FIRST CREDIT 5

This is the fifth and last in a multi-part blog on the topic of FIRST CREDIT in the sciences.

Sometimes, credit falls on the person who least understood the significance of his own work. In 1771, Charles Messier (1730 - 1817) , selected 103 heavenly objects that have captured the rapt attention of astronomers for nearly two and a half centuries. Messier selected regions of space that were nebulous, and obscured his view of comets (his sole interest). He made a point of categorizing the Messier objects as areas of space that should be avoided by serious astronomers. In 1771, his chosen spots might have been accurately called the Messier non-objects.


Charles Messier.
Source: Wikipedia, public domain.

Today, the Messier objects are credited with holding some of the most fascinating galaxies and cosmologic curiosities in the known universe. Though Messier was completely wrong, he has achieved scientific immortality, just the same.


Messier object 51.
Source: Wikipedia, public domain NASA image.

The first observation of a particular type of anemia associated with sickled red blood cells, was made by Ernest E. Irons (1). Dr. Irons was a young intern when he encountered a patient, Walter Clement Noel, and made his historic observation. He alerted his attending physician, James B. Herrick. Irons sketched the shaped of the cells directly into the patient's hospital record. Herrick wrote the 1910 case report as a single author submission, excluding Irons (2). To this day, the disease sickle cell anemia carries the eponym, Herrick's disease (not Irons disease).

Sometimes first credit goes to the wrong species. Salicylic acid has been used as a medicinal by several different ancient cultures. In the western tradition, Hippocrates (5th century BC) claimed that a bitter powder extracted from willow bark could ease aches and pains. How did the ancients know that willow bark would relieve pain? Bears were observed rubbing against the bark of willow trees when wounded. The humans stole credit for an ursine discovery.

[1] Savitt TL, Goldberg MF. Herrick's 1910 case report of sickle cell anemia: the rest of the story. JAMA 261: 266-271, 1989.

[2] Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med 6:517-521, 1910.


This is the last entry on the topic of FIRST CREDIT in the sciences. If you have read the five-part series, I'd appreciate reading your comments.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

FIRST CREDIT 4

This is the fourth in a multi-part blog on the topic of FIRST CREDIT in the sciences.

Johann Franz Encke (1791 - 1865) is given credit for the discovery of [Encke's] comet (1818), but Encke merely calculated the orbit, using a technique first developed more than a century earlier by Edmond Halley (1656-1742). In 1705, Halley applied Newton's laws of physics to correctly predict that a particular comet (known today as Halley's comet), observed in 1531, 1607, and 1682, would return in 1758. The comet known today as Encke's comet was named after a person who neither first-sighted the comet nor discovered the methodology to predict the comet's orbit. The person who made the first sight of the commet has descended into scientific obscurity.


Johann Franz Encke.
Source: Wikipedia (public domain).

When a new technology becomes available to the practitioners of a field, it often happens that a new discovery is made by multiple independent researchers, simultaneously. For example, sunspots were discovered by Thomas Harriot (England, 1610), Johannes and David Fabricius (Frisia, now parts of The Netherlands and Germany, 1611), Galileo Galilei (Italy, 1612), and Christoph Scheiner (Germany, 1612). First credit usually goes to the most influential of the discoverers.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

FIRST CREDIT 3

This is the third in a multi-part blog on the topic of FIRST CREDIT in the sciences.

"If you want to make an apple pie from scratch, you must first create the universe."

- Carl Sagan

Carl Wilhelm Scheele (1742 - 1786) made some of the most important discoveries in the field of chemistry, but, through a series of bad breaks, lost first credit for all of them. Scheele discovered Oxygen a full two years before Priestley, but Scheele sent his manuscript to a publisher who held the work for several years, during which time Priestley got his discovery into print. Today, Joseph Priestley (1733 - 1804) is widely held to be the discoverer of Oxygen. In 1774, Scheele laid the groundwork for the discovery of Manganese, but Johan Gottlieb Gahn (1745 - 1818) finished the task and received the credit. Also in 1774, Scheele isolated chlorine but failed to identify it as an element; credit eventually went to Humphry Davy (1778 - 1829). Scheele did great service to science during his 46 years on earth.


Carl Wilhelm Scheele. Source: Wikipedia, public domain

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

FIRST CREDIT 2

This is the second in a multi-part blog on the topic of FIRST CREDIT in the sciences.

