New Monitoring System Approved by FDA- Potential for Future Robotic Diagnostics

Posted on April 2, 2008 by Steven F. Palter, MD

The FDA has just approved the FreeStyle Navigator Glucose Monitoring System – a glucose sensor that reports glucose values continuously for up to 120 hours. Here is a copy of the FDA PMA letter. This device is interesting to me since it works with a sensor inserted in either the abdomen or the back of the upper arm. The device then continuous provides glucose readings and updated glucose trend information for viewing and contains a built-in alarm that can be programmed to alert the user when results fall below pre-set values. Other similar devices have been approved that monitor for 7 days.

Potential for Future Robotic Diagnostics I have written before that I predict a whole new field of chip based biologic disease screening and monitoring in the future. This is another step to that result. Here a sensor is placed under the skin that measure blood sugar. In the future minitaturized chips could be placed in any body cavity or organ to sense any imaginable molecule.

Options for Future Diagnostics:

DNA based sensors screen for cancer metastasis or recurrances such as an intrabdomnal ovarian cancer detector.
Sensore that measure drug levels in target tissues – chemotherapy of course comes to mind
protein sensors that look for the earliest stages of disease development.

As personalized genetics becomes more widespread, we will identify individuals at particular risk for particular diseases before they occur. Since the genetic basis of these diseases will be known markers will likely exist. Implanted chip sensors could then be placed to sniff for these markers and wireless transmit the alarm- or even deliver a predetermined treatment agent- all before there is any external sign of the disease. First generation implantable devices such as this for blood sugar monitoring are lisated here (none yet available):

Here are links to some of the technology that will be involved for these future diagnostics including tiny sensors that transmit with RFID, smartdust sensors the size of a speck of dust or less, smart pills that travel through the body transmitting data and the concept of personalized genetic information based diagnostics and personalized genetics in general.

All approved continuouis blood sugar monitoring devices are here and a comparison from a patient site here:

As an aside – in terms of glucose monitoring the use of thse devices may come into question. An ongoing diabetes study called ACCORD was cut short in one treatment arm when it was shown that ultra tight strict blood sugar control in diabetics with heart disease actually WORSENED outcomes!

Google Finished With Cataloging the Internet Moving on to Your DNA

Posted on March 4, 2008 by Steven F. Palter, MD

It was just reported today that: “A Harvard University scientist backed by Google Inc. and OrbiMed Advisors LLC plans to unlock the secrets of common diseases by decoding the DNA of 100,000 people in the world’s biggest gene sequencing project.”

What nothing better to spend $1Billion on? Why are they doing this you ask….

Harvard’s George Church plans to spend $1 billion to tie DNA information to each person’s health history, creating a database for finding new medicines. The U.S., U.K., China and Sweden this year began working together to decipher the genetic makeup of 1,000 people at a cost of $50 million.

Google, owner of the most popular Internet search engine, is looking for ways to give people greater control over their medical data. Along with the unspecified donation to Church, the Mountain View, California-based company said last week that it would work with the Cleveland Clinic to better organize health records, and last year gave $3.9 million to 23andme Inc., a seller of genomic data to individuals.

Church’s plan “would be the largest human genome sequencing project in the world,” Stephen Elledge, a geneticist at Harvard Medical School in Boston, said in a telephone interview today. “The genetic variations are what make people different, and we need to understand the connections to human disease. They’ll get a tremendous amount of information from this,” said Elledge, who isn’t involved in the project….“If we can expand the project, we’ll probably go for a million genomes,” Church said.

Personalized genetics and genomics are hot topics – Read more about the concepts here. With these two you either look to an individual’s genetics to see how it will impact a disease or a treatment (a single gene) or with genomics “This is the dream of everyone gets a genome sequenced at birth, we assess risk, create prevention plans, identify idosyncratic drug reactions prior to medication therapy”.

The medical and financial impact for the company owning this data in unimaginable. The source of individual variability of response to drugs and individual susceptability to disease could be greatly unlocked – as well as mined for new therapeutics. Google of course is getting into all medical databasing starting with your health record and I predict images of your diseases next.

New Visual Search Engine Debut-Works with a cell phone photo! Medical Uses Next?

