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Friday, July 20, 2018

These Indian fishermen take plastic out of the sea and use it to build roads 07-20




Every one of India’s 1.3 billion people uses an average 11kg of plastic each year. After being used, much of this plastic finds its way to the Arabian Sea and Indian Ocean, where it can maim and kill fish, birds and other marine wildlife.

Fisherman in India’s southern state of Kerala are taking on the battle to cut the level of plastic waste in the oceans.

When the trawlers drag their nets through the water, they end up scooping out huge amounts of plastic along with the fish. Until recently the fishermen would simply throw the plastic junk back into the water.

But last summer Kerala’s fisheries minister J. Mercykutty Amma started a scheme to change this. Under her direction, the state government launched a campaign called Suchitwa Sagaram, or Clean Sea, which trains fishermen to collect the plastic and bring it back to shore.

In Suchitwa Sagaram’s first 10 months, fisherman have removed 25 tonnes of plastic from the Arabian Sean, including 10 tonnes of plastic bags and bottles, according to a UN report on the scheme.

From waste to roads

Once all the plastic waste caught by the Keralan fishermen reaches the shore, it is collected by people from the local fishing community - all but two of whom are women - and fed into a plastic shredding machine.

Like so many of India’s plastic recycling schemes, this shredded plastic is converted into material that is used for road surfacing.

There are more than 34,000km of plastic roads in India, mostly in rural areas. More than half of the roads in the southern state of Tamil Nadu are plastic. This road surface is increasingly popular as it makes the roads more resilient to India’s searing heat. The melting point for plastic roads is around 66°C, compared to 50°C for conventional roads.

Using recycled plastic is a cheaper alternative to conventional plastic additives for road surfaces. Every kilometre of plastic road uses the equivalent of a million plastic bags, saving around one tonne of asphalt. Each kilometre costs roughly 8% less than a conventional road.

And plastic roads help create work. As well as the Keralan fishing crews, teams of on-land plastic pickers across India collect the plastic waste. They sell their plastic to the many small plastic shredding businesses that have popped up across the country.

Plastics ban

The need for schemes such as Suchitwa Sagaram is emphasised by research that shows 90% of the plastic waste in the world’s oceans is carried there by just 10 rivers - two of which are in India.

According to a study by the Helmholtz Centre for Environmental Research, India’s Indus and Ganges rivers carry the second and sixth highest amounts of plastic debris to the ocean. The Indian Ocean, meanwhile, is choked with the second highest amount of plastic out of all of the world’s oceans. 



Like Kerala’s fisheries minister, Indian politicians appear to be taking action in the face of this mounting crisis.
This month India’s prime minister Narendra Modi pledged to eliminate all single-use plastic in the country by 2022, starting with an immediate ban in urban Delhi.
The move came just three months after India’s western state of Maharashtra issued a ban virtually all types of plastic bag, disposable cutlery, cups and dishes, as well as plastic containers and packaging.
Residents face fines from 5,000 rupees (US$73) for a first time offence to 25,000 rupees ($367) and jail time for repeat offenders, while the state’s Environment Department is also encouraging people to recycle bottles and milk bags through a buy-back scheme.
While’s India’s plastic problem is substantial due to the size of its population and its rate of economic growth, schemes such as those in Maharashtra, Delhi and Kerala set an example to western nations.



In the US, for example each person on average generates up to 10 times the amount of plastic waste generated by their Indian counterpart.
If western nations followed India’s lead of combining political pressure with entrepreneurial ventures, perhaps the world will stand of a chance of avoiding the predicted catastrophe of there being more plastic than fish in the sea by 2050




Tuesday, July 17, 2018

Why diagnosing Alzheimer’s today is so difficult—and how we can do better 07-17
































Shyam's take....

Bill Gates's next investment in Alzheimer’s research is in a new fund called Diagnostics Accelerator. This project of the Alzheimer’s Drug Discovery Foundation (ADDF) aims to accelerate bold new ideas for earlier and better diagnosis of the disease. Bill Gates is planning to invest more than 30 million for this cause. 