Antonie Philips van Leeuwenhoek (1632-1723) is sometimes credited with inventing the modern microscope. Not so. Leeuwenhoek improved the microscope with his superb lens grinding technique, but he did not invent the microscope and did not make any particularly important modifications to the design of the microscope.


Source: Garrison FH. History of medicine.
WB Saunders, Philadelphia, 1921.

In 1595, fifteen-year old fledgling Dutch lens grinder (and part-time counterfeiter), Zacharias Jansen (1580 - 1638) placed two lenses in a tube, and created the first compound microscope.


Source: Wikipedia (public domain)

This amazing invention sat dormant until 1667, when Robert Hooke (1635 - 1703) studied insects and plant material, particularly cork, with this 72 year old invention. Hooke used the word "cell" to describe the complex, living structures that compose every organism. In 1675 (eight years after Hooke), with improved lenses, Leeuwenhoek studied micro-organisms in water and cells of the human body. Hooke and Leeuwenhoek kick-started modern microscopy, but Zacharias Jansen invented the microscope.

Smallpox was the first disease for which vaccination was successful. As early as 200 B.C.E. in China and 1000 B.C.E. in India, physicians knew that infection with smallpox conferred immunity against subsequent infection. Based on this observation, they were the first to develop a vaccination, administered nasally, of attenuated virus. Arabic doctors developed their own treatment, consisting of transferring material from an infected pox blister to another person via a small cut. Emmanuel Timoni (1670 - 1718) was a physician practicing in Constantinople. He introduced the Arabic vaccination process to West, in 1717. In 1796, Edward Jenner (1749 - 1823) developed a new vaccine, developed from a bovine pox virus (vaccinia) that seemed to confer cross-immunity against smallpox (variola). When you consider that the word, "vaccine", derives from Jenner's choice of inoculum (vaccinia), it seems reasonable to give Jenner the credit for developing the first effective vaccine. Incidentally, Jenner's paper describing his smallpox vaccine was rejected, in 1976, by a peer-reviewed journal (1).


Source: Garrison FH. History of medicine.
WB Saunders, Philadelphia, 1921.

If you want to give credit to the first person to save European lives by immunizing against smallpox, you would need to go 80 years earler than Jenner; to Timoni. To be really fair, you would need to go back many centuries, to the Chinese, Indian and Arabic physicians, to find the origin of human immune treatments.

[1] Altman LK. When peer review produces unsound science. The New York Times June 11, 2002.

-- TO BE CONTINUED --

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

FIRST CREDIT 1

This is the first in a multi-part blog on the topic of FIRST CREDIT in the sciences.

Stigler's law of eponymy, "No scientific discovery is named after its original discoverer."

- SM Stigler (1)

According to Stigler, credit always goes to the wrong person, and this is the essence of Stigler's law of eponymy (which, according to Stigler, must have been invented by someone other than Stigler). Stigler provides numerous examples of credit going to the wrong scientist (1). "Laplace employed Fourier Transforms in print before Fourier published on the topic, that Lagrange presented Laplace Transforms before Laplace began his scientific career, that Poisson published the Cauchy distribution in 1824, twenty-nine years before Cauchy touched on it in an incidental manner, and that Bienayme stated and proved the Chebychev Inequality a decade before and in greater generality than Chebychev's first work on the topic."

Yes, misleading eponymous terms are commonplace in the sciences. Marcello Malpighi (1628 - 1694) was an Italian physician who was one of the earliest scientists to use the microscope to describe tissues and their diseases. He was the first to describe lymphoadenoma, the lymphoma known today as Hodgkin's disease. More than a century later, Thomas Hodgkin (1798 - 1866) wrote a manuscript and credited Malpighi with the first description of the disease. Nonetheless, the eponym for the lymphoma went to Hodgkin.


Source: Garrison FH. History of medicine.
WB Saunders, Philadelphia, 1921.

Likewise, the Wheatstone bridge, introduced in 1843, was not invented by Charles Wheatstone (1802 - 1875). Wheatstone, working from the prototype, improved and popularized the device. The eponym was bestowed on Wheatstone, despite his protestations. The original bridge was invented by Samuel Hunter Christie (1784 - 1865), in 1833.

