MinION conference continues

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Thomas Hoenen speaking on Ebola. Image source: Nigel Chapman

I wrote about the first day of the conference here.

The second day of the conference also had an infectious diseases focus, where we learned how the MinION was used to identify the two major Ebola lineages in West Africa. The MinION has environmental applications, too, as Brook Milligan showed that the MinION was used to trace illegally traded timber, which accounts for $100 billion annually in lost revenue, he said.

Non-infectious clinical applications were less frequent at London Calling. However, the MinION’s long reads have an advantage that was reflected in Ron Ammar‘s pharmacogenomics talk.

Ron showed that Haplotyping the Thiopurine S-Methyltransferase (TPMT) gene at two SNPs (rs1142345 and rs1800460) influenced the immunosuppressive Thiopurine drug dosage more precisely than having the SNPs information separately.

After the two pleasantly exhaustive days, I returned to Kuwait with a personalized Fahd Al-Mulla MinION that dazzled staff at my University and Genatak. I am planning to use it, ASAP, and present my personalized vision for the MinION conference next year. However, while at the conference a colleague and I cautioned Oxford Nanopore staff about the need to validate each MinION before use in the clinic. This will be difficult to do if they keep changing the models so frequently. Perhaps clinical validation will be done on the more accurate and enhanced models soon, and I would be glad to be part of the process.

Before the conference, I had heard competitors project a gloomy picture for the MinION, and I wanted to understand why. After the conference, I formed a theory: When Oxford Nanopore management decided to partner directly with scientists to test and enhance their products, these busy scientists did not act quickly and ended up delaying the progress of MinION. More importantly, the first generation MinION’s flow cells, which worked perfectly well at the source, did not work very well after shipment! It turns out that microbubbles were forming in the not-so-well degassed and shipped reagents and flow cells.

This reminded me of my first trip to Kuwait from Glasgow, where I took my engineered cell lines in a flask half-filled with growth media. It appears that the constant shaking and formed bubbles dislodged my attached cells, and they died. I learned, as did Oxford Nanopore Technologies, to de-gas the media well and fill the flask to the rim with media. I’ve now had the cells for many years in Kuwait, living happily ever after, and I am glad to say that the new flow cells appear green on the computer screen indicating that almost all the nanopores are working to full capacity.

The meeting created a tight bond between researchers and Oxford Nanopore, because this time scientists were offered a product that they then can sculpt into their own scientific achievements. One can only imagine the joy we shared when we were handed the keys to a futuristic technology, and we were asked to assist perfecting it!

It made me think how other companies and entrepreneurs should learn from the sharing business model adopted by Oxford Nanopore Technologies.

Fahd Al-Mulla

 

 

 

 

Two Days of MinION

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Audience members inspecting their free MinION. Source: Nigel Chapman

Oxford Nanopore Technologies invented the MinION device – a pocket-sized DNA/RNA sequencer that is based on protein nanopores set in an electrically resistant polymer membrane. It works by passing an ionic current through the nanopores, creating a specific disruption pattern in the current that is used to identify the molecule. This is similar to the antennae of insects, and it fascinated me. So, I wrote to Oxford Nanopore expressing my wish to join its MinION Access Programme (MAP).

MAP is a community-focused access project that started in Spring 2014. Its philosophy is to enable a broad range of scientists to explore different ways MinION may be useful to them, to contribute to developments in analytical tools and applications and to share their experiences and collaborate. This year I received an invitation to submit an abstract to a conference hosted by Oxford Nanopore called “London Calling.” The two-day conference was opened by Dr. Gordon Sanghera, the CEO of Oxford Nanopore Technologies, who explained to the international audience that London Calling is the third studio album by the English punk rock band the Clash.

The first question one might have is, Does the Nanopore technology actually work? The answer is yes. All speakers, who were part of the early group of MAP users, produced sequences using MinION. Nick Loman showed that he could identify Salmonella as the source of food poisoning in just 100 minutes of sequencing. Moreover, Jared Simpson produced a complete Escherichia coli K-12 MG1655 genome assembly having 98.4% nucleotide identity compared to the finished reference genome. This means that the MinION sequencing data can be used to reconstruct bacterial genomes without the need for a reference sequence.