It is not for the first time, that research in Alzheimer disease management or prevention research has received attention or funding. However, when a person like Bill Gates devotes time and funds for a cause, the cause itself receives widespread attention from people all over the world. The awareness for the cause increases manifold. It gives direction to many philanthropists as to which cause they should invest. It simultaneously encourages the devoted scientists, researchers and the medical professionals working for this cause. These people not only find light at the end of the tunnel, they feel the entire tunnel has brightened up. This way Bill Gates involvement, more than the investment proves to be driver and huge catalyst. For me, his devoting time for the cause, is more important than his investment. I also like his idea of  venture philanthropy, it could mean that research could at least fund itself partially and the end product could bring back some returns for the investors or help create a corpus, that could fund further research.  Kudos Mr. Gates.

Now please read the article.....

When I announced that I was investing in Alzheimer’s research for the first time last fall, I thought I knew what to expect. I knew I would get to engage more deeply with the brilliant scientists and advocates working to stop Alzheimer’s—and I haven’t been disappointed. The things I’ve seen over the last seven months make me more hopeful than ever.


What I didn’t see coming was the amazing response I got from the Alzheimer’s community at large. Because my family didn’t talk publicly about my dad’s diagnosis before the announcement, I had yet to experience how remarkable the support community is. So many of you have shared your personal experiences with me, both in person and online (including here on TGN). It helps to hear from others who are going through the same thing.


Alzheimer’s research is a frontier where we can dramatically improve human life—both the lives of people who have the disease and their loved ones. I’m optimistic that we can substantially alter the course of Alzheimer’s if we make progress in several key areas. One of the biggest things we could do right now is develop a reliable, affordable, and accessible diagnostic.


The process of getting diagnosed with Alzheimer’s today is less than ideal. It starts with a cognitive test. If you don’t perform well, your doctor needs to rule out all other possible causes for memory loss, like stroke or a nutritional deficiency. Then your doctor can order a spinal tap or PET scan to confirm you have Alzheimer’s. Although these tests are fairly accurate, the only way to diagnose the disease definitively is through an autopsy after death.


There are two big problems with this process. First, it can be expensive and invasive. Most insurance plans in the United States won’t reimburse tests for Alzheimer’s. Patients often pay thousands of dollars out of their own pockets. Meanwhile, spinal taps can be scary and uncomfortable, and PET scans require the patient to stay perfectly still for up to 40 minutes. That’s difficult for anyone to do—but especially someone with Alzheimer’s.


Second, patients aren’t being tested for the disease until they start showing cognitive decline. The more we understand about Alzheimer’s, the clearer it becomes that the disease begins much earlier than we previously thought. Research suggests Alzheimer’s starts damaging the brain more than a decade before symptoms start showing. That’s probably when we need to start treating people to have the best shot at an effective drug.


This delay is a huge problem in the quest for a scientific breakthrough. It’s currently so difficult to find enough eligible patients for a clinical trial that it can take longer to enroll participants than to conduct the study. We need a better way of diagnosing Alzheimer’s—like a simple blood test or eye exam—before we’re able to slow the progression of the disease.  


It’s a bit of a chicken and egg problem. It’s hard to come up with a game changing new drug without a cheaper and less invasive way to diagnose patients earlier. But most people don’t want to find out if they have the disease earlier when there’s no way to treat it. The commercial market for Alzheimer’s diagnostics simply isn’t there. There’s promising research being done, but very few companies are looking at how to turn that research into a usable product.


That’s why my next investment in Alzheimer’s research is in a new fund called Diagnostics Accelerator. This project of the Alzheimer’s Drug Discovery Foundation (ADDF) aims to accelerate bold new ideas for earlier and better diagnosis of the disease. Today I’m joining Leonard Lauder, ADDF, the Dolby family, the Charles and Helen Schwab Foundation, and other donors in committing more than $30 million to help launch Diagnostics Accelerator.


Diagnostics Accelerator is a venture philanthropy vehicle, which means it’s different from most funds. Investments from governments or charitable organizations are fantastic at generating new ideas and cutting-edge research—but they’re not always great at creating usable products, since no one stands to make a profit at the end of the day. Venture capital, on the other end of the spectrum, is more likely to develop a test that will actually reach patients, but its financial model favors projects that will earn big returns for investors.


Venture philanthropy splits the difference. It incentivizes a bold, risk-taking approach to research with an end goal of a real product for real patients. If any of the projects backed by Diagnostics Accelerator succeed, our share of the financial windfall goes right back into the fund.


