Nature Biotechnology | Trade Secrets

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

Comments

  1. Report this comment

    GR Taylor said:

    I suppose every relationship that each of us has is a mixture of competition (for resources) and co-operation (to share benefits). The law dictates where the boundaries are supposed to lie, but it struggles to keep up with the pace of science and technology. As scientists at University we used to joke about why Law students didn’t look out of their windows in the morning (answer: so they had something to do in the afternoon). One consequence of that lazy attitude (only joking, lawyer friends) is the US patent law doesn’t seem to distinguish between invention and discovery, and so allows discovery (e.g. of genes or gene variants, which are naturally occuring) to be used to grant patent rights

  2. Report this comment

    Julia Hasler said:

    Of course you raise a vital question for which there may be no easy answers. I wonder if there has to be something eventually at highest government levels (like the Kyoto protocol or the Convention of Biodiversity) to deal with it.

  3. Report this comment

    M. Kabir az-Zubair said:

    I think there is a need for an international protocol with respect naturally occurring, as opposed to artificially generated, genetic sequences that disallow their patenting and exploitation for financial gain. Any naturally occurring genetic sequence must not be allowed to be patented. This will allow for the discoveries to be used widely for advancing our understanding of humanity. It’d also make it easier for people to volunteer samples, if they know it’d be used to benefit them without costs.

  4. Report this comment

    BELHOCINE MOHAMED said:

    In France for example, the legal protection of inventions was dedicated to “all sorts of industry” according to the decrees of 30 December 1790 and January 7, 1791. The exclusion of living has long existed, however, tacitly. A commercial court has also said the human body as unpatentable in 1844, declaring that the human body could not be ranked among the objects Industry. Later, this view evolved and Louis Pasteur in 1873 obtained a patent for a living organism, a strain of yeast used in brewing beer.
    The current legislation relating to patents on life is a national law subject to certain international guidelines of the ADPIC (Agreement on intellectual property rights related to trade) and the European Patent Office (EPO). ADPIC are intended to harmonize the laws of different countries. They were created during the Marrakech Accords in 1994 which saw the birth of the OMC and therefore they respond to a desire to globalize trade. They exclude from patentability plants and animals out microorganisms.
    In 1990, Craig Venter and the National Institutes of Health patenting the human genome in the United States.
    In 2000 came into force in Europe Directive on the patentability of biotechnological inventions, which involves, among other things, ethical principles to limit patentability, while allowing the intellectual protection of biotechnological inventions.
    From a genetic, DNA sequence without indication of any technical function (use in a diagnostic, therapy …) is not an invention is not patentable because a technical education. To patent a gene, a simple analysis based on bioinformatics data is not sufficient, you have an experimental demonstration. Additionally where a claim relates to a gene sequence, this claim is limited to the part of the sequence linked to the specific technical functions described in the patent specification
    Many controversies revolve around the patenting of life: The living, including the human body through the genes, according to some should not be part of a process of commoditization equivalent to that charged for other thinks, and for reasons ethical.
    The best known example is that of Myriad Genetics, a U.S. company that filed in 1997 several patents on BRCA1 and BRCA2, which are related to familial forms of breast cancer. This patent gave them total exclusivity testing. This patent was highly controversial, other laboratories denouncing prices, slow performance and ownership statistics on screening. In Europe, the original patent was challenged by several institutions, including among others, the Curie Institut and Gustave Roussy Institut in France and the Belgian Society of Human Genetics. In 2005, in the first instance, the European Patent Office decides to invalidate the patents by Myriad Genetics. Myriad Genetics appealed and after reducing some of its original claims, eventually succeed in November 2008.

  5. Report this comment

    PRASHANT BAVI said:

    I found your post very informative and interesting.
    Patents for novel genetic mutation screens will only increase manifold with the advent of next generation sequencing technologies which will sequence a patient’s whole genome. Deep sequencing will only fuel the an age old dilemma of filing for a patent as opposed to sharing it on a free site like The Insight Group curated for by the HVP- this site is extremely good and will only become better.

