Tuesday, July 23, 2013

An insider view of the need for human biospecimen research; an interview with a leading human tissue sample supplier.

Bob: Thank you for talking with us Dr. Clotworthy. Could you start by telling us a little about your training and experience?

MC: Thanks, Rob. I studied biotech at Dublin City University & worked in in vitro testing labs every summer before doing a PhD in cell biology at the University of Cambridge/Medical Research Council Laboratory of Molecular Biology (where Watson & Crick figured out the structure of DNA). I then spent several years as a science consultant at a patient safety charity where I organised conferences on new technologies in drug safety evaluation & human tissue research.

Bob:  What drew you into the commercial world?

MC: I came to realise that there was a real gap between those at the cutting edge of developing new treatments & those with human biosample resources and/or expertise in testing those new treatments using innovative in vitro models. This clearly represented an opportunity to impact the efficiency of medical research- an opportunity that seemed best fulfilled by providing a high quality, independent, commercial service. So, I got together with partners with expertise in database management and business skills to form Human Focused Testing.

Bob:  Tell me a little about the Human Focused Testing business model.

MC: We reach out to researchers across the biomedical R&D spectrum, in pharma, biopharma, diagnostics, devices and academic research, as well as those developing cosmetics or cosmeceuticals and other chemicals to find out how we can help them push their research forward. Once we understand their needs, we go out to the world’s biggest network of independent sources and service providers and match researchers’ needs to the sources that can best meet those requirements. Introductions are direct, as are most contracts, meaning that we can work with a variety of sources (including reputable commercial organizations and not-for-profit organisations) and genuinely offer researchers the best range of options to suit their particular needs. This transparency is also reassuring to sources who know exactly where their samples are going and who they are working with. 

Bob:  Where do human biospecimens come from, and why are they so important in modern medical research?

MC: Human biospecimens include biofluids such as blood (and derivatives such as serum or plasma), urine, sputum and CSF, as well as solid tissue samples. Some of these samples are routinely available from donors, but other samples, particularly solid tissues may be available as biopsies or tumors removed for therapeutic purposes, for example. Sometimes deceased donors or their relatives kindly donated their loved one’s organs for transplant, but if they can not be used for transplant for some reason, then they may give permission for them to be used in research. Immensely useful tissues also come from deceased donors who have generously decided to donate their bodies for medical research or education.

Human samples are useful throughout biomedical research, from comparing healthy & diseased tissues to determine why a disease occurs or to develop a new diagnostic to find out how to differentiate between different disorders, exploring possible therapeutic targets, to testing cells and tissues to find out whether treatments are likely to work and be safe. All these tests are necessary before you can think of testing a new treatment in people. Human samples are also useful for developing biomarkers- measurable indices of disease, prognostic indicators, damage or improvement- that can be used for streamlining clinical trials and understanding patients’ progress. Biomarkers may also be developed as diagnostics and used as part of ‘personalized medicine’. Personalized medicine recognises that each person may react differently to a treatment, partly due to differences in the disease but also due to the metabolic idiosyncrasies that make each of us unique. Personalized or stratified medicine seeks to find ways of identifying in advance who will respond to what treatment, without wasting precious time and potentially exposing patients to unnecessary side effects.

Bob:  How is the collection and use of biospecimens regulated in the UK?  

MC: The collection and use of biospecimens is tightly regulated in the UK. We work with researchers and sources worldwide and it’s interesting to see how local regulations differ. In the UK, human tissue storage is regulated by the Human Tissue Authority, set up under the auspices of the Human Tissue Act, which came into force in 2006. The UK is seen as having some of the tightest regulations in the world, although Sweden is even stricter in some areas. Certainly, the UK has tighter rules around human sample procurement than the US, but that doesn’t necessarily mean that the US has ‘got it wrong’; there are cultural differences.

Bob:  Currently there seems to be a mosaic of different kinds of regulations in different parts of the world that mandate or at least suggest how biospecimens may be collected, distributed and used. One challenge faced by the biospecimen industry is trying to understand where different types of specimens can be most easily and ethically procured, and then trying to match specimens collected in one part of the world with researchers who need them elsewhere. What kinds of supply and demand problems or opportunities has this led to, and how do you see the global biospecimen industry changing over the next few years?