My hope is that this investment builds a bridge from academic research to a reliable, affordable, and accessible diagnostic. I expect to see lots of new players come to the table, who have innovative new ideas but might not have previously had the resources to explore them. If you think you’re one of these bold thinkers, we want to hear your great ideas. I encourage you to apply for funding on the new Diagnostics Accelerator website here.


Imagine a world where diagnosing Alzheimer’s disease is as simple as getting your blood tested during your annual physical. Research suggests that future isn’t that far off, and Diagnostics Accelerator moves us one step closer.

Monday, July 2, 2018

India's Biotech Queen Kiran Mazumdar Elected As MIT Board Member 07-03


India's biotech queen Kiran Mazumdar Shaw gets elected as a full-term member of the MIT Corporation, the Board of Trustees of the Massachusetts Institute of Technology (MIT),




A first-generation entrepreneur and a thought leader, Ms Shaw is ranked among the world's most influential people in bio-pharma.


Ms. Shaw is also on the board of directors of the US-India Business Council.
"Shaw is among the eight members who will serve the five-year term on the Board from July 1," the Bengaluru based biotech firm in a statement.

Ms Shaw, 65, is a pioneer of the Indian biotech sector and founder-chairperson of Biocon, a global drug maker for affordable and accessible healthcare.
"I am honoured to be elected as a full-time member of the MIT Board and look forward to contributing to its journey of making a difference in solving challenges of the world," she said.
A first-generation entrepreneur and a thought leader, Ms Shaw is ranked among the world's most influential people in bio-pharma by Fierce Biotech, Forbes magazine's 'World's 100 Most Powerful Women' and Fortune's 'Top 25 Most Powerful Women in the Asia-Pacific region'.
She has also been ranked number one in the Business Captains category on 'Medicine Maker Power List' 2018, an index of the 100 most influential people the world over in medicine where she has been among the top 10 since 2015.
"It is inspiring to be a part of a premiere research university like MIT, which is engaged in advancing knowledge, leveraging science and technology to address fundamental human needs for food, shelter, energy, transportation and social harmony," said Ms Shaw, who holds key positions in educational, industrial and government bodies, including expert committees of the Department of Biotechnology and governing councils of its institutes.
She is also on the board of directors of the US-India Business Council and the board of trustees of the Keck Graduate Institute at California's Claremont.
Ms Shaw was elected a foreign member of the Royal Swedish Academy of Engineering Sciences in 2006.
She has established a 1,400-bed medical center in Bengaluru to deliver affordable cancer care to patients and a non-profit research institute dedicated to treating diseases.
Ms Shaw graduated from Bangalore University and has a master's from Ballarat College of Melbourne University in Australia.
Ranked among the world's leading universities, the 157-year-old MIT is an independent, co-educational and privately-endowed institution, with 1,000 faculty members, 11,000 under-graduate and post-graduate students and 130,000 living alumni.

Saturday, June 2, 2018

The 3 Types of Diversity That Shape Our Identities.06-03






Diversity means different things to different people. In a study of 180 Spanish corporate managers, we explored perceptions of diversity and found that depending on who is answering, diversity usually means one of three things: demographic diversity (our gender, race, sexual orientation, and so on), experiential diversity (our affinities, hobbies, and abilities), and cognitive diversity (how we approach problems and think about things). All three types shape identity — or rather, identities.

Demographic diversity is tied to our identities of origin — characteristics that classify us at birth and that we will carry around for the rest of our lives. Experiential diversity is based on life experiences that shape our emotional universe. Affinity bonds us to people with whom we share some of our likes and dislikes, building emotional communities. Experiential diversity influences we might call identities of growth. Cognitive diversity makes us look for other minds to complement our thinking: what we might call identities of aspiration.

It is important to remember that categories only serve the purpose of classification; in the real world, differences between these categories are blurred. Diversity is dynamic. But we believe this diversity framework, though somewhat artificial (as all frameworks are) can be useful to companies who are trying to refresh their approach to managing diversity. What kind of diversity does your company focus on? Could you benefit from broadening your perspective? Let’s take a closer look at each in turn.

