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Research Methods in Biomedicine and Applications to Botanicals

In my last post, I gave an overview on the basics of botanical research. To compile meaningful information you frame your question, structure your inquiry, search the appropriate databases, store and organize your information for easy access, and understand that you have to interpret the information. This last step is the hardest part.

After you’ve completed your literature search, you’ll want to look at the quality and nature of the information in front of you. The best way to assess the strength of the evidence is to know the research methods that were used–and their limitations.

In vitro studies

In vitro means ‘in glass’, and describes laboratory research conducted on cells or molecules outside of their biological environment. It is the least expensive and easiest type of research to conduct in comparison to other methods. It’s therefore used in bioprospecting and pharmaceutical screenings. Often, a group of researchers hear of a traditional use of a particular plant and that’s their clue to investigate its biological activity starting in vitro or in animals. These are also known as mechanism of action studies, as studying those cells up close can shed light on how particular herbs or compound are affecting certain cells.

In vitro studies usually test isolates or purified extracts. Sometimes, as in the case of oncology bioprospecting at the National Cancer Institute, important compounds like tannins are removed (Mills & Bone 2013). Tannins bind nonspecifically to many proteins and enzymes, and the removal of them drastically changes their biological activity. These purified extracts or compounds are added to a culture medium and incubated with cells, and changes are noted and documented. This brings us to a serious drawback of in vitro data: the difficulty of extrapolation.

For example, a 1999 in vitro study tested the effects of several botanical extracts (Echinacea, Ginkgo biloba, Saw palmetto, and St. John’s wort) on fertility. To do this, they cultured hamster oocytes (eggs) with pretty high concentrations of these extracts (upwards of 0.6mg/mL) and then tested sperm penetration (Ondrizek et al 1999). When you’re reading a study or abstract, try to envision what’s actually going on. Is it relevant? For reference, concentrations above 0.1mg/mL are unlikely to be achieved in people taking herbs orally.

Furthermore, and more troubling, is that you can’t get product preparation or extraction details from an abstract or even a full text sometimes. I’m consistently surprised to see how often authors neglect to describe the extract type (aqueous or ethanolic? Crude herb?). This is especially prolific in the mushroom literature, where extraction methods are crucial yet strangely absent from the abstracts.

In vitro data should be carefully examined before conclusions are made. Again, this is usually Step 1 in the process of seeing if a particular herb merits further study. Read more

Narrative medicine in the practitioner-client interaction

Nature abhors a vacuum. The less defined or understood a particular condition or disease is by the medical establishment, the more it exposes the explanatory frameworks of the individual practitioner or client. This goes especially for complex issues like chronic infections, metabolic or endocrine imbalances, inflammatory conditions, and degenerative diseases. When there aren’t agreed upon explanations for causes, treatment, or prognosis, it becomes a hazy blank canvas for individuals to paint a story. Is that a helpful story? Narrative medicine is not just a tool in the toolbox. It’s an entire dimension of the healing process that is either working with you or against you.

Addressing narrative is a missing piece in many medical or healing practices, including herbal medicine. Health and illness narratives affect our entire operational framework of a particular health issue. And these are huge blind spots in the practitioner and client relationship. Read more

Basics of Botanical Research

The research process is beautiful. And fun! You get to navigate and interact with the landscape of information about a subject, and figure out where the strengths, weaknesses, and opportunities exist in our knowledge base. In the process of digging into research, you can see the origins of the rumors spread about herbs, gain some clarity about it and weed through misinformation. Certainly, botanical preclinical and clinic research is an incremental way of building undertanding, much like an ant procuring crumbs of food to bring back to the colony. And it doesn’t tell us everything: there are many rich sources of information to draw from in botanical medicine, with traditional use chief among them. The skilled herbalist exercises good judgment and critical thinking by achieving fluency in these different areas, and knows how to apply them to help people.

I’ve been in the research field for 6 years–first in anthropological research at the Center for World Indigenous Studies, then as a botanical research assistant and writer for several clinicians, and now in R&D for a medicinal mushroom company. And I’m passionate about supporting herbalists in navigating the scientific research about botanicals and supplements to improve decision-making.

Let’s use an example. Say you’ve been heard about Thyme Oil as a Powerful Natural Antibiotic on social media sites and want to dig further into it. When we’re looking for at the evidence base of a claim, we want to go to the primary research and see the studies that have actually been done. Not reviews, not news articles, but real studies.

Frame the question to structure the inquiry.

I usually make 2 columns: the first lists the substance I’m searching for. This can be a specific plant, phytochemical, or just plants in general. Use the latin name for plants (in this case Thymus vulgaris), and include potential misspellings. Then in the second column is the subject: the name of a condition, keyword, or associated biomarker (you can use the term antibiotic or antibacterial). In this case, there’s a MeSH term for anti infective agents, which would cover the territory nicely.

Get better at searching.

