Killing Mosquitoes

The elimination of Malaria (438,000 deaths per year) and a number of other deadly/debilitating diseases (Zika, dengue fever, yellow fever, etc.) is often a war against the mosquitoes that carry these diseases.   Bill Gates has designated the mosquito “the deadliest animal in the world“, and fighting these diseases is a top priority for the Gates Foundation.  Another wealthy ExMicrosoft wizard, Nathan Myhrvold, has developed a prototype laser to zap the bugs selectively. And a recent Wall St. Journal article suggests a variety of genetic engineering attacks that are in development. With the spread of these diseases beyond their traditional “range”, their impact will increase as will the needs of a broader range of countries.

There are a number of Technology/Society impacts of interest here.  First, any objective for which there are multiple, diverse approaches that are likely to reach the objective are likely to be accomplished — don’t bet on the bugs here (I know, “Jurassic Park” seeks to make the point that “Nature will Find a Way” … and that is often true, but humans have been very effective at driving the extinction of so many species that geologists have declared this a new age, the Anthropocene.)

Second, if anyone wonders how to change the world, the answer clearly is technology — from DDT impregnated sleeping nets, lasers and genetic engineering we are talking tech— and “engineering thinking”. (My granddaughter has a T shirt: front side “A-Stounding”, back side “Stoundings: persons who like to solve problems rather than cause them.” )  I call those folks Technologists.  Bugs Beware — you have a whole generation of Robotics Competition and Mindcraft modders headed your way.

Third — is this a good idea?  Note, there are significant variations.  Some approaches target just one species (Aedes aegypti, at least outside of it’s forest habitat origin), others target a wider range of species, others focused areas.)  One recurrent human failure is anticipating consequences of our actions.  What animals depend on these critters for dinner, and so forth up the food chain. What plants depend on these for pollination?  We abound in ignorance on such matters, and we find it easier to fund the research for eradication than for understanding.

So .. should we eliminate the deadliest animal on earth?  (let me qualify, other than Homo Sapiens.)

 

Human Germ-line Modification Hiatus Proposed (too late?)

Nobel laureates David Baltimore and Paul Berg have recommended pausing active modification of the human germ-line cells until experts can convene a conference to consider the implications of this activity.  (WSJ 4/9/2015 “Let’s Hit Pause Before Altering Humankind”)   They point out that this parallel’s a similar action in 1975 when the emergence of recombinant DNA technology triggered a conference on that topic.

This is a bit afield from IEEE’s domain of affairs, but quite relevant to the Society on Social Implications of Technology dialogs. Let me outline key concepts they put forward to help build a common vocabulary, and then focus on parallel’s in IEEE’s areas of work.

They point out the advent of a bio-tech (CRISPER/Cas9) that simplifies the modification of germ-line DNA alterations that are “quite precise with no undesired changes in the genome.” They point out that modifications can be within an individual without inheritability (somatic cell alteration.) They can be applied to germ-cells, affecting all future generations from that line either to eliminate a defect (therapeutic germ-line alteration.) Although they point out that similar benefits for the next generation may be attainable via embryo-selection methodology.  Finally there is the potential for “voluntary germ-line alteration”, to increase traits parents currently consider desirable. They point out that “we often do not know well enough the total range of consequences of a given gene alteration, potentially creating unexpected physiological alterations that would extend down through generations to come.” (A.k.a. the law of unintended consequences.)  Ergo they recommend a moratorium and conference to address the implications involved.

This is an excellent example parallel to IEEE’s Code of Ethics which includes “to improve the understanding of technology; its appropriate application, and potential consequences.” Actually, it goes one step further in taking action to manage potential consequences before they are fully realized.

If we look at the fields where IEEE’s technologists are engaged (with computing, robotics and bio-medical systems included, there are few areas we don’t touch), there are some interesting examples.  There is some discussion (although no suggested moratoriums) in areas like self-driving or remotely controllable cars, some of these fields are outgrowths of simple ‘improvements’, such as automatic breaking systems or parallel parking.  Others are unintended consequences of remote monitoring services.

Observation #1: we (technologists, our employers, and indirectly stockholders and customers) may not be applying sufficient diligence in considering potential consequences.  In part we may not be providing the time and incentives for quality engineering of quality products. A quality product should not be subject to hacking that can affect public safety and health for example.

Observation #2: The bio-genetics world is miles ahead of our technology in their limited understanding of what may result from their work.  For example, the concept of emerging artificial intelligence and it’s impact is getting coverage in science fiction, and even some awareness in research and industry, but we have very little insight on the potential consequences of passing over some nebulous lines in paths that lead towards intelligent and./or conscious systems.