[1] Stigler SM. Statistics on the table: the history of statistical concepts and methods. Harvard University Press, Cambridge, p 277, 1999.

-- TO BE CONTINUED --

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

INTELLECTUAL PROPERTY 6

This is the sixth and last in a multi-part blog on the topic of INTELLECTUAL PROPERTY in the sciences.

"Most people are other people. Their thoughts are someone else's opinions, their lives a mimicry, their passions a quotation."

- Oscar Wilde

In earlier blogs, we covered uses of the patent system that had dubious societal value, specifically:

1. Patenting to suppress innovation.
2. Patent farming.
3. Patent spreading.
4. Patent holding.
5. Patent shifting.
6. Remixing prior patents.
7. Patenting the uses of unpatented inventions.
8. Patenting the obvious and the previous.
9. Patenting life.
10. Viral patenting.
11. Royalty stacking.
12. Reaching through a patent.

The government awards patents, but when someone infringes on a patent, the government takes no action. Only the patent holder is harmed, and only the patent holder can litigate against the infringing party. For this reason, a patent is sometimes referred to as the right to sue. Paradoxically, the typical patent holder is terribly frightened of lawsuits and will do almost anything to avoid a court appearance. Why?

I am not a lawyer, and the following paragraphs should not be construed as competent legal advice. They are included here to indicate that some patents, software patents in particular, sit on shaky ground, and that they are often vulnerable to declaratory judgments.

Imagine that you hold a software patent, and you have identified a person whose software contains some code that seems to infringe on one or more of the claims contained in your patent. Your lawyer sends this person a letter claiming infringement and demanding that the person either stop using the patented property or begin paying an assigned royalty. This is the so-called "demand letter" that every software programmer fears.

The alleged infringer, if smart, will seek remedy in a federal court, arguing that your patent is invalid or unenforceable, or that he did not infringe. He will ask for a declaratory judgment to stop you from pursuing your patent demands.

The declaratory judgment is a preventive adjudication. Its purpose is to clear the air, so that the person who received the demand letter need not labor under the constant fear of an impending lawsuit filed by the patent holder (1). Your alleged infringer will bring his case to a federal court venue, near where he lives (you and will need to travel to the location), giving him the home court advantage. If he asks for a declaratory judgment based on non-infringement, you will be required to pursue a counterclaim of infringement; an action that you may not be prepared to pursue. In the case of software patents, virtually every patent holder stands on very weak ground. All software is derivative of someone else's work; hence, every software patent is vulnerable to a declaratory judgment. You may have spent millions of dollars developing your invention and seeking your patent, but all of your investment could be lost through a declaratory judgment.

Declaratory judgment cases must be triggered by a significant controversy, usually a threat of litigation. Your demand letter, indicating infringement and requiring compensation, is often sufficient to trigger a claim for declaratory judgment. This means that, if you have a vulnerable patent, you must NOT send a demand letter that has the effect of a threat.

You may try having a salesman send the letter (not a lawyer). A letter from a salesman is less likely to imply the threat of legal action than a letter from retained counsel. In the letter, you might want to simply identify the patent and indicate that it was available for licensing. It may be wise not to suggest that infringement has occurred.

The purpose of a "demand" letter is to motivate the receiver to buy a license, without triggering a declaratory judgment action. If the letter is sufficiently bland and non-threatening, it may do the trick. Remember, though, that the receiver will likely interpret your letter as a thinly veiled threat. When determining jurisdiction for a declaratory judgment, courts look at all the relevant circumstances. If you have a history of vigorously pursuing patent claims, or you have a history of intimidating people with the implied threat of legal action, a court may interpret any letter from you, no matter how bland, as an intent to litigate.

What is the moral of this multi-part blog on INTELLECTUAL PROPERTY? The patent system does not always work to the benefit of the patent holder, or of society. Scientists who develop basic algorithms, or implementations of existing patents, or whose works do not qualify as inventions or devices, or whose discovery was a creation of nature, or a finding of vital importance to the health of others, should think very deeply before seeking patent protection for their works.

[1] Uniform Declaratory Judgments Act. National Conference of Commissioners on Uniform State Laws. August 2 - 8, 1922.

PLEASE POST COMMENTS ON THIS SERIES: INTELLECTUAL PROPERTY IN THE SCIENCES.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

INTELLECTUAL PROPERTY 5

This is the fifth in a multi-part blog on the topic of INTELLECTUAL PROPERTY in the sciences.