You can then use this basic format to search the databases. Searching MEDLINE via PubMed will be more helpful with complex searches, as you can specify which fields you’d like to search. I also like to search Google Scholar. It indexes MEDLINE as well as other databases. The search is wider and you get more results, but you can’t customize it as well as you can with PubMed. Below is the search builder on PubMed. As you can see, you can add lots of different criteria for more wheat and less chaff.

Screen Shot 2014-12-13 at 10.14.37 AMAnd get to know your journals–PLOS, PubMed Central, BioMed Central, and anything from the Hindawi Publishing Group is free full text. My favorite botanical/phytotherapy journals are Fitoterapia, Phytotherapy, Phytotherapy Research, and Planta Medica. The Journal of Ethnopharmacology is also a great one, but I get the feeling that it’s a bioprospecting publication.

Use reference management programs to store and organize citations.

Once you start generating citations, programs like EndNote, Papers, Mendeley (free), Zotero (free), and Sente (pictured below, my personal favorite) can store, track and organize your citations. With any software, each have their different strengths and weaknesses. For example, EndNote is great for formatting citations in a final publication, but not the best at organizing into folders, tagging, storing PDFs. Sente is my personal favorite because I can sync these libraries with research colleagues, store and annotate PDFs, and having standing searches to keep up on new search results as they come in. Mendeley is a nice free/open source program, and is a good place to start.

Sente screenshotI have several of these programs installed. I can import and export citations as needed, depending on the project.

Going from A to B: know how to extrapolate and interpret data relevant to your inquiry.

This is where the true skill lies in research. Investigators set up replicas of reality in their labs. I can’t stress enough that research findings are specific to that setting, model, and process. Assessing the relevance of a finding is crucial. How do we translate study A to real world situation B? This takes some understanding of human biology, test methods, and the strength of different types of research methodologies and evidence (which I’ll address in future posts).

Back to thyme oil: once you complete your search, you’ll see that there is some data on antibacterial effects. Great! You have something to work with. Then the researcher should consider:

  • Were these done in test tubes (in vitro), animals, or humans?

In vitro studies are done in test tubes, often by culturing cells with botanical extracts, concentrates or isolates. They’re done to investigate the mechanism by which something works, and/or to see if there’s enough of an effect for research efforts to progress to animal studies. As the body would metabolize these compounds differently than what’s done in petris, findings should be taken with a grain of salt as they’re difficult to extrapolate to real world situations.

  • What kind of bacteria? What exactly were the effects?

This is very important! Just because a substance has an effect on a particular genus, species, or class of bacteria doesn’t mean that it will be effective in others. This error in applying a finding to other non-related pathogens or conditions is rampant in discussions about herbal medicine (see my post on Herbs for Ebola). Remember: this information is for a certain preparation in a certain type of experimental model. A may not always translate to B.

  • Is the dose and preparation relevant to what people would actually use?

I can’t stress this enough. Many natural substances can have an effect in test tubes and animals, but getting those amounts in humans would not be feasible. If possible, a critical examination of study doses and concentrations should be part of your research toolkit.

This is the first of a series on botanical research. Please leave your questions and feedback in the comments!

On the Subject of “Herbs for Ebola”

In October there was a torrent of Facebook and blog posts on herbal remedies for treatment of Ebola virus infection. The outbreak has been raging in West Africa for several months. But when the possibility of one on US soil emerged, so did the hysteria. Common suggestions for antiviral treatment by posters on the net included “classic antivirals” like elderberry, lemon balm, St. John’s wort. Elderberry has been studied for influenza A/B, lemon balm with HSV, and hypericin (from St. John’s Wort) has shown some in vitro activity against a few viruses, but when it comes to testing them in humans against Hep-C and HIV infections, effects were nil. Garcinia kola seeds were a popular remedy-turned-meme based on a single 15-year old lab test.

I know there is little harm in these thought experiments of devising treatments for these deadly outbreaks. Similar conversations occurred during the fear of the swine flu pandemic. Is it not better to speculate about protocols than do nothing?

When it comes to terms like herbal antivirals (or herbal antibiotics, etc)–I don’t think this is an a good way to describe the ways in which herbs work. Herbs are chemically complex molecular multitaskers–the polar opposite of single agent pharmaceuticals with a single biological target. Calling something an ‘herbal antiviral’ is cramming a square peg into a round hole and does not play to the strength of herbs either. When you’re holding a hammer, everything looks like a nail. But it behooves a practitioner to be aware and cognizant of the limits of tools and methods. If not, than you’re just a prosletyzer, preaching the endless merits of your chosen practice. Are you a pragmatist or a preacher?

What I take issue with the most is the misinformation clustered around this topic. First, most the information used in the development of these protocols are gleaned from in vitro data. Many substances and phytochemicals exhibit antiviral properties in vitro, and these are usually isolates or concentrated extracts, on organisms in test tubes. This makes extrapolation into a live human body difficult.