Managing identities of origin. Since the 1980s, most global companies have developed diversity and inclusion policies led by human resources. The most frequent include: assessment tools (climate surveys, statistics monitoring, minority targets), human resources programs (flexible policies, mentoring or coaching), communication campaigns, and training programs.

Consider Sodexho. In 2002 the company hired a chief diversity officer, Anand Rohini, to make diversity a priority. Some of the diversity priorities at Sodexho focused on gender, ethnicity, disabilities, and age. Its diversity strategy included a series of systems and processes covering human resources policies (such as flexibility measures, training, selection processes and career services); diversity scorecards; and quantitative targets, mainly regarding numbers of women and minorities, not only in the organization in general but also in leadership positions. By 2005 Sodexho was widely recognized as a diversity champion. For more than a decade it has been consistently ranked among the best of the DiversityInc top 50 list, and Anand Rohini has been widely recognized as a global diversity champion.

For Sodexho and other companies taking a similar approach, the result is an enhanced company image and reputation. Talented individuals in general, but from minorities in particular, select companies in which they expect to feel appreciated.

Managing identities of growth. Identities of growth often provide us with a feeling of security. Our likes and dislikes change over time, and so our affinity groups change. Identities of growth dictate who we spend time with.

Many companies have developed friendship-based communities among employees, typically organizing activities such as weekends away, departmental Christmas parties, and so on, in a bid to create emotional ties between workers and the company. But because emotional communities are held together as much by the likes as by the dislikes of members, they can be unpredictable and difficult to manage in the long term. As a result, these emotional communities can sometimes work to the benefit of organizations, but they can just as often end up having the opposite effect, particularly when people share a dislike for certain policies, a particular boss, or for what they consider to be an unfair situation.

Our research suggests that the best policy for dealing with communities of growth is through minimum intervention. Emotional communities will emerge in organizations, whether management likes it or not, and will have a life of their own. For that reason it is best to take a neutral position. Creating affinity groups is positive for the company. But these groups should always be voluntary and develop at their own pace, without management interference.

Managing identities of aspiration. Our cognitive differences find their place in a community of aspiration. In those communities, we are valued for our unique way of understanding and interpreting the world. A community of aspiration is a space where our ideas are valued for their contribution to a common project, regardless of our different traits or individual likes or dislikes.

Innovative organizations are shifting from managing units to managing challenges or projects, asking employees to voluntarily join projects, creating structures where employees can move out of their comfort zones to join temporary communities of aspiration that strengthen cross-organizational ties and help the company achieve its strategic goals.

Corporate experience shows that the most effective strategy for companies to manage communities of aspiration is to create the contexts and the projects for them to emerge.

Valve Corporation, a video game developer, has defined a unique corporate structure with no bosses or managers at all. Each member of the company is invited to define their contribution to the company according to their choices and preferences. A highly talented developer specialized in graphics animation might choose to work on a game by assuming a “group contributor role,” becoming part of the group developing that game.

After finishing this “group contribution,” the same person might choose to work in a more individualistic fashion on the next task. This “free to choose” approach is mirrored in the firm’s office design. Valve offices incorporate wheeled desks to foster mobility and allow the fast configuration and reconfiguration of groups as well as individual work.

Understanding multiple types of diversity is particularly relevant in our tribal times. Individuals now construct identities consciously. We want to play with a multiplicity of identities and use them in as many different roles as their different affiliations allow.

We live in complex times, when complex solutions are need it and where a one solution for all approach no longer works. Each form of diversity is different and requires its own management strategy to effectively integrate people. Diversity is a journey and, like any journey, requires careful navigation.

View at the original source

Monday, May 28, 2018

2018 Military Strength Ranking 05-31





















The complete Global Firepower list for 2018 puts the military powers of the world into full perspective.

The finalized Global Firepower ranking relies on over 55 individual factors to determine a given nation's PowerIndex ('PwrIndx') score. Our unique formula allows for smaller, more technologically-advanced, nations to compete with larger, lesser-developed, ones. Modifiers (in the form of bonuses and penalties) are added to further refine the list. Some qualities to observe in regards to the finalized ranking:

+ Ranking does not rely solely on the total number of weapons available to any one country (though it is a factor) but rather focuses on weapon diversity within the number totals to provide a better balance of firepower available. For example, fielding 100 minesweepers does not equal the strategic / tactical value of fielding 10 aircraft carriers.

