A Botanical Look at the Changing Face of Drug
Discovery and Development

Plant-focused nonprofit and for-profit companies working to address the global disease burden

Many people say the world revolves around money. There is perhaps no other place where this rings truer than in the drug discovery and development industry. Because conventional pharmaceutical drugs are wildly expensive to bring to market—costing from $800 million to $1.3 billion for a single new drug product^1,2—pharmaceutical companies must obtain large sums of money from investors. While types of investors and their aims vary, most wish to a see a maximized return on their investment, which often leads the company to focus on drugs that will eventually make even more money than was required to fund their costly journey to consumers’ hands.³

Though this for-profit model has been successful in creating most new pharmaceutical innovations during the last 3 to 4 decades, gaps in its ability to address the vast global disease burden are being realized.^3,4 Diseases that drastically affect poor populations, such as dengue fever and tuberculosis, continue to be neglected by a large part of the pharmaceutical industry, as developing—and even donating—drugs for these conditions does not usually bring large enough returns to appease most investors. Likewise, many companies have little incentive to invest time and money in searching for or developing novel therapeutics, including (mostly unpatentable) herbal medicines. Fortunately, however, an increasing number of companies and organizations, including several focused on plant-based drugs, are taking a different approach.

Nonprofit organizations are being referred to as “more vital than ever in the advancement of new therapies,” and as playing an “increasingly important role in drug discovery and development for diseases that are neglected by the pharmaceutical industry because of low or absent commercial incentives.”^3,4,5 A typical nonprofit drug company follows a moderate profit-generating model in order to have funds to reinvest in future projects and to subsidize charitable projects. Instead of depending heavily on investors, nonprofits seek donated revenue from sources like philanthropic organizations (such as the Bill and Melinda Gates Foundation, a major funder of nonprofit health initiatives) and have low overhead costs and minimal infrastructure. And because they do not have the obligation to produce financial returns for investors, nonprofits can make their medicines available at a much lower price, thus reaching underserved populations, focusing on neglected diseases, and paying attention to novel therapies.

Dozens of nonprofits are currently and successfully working across the world to discover and create new drugs, including the Institute for OneWorld Health, the Myelin Repair Foundation, Medicines360, Battelle, and SRI International, among others.^5,6  Additionally, New Earth BioMed (NEBM), a newly created nonprofit, focuses solely on discovering multi-compound botanicals to treat cancer. It receives its funding as donations from individuals, corporations, and foundations, and through public grants.⁷ So far supporters include Eric Potma, PhD, an assistant professor of chemistry at the University of California-Irvine, who collaborated in developing a “laser bioassay system for measuring drug effects in three-dimensional co-cultures of cells.” (Individuals can also donate to NEBM via a simple form on its website.)

NEBM President, John Boik, PhD, founded the organization in January of 2010. “I realize that a lot of innovation and beneficial products have been produced by profit-maximizing corporations,” said Dr. Boik, “but at the same time I see that profit maximization is not always in line with maximizing the benefit to humanity. I simply wanted to keep some distance from the for-profit world, as I thought that in the long run it would allow me greater freedom. Of course, that also means that our organization is at the mercy of funders” (e-mail, January 27, 2011).

But because NEBM focuses on the pre-clinical drug discovery phase of bringing a drug to market, obtaining adequate funding is, theoretically, somewhat less of a hurdle than if it focused on the following and most expensive phase of drug development, mostly due to expensive clinical trials. “So while we do not need several hundred million dollars to do our work, we still will need 10 million or so to get all our work done. Our plan is to start with one study and move on from there, building funding relationships as [we] demonstrate more and more success.”

Still, this experience has not been easy, as NEMB needs to obtain the remaining funding for its first research project, which is projected to cost about $300,000 and of not all of which has been covered yet. Making this particularly challenging is NEMB’s unique situation. Not only is it a nonprofit drug company, it is also a nonprofit drug company that focuses on botanicals. “It is quite difficult to convince foundations and other donors that ours is a worthy cause. It is especially difficult in these hard economic times, as foundations are beseeched with requests. In addition, we have the handicaps that we are a new organization, without a track record, and that we are studying something very unusual. We don't just study natural products against cancer; that is unusual enough. We study large mixtures of natural products, containing say, several dozen compounds.”

But this aspect of NEBM that might surprise potential donors is what fuels the optimism in Dr. Boik, who is an acupuncturist and Chinese herbalist and has a doctorate degree in cancer research. He has also authored 2 books, Natural Compounds in Cancer Therapy (2001) and Cancer and Natural Medicine (1996) (both of Oregon Medical Press). While creating his own Traditional Chinese Medicine practice in Portland, Oregon, he wanted to focus on a specific condition in order to set his services apart from the milieu of others in the city. “I thought about it overnight,” he said, “and by the morning had chosen cancer. That defining decision changed my life, and from that moment on cancer ruled me. I believe the work [NEBM is] doing is very worthwhile. We are pushing the envelope and I am optimistic we will find the support we will need, or the support will find us.”