My concern is not that herbalists stretch botanical therapeutics and try to come up with something new. Instead, I take issue with the assertion of a ‘remedy’ without consideration or discussion of where the information originated.

My parting words on Herbs for Ebola: critically appraise the origins and habitat of information, and be transparent about it. Always look under the hood, because it’s common for people to stretch or sweep away information.

Exponential Medicine – Recap & Reflections

I just got back from attending the Exponential Medicine (#xMed on Twitter) conference hosted by Singularity University in San Diego. This conference, similar to TEDMED, aims to share innovative ideas and developments in medicine and healthcare. It seeks to answer “what’s next?” in these fields.

The conference and innovation lab was predictably occupied with speakers and companies in the fields of stem cell research, tissue engineering, bioprinting, regeneration, synthetic biology, big data, mobile app technology, AI.

I’m very intrigued on conversations about the future of anything, but most importantly when it comes to medicine or healthcare. These fields are vital for the continued evolution of humanity, and all life on earth. When something becomes ordained as The Future of X, it becomes a self-fulfilling prophecy. We race to get to the future first, chasing the next big thing. So I watch these developments with as much of a critical eye as I can muster, especially attentive to the origins, trajectories, and meanings of these ‘futures’. These innovators rarely, however, examine our past or roots. Or the ecological context in which they are an inextricable part. They can’t. The whole field is too specialized. But how can you assert a future without a global view?

I am not against technological development or advancing medical technology as much as possibly. On the contrary: these technologies can and will save lives and improve quality of life for those who can access it. But I stand as an outsider looking at the greater social context, and wonder.

I did not see anyone questioning the fundamanetal tenets of their field– a practice which could surely expose blind spots or reveal some kind of blue sky for future developments. A couple speakers argued that better access and more meaningful patterns from big data can provide patients and providers with more relevant and actionable knowledge than RCTs–a good point. Data mined from real patients in real situations is more realistic than trial patients, who are often excluded if they have a comorbid condition. (That and I think RCTs testing treatments against placebo is unethical, but that’s another post.) No one, except for Paul Stamets (pictured above), advocated for even a remotely ecological or cross-species view of health. With an increasingly myopic view of heathcare, we lose context and are therefore subject to poorly performing interventions.

These technologies are beautiful. I’m excited for what they can bring. But we may well go even further by flipping the subject and seeking innovation in tradition, examining why we do what we do, how we know what we know. I’d love for medical educational programs conferences to philosophize a bit more with these subjects. I think only then do we fully engage the subject and envision the future we want to create.

And the setting? Lovely.


Hotel Del Coronado

What Is Botanical Medicine?

Botanical Medicine – also known as Herbalism, or just Herbal Medicine – is the study and practice of safe & sustainable use of herbs for whole-person health, including gathering & use of safe/available plants, basic medicine making & basic nutrition. In the process, we learn more about our environment and the natural world. Read more

The Herbalist’s Chain of Custody

In my practice I often play the role of an ambassador, explaining the thought processes & approaches of a clinical herbalist. One of the ways that makes practicing herbalists distinctive from other professions is the chain of custody of their medicines, and their embedded connection with the living, breathing landscape.

Herbalists occupy & triage the continuum between patient, practice & Earth. This is especially true when they make their own medicines–they oversee and craft a chain of custody. When I supply a formula of marshmallow root & chamomille flowers that have come from my garden, I’m not offering just a product. I’m offering a deep understanding of how those plants grow, evolve, and interact with their environment. In overseeing the craft of that product, it’s not just better quality–we invite a dimension of knowing unique to our practice. We are helping our patients evolve their narrative and understanding. This is an important aspect of the long-term healing process.

It’s as if we have one hand stretching into the landscape; formulating, crafting. And with the other, we can offer another a connection, language and, in some ways, a truth.

Herbal Terminology Demystified: A Bit on Herbal Actions, Energetics & Listening to the Language of the Plants with our Bodies

(For a PDF handout version, see Resources.) Plants are complex, living beings—just as we are. And their interactions with our bodies in the context of healing can begin to be understood in terms of patterns of basic energetics: heating & cooling, drying & moistening.

Photo Nov 24, 10 53 20 AM

Herbal actions describe the observable effects of herbs in the body. Energetics refers to the overall characteristic or quality of an herb— for example, we know cucumbers are cooling and ginger is warming. This language of energetics & actions gives us a way to understand the broad spectrum of plants in a healing context. It also allows us to get creative with plants and determine substitutes when our first choice isn’t available. A number of bitter plants can be used to assist digestion. Similarly, a wide range of antiinflammatories can be called in to relievethe pain & tension associated with certain types of inflammation. Familiarity with the language of herbal actions and energetics opens our senses & imaginations to the plants around us, and ultimately helps deepen our practice with them.

Botanical medicine is an art & a science. And this is the art part. The way plants flow through us can be perceived & described in several ways. Read more