What other areas do you see that might warrant some serious consideration before we proceed?

[April 24th, Chinese researchers indicate they have completed a trial of this concept, with some ‘off target’ effects.]

Prenatal Genomics

A genomics researcher, Razib Khan, sequenced his child’s genes prior to birth, a first for the U.S. with a “normal” child.  This is described, with some of the legal and other issues in an article in MIT’s Technology Review. Khan comments on the issue of “who owns a genome” in this article and part of a regular Blog he posts. Just to be clear, this is the 6 billion base pair analysis, not the half billion 23andMe form, so he now has most of the story.  I don’t think full Genome analysis addresses epigenetic information such as methyl groups and histone variations. These can affect gene expression, and also reflect a path for passing information from generation to generation without mutation and as a result of the activities of the parent.  So, yes, it appears your smoking, drinking, etc. can affect your children and grandchildren — actually one of the evident connections is between famine and longevity of grandchildren.

The FDA is currently blocking 23andMe from providing health analysis related to their genomic testing, but for clients, the results are available in raw form, and online sites allow cross checking. Of course in the world of the Internet, most attempts to control information are futile.  A software package Promethease provides analysis via a literature search “for free”.  Of course one might worry about what the creators of that package do with the information besides telling you about the genome you submit (presumably your own).  It seems that the FDA, while trying to protect consumers from “medical advice not provided by a professional”, have pushed the  liability and challenges associated with this from a contractually obligated partner to the open internet.

Looking forward, we can anticipate that genome sequencing will be available to the public, at least in “free” countries, and that analysis will be possible with varying degrees of quality control in such environments.  It would seem the medical, policy, and ethical community might be better served by focusing on articulating the issues and educating the public rather than trying to get the genie back in the bottle (or should I say the Genome back in the bottle.)

What’s New in DNA – What Does It Mean?

Ok, this one took me by surprise.  “Man-made DNA“, the headlines don’t seem that shocking.  But then I looked a bit inside.  The folks here are not just doing genetic engineering, but actually adding new base pairs to the DNA alphabet.

It’s not your grandmother’s DNA! … she had four base pairs with the ability to create twenty amino acids — all of which is a shared organic chemistry with every other living thing on earth (and I’d assumed, until today, other “goldilocks” planets.)  I recently competed the free Udacity course, sponsored by 23-and-Me, on how the … what do we call them now … “legacy” DNA pairs… work.  Researchers at Scripts Institute in San Diego have managed to find two additional molecules for a new base pair set, that “works” in DNA. They can insert them into bacteria, the bacteria reproduce, and these pairs get copied just like the legacy pairs.  This expands the range of amino acids that can be produced to one hundred and seventy two — that’s one hundred and fifty two more building blocks to play with in building organisms.  Depending on how “likely” these two additional bases are in a given planetary chemistry set, this means we might find DNA based life-forms that simply don’t use the same base pairs that we use.

So what? That’s the big question in my mind.  Our ability to understand the translation of base pairs into proteins into amino acids into cellular components into cells into life forms is somewhat limited at this point.  Give a genetics wizard a new mutation and ask what impact it will have and she won’t have a clue.  Needless to say, give our wizards one hundred and fifty two new building blocks and they will be clueless.  If some of these do good things, we can expect some of them to do bad things — although it is likely that most will do nothing at all.

It took four and one half billion years of playing with the chemistry set on Earth to come up with the thousands of species we have, and thousands of extinct species — presumably guided by the “invisible hand” of evolution.  No doubt we can incorporporate these additions to our “kit” in a tenth of that time (i.e. five hundred million years.) — (are we there yet?) … with a bit more carefully managed range of speciation and extinction.  It’s just the first million years I worry about.

Humans have not demonstrated a great deal of global responsibility in dealing with today’s challenges — governments, corporations, institutions and individuals tend to operate with short-term, self-serving agenda’s — even when they are presented with fairly solid evidence that their courses of action are harmful.  The new Cosmos series on TV does an excellent job of demonstrating that in a recent sequence on the dating of the universe (the transition of uranium into lead) and the closely related battle to stop poisoning the planet with lead in gasoline.  When we move forward into an arena where we have limited or no visibility we need to tread very carefully, at least.

How do you see this next opportunity in evolution?

 

New Genomics Monkey Business

MIT’s Technical Review announced that scientists in China have created viable monkey twins with explicit genetic modifications using the CRISPR genetic engineering methodology.

The Good news — this will allow the creation of primate models for testing diseases and treatments that are not common outside of humans.  Well, good news if you don’t have any concerns about using primates in such testing.