    Personally I feel that there should always be a choice available to access genomic information freely from an open source site and also from an entrepreneurial-patented site. Both these options complement each other and foster growth in these two opposing principles. An example is Myriad Genetics patented BRCA mutation screen for hereditary breast cancer that led to an open access Salzburg screen. In an effort to encourage a “Do-it-yourself” approach to BRCA diagnostic testing, Stephen Salzberg and Mihaela Pertea published the Salzberg Screen(http://www.genomicslawreport.com/index.php/2010/10/11/a-do-it-yourself-genomic-challenge-to-myriad-the-fda-and-the-future-of-genetic-tests/). This screen analyzes previously obtained genomic sequence data (e.g., from whole-exome or full-genome sequence data, which is commercially available) for BRCA mutations by querying publicly available resources.

    Ethnic differences do exist and with the advent of theranostics, deciphering the molecular signature of tumors in unique populations like Arabs, Asians that have never been fully studied like Europeans and Americans is vital. Dr Fahad, it is a daunting endeavor but you are absolutely on the right track and I wish you all the best to harness the human sharing and entrepreneurial to better understand cancer genomics.

  6. Report this comment

    Ghulam Mohammad said:

    I think this is valuable information, Thanks for sharing. Definitely this innovation will be helpful for humanity and I think you should go for patenting. But we should not forget the disadvantages cause by it as patent made research commercial which lead premature implementation of technologies, stop researchers from sharing information and can distort research results for their benefits. So for patenting gene we should have some other policies.

  7. Report this comment

    Richard Cotton said:

    maybe this is a topic that the Human Variome Project can push with the help of UNESCO and WHO if they agree.

  8. Report this comment

    Richard Litman said:

    The purpose of the patent system is to encourage inventors to develop useful inventions. The patent system, like technology, is evolving. Genetic innovation and patents for this innovation will reach a proper balance over time. As with any invention, it is best to file a patent application before public disclosure to avoid losing potential rights. If a scientist does not believe in patent rights on genetic research, then the invention will become public domain.

  9. Report this comment

    Mehrez Jadaon said:

    Dr. Fahd. This is a very interesting subject. I have followed the debate of patenting human DNA sequences in the past few years, through the Association for Molecular Pathology (AMP), which was one of the parts in the court case against that. Personally, I could not understand how to patent a human DNA? I believe what is inside a human is owned by human, belongs to human, not to greedy companies (excuse me for saying this). If it has to be patented, then it should be registered by the name of God who created it, in a right or wrong way (as mutations). The comments I read on your article have mentioned what I believe in: there should be a difference between “invention” and “discovery”. Between “making” and “uncovering”. If you “make” a test, own it and make money. But do not own something you “uncover”. OK, take the credit for this “discovery”, and maybe one day you get a Nobel prize for this great “discovery”, congratulations in advance. But I believe you do not have the right to claim possessing it, especially when it comes to human beings. Zoologists and botanists almost every day “discover” new species somewhere around the Globe. I never heard them saying that they “own” these new species. They may give those names after their own names or their countries’ names, but they never said that others cannot now approach or study these species without paying! Just last week I read about “discovering” the shortest lizard, and they did not patented it!

    Ironically, this reminds me with that Yemenite guy who filed a case against the American Government for invading his property in 1969. To be clear here: for going to the Moon, which he claimed to own!

    And what you questioned at the end is crucial indeed: shall we start patenting anything we find in the human genome? Maybe this will be a great chance for us in the Arab world to make huge amount of money since the Arabic genetic pool has not be investigated enough and we can fish a lot there. But I feel it is an invasive, immoral, and even unethical thing to claim patenting something inside a human.
    I personally have “discovered” a new mutation ‘Factor V Kuwait mutation’ in Arabs about 7 years ago. Was I that fool not to patent it and start making money since then? No. I never thought of that. I just felt I did not, and I still do not and will never, own it to claim for it. As simple as that.

    The companies invested money: understood. They want now to make money back: Understood. But still, they do not own it, no matter what they claim.

    Now I have my own question: what about non-rich (so that I do not say poor) countries? Will they have to pay the bill? I believe not. There is still a window to escape this. I still remember the workshop you, Dr. Fahd, arranged few years back in Kuwait University on patenting. The smart speaker had said it clearly: If not patented in your country, copy it! Seems immoral? From commercial point of view, YES; from human point of view: NO. At least in this case. It happened with the AIDS drugs in India and South Africa (as far as I can remember).

    Still, there is a hope to give it a true human spirit. Even if one has to be a Robin Hood.