Posted on March 4, 2008 by Steven F. Palter, MD

I have been following the consumer device CeBIT show in Germany. Pocket-lint UK reports:

At the CeBIT show in Germany, Vodafone is demonstrating a trial service called “Otello”, which is a search engine that uses images, rather than words. Rather than use a word as a search term, Otello users can send images via MMS from their mobiles and the search service which then returns the results to the user’s phone as an “ordinary” search result.

A picture from a newspaper, billboard, book cover or place are all examples of what can be searched for.

Vodafone is running trials with a German newspaper that lets users find out more about stories by photographing the images that appear in the article and MMSing the images.

There’s no word on breaking this out of trial phase at this stage.

I just had a meeting with reps from a major medical device company where I discussed the potential for smart image tagging and identification in medical imaging. Just think of the potential when this smart technology could be applied to image pattern recognition for skin lesions, radiologic images, and pathology slides. Rural medicine will never be the same! Cell photo snap an image and link to a search engine to get a diagnosis (we know who wants that to happen). Right now the system is prepopulated with images then recognized. In the future neural net and patern recognition technology will take this a step forward. Similar systems already exist for pap smear screening of cytologic abnormalities including a commercially available system papnet (made by Neuromedical Systems, Inc. who filed for chapter 11 and sold their intellectual proprty to Autocyte Inc).

The Bigger Story Behind the 3 Parent Embryo- Human Embryo Genetic Experimentation

Posted on March 3, 2008 by Steven F. Palter, MD

Countless sources are reporting on the “three parent embryo” created as a potential treatment for infertility. What has not been reported is that ther is an almost 10 year history of unreagulated human experimentation in this arena which led to a rare federal ban on specific fertility treatments. Is this hope, hype or dangerous human experimentation? Read on to see!

Background- what are mitochondria? Mitochondria are tiny primite organisms that millions of yers ago became incorporated into human cells. They exisit in every cell but have their own unique genetic material. They function as the engines of the cell providing energy for metabolism. I wrote an review of how they got there and what they do that you can read here. In short mitochondria have their own DNA (similar to that of bacteria) and reproduce independently of the cell in which it is found. We now have a symbiotic relationship with them.

First – the details receontly reported by the BBC. Diseases of the function of mitochondria exist. “About one in every 6,500 people is affected by such conditions, which include fatal liver failure, stroke-like episodes, blindness, muscular dystrophy, diabetes and deafness.” Details of their human experiment: Scientists in the UK experimented on 10 embryos left over after IVF fertility treatments. They microsurgically removed the nucleus, containing the embryo’s DNA and implanted it into a donor egg whose DNA had also been removed. The donor egg while missing its DNA still contained its mitochondrial DNA. They watched these embryos grow in the petri dish for 6 days.

Therefore the resulting embryo will have the DNA of the donated nucleus but the mitochondrial DNA of the host cell- curing and potentially eradicating – the mitochondrial illness.

This is not the first time this has been done. The fertility treatment history of human experimentation on this: While I was teaching at Yale Medical one of my partners and mentors in the fertility department (Dr David Keefe) was actively pursuing research on mitochondrial dysfunction as a cause of human infertility. At that time a few fertility doctors in the US theorized that one cause of human reproductive aging was accumulated damage to the mitochondria in the egg. They thought the genes of the egg could be healthy but the rest of the egg that supports its become faulty. They experimented with a technique called cytoplasmic transfer. Using a microscopic needle tiny drops of fluid were sucked out of a donor’s egg and injected into that of an older infertile woman hoping to breath new energy and life into it. Unfortunately most research groups found it did not seem to offer any benefit.

Reasons why it likely did not work:

using minute drops of fluid from a donor egg into a recipient is just not enough to correct the metabolic problem or defect
my collegues at Yale found that the mitochondria in the egg is often tightly joined to the nucleus so the cytoplasmic transfer did not move enough of them
a huge proportion of age related egg defects are related to nuclear not mitochondrial DNA defects.

The federal government banned this treatment in 2001. Some feared that chromosomal abnormalities and birth defects could result if there were three people’s DNA in one embryo. Federal officials decided that any method involving the transfer of genetic materials without the fusion of egg and sperm requires the oversight and involvement of the Food and Drug Administration. The US legislation leading to the FDA taking jurisdiction over human eggs sperm and embryos is a whole other topic to be covered in later posts. A brief overview of this from Rodger Gosden (who I know and respect as a leading reproductive biologist) is posted here from 1999 when this treatment was at its heyday with references justifying its use from mouse research.