In the blogs from yesterday and the day before, we covered uses of the patent system that had dubious societal value, specifically:

1. Patenting to suppress innovation.
2. Patent farming.
3. Patent spreading.
4. Patent holding.
5. Patent shifting.
6. Remixing prior patents.
7. Patenting the uses of unpatented inventions.
8. Patenting the obvious and the previous.
9. Patenting life.

Here are three more common practices:

10. Viral patenting. Asserting a patent on the manufacturer of an assembled device, and asserting the same patent on the users of the manufactured device. Viral patenting is risky for the patent owner. In a precedential case, the U.S. Supreme Court unanimously ruled that LG Electronic could not assert a patent against Intel (the manufacturer that implemented a memory-technology patent owned by LG Electronics) and on the computer makers that install Intel chips in their computers (1). The patent power to collect royalties was effectively exhausted by its first license (with Intel).

11. Royalty stacking. For a complex process, it may be possible to assert different patents on various steps in a process. For example, a medical test may involve processing cells using a patented technology, using a one or more patented reagents, performing a patented analytic process, using a patented machine, and evaluated using patented software. After all the royalties are stacked, the costs are transferred to the patient or to a third party payer (2).

12. Reaching through a patent. Savvy patent holders may issue licenses that contain an insidious "reach-through" clause. The clause may stipulate that license holders can use the patent under the condition that any future technologies, that the license holder develops with the licensed technology, will be assessed a royalty. The clause allows the patent holder to reach through into the intellectual property created by the license holder, and impose an additional royalty.

Of course, nobody is obligated to patent his discoveries. On November 8, 1895 Wilhelm Roentgen performed the experiment that marked the discovery of X-ray imaging. Six years later, in 1901, Roentgen's effort was awarded with the Nobel prize. Roentgen declined to seek patents or proprietary claims on his discovery and even declined, unsuccessfully, the eponymous appellative, "Roentgen ray." Such altruistic behavior is uncommon.

The government awards patents, but when someone infringes on your patent, the government takes no action. Only the patent holder is harmed, and only the patent holder can litigate against the infringing party. For this reason, a patent is sometimes referred to as the right to sue. Paradoxically, the typical patent holder is terribly frightened of lawsuits and will do almost anything to avoid a court appearance. Why? This will be answered in tomorrow's blog.

-- TO BE CONTINUED --

[1] U.S. Supreme Court ruling sets limits on patent royalties. The New York Times June 9, 2008.

[2] Jones KJ, Whitham ME, Handler PS. Problems with royalty rates, royalty stacking, and royalty packing issues. In: Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices, eds. A Krattiger, RT Mahoney, L Nelsen, et al. MIHR, Oxford, U.K., pp. 1121-1126, 2007.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

INTELLECTUAL PROPERTY 4

This is the fourth in a multi-part blog on the topic of INTELLECTUAL PROPERTY in the sciences.

In yesterday's blog, we were discussing uses of the patent system that had dubious societal value. We covered:

1. Patenting to suppress innovation.
2. Patent farming.
3. Patent spreading.
4. Patent holding.
5. Patent shifting.
6. Remixing prior patents.

TO CONTINUE:

7. Patenting the uses of unpatented inventions. The wheel is an unpatented invention. If you were to come up with a novel, useful, and nob-obvious application of the wheel, you might be able to patent your work. This means that when you use an invention that is not covered by a patent, your use of the invention may still constitute a patent infringement. Here is an example. DICOM (Digital Imaging and Communications in Medicine) is a freely available, unpatented standard for radiologic images. Currently, there is an effort to have all medical specialties adopt DICOM as the exclusive format for all medical images. Nonetheless, there there are specific circumstances for which the DICOM standard cannot be used without infringing on patented intellectual property. U.S. Patent 6725231, issued Apr 20, 2004, to Jingkun Hu and Kwok Pun Lee and assigned to Koninklijke Philips Electronics N.V., has the following claim.

"1. A method for mapping a DICOM specification into an XML document, comprising: mapping each entry of a DICOM table of the DICOM specification into a corresponding XML element of a plurality of XML elements,outputting each XML element of the plurality of XML elements to the XML document, in an output format that conforms to at least one of: an XML document-type-definition and an XML Schema."