The Bad news — this approach confirms something we have anticipated, which is the ability to perform specific genetic engineering on primates and have viable offspring.  The range of possible improvements is significant.  Clearly parents will want to eliminate defects that would affect the health of their child.  Some areas of potential “improvement”, such as intelligence, are not well understood — so will require a longer period of time before this becomes possible. — Well, good news if you don’t have concerns about GMO humans.

 

Fatalities in Patent Battles?

A recent patent suit involving heart valves creates the potential for folks to die.  An April 19th WSJ article outlines the situation. With a producing manufacture (Medtronic in this case) adjudicated as violating patent(s) of Edwards Lifesciences was issued an injunction against selling a heart valve.  All of this with patients lined up for valve insertion and limited supply from Edwards.  While both the court and Edwards have tried to provide for some limited continuation by Medtronic, it creates a rather interesting scenario on the ethical issues associated with the explicit monopoly associated patents and the use of injunctions when lives are at stake.  The article asserts that Medtronic offers valves in a wider range of sizes which can be used in patients where the Edwards offering would not work.  Edwards is seeking to limit use of Medtronic valves in any hospitals not currently using them.

This type of situation may be more likely in the bio-medical field than some other technology areas, but no doubt other examples may emerge.

Can a patent be used to prevent health or safety critical technology from being provided?  What about slightly less direct survival impact areas like food supply –seeds can be patented that may  improve yield, disease or environmental resistance, etc.   Patents are ‘national’, so situations can exist where a country specifically chooses to deny the applicability of some patents to benefit their populations.  Trade treaties, like NAFTA, can expand patents across international borders. (Eli Lilly has raised just such a suit.)

There is some good meat in all of this for a robust debate on ethics, patents and paths of legal recourse.

Is the Singularity Silly?

In the SSIT LinkedIn discussion a pointer was posted to a provocative article “The Closing of the Scientific Mind” from Commentary Magazine. It raises many issues, including skepticism about the “Singularity” and the Cult of Kurzweil (a delightfully evocative concept as well).  One comment posted in that thread suggested that the Singularity was ‘silly’ … which is not a particularly useful observation in terms of scholarly analysis.  That author sought to dismiss the concept as not deserving real consideration, a concept that deserves real consideration (IMHO).

First, let me provide a reference to the singularity as I envision it. The term originated with Vernor Vinge’s paper for a 1993 NASA Conference. It identifies a few paths (including Kurzweil’s favorite: machine intelligence) towards a ‘next generation’ entity that will take control of it’s own evolution such that our generation of intelligence can no longer “see” where it is going. Like a dog in a car, we would be along for the ride, but not have any idea of where we are really going.  Vinge includes biological approaches as well as machine (and perhaps underestimates bio-tech approaches) which establishes the concept beyond the “software/hardware” discussion in Commentary Magazine.

Why might we be able to dismiss (ignore) this concept?

  1. Because God will not allow man to create a  more powerful being. This has precedence in the tower of Babel. Interestingly in that situation God’s fear is that if man is not stopped he will become capable of anything.  (Mileage with your deities may vary.)
    I have not received any tablets or messages specific to the singularity from God, so I will not presume to state what She may or may-not allow. Presumably this will become evident in time and the interpretations of some are unlikely to dissuade others from their research and progress.
  2. It is impossible — Here we need to consider what “It” is. Clearly the creation of a conscious/intelligent being is possible (the current U.S. Congress not withstanding) because we appear to have at least one instance of this.  And since engineering of the current species into Homo Nextus is one of Vinge’s paths, we have the advantage of starting from that given.  So for the bio-tech path(s), presumably the “Impossible” is the significant differentiation needed to move beyond Homo Sapian understanding. Personally I suspect a species of folks who understand quantum mechanics might qualify. There are indications that this has happened before.  Once upon a time there were three or more humanoid species on earth (Neanderthal, Erectus and Sapians)  and indications they interacted (and interbred.)  One suspects that the Neanderthal’s were left scratching their heads as the Sapians started doing many strange things — which ones are the topic of diverse fiction stories.
    The AI/Machine Intelligence path certainly requires a larger leap of faith to either assert it as a certainty, or its impossibility. Note that “faith” is covered under point 1.
  3. It is too complex — This certainly has merits in both the bio and AI approaches.  It would seem axiomatic that a being at stage two cannot design and build a being at stage three.  However, Evolution is the counter point to this (Creationists please see point one) … wherein more complex and in some cases more intelligent beings have emerged from ‘lower’ forms.  Interestingly it is via “Genetic Algorithms”  that John Koza has created patentable devices that are outside of his expertise to create, and in some cases with capabilities he (and others) cannot explain.  An apparent pre-cursor to the singularity, since one would expect similar observations to occur when (if) that arises.
    Often this argument devolves to “since I (often expressed as ‘we’) cannot imagine how to do it, then neither can you”.
    Technology advances both surprise and dismay me — we should have had flying cars already, and where did 3-D printing come from? Vinge anticipates machine intelligence in 2023 and Kurzweil 2018-43; and of course, like the Turing Test, we won’t necessarily agree when it “happened”.

