Using animals in basic research is a division of basic research in general. Examining the value of basic research in biomedical research is a good place to begin our discussion.

Susan Hockfield, president of the Massachusetts Institute of Technology, wrote in an editorial for Science:

U.S. federal investments in basic research transformed life and commerce in the 20th century. They sent us to the Moon and beyond, revolutionized, helped to feed the planet, reinvented work processes, and drove the remarkable economic growth of the post-1950 s era in the United States. These advances and more grew out of the convergence between engineering and the early 20th-century discoveries in the physical sciences. The United States can anticipate comparable world-changing innovations in the 21st century if we adapt our education and research funding strategies to capitalize on new opportunities emerging at the convergence of the life sciences with the physical sciences and engineering [67].

Basic research in the United States began in earnest after World War II. This was due at least in part to the engineer Vannevar Bush, director of the Office of Scientific Research and Development. Bush wrote a report for president Roosevelt stating that "new knowledge can be obtained only through basic scientific research." [68]

This marked a turning point in research funding. In the 19th century, most research had been privately funded, with industrial and government funding increasing in the 20th century. After this report, government funded research, as opposed to privately funded research, became the norm. In the 19th century, research was expected to produce results. Not all did, and some was funded without such expectations, but overall the funders expected practical results. As a result of this report, the US government, in 1950, formed the National Science Foundation which has funded basic research ever since. (Today, NIH as well as other government agencies and charities also fund a large amount of basic research.) This emphasis on basic research spread across the Atlantic and has been the standard worldwide ever since.

Has the value of basic research in current-day medicine been proven? Everyone has anecdotes, sometimes many, to support their view that basic research, especially basic research using sentient animals, is vital for medical science to advance. But are there scientific data to support this view? The current emphasis on basic research in medicine, as opposed to applied research, grew out of a U.S. Defense Department study published in 1967 in Science that concluded that research performed with an end in mind was far more effective in improving a technology than research performed with no goal in mind, e.g., basic research [69]. This study led then-president Johnson to state: "[A] great deal of basic research [in medicine] has been done ... but I think the time has come to zero in on the targets -- by trying to get our knowledge fully applied ... We must make sure that no life-saving discovery is locked up in the laboratory [70]."

This perceived negative attitude about basic research led respiratory physiologist Julius Comroe and anesthesiologist Robert Dripps to conduct a survey concerning medical discoveries. The classic justification for basic research comes from that study published in 1976 [71]. Their paper "Scientific Basis for the Support of Biomedical Science," purported that 41 percent of all articles judged to be essential for later clinical advances in cardiovascular and pulmonary medicine and surgery, were not clinically oriented at the time they were conducted and that 62 percent of key articles were the fruits of basic research. This appears to be strong evidence that basic and translational research with animals is key to finding cures and was in fact seized upon by other countries. As noted by Grant et al.:

Since that analysis, support for basic research has increased in the G7 countries. In the UK, Research Council expenditure on basic research has increased from a low of £444 million (or 42 per cent of total civil R&D) in 1991/1992 to £769 million (or 61 per cent of total civil R&D). Although it would be difficult to argue that Comroe and Dripps were directly responsible for a strategic shift (or drift) in the type of science supported by research funders, their arguments are often cited (albeit at times implicitly) in support of increased funding for basic biomedical research [72].

A PubMed search (conducted on August 17, 2010) revealed 22 citations for the 1976 Comroe-Dripps paper. We believe this is very significant. Our claim that basic research, specifically basic research using sentient animals, is the accepted standard for advancing knowledge that will eventually be used to develop treatments, is supported by the paucity of references. The value of Comroe-Dripps is simply not questioned despite the far-reaching ramification as noted by Grant et al. above. Only recently [72] has the conclusion of Comroe-Dripps begun to be seriously questioned.