In addition, the patent owners have been granted a similar patent by the European Patent Office (EPO). Mapping image information from a free specification, such as DICOM, into another free specification, such as XML, is a common task for medical informaticians. Does this activity constitute an infringement on an existing "use" patent? These are the types of questions that keep patent lawyers busy.

8. Patenting the obvious and the previous. Take the time to visit the USPTO website. You might find that many patents in your field are trivial, obvious, derivative, or useless. True "Eureka" moments are rare. Those who file patents are often motivated by fear ("If I don't patent this, somebody else will, and I can't bear to think that I may be required to pay royalties for my own invention), opportunism ("Hmmm. I can't believe nobody has patented this! I'd better do it before someone else does"), security ("My boss will not give me that raise unless I produce another patent this year"), or greed ("I'll squeeze every penny out of my competitors"). To receive a patent, an invention should be novel, non-obvious, and useful, but the reviewers at the patent office cannot always reach a wise determination.

Software developers are among the angriest critics of the USPTO. In recent years, the USPTO has awarded many software patents, a practice that seems to counter the principle that "ideas" are not patentable. Software developers argue that all software is built from recycled algorithms whose original sources are lost to techno-history. You cannot create a software application without using bits of code that were developed by legions of software developers, over the past half century. Today, software developers live in fear that a line of their code or a brief algorithm included in a complex software application will infringe on one or more software patents. The ever-present risk of patent infringement is a nightmare for earnest software developers, and a dream-come-true for opportunists. If you can patent an algorithm or subroutine that every developer uses, you stand to make a fortune.

9. Patenting life. What must it feel like to own an entire species of living organism? It must be how God would feel, if God had the the Supreme Court on his side. In a 1980 5-4 ruling, the Supreme Court upheld that a living organism could be patented. The case was Diamond v. Chakrabarty and involved a dispute over a patent for a genetically modified bacterium (3), (4).

After a patent on life is awarded, the consequences can be far-reaching. For example, Monsanto developed and patented genetically engineered corn that is resistant to Monsanto's own Roundup weed killer. Using Monsanto's corn seed, robust corn grows in fields that are liberally treated with Roundup. This guarantees that farmers who buy Roundup-resistant corn will also buy Roundup, at Monsanto's price. When farmers buy Roundup-resistant corn, they agree not to collect seed (from their corn crops) for replanting. Each growing season, they must buy new seed from Monsanto, at Monsanto's price (5). The use of genetically engineered seed is rapidly spreading. As more and more farmers use Monsanto's seed, the risk increases that genetically engineered seed will drift (from the winds, or from passing seed transport trucks) onto the fields of farmers who chose not to use genetically engineered corn. After genetically engineered corn invades a field, Monsanto can assert its seed patent on the clueless farmer. As we come to rely on a small genetic pool of crop seeds, the risk increases that a newly emerging disease will decimate the world's food supply.

The Diamond v. Chakrabarty ruling extends "life" patents to genes and sequences of DNA. Jensen and Murray reported in 2005 that 4,382 of 23,688 human genes in National Center for Biotechnology Information had been patented (6). The two most highly patented genes were BMP7, an osteogenic factor, and CDKN2A, a tumor suppressor gene (6). These two genes are claimed in more than 20 patents.

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[1] Crichton M. Patenting life. The New York Times February 13, 2007.

[2] Thirty-five U.S.C. 287 Limitation on damages and other remedies; marking and notice. http://www.uspto.gov/web/offices/pac/mpep/documents/appxl_35_U_S_C_287.htm Comment. This important patent provisions provides a level of protection to healthcare practitioners from patent infringement claims. It permits healthcare practitioners to perform customary medical activities (e.g. surgical procedures), even when a patent claim may apply to the procedure.

[3] Poste G. The case for genomic patenting. Nature 378:534-536, 1995.

[4] Eisenberg RS. Biotech patents: looking backward while moving forward. Nature Biotechnology 24:317-319, 2006.

[5] Barlett DL, Steele JB. Monsanto's Harvest of Fear. Vanity Fair, May, 2008.

[6] Jensen K, Murray F. Intellectual property. Enhanced: intellectual property landscape of the human genome. Science 310:239-240, 2005.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

INTELLECTUAL PROPERTY 3

This is the third in a multi-part blog on the topic of INTELLECTUAL PROPERTY in the sciences.