+ Nuclear stockpiles are NOT taken into account but recognized / suspected nuclear powers do receive a bonus.

+ First World, Second World, and Third World statuses are taken into account.

+ Geographical factors, logistical flexibility, natural resources, and local industry influence the final ranking.

+ Available manpower is a key consideration; nations with large populations tend to rank higher due to the availability of personnel for supporting both war and industry.

+ Land-locked nations are NOT penalized for lack of a navy, however, naval powers ARE penalized for lack of diversity in available assets. For example, 100 patrol boats does not equate the same advantage that fielding 4 guided-missile frigates and 2 nuclear-attack submarines does.

+ NATO allies receive a slight bonus due to the theoretical sharing of resources should one of the members commit to war.

+ Financial stability / strength is taken into account as finances represent one of several important factors in running a successful campaign.

+ Current political / military leadership is NOT taken into account as this can be highly subjective and not necessarily influence in-the-field indivudal combat performance.

For 2018 there are a total of 136 countries included in the GFP database. New to 2018 are Ireland, Montenegro, and Liberia.

Arrow graphics correspond to each nation's placement against the previous year's list. Green Arrows indicate an increase in rank whilst Red Arrows reflect a decline. Gray 'Double Arrows' reflect no change in ranking; this does not necessarily indicate that no changes occurred across individual values but more so that changes were not great enough to affect year-over-year ranking. Increases/declines are based on many factors and can be related to attrition, financial instability, population fluxes and the like.

View the Global list

View India's Firepower Details  

View comparison between the fire power of China and India

Sunday, May 27, 2018

A Resolution Revolution,Single-cell Sequencing Techniques, 05-28








Despite its promise, a lack of spatial-temporal context is one of the challenges to making the most of single-cell analysis techniques. For example, information on the location of cells is particularly important when looking at how a common form of early-stage breast cancer, called ductal carcinoma in situ (DCIS) progresses to a more invasive form, called invasive ductal carcinoma (IDC). “Exactly how DCIS invasion occurs genomically remains poorly understood,” said Nicholas Navin, Ph.D., associate professor of Genetics at the University of Texas MD Anderson Cancer Center. Navin is a pioneer in the field, developing one of the first methods for scDNA-seq.

Cellular spatial data is critical for knowing whether tumor cells are DCIS or IDC. So, Navin developed topographical single-cell sequencing (TSCS). Navin and a team of researchers published their findings in February 2018 in Cell. “What we found was that, within the ducts, mutations had already occurred and had generated multiple clones and those clones migrated into the invasive areas,” Navin said.

Navin and his colleagues are also using single-cell techniques to study how triple-negative breast cancer, becomes resistant to the standard from of treatment for the disease, neo-adjuvant chemotherapy. In that work, published in an April 2018 online issue of Cell, using scDNA-seq and scRNAseq, Navin and his colleagues found responses to chemotherapy were pre-existing, thus adaptively selected. However, the expression of resistant genes was acquired by subsequent reprogramming as a result of chemotherapy. “Our data raise the possibility of therapeutic strategies to overcome chemoresistance by targeting pathways identified in this study,” Navin said.
Revealing Complexity.

The authors of research published in 2017 in Genome Biology also identified lineage tracing as one of the technologies that will “likely have wide-ranging applications in mapping developmental and disease-progression trajectories.” In March researchers published an online study in Nature in which they combined single-cell analysis with a lineage tracing technique, called GESTALT (genome editing of synthetic target arrays for lineage tracing), to define cell type and location in the juvenile zebrafish brain.

The combined technique, called scGESTALT, uses CRISPR-Cas9 to perform the lineage tracing and single-cell RNA sequencing to extract the lineage records. Cas9-induced mutations accumulate in a CRISPR barcode incorporated into an animal’s genome. These mutations are passed onto daughter cells and their progenies over several generations and can be read via sequencing. This information has allowed researchers to build lineage trees. Using single-cell analysis, the team could then determine the diversity of cell types and their lineage relationships. Collectively, this work provided a snapshot of how cells and cell types diverge in lineages as the brain develops. “Single-cell analysis is providing us with a lot of information about small differences at cell type-specific levels, information that is missed when looking at the tissue-wide level,” said Bushra Raj, Ph.D., a postdoctoral fellow in Alex Schier’s lab at Harvard University and first author on the paper.

