Starting from scratch, creating a complete pox virus

People talk about resurrecting the Mammoth, the Dodo, the Quagga, or the Tasmanian devil, or any number of extinct (or mostly extinct) creatures. I'm all for that. I suggest removing cattle farming in Nebraska, Wyoming, Montana and adjoining areas of Canada, and repopulating the region with extinct megafauna. That would just be cool.

There are difficulties with this, including figuring out exactly how to piece together the genome for the extinct animal, how to get a good level of genetic diversity in the neo-founding population, and how to raise the critter up from a zygote. For all these reasons, I've always thought we should start by resurrecting something that already exists. We normally do this sort of dry run or practice run with things we do. In baseball, golf, and other ball sports, athletes take pre-swings. We went "to" the moon a couple of times before landing "on" the moon. Etc. So, let's start by resurrecting a fruit fly, them maybe a chicken, then a dog. That sort of thing.

A potentially important public health concern is the re-emergence, one way or another, of small pox or something like small pox. In order to manage that, we would like to see more research involving vaccines. An ideal way to carry out vaccine research without risking the release of full blown small pox (which may or may not be frozen somewhere) on the population is to create a small pox virus (small pox is a virus) from scratch, using a known genetic code. In so doing, the parts of the virus that allow it to spread could be denatured, and the parts of the virus that allow research for vaccines or cures could be left in place.

In essence, creating such a Frankensteinian life form is like resurrecting an extinct species. And, some Canadian scientists stole my idea and went ahead and resurrected a non-extinct species in order to test out the plausibility of the method. The research is not published and likely won't be, because it would be too easily misused by nefarious actors. But, the results were discussed at a meeting several months ago, and now there is something new about it in Science:

Eradicating smallpox, one of the deadliest diseases in history, took humanity decades and cost billions of dollars. Bringing the scourge back would probably take a small scientific team with little specialized knowledge half a year and cost about $100,000.

That’s one conclusion from an unusual and as-yet unpublished experiment performed last year by Canadian researchers. A group led by virologist David Evans of the University of Alberta in Edmonton, Canada, says it has synthesized the horsepox virus, a relative of smallpox, from genetic pieces ordered in the mail. ...

The story is also covered by the Washington Post.

And, here is a previously released press release:

Tonix Pharmaceuticals Announces Demonstrated Vaccine Activity in First-Ever Synthesized Chimeric Horsepox Virus

Pre-Clinical Smallpox-Preventing Vaccine Candidate TNX-801 May Qualify for Priority Review Voucher if FDA-Approved Under Provisions in the 21st Century Cures Act

NEW YORK, March 02, 2017 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq:TNXP) (Tonix), a company that is developing innovative pharmaceutical products to address public health challenges, working with researchers from the University of Alberta, a leading Canadian research university, today announced the successful synthesis of a potential smallpox-preventing vaccine. This vaccine candidate, TNX-801, is a live form of horsepox virus (HPXV) that has been demonstrated to have protective vaccine activity in mice.

“Presently, the safety concern of existing smallpox-preventing vaccines outweigh the potential benefit to provide immunization of first responders or the general public. By developing TNX-801 as a horsepox vaccine to prevent smallpox infection, we hope to have a safer vaccine to protect against smallpox than is currently available,” stated Seth Lederman, M.D., president and chief executive officer of Tonix. “Vaccines are a critical component of the infrastructure of global public health. Vaccination protects those who are vaccinated and also those who are not vaccinated, by decreasing the risk of contagion.”

“Our goal is to improve on current methods that protect the public from possible viral outbreaks,” said Professor David Evans, Ph.D., FCAHS, Professor and Vice-Dean (Research), Faculty of Medicine and Dentistry at the University of Alberta, in Edmonton, Alberta, Canada, and principal investigator of the TNX-801 research project.

HPXV was synthesized by Professor Evans and Research Associate Ryan Noyce, Ph.D., at the University of Alberta, with Dr. Lederman as co-investigator of the research and co-inventor of the TNX-801 patent. Under their research and development agreement, Tonix wholly owns the synthesized HPXV virus stock and related sequences. Professor Evans and Dr. Noyce also demonstrated that HPXV has protective vaccine activity in mice, using a model of lethal vaccinia infection. Vaccine manufacturing activities have been initiated by Tonix to support further nonclinical testing of TNX-801.

Dr. Lederman stated, “Our research collaboration is dedicated to creating tools and innovative products that better protect public health.”

About Horsepox (HPXV) and Smallpox

Horsepox, an equine disease caused by a virus and characterized by eruptions in the mouth and on the skin, is believed to be eradicated. No true HPXV outbreaks have been reported since 1976, at which time the United States Department of Agriculture obtained the viral sample used for the sequence published in 2006 that allowed the synthesis of TNX-801. In 1798, Dr. Edward Jenner, English physician and scientist, speculated that smallpox is a human version of pox diseases in animals. Jenner had a strong suspicion that his vaccine began as a pox disease in horses and went on to show that it could be used to vaccinate against smallpox. Smallpox was eradicated as a result, and no cases of naturally occurring smallpox have been reported since 1977. Jenner’s vaccine appears to have evolved considerably in the vaccinia stocks maintained in different countries around the world, since vaccinia was mostly selected for growth and production. Being able to provide safe and effective smallpox-preventing vaccines remains important and necessary for addressing and protecting public health.