At this point in time we begin to see a dichotomy in how scientists explain the value of basic science research to society. Because of comments by Johnson and others and the great advances in applied research, some in the basic research community began feeling pressure from society to justify their research on grounds other than knowledge for knowledge sake. This break from the past has direct implications for our discussion. Society was already hinting that there are limits to what it would fund in terms of knowledge for knowledge sake. It is our contention that much current basic research is done under the guise of applied research because it increases the likelihood that the project will be funded by a granting institution [2]. For example, Freeman and St. Johnston in 2008:

Many scientists who work on model organisms, including both of us, have been known to contrive a connection to human disease to boost a grant or paper. It's fair: after all, the parallels are genuine, but the connection is often rather indirect [73].

Using animals as causal analogical models [74] or predictive models is not basic research; it is applied research. The real crux of the argument for some seems to be: "Give us money for basic science research using sentient animals because our research is predictive for humans" [[2]b]. When such research turns out not to be predictive, however, they state: "Our research is basic research so it is not supposed to be predictive." Even those who admit that basic research using sentient animals is not predictive hide under the umbrella of "animal models really are predictive" to increase their likelihood of obtaining grant money [[2]b].

(We should here point out that we do not believe the scientist-reader so naïve as to not understand what we are referring to. We, and we feel sure the scientist-reader, are very aware that in order to gain funding from institutions like NIH, the applicant is under pressure to show that the research in question ties in directly with a human disease [unpublished observations]. The applicant is under pressure to turn, what has been considered basic research, into applied research. The problems with this condition are numerous, nevertheless are not part of our considerations at present. Suffice it to say we are attempting to use words and phrases, like basic research, that have meaning consistent with reality as opposed to the meanings attributed to them in the grant-funding process.)

Comroe and Dripps were basic research and animal testing enthusiasts. They had criticized President Johnson's administration for coming out in favor of applied, not basic, research. They also criticized the first heart transplant surgeons for failing to publicly state that the operation, in their opinion, was only possible secondary to the use of animals in basic research [71, 75–77]. Comroe had also written a critique of medical progress stating that all major discoveries had been a result of basic research involving animals [76, 77]. Comroe was also critical of clinical research:

Let's not live in constant fear of the great god Randomization [clinical research], his (or her) appetite is huge, and, if fed continuously, could consume much of the nation's research dollars and personnel, and even the lives of patients [78].

The above statement is still quoted as a reminder that many have historically held and still hold clinical research in disdain. Silverman in 2004:

At the time of the 1969 debate [regarding optimal oxygen levels in premature babies], I found it hard to understand why those who spoke against a formal controlled trial won the "methods" debate so easily (the power of RCT [randomized controlled trial] format had been firmly and widely established following the famous clinical trials in Britain in the 1940 s and 1950s). But I had underestimated the influence of the counteroffensive mounted in the U.S. by prominent laboratory-oriented researchers. For example, one celebrated leader wrote ...

Here, Silverman quotes Comroe (the "great god Randomization" quote referenced above) then continues:

These dismissive comments concerning the use of statistical methods in clinical studies was a reminder of the disturbing split in outlook about how the medical profession should go about solving puzzles that turn up on the wards [79].

Comroe and Dripps surveyed the "scientific community" to determine which discoveries were important. They sent a number of surveys (some have estimated approximately one-half) to scientists performing basic science experiments. Not surprisingly, these scientists concluded that basic science animal studies had been invaluable. As the then-assistant editor and future editor of the British Medical Journal pointed out, the report entirely left out the clinical discovery of the effects of smoking on heart and lung disease, though this link was the "most important therapeutic maneuver for most doctors treating lung and heart disorders." [80] (Emphasis added.) Clinicians, in all likelihood, would not have left out that discovery, lending credence to the notion that Comroe and Dripps favored basic researchers when sending out their survey.