The next brouha using the technique in humans in 2003: Related research on nuclear transfer was again presented at the annual ASRM meeting in San Antonio in 2003. I was in the audience for the talk and remember it well. One of the researchers was an American out of NYU Dr Jaime Grifo who also used to be in my ex-department at Yale. He is also a repected researcher who I know well. Unable to perform the research in the US- the experiment was performed in China. as reported here and here

Researchers at Sun Yat-sen University in Guangzhou implanted three embryos in the womb of a 30-year-old infertile woman… A triplet pregnancy resulted, they announced at the annual meeting of the American Society for Reproduction Medicine in San Antonio, Texas this week. One of the foetuses was “reduced” to ensure the viability of the pregnancy, but the other two died anyway at 24 and 29 weeks.

With this technique, called nuclear transfer, the doctors fertilised an egg from their patient and an egg from a donor. Two embryos resulted. The nucleus of both women’s embryos was extracted, and the patient’s genetic material was inserted into the empty “eggshell” of the other embryo which, however, contained mitochondria with the other woman’s DNA. The procedure gives the infertile woman’s embryo the healthy mitochondria it needs to develop — but it also results in a child with genetic material from one father and two mothers.

Dr Grifo has maintained that he was an advisor and did not partake in the actual experiment. NYU issued a statement that if the research was performed in China their IRB did not have oversight (different than my department where all work I did anywhere fell under the IRB as a faculty member). I have never asked him his take on this but do respect him and strongly do not believe he is someone who would knowingly break the law or do what he felt was wrong.

Nonetheless- the ASRM responded with a moratorium on any future presentations on cloning (whether this was cloning is a whole other debate- many feel not).

The technique is still undergoing related research: I chair the video committe of the American Societry for Reproductive Medicine (ASRM) the largest international fertility research society. Just this past year we accepted a video presentation on how to technically perform the procedure from a research team in Japan. The paper- Embryonic Development Following the Nuclear Transfer of In Vitro Matured Metaphase-II Oocytes into Enucleated Freshly Ovulated Metaphase-II Oocytes by Tanaka and collegues investigated the possibility of repairing either mitochondrial diseases or female infertility due to ooplasmic deficiency and abnormalities. They demonstrated embryonic development following the nuclear transfer of in vitro matured metaphase-II oocytes into enucleated freshly ovulated metaphase-II oocytes and concluded it could be applied to the treatment of mitochondrial diseases or female infertility due to ooplasmic deficiency and abnormalities.

More is certainly to come.

How Smartdust, Souveillance, Web 3.0, and Personalized Genetics Will Transform the Future of Medical Diagnostics

Posted on February 25, 2008 by Steven F. Palter, MD

There has been a flurry of debate in the military, industrial, and privacy sectors on “smartdust” and the concept of “souveillance” – but no one has yet realized this technology is poised to springboard into medicine and transform medical diagnostics. Here I wanted to give you an overview of what this idea is and why you should keep your eye on it.

First the general concept background:

“Smartdust” refers to micro devices (called motes) which are detection microchips each potentially the size of a speck of dust. These grains of sand however can automatically self-network. So far people have conceived of these low-power distributed sensing networks as having functions for climate control systems, entertainment devices and especially for big brother type surveillance systems.

Wikipedia wrote “the smartdust concept was introduced by Kristofer S. J. Pister (University of California) in 2001 , though similar ideas existed in science fiction before then. A recent review discusses various techniques to take smartdust in sensor networks beyond millimeter dimensions to the micrometre level. A typical application scenario is scattering a hundred of these sensors around a building or around a hospital to monitor temperature or humidity, track patient movements, or inform of disasters, such as earthquakes. In the military, they can perform as a remote sensor chip to track enemy movements, detect poisonous gas or radioactivity. The ease and low cost of such applications have raised privacy concerns.” Beyond web 2.0 vast networks of these real time sensors are once possible technology leap of the yet inknown web 3.0.