Raj’s collaborators included University of Washington’s Jay Shendure, Ph.D., and Harvard Medical School’s Allon Klein, Ph.D., pioneers in the field of single-cell analysis. The team sequenced 60,000 cells from the entire zebrafish brain across multiple animals. The researchers identified more than 100 cell types in the juvenile brain, including several neuronal types and subtypes in distinct regions, and dozens of marker genes. “What was unknown was the genetic markers for many of these cell types,” Raj explained. “This work is a stepping stone,” she added. “It’s easy to see how we might one day compare normal gene–expression maps of the brain and other organs to help characterize changes that occur in congenital disease or cancer.”

Raj credits single-cell analysis with accelerating the field of developmental biology.
“People have always wanted to work at the level of the cell, but the technology was lacking,” she said. “Now that we have all of these sequenced genomes, and now that we have these tools that allow us to compartmentalize individual cells, this seems like the best time to challenge ourselves as researchers to understand the nitty-gritty details we weren’t able to assay before.”

A gold leaf paint and ink depiction of the Plasmodium falciparum lifecycle by Alex Cagan.
Human disease-relevant scRNA-seq is not just for vertebrates. For example, a team of researchers at the Wellcome Sanger Institute are working on developing a Malaria Cell Atlas. Their goal is to use single-cell technology to produce gene activity profiles of individual malaria parasites throughout their complex lifecycle. “The sequencing data we get allows us to understand how the parasites are using their genomes,” said Adam Reid, Ph.D., a senior staff scientist at the Sanger. In March 2018, the team published the first part of the atlas, detailing its results for the blood stage of the Plasmodium lifecycle in mammals. Reid contends these results will change the fight against malaria. “Malaria research is a well-funded and very active area of research. We’ve managed to get quite a bit of understanding of how the parasite works. What single-cell analysis is doing is allowing us to better understand the parasite in populations. We thought they were all doing the same thing. But, now we can see they are behaving differently.”

The ability to amplify very small amounts of RNA was the key innovation for malaria researchers. “When I started doing transcriptome analysis 10 years ago, we needed to use about 5 micrograms of RNA. Now, we can use 5 pico grams, 1 million times less,” Reid said. That innovation allows scientists like Reid to achieve unprecedented levels of resolution in their work. For Reid, increased resolution means there is hope that science will be able to reveal how malaria evades the immune system in humans and how the parasites develop resistance to drugs. Reid predicted the Atlas will serve as the underpinning for work by those developing malaria drugs and vaccines. “They will know where in the life cycle genes are used and where they are being expressed,” he said. Drug developers can then target those genes. The Atlas should be complete in the next two years, Reid added.
In the meantime, Reid and his colleagues are focused on moving their research from the lab to the field, particularly to Africa. “We want to look at these parasites in real people, in real settings, in real diseases states,” he explained. Having access to fresher samples is one reason to take the research into the field. “The closer we can get to the disease, the better chance we have of making an impact.” Reid anticipates that RNA-seq technology is on the verge of being portable enough to go into the field (see Preparing scRNA-seq for the Clinic & the Field). Everything from instrumentation to software is developing rapidly, he said. Reid also said that the methods used to understand the malaria parasite will likely be used to understand and create atlases for other disease vectors.

Path Ahead

It is clear to those using single-cell analysis in basic research that the path ahead includes using the techniques in the clinic. “As the technologies become more stable, there will be a lot of opportunities for clinical applications,” Navin said. These include early detection by sampling for cancer markers in urine, prostate fluid, and the like. It also includes non-invasive monitoring of rare circulating tumor cells, as well as personalizing treatment decisions using specific markers. These methods will be particularly useful in the case of samples that today would be labeled QNS, or ‘quantity not sufficient.’ “Even with QNS samples, these methods allow you to get high-quality datasets to guide treatment decisions.” 



Sunday, May 20, 2018

For new medicines, turn to pioneers 05-21





Most transformative medicines originate in curiosity-driven science, evidence says....

