and justified?  Or is it only the final experiment directly preceding the development of the new therapy that was justified?

Q4. Five years after her discovery, and with the new knowledge acquired, one of Dr. X’s colleagues comments that it was obvious some of the ideas she had tried could not have worked.  With 20/20 vision, Dr. X agrees.  Does her admission mean the experiments testing those ideas were scientifically unnecessary or ethically indefensible?

Submit your answers in the comments section below!

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A Proposal for the Labeling of Medicines

Posted on January 12, 2012 | 4 Comments

In a recent poll conducted by Zogby, 2,100 adults in the U.S. were asked the following question.

Do you agree or disagree with medical and scientific research that requires lab animals?

The results showed  a similar outcome to that of other recent polls.

About 52% of the population approve of animal research in various degrees, about 27% disapprove in various degrees, 15% are neutral and 6% are unsure about their position.

Despite the many polls done on the subject it remains unclear on what grounds do some people object to the use of animals in science.

Is it perhaps that they find the work morally wrong?  Is it that they believe all living beings have the basic rights to liberty and freedom?

Some insight into these questions can be gained by asking the same group of people what would the do in the following scenario.

Suppose you suffer from a leaky heart valve, and that doctors say you have two years left.   You could have a valve replacement surgery that might save your life.  But, in order to obtain the replacement tissue necessary for a surgery, a pig must be killed.

Which of the following statements best reflects what you would do if faces with a similar situation?

Statement A: I would have the surgery.  I think it is ethical.
Statement B: I would have the surgery, but I think it is unethical.
Statement C: I would not have the surgery, but I think it is ethical.
Statement D: I would not have the surgery because I think it is unethical.

Here are the results from the same poll:

Now, if one believes animals have rights they surely ought to be respected.  If you believe a pig has the same basic rights to life and freedom as your neighbor, then you ought to refuse the surgery for the same reason that you would not kill your neighbor to save your own life.

However, only a mere 3% of those asked appear ready to act in a way consistent with such a position.  It is interesting to note that also about 3% of the US population are vegetarian, although most of them do it for health reasons and not ethical objections to the use of animals as food.

Thus, those that oppose research do not appear to do so because of belief that all living beings have the same basic rights to life as that of fellow humans.

Another small minority, 2%, would not have the surgery despite the fact they think such surgical intervention is ethical.  It would appear this group simply is uncomfortable with the notion that pig tissue would be implanted in their human hearts.

About 12% of the group would opt to save their lives despite having ethical objections.  It appears this group feels there is something inherently wrong in killing an animal to allow them to survive and yet, if faced with the situation they would nonetheless go ahead with the surgery.  Arguably, this group realizes that the pig is a living being that we owe moral concern, but that when human and animal lives are at stake, opting to save the human is morally permissible.  Alternatively, they may genuinely opt for behaving in an immoral fashion when it comes to saving their own lives.

Finally, the vast majority, 73% of them, will opt for the surgery without having any moral concerns whatsoever.   None at all.   That is roughly 3 out of 4 people in the US population.

A natural question is then why wouldn’t the same group, at the very least, be in favor of animal research that advances medical knowledge and human health?

One likely possibility is that they fail to see the direct link between research and the therapies and medicines that it produces.  They fail to see that the medicine that will save their lives next time they visit the emergency room will be, in all likelihood, the result of animal research.  They may wrongly perceive basic and translational research as two being completely different things.  The contribution of basic knowledge to human health may be lost in translation.

So, what can be done?

Aside from scientists and physicians reaching out to educate the public on this matters, we could begin by labeling each and every single medication that resulted from basic research in animals with such basic information.  Note that I am not talking about safety testing in animals — which is required by the law.  Instead, I am referring to medicines developed through the identification of molecular targets or the discovery of specific mechanisms with the use of animals in basic research.  In other words, I propose to label medicine as derived from animal research if it actually produced the knowledge that actually allowed scientists to understand how a particular therapy could be developed.

Shouldn’t the public be entitled to know where their medicines come from? Shouldn’t the public be entitled to understand the range of benefits produced by their tax dollars?

What do you think?

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Ignorance or Deception?

Posted on January 9, 2012 | 3 Comments

Animal rights activists may want to start cooling down their engines.

Apparently, by 2050 we can expect the complete elimination of animal use in science.