General concept – What is Souveillance?: is a term from Steve Mann that refers to “bottom up” surveillance using smart dust as opposed to “top down” big brother networks looking at us little people. Here instead activities are recorded from the “perspective of a participant in the activity, typically by way of small portable or wearable recording devices that often stream continuous live video to the Internet.” Remember the impact of the Rodney King video and of all the user generated video content on the web. Now fast forward to a world where a large segment or even a majority of the populice had real time streaming video devices on all the time (no we are not going to discuss the porn angle on this). This has also been called “inverse surveillance”.

Privacy advocates have been debating the merits or horrors of this type of sensor technology. I serve on the Scientific Advisory Board of the Lifeboat Foundation which is dedicated to protecting us from future technological threats through advocacy research and education. They have been having a heated debate on the “paradox of smart dust: we may not live without the greater security provided by smart dust, but many think they could not live with smart dust impinging on our privacy.’

Medical Implications: I have a vision that once this type of low power networked microsensor technology exists it will logically lead to medical sensor technology. Potential uses I see include:

mass screening for infectious disease or bioterror agents. Subjects walking into screening areas could be checked for signature molecules associated with infectious agents. Just as we have metal detectors and now have molecular signature detectors (the litle wipe test for explosives at the airport) we will have such biological screening techology.
The next step will be similar screening for disease states. Metabolomics is one such technology. Metabolomics is the study of the small-molecule metabolite byproducts left behind from cellular processes. In simple terms it’s like examining poop. The concept is that by measuring the collection of all the byproducts of the cells metabolism you can get a snapshot of the physiology of a cell or organism that translates to health. One such sensor is being developed as a breath sensor for disease. This could lead to Star Trek like medical sensors.
Similarly, such technology will lead to individual genetic screening for disease risk using chips that interact with the tiny bits of DNA we shed every time we touch something. Companies commercializing this approach also already exist and have products.
Taking a clue from smart dust we will then inject such sensors into our bodies where thy could circulate in the bloodstream or sit in the abdminal cavity silently sensing for disease, infectious agents, or the DNA or signature molecules of a cancer cell. Alternative chips could exist that sit and slowly release drugs when such cell reappear once a patient is diagnosed.

I will be writing more about the details of these concepts and devices being developed in future posts now that I have introducted the concepts. Let me know what you think!

Second Life for Medicine

Posted on February 14, 2008 by Steven F. Palter, MD

More and more social networking sites, web 2.0 sites, and other initially recreational new internet systems are migrating to work and educational related functionality. The potential for medical uses, online research, education, and patient networking is seemingly endless.

This wiki lists general grid and teen grid educational sites on second life as does this very comprehensive one.

On May 25, 2007, 1300 educators from around the world gathered at the Second Life Best Practices in Education: Teaching, Learning, and Research 2007 International Conference in the virtual world of Second Life. The event was the first 24 hour, international conference ever to take place entirely within a virtual world. Details are here.

My award winning friend-blogger Bertalan Mesko has the most comprehensive blog on web 2.0 medical resources has put together this great list of everything about seond life and medical education.

Check this out. I’ll be writing much more about vitual communities in the future and medical uses.

New HD Disk Format

Posted on February 13, 2008 by Steven F. Palter, MD

EngadgetHD reports on New 3xDVD;

Comin’ straight outta Thuringia is the first news we’ve heard in a year about HD DVD’s red-laser cousin, 3X DVD. CDA Datenträger Albrechts GmbH has announced its started production of 3X DVDs, which are basically HD content, compressed with VC-1 or MPEG-4 and AACS DRM, on a standard red laser DVD that is readable only by HD DVD players. The advantage is that it costs the same to produce as a regular DVD, and CDA is apparently producing dual-sided DVD-10 discs, with standard DVD content on one side, and HD on the other. Of course, with several German studios dropping HD DVD support (along with a few others you may have heard of) its hard to see who will take advantage of CDA’s new capabilities.

Someone needs to step up and put a recordable HD format onto the HD endoscopy sets in the OR. Even the HD systems record in SD. I am waiting for recordable Blu-ray or even better a flash or disk based AVCHD solution.