Would we be wise to prioritize “shovel-ready” science over curiosity-driven, fundamental research programs? In the long term, would that set the stage for the discovery of more medicines?
To find solid answers to these questions, scientists at Harvard and the Novartis Institute for Biomedical Research (NIBR), publishing in Science Translational Medicine, looked deep into the discovery of drugs and showed that, in fact, fundamental research is “the best route to the generation of powerful new medicines.”

“The discoveries that lead to the creation of a new medicine do not usually originate in an experiment that sets out to make a drug. Rather, they have their origins in a study — or many studies — that seek to understand a biological or chemical process,” said Mark Fishman, one of three authors of the study. “And often many years pass, and much scientific evidence accumulates, before someone realizes that maybe this work holds relevance to a medical therapy. Only in hindsight does it seem obvious.”

Fishman is a professor in the Harvard Department of Stem Cell and Regenerative Biology, a faculty member of the Harvard Stem Cell Institute, and former president of NIBR. He is a consultant for Novartis and MPM Capital, and is on the board of directors of Semma Therapeutics and the scientific advisory board of Tenaya Therapeutics.

CRISPR-cas9 is a good example of discovery biology that opened new opportunities in therapeutics. It started as a study of how bacteria resist infection by viruses. Scientists figured out how the tools that bacteria use to cut the DNA of an invading virus could be used to edit the human genome, and possibly to target genetic diseases directly.

The origins of CRISPR-Cas9 were not utilitarian, but those discoveries have the potential to open a new field of genomic medicine.

Blood pressure medicines would never have been created without the discovery of the role of renin (a renal extract) in regulating blood pressure in 1898.

Blood pressure medication is another example of how fundamental discoveries can lead to transformative medicines.

People who suffer from high blood pressure often take drugs that act by blocking the angiotensin-converting enzyme. Those medicines would never have been created without the discovery of the role of renin (a renal extract) in regulating blood pressure in 1898, or without the discovery of angiotensin in 1939, or without the solid understanding of how the enzyme works, shown in 1956.

This work was not tied earlier to making pills for hypertension, mainly because hypertension was generally believed to be harmless until the 1950s, when studies showed its relationship to heart disease. Before then, the control of blood pressure was itself a fundamental science, beginning with Stephen Hales’ measurement  of blood pressure in a horse in 1733.

The discovery of ACE inhibitors really reflects the convergence of two fields of fundamental, curiosity-driven discovery.

Yet some observers believe that projects that can demonstrate up front that they could produce something useful should take priority over projects that explore fundamental questions. Would there be many more medicines if academics focused more on programs with practical outcomes? How would that shift affect people in the future?

To find answers, Fishman and his colleagues investigated the many scientific and historical paths that have led to new drugs. The study they produced is a contemporary look at the evidence linking basic research to new medicines.

The authors used a list of the 28 drugs defined by other scientists as the “most transformative” medicines in the United States between 1985 and 2009. The group examined:
Whether the drug’s discovery began with an observation about the roots of disease;
Whether the biologist believed that it would be relevant to making a new medicine; and
How long it took to realize that.

To mitigate bias, the researchers repeatedly corroborated the assignment with outside experts.
They found that eight out of 10 of the medicines on their list led back to a fundamental discovery — or series of discoveries — without a clear path to a new drug.

The average time from discovery to new drug approval was 30 years, the majority of which was usually spent in academia, before pharmaceutical or biotechnology companies started the relevant drug development programs.

Fishman concluded, “We cannot predict which fundamental discovery will lead to a new drug. But I would say, from this work and my experiences both as a drug discoverer and a fundamental scientist, that the foundation for the next wave of great drugs is being set today by scientists driven by curiosity about the workings of nature.”

What industry and academic leaders say..

Leaders in biomedicine from industry, business, and academia warmly welcome this new body of evidence, as it supports the case for funding curiosity-driven, non-directed, fundamental research into the workings of life.

“This perspective on drug discovery reminds all of us that while many in both industry and academia have been advocating for a more rational approach to R&D, the scientific substrate we depend on results from a less than orderly process. The impact of basic research and sound science is often unpredictable and underestimated. With several telling examples, the authors illustrate how they can have a ripple effect through our field.”

– Jean-François Formela, M.D., Partner, Atlas Venture...

“The paper presents a compelling argument for investing in fundamental, curiosity-driven science. If it often takes decades to recognize when a new discovery should prompt a search for targeted therapeutics, we should continue to incentivize academic scientists to follow their nose and not their wallets.”