All of the first-wave of MAP winners utilized the first generation application-specific integrated circuit (ASIC), which has 512 channels to prepare and relay the information from each nanopore to the host laptop (read 30 bases/sec). Imagine what they could have done if they had the next generation MkII MinION device with the next generation of ASIC, which has 3,000 channels. The new method of analysis, Fast Mode, plans to increase the speed from 30 bases per second per nanopore to around 500 and the ASIC is capable of going up to 1,000!

I was also interested to see two new additions:  the PromethION, which is expected to contain 144,000 channels across 48 flow cells, each capable of running multiple separate samples yielding up to 6 Terabases per day; and the Voltrax, a device that fits on top of the MinION or the PromethION and automates the 6-12 samples preparation.

That has me thinking about how these products will be suited to sequence whole human genomes, and the applications of this in the field of genomic medicine.

When the day was over, we went to the conference dinner at the Skyloft, which had panoramic views of London. Yet this was overshadowed by the news of MinION going to space. Yes, NASA’s Astromaterials Research and Exploration Science division plans to fly a few MinIONS to the International space station. Given the confined space within the International Space Station and the necessity to conduct experiments within it, the mere size of the MinION makes it an ideal instrument to study the existence of terrestrial nucleic acids and proteins, as well as possible infectious outbreaks in space stations of the future.

Up next: Day 2 of the conference

Fahd Al-Mulla

A true reflection of the human spirit

The author, at the Great Wall of China.

On the 8th of December 2011, I was invited to represent Kuwait at the Human Variome Project (HVP) meeting, being held for the first time in Beijing, China. The meeting was a result of many months of negotiation and the finalization of a historic partnership agreement between China and the Project.

HVP is an international consortium of researchers and clinicians, and later UNESCO representatives from more than 30 countries.  It formally inaugurated in 2006 in Melbourne, Australia, with the major goal of documenting (and placing in a database) all polymorphisms and mutations in human sequences, as well as associate these with human health and diseases. This ensures that global information on genetic variation is collected, curated, interpreted and shared freely and openly.

I want to stress the words “openly” and “freely,” because for a scientist this is the best way to share data. For an entrepreneur, though, this is a waste of effort, growth, and potential income, if not secured first by patenting.

Let me explain the problem. There is no doubt that the HVP will uncover thousands of DNA changes associated with disease predisposition and outcome, and they will be useful for disease diagnosis, prognosis and theranostics.  For example, yesterday I found a base substitution in the MLH1 gene of an Arab patient with hereditary non-polyposis colorectal cancer (HNPCC). The genetic change was non-synonymous (meaning it changed the amino acid composition of the MLH1 protein from proline to serine). The DNA change may have altered the protein function, predisposing the individual to cancer. However, one really cannot tell for sure because it can be a polymorphism found in the normal population.  One of the major aims of the HVP is to stratify these DNA changes into polymorphisms or disease causing mutations.

This is achieved for HNPCC by the Insight group, one of many databases curated for the HVP.  Now that federal appeals court ruled that genes (or more accurately, DNA sequences) can be patented, overturning a lower court decision by Judge Sweet, biotechnology companies are rushing to gain from genome wide association (GWAS) and linkage studies.

On the 18th of January 2012, we learned that Myriad Genetics has acquired exclusive license to intellectual property covering the analysis of the RAD51C gene for risk of hereditary breast and ovarian cancer. The six heterozygous mutations found in the RAD51C gene by a German group confer increased susceptibility to breast and ovarian cancers (for more info, click here).

My dilemma, and the reason behind my post, is to ask how will the patenting industry cope with thousands or more disease-associated DNA sequences coming out from the HVP? Moreover, after further validation, do I submit my unique sequence I found in the MLH1 gene to the Insight database, where it may help clinicians and patients, or do I patent it first?

By the way, I know that I and my colleagues in the Middle East and beyond have hundreds of these risk-associated sequences. We do want to do something with them that reflects the true human spirit!