I can envision one bio-tech path towards a new species, it is outlined in Greg Stock’s TED talk on upgrading to humanity 2.0: We add a couple of chromosomes for our kids. I’m thinking two — one has “patches”, for the flaws in our current genome (you know, pesky things like susceptibility to diabetes, breast cancer and Alzheimers), the second has the mods and apps that define “The Best that We Can Be” at least for that month of conception.  Both of these will warrant upgrades over time, but by inserting the double hit of both into the the genome (going from 46 chromosomes to 50)  the “Haves” will be able to reproduce without intervention if they wish (of course not as successfully with have-nots due to a mis-match in the chromosome counts.)  Will such a Homo Nextus species actually yield a singularity?  Perhaps.  Is this a good idea?  — Well that is debatable — your comments welcomed.

Will Technology Kill Insurance?

A Dec. 17 Wall St Journal article outlines how data mining is being used to identify persons with selected illnesses. While the objective in this case is to find patients for clinical trials, the same approaches are used to target folks for ads, and potentially could influence heath, long term care, or life insurance.  For anyone close to the U.S., it would be hard to avoid the political football being played with health insurance over the last few years. But there is a fundamental question about the nature of insurance in a data mining world: is it no longer ethical?

First you need to really consider what insurance is.  If you have 1000 homes in a town, one burns down each year, the average replacement cost is $100,000 then a premium of $100/year is the minimum for an insurer to break even. But most insurance companies are “for profit”, and do not want to break even.  Actually, they do best when they don’t pay out benefits at all.  And here we see the essential tension between the insurer and the insured.  Is it any surprise that when a new health care law takes effect in the U.S. that health insurance companies are dropping their higher risk patients?  This is what for-profit means! When you can reduce your risks and raise your revenues you deliver profit.

But the WSJ article points out a disturbing trend — data mining to isolate affected individuals. The article points out that the records used; credit card records, online shopping, search preferences, TV viewing habits, vacation styles, cars driven are part of the mix.  “We are now at a point where, where based on your credit-card history, and whether you drive an American automobile and several other factors, we can get a very, very close bead on whether or not you have the disease state we’re looking at.” Roger Smith, Sr. VP of Acurian. (WSJ)

If Insurance companies can sort out higher risks, then the amortization of risk over large populations can be eliminated. In effect the insurance premium becomes a pre-payment of future expenses (plus overhead and profit.)  Increasingly insurance companies are following this path. Flood insurance (historically supported by US Government reinsurance) is rising in price dramatically, and home-owners in wildfire risk areas are being dropped, potentially if their neighbors have not cleared their properties. It is easy to argue that folks who build glass houses should have higher ‘stone’ insurance rates, but as this moves from a large “pool” to a “pool-of-one” the concept of insurance disappears.

With the emergence of full genome mapping, individual life style tracking, big data and data mining, the profit opportunity will drive insurance companies to sort customers as accurately as possible. The result may be the elimination of insurance, at least in certain areas, as a way to manage risk.

An informative counter-point is the U.S. medicare system, this spreads premiums over all employed persons and insured persons, and does not discriminate by preexisting conditions or the more advanced technology that is emerging.  Of course it is a not-for-profit government program which is yet another political football.

Has your insurance been affected by these processes? … Don’t comment if so, this blog is mined!

Who owns your genome, redux

This week (WSJ Nov 26, 2013) the US  FDA warned 23andMe to stop marketing their genome analysis services.  It is worth taking a look at the issues raised since they vary from lab procedures to the nasty question of who owns your genome (in the U.S.)

An issue identified by the WSJ article is “scrutiny of their laboratory processes.”  This is then reiterated in part by the phrases “false negative” and “false positive”.  It certainly seems reasonable that a service in this business should have as high of assurance that you get results based on the materials you submit, and that the genes identified are actually in your genome. However it appears that this concern is not the real FDA target.

