The importance of human-based research

What is human-based research? 

Human-based research covers a wide range of innovative methodologies and biotechnology or New approach methodologies (NAM), relevant to humans as they use advanced current knowledge on human biology, to study diseases and develop safe and effective drugs in humans, recognizing the importance of species-specificity (1-4). Human-based methods have already proved useful for understanding human pathologies and predicting human responses, even better than traditional in vivo models can (5-9). Despite this, their potential is limited by regulatory restrictions and their non-adoption by regulatory authorities. Moreover, they are still poorly considered in basic research, still dominated by traditional approaches and reductionist thinking, a legacy of the past (10-13).

With adequate public funding, the updating of regulations, which date back more than 70 years, and the correct training of future researchers, the human-based approach will accelerate the development of effective drugs and the discovery of cures for diseases that afflict humanity.

How human-based research helps patients

Drugs that look promising in the early stages of research (preclinical, in vitro and in animals) rarely reach pharmacy shelves. A large percentage of drugs (90-96%) which have passed the preclinical phases, fails in fact during clinical trials, on humans (14, 15).

This has largely been attributed to the inadequacy of traditional models (in vitro and animals)(16). The reasons why potential drugs do not pass human tests relate to both efficacy and toxicity problems (16, 17). Hence the urgent need for a paradigm shift in biomedical research, shifting the focus towards human-based methods, and to use an approach that is physiologically more relevant (1, 18-20).

Research based on human biology is essential to protect volunteers in clinical trials

Replacing animal testing with modern human-based approaches is essential to prevent harm to human volunteers in clinical trials. Outdated regulations requiring preclinical animal testing were intended to protect people at a time when today’s possibilities and technologies did not exist and the limits and dangers of over-reliance on animal models were not known. In the light of current knowledge, it is now recognised that the unreliability of animal test data not only risks making us bin potential cures (21) but also exposes human volunteers to serious risks (22). To give an example, the case of TeGenero, where 6 healthy volunteers risked their lives and suffered serious permanent damage as a result of taking the drug TGN1212, which had previously proved completely harmless in animals (23, 24). Some human-based tests such as “Skimune” (6, 7), developed by a team at the University of Newcastel, or a micro-engineered on-chip vascular system (8) would have been able to predict the adverse reaction instead, avoiding tragedy. This is just one example that teaches us the scientific, and not just ethical, importance of an approach focused on human biology and how misleading and dangerous it can be to see the animal model as the best option, the gold standard, as an in vivo model.

How human-based research could positively affect the reputation of universities and Italian research

Politically and economically supporting human-based research would mean allowing our country the opportunity to contribute to the world leadership in innovations without laboratory animals that will be awarded by 2025, keeping up with the rest of Europe. This would also allow researchers and new talents who wish to work with the new methodological approaches to stay in Italy, avoiding the brain drain and the loss of resources.


1.Langley GR, Adcock IM, Busquet F, Crofton KM, Csernok E, Giese C, et al. Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations. Drug Discov Today. 2017;22(2):327-39.

2.Langley G, Austin CP, Balapure AK, Birnbaum LS, Bucher JR, Fentem J, et al. Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research. Environ Health Perspect. 2015;123(11):A268-72.

3.Ward SE. Human-Based Systems for Translational Research. Edited by Robert Coleman. 2015;10(7):1273-4.

4.Body M, Marks V. The new frontiers of science. Experimental models for 21st century biomedical research: Aracne; 2019.

5.Barrile R, van der Meer AD, Park H, Fraser JP, Simic D, Teng F, et al. Organ-on-Chip Recapitulates Thrombosis Induced by an anti-CD154 Monoclonal Antibody: Translational Potential of Advanced Microengineered Systems. 2018;104(6):1240-8.

6.Ahmed S, Bibby L, Dickinson A. Predicting adverse immune reactions to biopharmaceuticals using a human in-vitro skin explant test: a promising tool for biopharmaceutical R&D development. 2017.

7.Ahmed S, Chauhan VM, Ghaemmaghami AM, Aylott JW. New generation of bioreactors that advance extracellular matrix modelling and tissue engineering. Biotechnol Lit. 2019;41(1):1-25.

8.Goyal G, Long J, Ingber DE. Microenginered human lymphoid tissue on chip. Cancer Immunology Research. 2018;6(9 Supplements):A76.

9.Hartung T. AI more accurate than animal testing for spotting toxic chemicals 2019 [Available from: ]

10.Tralau T, Riebeling C, Pirow R, Oelgeschlager M, Seiler A, Liebsch M, et al. Wind of change challenges toxicological regulators. Environ Health Perspect. 2012;120(11):1489-94.

11.Tralau T, Luch A. Drug-mediated toxicity: illuminating the ‘bad’ in the test tube by means of cellular assays? Trends in pharmacological sciences. 2012;33(7):353-64.

12.Rovida C. Food for thought … why no new in vitro tests will be done for REACH by registrants. Mr Altex. 2010;27(3):175-83.

13.Archibald K, Drake T, Coleman R. Barriers to the Uptake of Human-based Test Methods, and how to Overcome Them. 2015;43(5):301-8.

14.NCATS-National-Insitute-of-Health-NIH. Transforming Translational Science. 2018.

15.DiMasi JA, Feldman L, Seckler A, Wilson A. Trends in risks associated with new drug development: success rates for investigational drugs. Clinical pharmacology and therapeutics. 2010;87(3):272-7.

16.Hartung T. Look back in anger – what clinical studies tell us about preclinical work. Mr Altex. 2013;30(3):275-91.

17.Van Norman GA. Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?.JACC Basic Transl Ski. 2019;4(7):845‐854.

18.HumamToxomeProject.  [Available from: ]

19.Nrc. Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC: The National Academies Press; 2007. 216 p.

20.Archibald K, Tsaioun K, Kenna JG, Pound P. Better science for safer medicines: the human imperative. Journal of the Royal Society of Medicine. 2018:141076818812783.

21.Hartung T. For aspirin ad astra. Alternatives to laboratory animals : ATLA. 2009;37 Suppl 2:45-7.

22.Greek R, Pippus A, Hansen LA. The Nuremberg Code subverts human health and safety by requiring animal modeling. BMC medical ethics. 2012;13:16.

23.Attarwala H. TGN1412: From Discovery to Disaster. Journal of young pharmacists : JYP. 2010;2(3):332-6.

24.Hunig T. The storm has cleared: lessons from the CD28 superagonist TGN1412 trial. Nature reviews Immunology. 2012;12(5):317-8.