New Generation of Performance Enhancing Drugs

Posted on February 12, 2008 by Steven F. Palter, MD

NatureNews has just reported on a new drug that plugs calcium leaks in muscles and boosts stamina (in mice). I have previously written of the next wave of what I call “designer drug abuse” coming- performance enhancing drugs. The first batch are called eugeroics and offers improved memory, mood enhancement, improved alertness and cognitive powers without any of the nasty side effects and mass murder of speed and crank. This new class is a physical performance enhancer. You can read my thoughts on how far people will go in the future to enhance their bodies here. If you think plastic surgery is the rage of body enhancement – wait until we get performance and congnitive enhancing bionics, drugs, and implants!

Nature writes of the published in the online edition of the Proceedings of the National Academy of Sciences today (Bellinger, A. M. et al. Proc. Natl Acad. Sci. USA 105, 2198-2202 (2008).

Researchers have shown how intense exercise can damage muscles, and developed a drug that can hinder the effect in mice. Mice on a taxing work-out schedule were stronger and had more endurance when given the drug.

The drug, called S107, prevents calcium from leaking into muscle cells. Calcium causes muscles to contract, but calcium leaks can reduce the force of contraction and activate an enzyme that chews up muscle protein.

They go on to say that “leaky calcium channels have been associated with the fatigue and soreness that follows intense, sustained exertion, such as running a marathon or long-distance cycling. This weakness can last for days or weeks, and is not the same as the brief discomfort that follows a typical work-out.”

As expected there is a start-up ARMGO Pharma, that plans to develop S107 and others like it for clinical use in patients with chronic tiredness from disease.

Nature hits upon the potential for abuse just as I predicted. “Don Catlin, director of the Olympic Laboratory drug-testing centre at the University of California, Los Angeles, says that a drug such as S107 could also become prime fodder for athletes looking to improve their stamina.

I myself had dinner with the former chief medical director of the olympic committee (the guy in charge of thesting if the women really are women and vice versa). He told me he is very concerned about athletes and students using performance enhancing drugs. Imagine a high school athlete or student offered a pill that could makethem run faster or longer or increase memory without adverse effects. How many do you think would take them. I recall his worry- your child saying daddy I want to be a track star- can you amputate my legs so I can get the new bionic ones.

Next Gen Mini-PS3 Cell Chips -Next Medicine Imaging Revolution?

Posted on February 8, 2008 by Steven F. Palter, MD

“ Though sold as a game console, what will in fact enter the home is a Cell-based computer. ” – Ken Kutaragi

“Cell-based computers will revolutionize medical imaging” – Docinthemachine

The IBM Cell graphics processor at the heart of the PS3 is a remarkable chip. Cell is shorthand for Cell Broadband Engine Architecture. It has been described as “seemingly obscene computing capabilities for what will rapidly become a very low price.”

A newer miniaturized lower power version has just been announced by ars technica that I predict will make it to medical video and VR processing. I recently led a session on the use of VR in medicine where Andy Van Dam (VR pioneer , professor of computer science at Brown, and founder of Siggraph) and I spoke about the future of VR processing. He predicted that the video grame industry hardware innovations will make the most dramatic strides and that this technology will then trickle down to VR due to its sheer massive computational power- beyond that of the old CAVEs of DARPA.

You may be unaware that this represent a new form of computer processing:

The Cell concept was originally thought up by Sony Computer Entertainment inc. of Japan, for the PlayStation 3. The genesis of the idea was in 1999 when Sony’s Ken Kutaragi “Father of the PlayStation” was thinking about a computer which acted like Cells in a biological system. A patent was applied for listing Masakazu Suzuoki and Takeshi Yamazaki as the inventors in 2002

The architecture as it exists today was the work of three companies: Sony, Toshiba and IBM. Sony and Toshiba previously co-operated on the PlayStation 2 but this time the plan was more ambitious and went beyond chips for video games consoles. The aim was to build a new general purpose processor for a computer.

In lay terms here is the muscle behind the processor:

The setup of the Cell processor is like having a team of processors all working together on one chip to handle the large computational workload needed to run next-generation video games. In order to understand how the Cell processor works, it helps to look at each of the major parts that comprise this processor.

The “Processing Element” of the Cell is a 3.2-GHz PowerPC core equipped with 512 KB of L2 cache. The PowerPC core is a type of microprocessor similar to the one you would find running the Apple G5. It’s a powerful processor on its own and could easily run a computer by itself; but in the Cell, the PowerPC core is not the sole processor. Instead, it’s more of a “managing processor.” It delegates processing to the eight other processors on the chip, the Synergistic Processing Elements.