The false positive concern, expressed by the FDA as ”  For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery…”  Which seems to presume that a Doctor would undertake such surgery without obtaining confirming lab results, a path towards malpractice. The false negative concern has more merit … folks convinced by the results that they are not at risk for a disease and ignore the symptoms.

23andMe has a detailed, readable  (!) and informative Terms of Service statement.  It covers the types of disclaimers that one would expect, and also some interesting warnings such as “knowledge is irrevocable” — you may not like what you find out.  “You may learn information about yourself that you do not anticipate” ancestry, parentage, etc. may not be what you think.  Genetic Information you share with others could be used against your interests”— such as health care providers, insurance companies, employers etc. Including the fact that you can not claim that you have not been genetically tested to an insurance company, or answer some questions like “do you have any reason to believe…” on health questionnaires. While, in the U.S., there are laws limiting abuse of genetic information (see http://www.genome.gov/10002328), and in theory it cannot be used in Health Insurance, it can be used in life insurance or long term care insurance descisions.

The philosophic crux of the situation is captured in this phrase: “the risk that a direct-to-consumer test result may be used by a patient to self-manage, serious concerns are raised if test results are not adequately understood by patients…” This is where the question of data ownership surfaces.  Do you have a right to know all or part of your genome?  This phrase suggests you do not.  “Direct to consumer” bypasses an important (political funding) constituency known as the medial professionals. And while I am sure there are persons who are not competent to handle genomic information about themselves, it is unclear that regulatory restrictions should prohibit all of us from such information. Ultimately knowledge is power, and when such analysis is done, we have to ask who holds the power aka knowledge?  IEEE Spectrum ran an article about the full genome analysis in March 2013.  I was surprised that the writer was not allowed access to her results, but only though a medical interpretation of a community of doctors. In essence the companies running the tests and the genetic counselors interpreting them do not recognize the right of an individual to know themselves at the genomic level.

23andMe only evaluates genes of interest, not a full genome report. This reduces the possibility that next week’s research will disclose a new genome associated risk that is evident as a result of your already competed tests.  What will you do if a “dumb” gene is discovered, and you have it? (ok, you wouldn’t be reading this blog is my guess.)

Action? — A petition exists at Whitehouse.gov to ask the President  to override the FDA warning. However, this only touches on the essential question of genomic ownership and rights. Some of these questions were raised in this blog in March, and need serious consideration.  This area is moving forward on all fronts.  The supreme court has ruled that genetic content cannot be patented, public figures have undergone preventive surgery, and patents have been issued for designer babies.

So who should have the rights to your geome, and why?

Prophets of Science Fiction – vivisection and transplants

Science Fiction provides a delightful opportunity to look at the possible social implications of technology before it emerges into reality.  A recent series on the Science Channel, “The Prophets of Science Fiction” reverses this logic and explores how early works of ScFi have anticipated both technical and social aspects of today.

The first program focuses on Frankenstein. It combines a perspective of the environment in which Mary Shelley wrote the book, and her own personal life.  It moves back and forth from her context to the 21st century pointing at both scientific advances that realize part of her vision, and also social variations that reflect differences between the two centuries.

Shelley’s story, often misrepresented in movies and public perception, focuses on a super-human creation of Dr. Frankenstein that, if it had been given proper attention in its formative months (rather than abandoning it) might have been the basis for a successor species beyond humans. Dr. Frankenstein prevents this by destroying the female version, and once again abandoning his creation.

Part of the horror of the story for Shelley’s 19th century audience was the combining of various human and animal parts used in creating the creature.  This theme of mix and match body parts is raised again by HG Wells in The Island of Dr. Moreau. Here it is vivisection that is the abomination. A parallel anti-vivisection movement emerged in England, and has continued advocacy for animal rights, or at least ending cruelty to animals.

In the 21st century we have much fewer concerns about many of the issues that dominated the horror of these books in the 19th century.  Animal experiments, in many countries, are managed with strict ethical guidelines and oversight committees.  We cut humans open and re-engineer them using donor organs (from living or dead humans), animal components, and when possible, from the patient themselves.

There are really two social impact issues (at least) here:
a) the question of what is “human” as we start moving to the next generation of mix and match solutions, some of which will involve genetic manipulation as well as a collage of donor and cyber components;
b) the transition we have made socially in terms of mostly embracing the concepts of transplants, animal experimentation, and other technologies that are a significant part of medical treatment and research.

One last SciFi reference (at least) is needed in the context of these two points: Robert Heinlein’s “Fear No Evil” explores the ultimate transplant of a human brain. In this vision, the result is a person with the awareness of both the body donor and the brain donor.

Any other stories or considerations you would like to add to this area of prophecy?