Specifically, Dr. Boik believes that large, nontoxic, and synergistic mixtures of natural products from the plant world have vast potential to treat cancer. “Think of these mixtures as a magic shotgun shell against cancer,” he said. “From a biological perspective, it makes more sense than a magic bullet, which is the kind of drug that most pharmaceutical firms focus on. The more key processes you can affect in a cancer cell, the better your chances of thwarting its proliferation. Not only can a large mixture affect many biologic processes, each individual compound can be used at a low and nontoxic dose. Thus both efficacy and safety could be increased.”

NEMB’s long-term goal is to conduct a screening program of natural product mixtures against cancer cells. Meanwhile, it is at work on its short-term goal of developing a 3-dimensional bioassay co-culture that more closely resembles the nature of tumor growth in humans as opposed to the 2-dimensional, flat, and single-cell bioassay systems typically used in cancer drug discovery. “If we are successful,” said Dr. Boik, “it will bring us a huge step closer to being able to develop a mixture screening program that produces results that are highly relevant to what might occur in humans. [In addition], there could be some intellectual property developed that has value, and in time it could help us pay for continued research work.”



While nonprofits are serving a very important role in drug discovery and development, sometimes their success and level of impact are dependent upon collaboration with for-profit drug companies, quite a few of which are doing their part to address the global disease burden. Johnson & Johnson, for example, granted development and access rights of its experimental tuberculosis drug, TMC207, to the nonprofit Global Alliance for TB Drug Development in 2009,⁸ and Glaxo Smith Kline, in partnership with the Malaria Vaccine Initiative, worked to develop a malaria vaccine for African children. ³

Likewise, Napo Pharmaceuticals—whose lead drug candidate, crofelemer, is an isolated and purified extract from the bark latex of the Amazonian Croton lechleri tree—aims to focus on international public health issues and ensure that crofelemer is accessible to all people who need the medicine, especially pediatric populations. According to Steven King, PhD, Napo’s vice president of sustainable supply and ethnobotanical research, the company is able to do this through partnering with nonprofits, such as the International Centre for Diarrheal Disease Research in Bangladesh and Direct Relief International, the latter of which distributed the dietary supplement version of crofelemer to clinics in 30 countries that treat HIV/AIDS patients (e-mail, January 24, 2011).

“In many ways,” said Dr. King, “we are working to change the paradigm of for-profit drug development companies by focusing on global populations simultaneously via our international partnerships so that people most in need will also have access to this anti-diarrheal drug. It has been and continues to be part of our core values to implement this strategy and vision.”

Additional charitable activities include Napo’s partnering with the Healing Forest Conservancy (HFC), which was developed by Shaman Pharmaceuticals, Napo’s precursor.⁹ HFC returns benefits to and shares profits with the indigenous cultures that work at harvesting or replanting medicinal plants used by the company or who have traditional knowledge. Additionally, Napo’s B Corporation subsidiary Crofelemer Access Program Global provides “economic alternatives to tropical deforestation in rainforest areas of different biodiversity-rich Andean nations.”

In addition to partnering with nonprofits, Napo also creates innovative partnerships with other for-profit companies and has a number of investors who are interested in putting money toward the company’s triple bottom line approach. This approach, explains Dr. King, includes traditional investors; Napo’s partners in Latin America who have traditional knowledge on Croton lechleri, sustainably harvest the latex from the tree, and also work to create sustainable alternatives to deforestation; and persons who are dying of diarrheal diseases from unclean water, cholera, and other infectious origins.

Even as a for-profit drug company, Napo’s (and Shaman’s) journey has not always been smooth. Near the end of 1998, Shaman had almost run out of money and in 1999, results from a clinical trial focusing on crofelemer for chronic diarrhea (as opposed to acute) showed that patients taking crofelemer did not improve significantly more than those taking a placebo.¹⁰ The company’s stock fell, Nasdaq removed it from its listing, and many of Shaman’s employees were let go. But in 2000, founder Lisa Conte refined her focus on proving that crofelemer could treat HIV- and AIDS-related diarrhea with an extended application to irritable bowel syndrome (IBS). Conte brought Shaman into bankruptcy, founded Napo, and began new clinical trials. Crofelemer has since received fast-track status from the US Food and Drug Administration for its IBS and HIV indications.^9,10

“There are several important drugs for international public health programs either on the market now or in process,” said Dr. King. “We feel crofelemer will be a very important tool [for] global public heath and also an important product for the Western developed market or ‘biodiversity poor nations’ as well.”

—Lindsay Stafford

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