The computational workload comes in through the PowerPC core. The core then assesses the work that needs to be done, looks at what the SPEs are currently processing and decides how.

Watch out for our robot PS3 overloards. This Chip has the potential to expand itself and distribute workloads over networks. Don’t worry this is not some Singularity scenario where the chips start to think on their own. Here is a review of the potnetial of the chip:

Chip giants such as Intel have already started working on dual-core chips, but Cell goes several steps further by giving processing units a measure of independence. Current multicore chips typically chop a single computing task into parts, which are distributed among processing units. Cell’s processing units–called “software cells”–can handle completely separate jobs.

“The software cells are designed to be kind of self-contained–they can kind of roam around,” Halfhill said.

Cells can even roam over a network, allowing the processor to perform a type of distributed or grid computing, an increasingly popular enterprise technique in which demanding tasks are divvied up among a gang of networked computers. A PlayStation 3 could borrow unused processing power from other consoles on a network, for example, to complete a demanding task such as delivering streaming video.

“The Cell architecture is designed to make grid computing almost universal,” Halfhill said. “It makes distributed processing part of the design. If you have several of these machines on a network, the work can be spread across a network.”

The cell design can allow cooperation between video devices: “This architecture is not fixed, if you have a computer, PS3 and HDTV which have Cell processors they can co-operate on problems. They’ve been talking about this sort of thing for years of course but the Cell is actually designed to do it. According to IBM the Cell performs 10x faster than existing CPUs on many applications. This may sound ludicrous but GPUs (Graphical Processors Units) already deliver similar or even higher sustained performance in many non-graphical applications.”

Medical uses: We are at the cusp of a revolution due to the integration of computer video processing and surgical and radiological imaging. Details of this concept of mine are here and a podcast here. As we move ahead with virtual imaging and newer forms of optical processing it is the computational power of these kinds of chips that will be enabling.

Disclosure: As I previously wrote, I was chosen to be a Sony Medical HD Luminary Site. I receive no financial payment for this relationship which is only with Sony’s Medical division and is part of my medical research work on surgical tools and imaging. Heck- I had to buy my PS3 at Best Buy just like anybody else.

Sperm Made from Female Stem Cells- All Female Baby Possible

Posted on February 4, 2008 by Steven F. Palter, MD

Scientists in the UK have successfully tricked stem cells from a female to develop into sperm. If these cells are functional then the possibility exists for an “all-female” baby to be made from the cells of a same sex female couple. This is the next step forward from a group that earlier did the same thing with cells from a man.

This study was reported in the British Telegraph Newspaper. They listed it as embryonic stem cells from a female human embryo - they are likely wrong - as I read the report it appears to be cells isolated from an adult female human bone marrow.

This same group from Newcastle University led by Prof. Karim Nayernia reported last year that they had made a sperm from the bone marrow of an adult man. I reported on this research in my previous post Babies Without Men and how it opened the possibility of making sperm from a female and creating a female-female baby. The details of the original project, ethical and genetic risks and heated (and sometimes nasty) debate on lesbian-lesbian parenthood are here.

He now reports that he has repeated the experiment and made the sperm from the marrow cells of a female. The work has not yet been published not subjected to peer review.

I previously reported that I think there is a ticking genetic time bomb here due to imprinting errors. The genes that come from your mother and father are in some cases marked as such genetically and one copy may be shut off. In some cases only the gene from mom is active in others only the one from dad. This new process may mess with this system – and imprinting errors are known to cause genetic diseases in some cases. In fact, the telegraph reports of some “problems”

Prof Nayernia showed the potential of the method in 2006, when he used sperm derived from male embryonic stem cells to fertilise mice to produce seven pups, six of which lived to adulthood, though the survivors did suffer problems.

They also report it could be used to make eggs from a gay man’s cells “a gay man to donate skin cells that could be used to make eggs, which could then be fertilised by his partner’s sperm and placed into the uterus of a surrogate mother.”

While they also report he is seeking permission to create a baby in this way, the UK is very restrictive on new reproductive technologies. They have a law- the 1990 Human Fertilisation and Embryology Act- that restricts what can and cannot be done.