Fahd Al-Mulla

Entrepreneurship and the Middle East

In my last post, I elaborated extensively on the demographic and unique cultural behavior that, in my opinion, makes the Middle East (ME) a fertile ground for novel biology-related discoveries.

I will now critically discuss the steps taken by local governments and related agencies in capitalizing on this immense and ‘hidden’ resource.

Oil and its derivatives have contributed greatly in the development of the ME. This fact is true for oil-producing countries or other countries of the ME and beyond, whose populations enjoyed the prosperity bestowed from the black gold. However, time waits for no one, and oil-producing countries have not capitalized on their huge resources as yet. A recent UNESCO report stated this deficiency loud and clear.

Let us look at what is available in the ME:

Virtually, all ME countries have universities and these institutes have been key in producing graduates. In Kuwait, for example, biotechnology and science-related graduates have been struggling to find suitable placements. I am not surprised, given the scarcity of biotech-related industries. It is personally disheartening to see a graduate in genetics employed in a bank, but this is not unusual these days, given the dissociation between ‘wishing to be’ and actual availability of biotechnology-related jobs. My personal experiences and observations are that ME-based universities are more concerned with generating graduates than with enhancing and encouraging entrepreneurship, which is looked at as a luxury and not a necessity for local economies. Nevertheless, people are trying against all odds to rectify this situation, though the pace has been too slow to have any impact.

In Kuwait, his Highness the Amir Sheikh Sabah Al-Ahmad Al-Sabah highlighted the importance of investing in human capital and promoting the culture of innovation by establishing a center: Sabah Al-Ahmad Center for Giftedness and Creativity (established May 2010). The goal is to sponsor talented/gifted and creative people in hopes of generating transformational effects across the community, which engenders social, economic and cultural development. The Center is headed by an ambitious, well-informed director, Dr. Omar Al-Banai, who also recognizes the importance of linking the University Technology Transfer Office to the development of patents and marketing.

In Qatar, the situation is rather mixed. There, research and development focus on foreign recruitments and some local input. The Qatar Science and Technology Park (QSTP) is the national agency charged with executing applied research and delivering commercialized technologies in four themed areas: energy, environment, health sciences, and information and communication technologies. QSTP is located in Qatar Foundation’s Education City and has access to the resources in leading research universities. In addition to QSTP’s centres, members include small companies, international corporations and research institutions, which have together committed to funding new ventures, creating intellectual property, enhancing technology management skills and developing innovative new products in line with the national vision. QSTP supports economic and human development in Qatar and has achieved recognition as an international hub for applied research, innovation and entrepreneurship. QSTP has ongoing projects in these four pillars.

In Dubai, the most ambitious of the United Arab Emirate states, the drive has been largely fueled by attracting foreign companies. The Dubai Biotechnology & Research Park is propagated as the major life sciences cluster in the ME. It is located in Free Zone that provides the ultimate platform for life sciences companies to set up operations and access the fast growing and emerging markets of the region.

To date, over 75 life sciences companies operate from the park, including Genzyme, Amgen, Pfizer, Merck-Serono, Maquet, National Reference Lab oratory and Firmenich. However, how these commercial entities integrate into local bio-entrepreneurship and most importantly the universities is rather unclear, at least to me.

During the last Human Genome Organization meeting held in Dubai, 14-17 of March, I had the great privilege of meeting the National Reference Laboratory representative, and we exchanged ideas. I was surprised to learn that the lab plans to export samples to the West for diagnosis. To me this action works against the local entrepreneurial spirit. The ME has suffered enough from the ‘Brain drain’ and the unique patients and samples drain. Let me just remind you of my first post on this blog where I have discussed the importance of our unique population in bio-discovery and the bioentrepreneurship processes.

Generally, I believe that there is a lack of understanding of the bioentrepreneurship ideology in the ME. Entrepreneurship must depend on local manpower, universities and research centers with the encouragement of outside contribution, support and partnerships. These efforts require more than 0.1-1% of GDP currently spent on research and development.

Ultimately we need to look forward and offer viable solutions to the future generations. A revolution in research and development is needed and urgently.