In the U.S., the first patents were issued in 1790; three in total. By 1800, there were 41 patents issued. In 1900, there were 26,414 patents issued. In the year 2000, there were 159,255 patents issued, of which 157,494 were inventions, 17,413 were designs, and 548 were plants (1). The reason that the rate of patent issuance has increased through the centuries has less to do with the heady pace of scientific progress and more to do with the profitability of holding intellectual property.

The original purpose of the patent system was to grant the inventor the exclusive right to make, use, or sell, or license his invention. Over the years, the uses of patents have expanded to include practices of dubious societal value, including the following:

1. Patenting to suppress innovation. If you were in the oil business, and an inventor developed a source of free, unlimited energy (e.g., solar power), you might be inclined to buy the patent for his solar energy invention for the sole purpose of halting its implementation. Likewise, if you held a patent on a gene or a drug, you could assert your patent to squelch research or medical testing on your property, for the duration of the patent (2).

In the case of healthcare, there are some limits on the use of patents to suppress a scientific discovery. In 1999, Congress passed 35 U.S.C. 287 specifying conditions that would limit the damages collected by patent holders from healthcare practitioners (3). If you held the patent on a new way of tying a knot, and if a surgeon required the knot to tie a ligature in a surgical procedure, the patent would probably not be enforceable on the surgeon, under 35 U.S.C. 287. For the moment, patent holders cannot stop physicians from saving lives.

2. Patent farming. If you hold a patent for an algorithm or a manufacturing process that could be used in other technologies, you might benefit by "seeding" your invention into the derivative technology. When the new technology is released, you can "farm" your patent by announcing that anyone using the new technology will need to pay you royalties. For example, if a committee is creating a new software standard, you might strive to become a member of the committee. If you can insert your algorithm or subroutine into the new standard, then your patent rights will extend to the final standard. If the standard is mandatory, you can expect to collect royalties from thousands or millions of unwilling users.

3. Patent spreading. Every patent contains a set of claims that specify the intellectual components that are protected by the patent. For example, a patent for a software application may claim each of the algorithms or subroutines that are featured in the application, the graphic user interface by which the application is accessed, and novel features included in the application. A cynical inventor will maximize his list of claims, dividing the patent into minimal patentable units. After the patent is awarded, the patent holder can spread his litigation over the many claims in his patent portfolio, effectively magnifying his intellectual property.

4. Patent holding. A shrewd capitalist can buy patents that cover fundamental processes that are necessary for a particular field. Whereas a single patent may be vulnerable to challenge, a collection of patents that insinuate their claims throughout a complex industry, might be impossible to fight. Patent holding companies (called patent trollers by their detractors) strategically collect patents on devices and processes that are vital to an industry. When the time is ripe, after a new technology has become an indispensable component of business, the patent holding companies can assert their portfolio.

5. Patent shifting. Sometimes, a patent holder may find himself in a position where it would be unwise to assert his patent. Large corporations and patent holding companies occasionally reach agreements with their competitors to hold each other harmless from patent infringements. These kinds of agreements can save companies a vast amount of time and expense. In such cases, a corporation may choose to sell various patents to a third party (an individual, a corporation, or a holding company). The third party, unrestricted by a non-litigation agreement (depending on the agreement's specific language), can prosecute the patent. This works best if the patent is not owned directly by the company that sells the patent.

For example, if a corporation sits on a committee that is developing a new industry standard, it may need to sign an agreement promising not to prosecute patents held by the corporation and implemented by the standard. This kind of agreement is developed by standards committees to discourage patent farming. The company can simply sell the patent to a holding company. Sometime in the future, when the standard becomes entrenched in an industry, the holding company would assert the patent against all of the patent users. The corporation that developed the patent would have made its profit up front, at the time of the patent's sale to the holding company.

6. Remixing prior patents. You can re-mix prior art to make a new device that you can patent for yourself. This provision in patent law is particularly useful for software corporations; virtually all new software is made by re-mixing old software. You must be careful, though, to produce a re-mixed product that is not obvious to your peers. In KSR v. Teleflex (April 30, 2007), the U.S. Supreme Court, in a unanimous opinion, reversed a Court of Appeals decision, and determined that a prior patent was unenforceable because it was obvious (4). The Supreme Court opinion discussed, at length, the principles of obviousness. In particular, the Supreme Court indicated that merely putting together prior art to make a new device can only qualify for a patent if the resulting device is unexpected by people working in the field; hence, not obvious.