About the Material Threat Medical Countermeasures Provisions in the 21st Century Cures Act

In 2016, the 21st Century Cures Act (Act) was signed into law to support ongoing biomedical innovation. One part of the Act, Section 3086, is aimed at “Encouraging Treatments for Agents that Present a National Security Threat.” This section of the Act created a new priority review voucher program for “material threat medical countermeasures.” The Act defines such countermeasures as drugs or vaccines intended to treat biological, chemical, radiological, or nuclear agents that present a national security threat, or to treat harm from a condition that may be caused by administering a drug or biological product against such an agent. The priority review vouchers are awarded at the time of FDA approval and are fully transferrable and may be sold to other companies to be used for priority review of any New Drug Application (NDA) or Biologic Licensing Application (BLA).

About Tonix Pharmaceuticals Holding Corp.

Tonix is developing innovative pharmaceutical products to address public health challenges, with TNX-102 SL in Phase 3 development for posttraumatic stress disorder (PTSD). TNX-102 SL is designed for bedtime use and is believed to improve overall PTSD symptoms by improving sleep quality in PTSD patients. PTSD is a serious condition characterized by chronic disability, inadequate treatment options especially for military-related PTSD and overall high utilization of healthcare services creating significant economic burden. TNX-102 SL was recently granted Breakthrough Therapy designation by the FDA for the treatment of PTSD. Other development efforts include TNX-601, a clinical candidate at Pre-IND (Investigational New Drug) application stage, designed for daytime use for the treatment of PTSD, and TNX-801, a potential smallpox-preventing vaccine.

*TNX-102 SL (cyclobenzaprine HCl sublingual tablets) is an investigational new drug and has not been approved for any indication.

This press release and further information about Tonix can be found at

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2015, as filed with the Securities and Exchange Commission (the “SEC”) on March 3, 2016, and future periodic reports filed with the SEC on or after the date hereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date hereof.


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Let's not just replace the cattle of Northwest America with extinct megafauna; let us also reverse-engineer the ancient human brain and replace it with robotic megafauna. Yesterday I was able to do some cross-fertilization of ideas in the HTM Forum of Numenta, about which in 2005 I wrote my only Slashdot story. Numenta is where serious AI enthusiasts are taking the laborious approach of reverse-engineering the neocortex of the
human brain. Then Mentifex here swoops in and claims to have solved AI with a totally top-down approach to how the mind works. The Mentifex AI Minds are based on theoretical ideas of the macro properties of neurons, such as extending spatially and temporally over a putative MindGrid and having as many as ten thousand synapses with other neurons. The Mentifex Minds use neural inhibition to dislodge briefly topmost ideas in favor of ascendant other ideas. Since Mentifex AI is concerned mainly with neuron-based concepts playing a role in thinking, I reverse-engineer neurons only enough to create AI software that can demonstrably think and reason in English, German and Russian. I hope to poach some great minds who think alike from the Numenta project. It could take a thousand years to reverse-engineer the neocortex, and Science-Bloggers who get tired of waiting for such a bottom-up approach are welcome to try out the top-down AI that runs in Strawberry Perl 5. My goal is to release basic AI software with sufficient intellectual functionality that individuals and teams, even if working in secret, will latch on to my existing codebase, reverse-engineer it, and and create from it even better AI Minds than we tenues grandia are capable of.

By Mentifex (Arth… (not verified) on 07 Jul 2017 #permalink

Go chew on your car, dude.

Hello... ...ello... ...ello...

Time cube... ...ube... ...ube...

By Bernard J. (not verified) on 08 Jul 2017 #permalink

De-extinction is close to my heart - I have colleagues from my postgrad days working on it. I tend not to comment on it too much for particular reasons, not all entirely unrelated to some of the points in Greg's piece, but that said I think that there are benefits to exercises such as Archer's enthusiasm for the thylacine. It's a flagship for the cost vs practicalities of getting to:

1) the point of having a defined potentially-operational extinct genome,

2) the point of reconstituting it in a surrogate such that it's possible to get the extinct species back, minus any sort of genetic pudding,

3) the point of having an immunological and non-immunological allelic diversity that will provide a minimum viable population, and

4) the point of learned behaviours that characterised the pre-extinction manifestations of the recovered species, and that are crucial to their integrations into a functioning ecosystem.

Compare the cost of achieving 1-4 with the cost of protecting species and their ecosystems from extinction in the first place, and I suspect the bean-counters will clutch their pearls in horror. It's such a shame that conservative minds are characterised by an inability to think broadly, and into the future, beyond their own immediate egocentric concerns.

On microbiological tinkering, all I will say is watch that space. This is one of the edges of science where the boundary between fact and fiction is at best akin to the braided ropes used to delineate the queues in cinemas and theatres.

By Bernard J. (not verified) on 08 Jul 2017 #permalink

People talk about resurrecting the Mammoth, the Dodo, the Quagga, or the Tasmanian devil, or any number of extinct (or mostly extinct) creatures.

I think you may have meant the Tasmanian tiger (aka thylacine, aka marsupial wolf) there, as the Tasmanian devil certainly isn't extinct, or even "mostly extinct". (Although it is endangered, largely due to a combination of road mortality and Devil facial tumour disease.)

Do you feel like smallpox could re-emerge in the next 5 years?

By Missy Barnes (not verified) on 25 Aug 2017 #permalink