The Comroe Dripps Report is still cited as essential by those who wish to justify the use of sentient animals in basic research. (It has been the authors experience that these discussions usually occur outside the scientific literature hence another reason for the low number of citations for Comroe Dripps.) However, it was (in 1987, Smith questioned their conclusions [80]) and still is criticized by numerous scientists and clinicians for faults of methodology and bias. How reliable is the Comroe-Dripps analysis? Grant et al. observe that due to methodological flaws, the work by Comroe and Dripps

... would probably not meet today's standards for peer review. As Farrar observed, among the methodological problems " ... was a lack of clarity over whose opinions had been surveyed, how clinical advances were assessed and how a key article was defined." [81]

Grant et al. concluded that it takes about 17 years for basic research to have a clinical impact. More importantly:

Using the revised bibliometric protocol, we have shown in this study that ... between 2 per cent and 21 per cent of research was basic. This corroborates the findings of the clinical guidelines study that showed ... only 8 per cent of research was basic. These two findings are at odds with Comroe and Dripps finding that 40 per cent of all research articles judged to be essential for later clinical advance were not clinically oriented at the time of the study, thus undermining the evidence base that has, in the past, supported the increased funding of basic research. [[72]b]

Grant et al. concluded that Comroe Dripps was "not repeatable, reliable, or valid [82]." Strong words indeed. Additionally, Grant et al. did not address whether the basic science breakthroughs that were instrumental and were made using sentient animals could have been made without using them. If one is analyzing the importance of using sentient animals (Grant et al. were not), this is not an unimportant point.

More recently, others have also questioned the translation rate of basic research in general into clinically useful treatments. In 2003, Contopoulos-Ioannidis et al. quantified the translation rate of "highly promising" basic research into clinical applications. They published a study in the American Journal of Medicine that revealed of 101 basic research papers published in the high-profile journals Nature, Cell, Science, the Journal of Biological Chemistry, the Journal of Clinical Investigation, and the Journal Experimental Medicine between 1979 and 1983, twenty-seven led to randomized clinical trials and only five eventually gave rise to licensed clinical application [83, 84]. They concluded that "[e]ven the most promising findings of basic research take a long time to translate into clinical experimentation, and adoption in clinical practice is rare [83]."

Contopoulos-Ioannidis et al. actually searched all the articles published in the above-mentioned journals between 1979 and 1983; a total of around 25,000. Crowley commented on this:

Of the 25,000 articles searched, about 500 (2%) contained some potential claim to future applicability in humans, about 100 (0.4%) resulted in a clinical trial, and, according to the authors, only 1 (0.004%) led to the development of a clinically useful class of drugs (angiotensin-converting enzyme inhibitors) in the 30 years following their publication of the basic science finding. They also found that the presence of industrial support increased the likelihood of translating a basic finding into a clinical trial by eightfold. Still, regardless of the study's limitations, and even if the authors were to underestimate the frequency of successful translation into clinical use by 10-fold, their findings strongly suggest that, as most observers suspected, the transfer rate of basic research into clinical use is very low[85]. Emphasis added.

The above casts severe doubt on the value of basic research in finding treatments and cures.

The Institute for Scientific Information (ISI) studied citation rates of papers published in journals indexed by the Institute between 1981 and 1985 and found that 55% of all articles were not cited within five years after publication [86]. The journals that ISI index are only the top ranked journals. The articles that appear in the lower ranked journals are not thought to receive as many citations as articles that appear in the top ranked ones. So the 55% figure is probably very high if all journals were considered. ISI also found that self-citation accounted for between 5% and 20% of all citations. The number of journals (science and nonscience) now numbers over 108,000 [86].

The actual results from years of rich funding to basic research is forcing some within the research community to acknowledge the failure of basic research to deliver on its promises [87]. Driven largely by this recognition, translational medicine has become a more frequent phrase in medical literature. Ioannidis, writing in the Journal of Translational Medicine presents a good example of this mindset: "There is considerable evidence that the translation rate of major basic science promises to clinical applications has been inefficient and disappointing [88]."