MC: There is indeed a great deal of complexity when trying to work out whether specimens collected correctly but in a different jurisdiction, under different laws or regulations, can be used by researchers in a different country where the requirements may be different. In some circumstances, as long as good local regulations have been fully followed, that’s fine; in other cases, researchers ask us to organise a prospective collection using their consent materials etc.

Bob: Why is it necessary to have commercial organizations involved at all? If the samples are donated mainly at academic research hospitals, why don't the academic organizations simply make their biorepositories available for free to any qualified research lab that needs them?

MC: Commercial companies bring a number of benefits to the organization of human biospecimen-based research. Academic biobanks/biorepositories do not usually have the resources required to find researchers who could make good use of their patients’ samples, and may be reluctant to pass samples on to commercial research organizations. Furthermore, researchers, frankly, have better things to do with their time than trawling search engines and calling hospital or university after university trying to track down someone who might be able to help them. We believe that hospital or academic biobanks should be able concentrate on caring for patients and processing samples to a high quality, while researchers should be allowed to get on with life-changing research, and it’s our job to bring the two sides together to mutual benefit. The involvement of a commercial organization also facilitates project management and oversight (particularly where multiple centres are concerned), QC measures and negotiation, including over project details and mediation should anything not go quite as planned. 

Bob:  Why can't scientific research organizations just use animal models or cultured human cell lines?

MC: Human cell lines are great, particularly at earlier stages of research when you may, for instance, have thousands of possible compounds to screen before deciding which ones to focus your efforts on. Great strides have been made in taking those cell lines further by incorporating them into sophisticated 3D models with multiple cell types, or using iPS or primary cells. However, the earlier you can begin to introduce human tissues into the process the more relevant your exploratory biological experiments or testing will become. Tissues enable researchers to study cells in their native conformation and, to some extent (improved with advanced bioreactor design) a more realistic and relevant context and environment, with the correct neighbouring cells for communication purposes. In the case of whole organs rejected for transplant, you really can’t get closer to the in vivo human situation without actually going into the clinic! Using tiny tissue or biofluid samples also effectively enables many different people’s reactions to be assessed in relatively quick, simple and cheap experiments, compared to the possible patient risks, and development time and costs involved in clinical trials. Animal models, on the other hand, represent a ‘whole system’ but do not represent a human system. Even if you change one aspect of the animal to make it more human-like, the rest of the system context belongs to a different species. When even individual people can react very differently to a treatment, how can you really trust results from a different species? The first time a new drug goes into a patient or volunteer is always an experiment, and personally, I’d prefer to see as much species-relevant information as possible first.

Bob: How can people who want to contribute to medical research go about donating samples?

Ask your doctor or healthcare provider about opportunities for donation and make your wishes well known to your family. 

Bob: Have you read Rebecca Skloot's  "The Immortal Life of Henrietta Lacks" or Lori Andrew's "Body Bazaar"? What did you think? 

MC: I read Rebecca Skloot’s book and found it a real eye-opener; I’d used HeLa cells but never really thought about where they came from. It was very sad to read about Henrietta Lacks’ unfortunate personal circumstances and the huge gaps in understanding amongst her relatives about what had happened and what the implications were. When the HeLa cell line sequence was initially published, and without permission from any relatives, this caused yet more controversy due to privacy concerns. It's easy to see how circumstances like this one reflect negatively on biomedical research, but nonetheless, there’s a real need to promote human biosample based research through public education and highlight the great good that can be done, just as the great gift of organ donation for life-saving transplants have been promoted. In general, informed consent and protection of privacy are the keys to avoiding controversy and allaying potential donor concerns.

Bob:  Do you personally ever feel conflicted about the type of work we do and its possible ramifications for healthcare or society in general? Genetics etc?

No! I think human tissue- based research is the way forward. There are potential privacy concerns and concerns about how information may impact, for example, insurance or employability, but these are issues that need to be legislated for.

Bob: Thanks for your time Margaret. Readers can learn more about Margaret's work in the these publications:

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