At least, this is the prediction made by Dr. Andrew Rowan, Chief Scientific Officer of the Humane Society of the United States (HSUS) in a recent article that appeared in The Scientist.

The title of the piece was “Avoiding Animal Testing.  Advances in cell-culture technologies are paving the way to the complete elimination of animals from laboratories”.

The first half of the article focuses on the development and adoption of alternatives to the use of animals in toxicology.  Our public health officials and the FDA have long made the sensible decision to require any company that introduces new chemicals or drugs into the market to provide an initial experimental assessment of their potential toxicity to humans.

This use of animals for such safety screening is typically called animal testing.

Dr. Rowan correctly points out that advances in the development toxicology methods may allow us eventually to relax the regulations that require the use of animals in testing.  But he rapidly moves to insinuate such advances imply that by 2050 we could see the end of animal use in laboratories:

This overall decline in animal use can be attributed to the advent of novel technologies such as improved cell-culture systems and micro-analytic techniques; more sophisticated model systems; improved understanding of signaling and metabolic pathways; and a host of other new methods that allow scientists to answer important questions about the functioning of healthy and diseased tissues without subjecting whole animals to harmful procedures. With a 50 percent decline in animal research since 1975, we are roughly at the halfway point towards the complete elimination of animal research. Thus, we argue that, by 2050, we might finally see the last of animal use in the laboratory, particularly if all stakeholders put their minds to it.

First, the assertion that the total use of animals is systematically declining is not supported by the data.  The slide below, for example, was taken from a recent talk Dr. Rowan gave at the University of Wisconsin.  It shows the total number of animals used has been stable since the mid 80s, with the number of non-genetically modified (Non-GM, faint dashed line) animals decreasing and stabilizing in the 90s (see also data here), while the number of  genetically modified (GM) animals, which are largely mice, has been systematically increasing.

Second, even if correctly asserting that we can expect a diminished need for animals in toxicology testing, Dr. Rowan’s generalization of such trend from a such narrow field to all of biomedical research is groundless and misleading.

Let us be clear, our universities do not engage in animal testing, but in animal research.

What’s the difference?

Scientists are largely concerned with elucidating the basic mechanisms of biological processes in health and disease.  We want to study how cells in our bodies work, how they communicate, how they develop, how they age and how they die.   We want to understand how the brain, our immune system, and internal organs work and how they fail.  And so on…

Why is it critical we develop such an understanding?

Because without this knowledge there will be no hope to combat disease. Indeed, the mission of the National Institutes of Health (NIH) recognizes this fundamental fact in its opening statement,

NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life and reduce the burdens of illness and disability.

Implicit in such declaration is the acknowledgment that it is basic knowledge that drives advancements in human health and well-being.  Basic knowledge of nature is what drives progress.  This point is critical –   translational or applied research would not exist without basic knowledge as the raw material.  Without knowledge there would be nothing to translate nor apply.

Those that declare an imminent end to the use of animals in science are effectively implying that they envisage all basic knowledge needed will be acquired by a certain date, or that we will have methods that would allow us to proceed with studies non-invasively in human volunteers. Dr. Rowan’s statement that “Advances in cell-culture technologies are paving the way to the complete elimination of animals from laboratories” is nothing short of utter scientific nonsense.

Is it possible for Dr. Rowan to be ignorant of the role of animals in scientific research?  Could he legitimately be confused about the difference between safety testing on one hand and the development of therapies and basic research on the other?

This seems highly unlikely giving his academic credentials and the fact that he has served on IACUCs before.  In fact, another slide from his talk, shows him delineating these different uses of animals, and illustrating that animal testing for human safety accounts for merely ~25% of total animal use.

No, Dr. Rowan is not confused at all.  He knows what he is talking about.  This is unfortunate as one can only conclude his article is simply a misguided attempt to deceive the public about the fields in which we might realistically expect science to successfully replace animals in the near future.

And I emphasized science above for a good reason.

As difficult as it is for animal advocates to understand, scientists also believe we will see a day when we can eliminate the use of animals in all animal research.  And the day will arrive because of the hard work, progress and achievements of dedicated scientists, such as this one, and not because of deception of those that want to oppose animal research at all cost.

For HSUS to suggest that all animal research could be eliminated by 2050 is  flatly wrong from a scientific point of view, and utterly irresponsible from a public health perspective.

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