– George Daley, M.D., Ph.D., Dean of the Faculty of Medicine, Caroline Shields Walker Professor of Medicine, and Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School

“There is a famous story of a drunk looking for his lost keys under a streetlight because the light is better there. As Mark reminds us, if we only look for cures where the light has already shone, we will make few if any new discoveries. Basic research shines a light into the dark corners of our understanding, and by that light we can find wonderful new things.”

— Dr Laurie Glimcher, M.D., President and CEO of the Dana-Farber Cancer Institute and Richard and Susan Smith Professor of Medicine at Harvard Medical School

“The importance of fundamental discovery to advances in medicine has long been a central tenet of academic medicine, and it is wonderful to see that tenet supported by this historical analysis. For those of us committed to supporting this pipeline, it is a critical reminder that young scientists must be supported to pursue out-of-the-box questions and even new fields. In the end, that is one of the key social goods that a research university provides to future generations.”

— Katrina Armstrong, M.D., M.S.C.E., Physician-in-Chief, Department of Medicine, Massachusetts General Hospital

“Human genetics is powering important advances in translational medicine, opening new doors to treatments for both common and rare diseases at an increasingly rapid pace. Yet, these discoveries still require fundamental, basic scientific understanding into the drug targets’ mechanism of action. In this way, the potential of the science can be unlocked through a combination of curiosity, agility, and cross-functional collaboration to pursue novel therapeutic modalities like gene and cellular therapies, living biologics, and devices. This paper illustrates the value of following the science with an emphasis on practical outcomes and is highly relevant in today’s competitive biopharmaceutical environment, where much of the low-hanging fruit has already been harvested.”

– Andy Plump, M.D., Ph.D., Chief Medical and Scientific Officer, Takeda Pharmaceutical Co.
“Medicine depends on scientists asking questions, collectively and over generations, about how nature works. The evidence provided by Fishman and colleagues supports an already strong argument for continued and expanded funding of our nation’s primary source of fundamental science: the NIH and the NSF.”

– Douglas Melton, Ph.D., Xander University Professor at Harvard, Investigator of the Howard Hughes Medical Institute, and co-director of the Harvard Stem Cell Institute

“Just as we cannot translate a language we do not understand, translational medicine cannot exist without fundamental insights to be converted into effective therapies. In their excellent review, Fishman and his colleagues bring the factual evidence needed to enrich the current debate about the optimal use of public funding of biomedical research. The product of public research funding should be primarily fundamental knowledge. The product of industrial R&D should be primarily transformative products based on this knowledge.”

— Elias Zerhouni, M.D., President Global R&D Sanofi, former Director of the National Institutes of Health, 2002-2008

“Fundamental research is the driver of scientific knowledge. This paper demonstrates that fundamental research led to most of the transformative medicines approved by the FDA between 1985 and 2009. Because many genes and genetic pathways are evolutionarily conserved, discoveries made from studies of organisms that are highly tractable experimentally, such as yeasts, worms, and flies, have often led to and been integrated with findings from studies of more complex organisms to reveal the bases of human disease and identify novel therapeutic targets.”

– H. Robert Horvitz, Nobel Laureate; David H. Koch Professor, Member of the McGovern Institute for Brain Research and of the David H. Koch Institute for Integrative Cancer Research, and Howard Hughes Medical Institute Investigator at Massachusetts Institute of Technology

“This meticulous and important study of the origin of today’s most successful drugs finds convincingly that the path to discovery lies through untargeted fundamental research. The authors’ clear analysis is an effective counter to today’s restless investors, academic leaders, and philanthropists, whose impatience with academic discovery has itself become an impediment to the conquest of disease.”

— Marc Kirschner, John Franklin Enders University Professor, Department of Systems Biology, Harvard Medical School

“Some ask if there is a Return on Investment (ROI) in basic biomedical research. With transformative therapies as the ‘R,’ this work traces the path back to the starting ‘I,’ and repeatedly turns up untargeted academic discoveries — not infrequently, two or more that are unrelated to each other. Conclusion? A nation that wants the ‘R’ to keep coming must maintain, or better, step up the ‘I’: that is, funding for curiosity-driven, basic research.”

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