I am looking forward to hearing your opinions on the points raised here. Why has it taken us so long to develop a proper research and development program in the ME? Why has the Western investment in the ME been so limited? Surely, such investment may be of benefit to all humanity.

Fahd Al-Mulla

The Bioentrepreneur’s Introduction to the Middle East

The Middle East occupies a culturally rich and versatile part of the world. The turbulent history marked by expansion and invasion by many cultures has culminated in enriching and diversifying this region’s population and contributed significantly to genetic heterogeneity (genetic diversity).

Yet the geographic separation of our major population centers, encouraged by the climate and cultural preservation, and influenced by restrictions on travel between those centers, has historically resulted in a high degree of consanguineous marriages. Even today, we witness the highest rates of consanguineous marriages in the Middle East (100 times that of the United States). Such unions account for between 20%-70% of all marriages in the Gulf States alone. Therefore, this ‘natural experiment’ bestows a rich ground for the emergence of a very high number of genetic related diseases (i.e., diabetic, autosomal recessive disorders and others).

This is a personal tragedy, but it does provide fertile fields for genetic-based research opportunities for bioentrepreneurs who can recognize these unique opportunities. Drawn to this opportune and needful population, the researcher and entrepreneur can combine their efforts to discover origins and cures for many diseases having both a regional and world wide impact.

But be warned that this entrepreneurial opportunity is not without its challenges. Just as the population genomics of the Middle East presents unique research and business opportunities, the legal, economic, governmental, and societal environment of the Middle East presents a special and unfamiliar business environment for the bioentrepreneur. I will discuss this in more detail in later posts, but of primary concern is first admitting that one is entering a cultural, economic, and scientific research environment that is unlike any other.

This means that the bioentrepreneur should seek out one who might best serve as a guide through the many potential obstacles to his success. For instance, a buyer’s market approach when selecting research development opportunities may be acceptable in Europe and America, but it is not in the Middle East. Also, while scientist and engineers in the Middle East are capable, motivated and inspired, the research infrastructure is still in a growing and developing state. Finally, while sophisticated research grows rapidly in Middle East research centers, it may initially seem to the Western entrepreneur that breakthrough technological discoveries are relatively sparse.

It’s also true that while the region offers very special resources and business opportunities, the legal, economic, governmental, educational and societal environment of the Middle East also present challenges for the entrepreneur and particularly for the Western entrepreneur making an initial foray into the region. The first thing to understand is that abundant Middle East oil resources have attracted oil-exploration teams, entrepreneurs, and investors and, as a result, the region has thrived on an oil-based economy. These regional oil reserves still remain plentiful, but there is a growing appetite for technological discovery and product development that is rapidly overtaking all aspects of modern Middle East society. The effect is that the Middle East is intent upon converting from an oil-based economy to a technology-based economy. Foremost in this rapidly evolving economy base is the need for biotechnology research, development, and capitalization.

The first order of business is for a bioentrepreneur to align with a guide or facilitator that can identify and then introduce him or her to the Middle East university, medical school, or research center scientist who has a head for scientific research and an entrepreneurial spirit for progress and discovery. First impressions are critical when building any alliance, and particularly when building alliances between entrepreneurs entering a new and different business environment – thus a guide can be invaluable to making that first step toward success here.

Finding a knowledgeable, helpful guide does not have to be difficult. Early in the development of our intellectual property we worked with a patent attorney who unfortunately did not serve our interest as well as we expected. Fortunately we found a new attorney who put our IP program back on track but who also was very well connected throughout the Middle East. Today, the bioentrepreneur doesn’t have to rely simply on good fortune to find a helpful guide and facilitator into the Middle East. We are familiar with an academic research information exchange website that facilitates making connections for universities and businesses from around the world: the Global Academic Innovation Network, through which reliable patent attorneys with experience in developing collaborative relationships in the Middle East can be easily located.

In my next post I will discuss some of the universities, science parks, and other research centers in the Middle East, what they have achieved, challenges they face, and what innovative research they are currently focused upon that may be of interest to the bioentrepreneur.

Fahd Al-Mulla