…and why we’re releasing it all free to the public as a protection against monopolies from big pharma and governments.
Long answer of why we’re doing this and why it’s important for people to torrent and donate is below.
Layman version – tl/dr is: While an entire plant genome can no longer be patented in the USA, specific strains can be, which can be bad for kratom users in general.
We beat big pharma to a public release and that’s good for keeping kratom from being locked down. Sequencing multiple strains with collected chemotype information is the best path forward.
We’re not trying to get a patent. We’re trying to block patents on one very common common strain (Red Vein Thai). To that end, so far we’ve sequenced and published 10X the number of nucleotides (bases) of the Kratom genome than the largest amount anyone else has released into (NCBI / NIH) to date.
With enough resources, we could sequence more of red, and also move on to white, green and other strains.
Pharmaceutical companies may be working on this but they haven’t published data so this work of ours is prior art to any attempt to capture patents on popular strains or varietals.
This info could also be used to do things like lift the chemical pathway from kratom into yeast to make it easy to ferment tons of organic material with the active substances in kratom easily so it can never be stopped.
^This graph is why we need the world to donate funds so we can inch the genome up the completeness curve. N50 is the mean length of the contigs (gap free stretches of ATC and Gs) in the genome. At 5X coverage we end up with N50s in 1-2 Kb range but this rapidly improves with more coverage. Doubling the coverage more than doubles the contiguity. We expect it will take 7 MiSeq runs to hit saturation and we will review each incremental run to assess strategy. We have access to Oxford nanopore sequencers. If funded, can layer in these reads to help mature a final assembly.
Open source Mitragyna speciosa
Despite the recent AMP versus Myriad1 supreme court rulings regarding the lack of patent eligibility of naturally occurring gene sequences and the recent Mayo versus Prometheus ruling2 regarding the patent eligibility of natural phenomena, cannabis plant and cannabinoid patents continue to issue. Cannabis remains federally illegal yet federal agencies are being awarded patents on their medicinal use (Hampson et al)3. Likewise, cannabis genotypes and their correlative chemotypes are now patent eligible despite these previous rulings. (US patents 6,630,507, 9,642,317, 9,095,554, 9370164, PP27,475)
Diamond versus Chakrabarty4 clearly sets a patent eligibility precedence for human modified organisms and as a result the patent eligibility in the genomics and biotechnology sector has never been more confusing or more in flux. We believe the best policy in a rapidly changing legal landscape is to be prolific with the publication of prior art to defend against current and future patent eligibility uncertainty. With the recent announcement of the FDAs desire to schedule more naturally occurring medicinal plants (Mitragyna speciosa), and the tendency of government agencies and corporations to patent such compounds or genotypes of said plants, we believe it is imperative to sequence and place public the Mitragyna speciosa genome to prevent future patent disputes over the medicinal activity of this natural plant. Mitragyna or “Kratom” has been reported to transition millions of people off of dangerous ethanol and opiates 5-10 and while cannabinoids are a safer alternative, they remain federally illegal.
A close examination of the opiate epidemic underscores the large regulatory hurdles put in place by the FDA. These restrictions create exhaustive barriers to entry to the drug market such that no corporation will approach the process without patent protection. Consider this incentive model combined with the PDUFA act of 199211 where the unelected FDA “defrays” their regulatory costs by taking payment directly from the companies they are supposed to regulate. This creates an enormous moral hazard in an agency that regulates 25 cents of every dollar. This poorly aligned incentive system leads to modification of safe compounds into patentable yet unsafe compounds that are killing over 100,000 US citizens annually. Peer to Peer rating technologies that regulate online economies for cars, hotels, and international crypto-currencies are demonstrating a safer decentralized model for communicating drug safety information.
In 2017, the FDA published a small sample of DNA sequence from Mitragyna speciosa in NCBI. Since patent applications usually require 18 months to publish, it is unclear if any patents have been applied for with this work. There do exist Mitragyna patent applications currently under review titled “Improved Methods For Making and Using Polynucleotide Sequences in the Synthesis of Alkaloid Compounds” and “Methods For Treating Withdrawal From Addictive Compounds”. We believe the opiate epidemic is a serious issue and patents related to promising solutions to the problem are destructive to society. For this reason we believe it is imperative to push the entire genome public as soon as possible.
- Myriad Av. https://en.wikipedia.org/wiki/Association_for_Molecular_Pathology_v._Myriad_Genetics,_Inc.
- Wikipedia. https://en.wikipedia.org/wiki/Mayo_Collaborative_Services_v._Prometheus_Laboratories,_Inc.
- Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences of the United States of America. 1998 Jul 07;95(14):8268-73. PubMed PMID: 9653176. Pubmed Central PMCID: 20965.
- Chakrabarty Dv. https://en.wikipedia.org/wiki/Diamond_v._Chakrabarty.
- Leon F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ. Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A. Natural product communications. 2009 Jul;4(7):907-10. PubMed PMID: 19731590.
- Halpenny GM. Mitragyna speciosa: Balancing Potential Medical Benefits and Abuse. ACS medicinal chemistry letters. 2017 Sep 14;8(9):897-9. PubMed PMID: 28947930. Pubmed Central PMCID: 5601368.
- Kumarnsit E, Keawpradub N, Nuankaew W. Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice. Fitoterapia. 2007 Apr;78(3):182-5. PubMed PMID: 17335995.
- Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction. 2008 Jun;103(6):1048-50. PubMed PMID: 18482427. Pubmed Central PMCID: 3670991.
- Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum and Kratom. Clinical toxicology. 2008 Feb;46(2):146-52. PubMed PMID: 18259963.
- Boyer EW, Babu KM, Macalino GE. Self-treatment of opioid withdrawal with a dietary supplement, Kratom. The American journal on addictions. 2007 Sep-Oct;16(5):352-6. PubMed PMID: 17882605.
- FDA. https://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act.
Presented within is a draft genome sequence of the Kratom genome (Mitragyna speciosa). This plant synthesizes compounds (mitragynine and 7-OH mitragynine) that have assisted millions of people abstain from opiate and alcohol abuse. Public sequencing of the Mitragyna speciosa genome can create prior art and thwart patent trolls that seek to exclusively own the benefits of this plant.
This is an incremental draft assembly of the first 42 million reads to gauge the size of the genome and its complexity. It is 65% AT and kmer analysis implies there are over 327 million bases in its genome.
This genome is a public fund drive. For each $2000 donated we will sequence more and re-assemble the genome bringing it closer to completion. Already large mitochondrial and chloroplast contigs are assembling and 100% of the 40 Mitragyna sequences in NBCI have strong and perfect ITS BLAST hits this assembly. While this expands the DNA sequence of this organism more than 10 fold from what was known previously, we still need your help. This is not a complete genome and it likely requires 10x more sequence to establish a complete prior art picture. Crypro-currency addresses are included to bring more support for this important plant.