-- TO BE CONTINUED --

[1] U.S. Patent Activity Calendar Years 1790 to the Present. U.S. Patent and Trademark Office. April 16, 2009.

[2] Crichton M. Patenting life. The New York Times February 13, 2007.

[3] Thirty-five U.S.C. 287 Limitation on damages and other remedies; marking and notice. http://www.uspto.gov/web/offices/pac/mpep/documents/appxl_35_U_S_C_287.htm

[4] KSR International Co. v. Teleflex Inc. et al. Supreme Court of the United States April 30, 2007.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

INTELLECTUAL PROPERTY 2

This is the second in a multi-part blog on the topic of INTELLECTUAL PROPERTY in the sciences.

"What is mine is mine. What is yours is negotiable."

- Nikita Khruschev, who is credited with using it to describe the American approach to arms control negotiations with the former U.S.S.R.

Though depriving society of a medical advance is not a crime, few holders of intellectual property resort to secrecy nowadays; they use patents, copyrights, and courtrooms to protect their interests. The modern patent is a property right (lasting 20 years) given by a government to an inventor of a method, or invention, or a novel item. Patent means "open," so named because the patent process opens the invention to scrutiny. The U.S. Patent and Trademark Office (USPTO) publishes detailed descriptions of every awarded patent, and equivalent patent archives are available in other countries. The right to patent is sometimes referred to as the right to sue patent infringers. The idea is that patents are made public. Users of patented inventions must pay the patent holder a royalty. In return for a royalty, the patent holder refrains from taking legal action against the user.

When a patent or a copyright has expired, the work falls into the public domain and can be used freely. Many patent holders have been ruined by poor timing. Patent holders need to recoup their investment and earn all their profits within a twenty year window. When a patented invention requires twenty years or more to develop a market, the patent holder cannot profit from his work, unless he sells or licenses his patent during the patent's life. Likewise, patent holders may not profit if the practical implementation of their invention requires a second technological advance, that comes twenty years later.

A fine example of a patent issued before its time is the Lamarr/Antheil patent for Frequency Hopping Spread Spectrum (U.S. patent 2,292,387, 1942), issued to Hedy Lamarr and George Antheil. Circa WWII, Hedy Lamarr was a glamorous actress, and George Antheil was a Hollywood music composer. The two came up with and idea for secretly passing messages by jumping a signal from frequency to frequency, giving it the appearance of noise to enemy interceptors. When the sender and the receiver change frequencies simultaneously, the message can be retrieved. Their patent preceded the technology required to implement the idea. Today, decades after the patent expired, spread spectrum radio uses the Lamarr/Antheil technique. In a symbolic gesture, Wi-LAN, a telecommunications firm, purchased the original patent as an historical document, for an undisclosed amount. This was the only income that Hedy Lamarr and George Antheil received from their patent.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

INTELLECTUAL PROPERTY 1

This is the first in a multi-part blog on the topic of INTELLECTUAL PROPERTY in the sciences.

"Don't worry about people stealing your ideas. If your ideas are any good, you'll have to ram them down people's throats."

- Howard Aiken (American computer engineer and mathematician 1900-1973)

Intellectual property is the "dark matter" of the scientific world. We know that there's a lot of it, that it's everywhere, and that it has a strong effect on our lives, but it's all quite invisible to our senses.

When we think of intellectual property, we usually think in terms of patents (for inventions and processes) and copyright (for literature). Patents are rights assigned to an inventor, for a specified interval, in exchange for disclosing his invention to the public. Patents probably came to us, like most great ideas, from the acient Greeks. In 500 B.C.E., the Greek colony Sybarus (in Southern Italy), gave inventors the exclusive rights to profit from their invention for a period of one year. The length of a patent grew over the centuries. In 1449 King Henry VI granted a 20-year patent to John Utynam, who brought colored glass-works to England. The holder of a patent collects royalties from those who use the patent. The term royalties carries the idea that money that would ordinarily go to the king is assigned to the patent holder.

The idea of copyright seems to descend from the settlement of sixth century Irish dispute over the copies of a book of psalms. King Diarmait reasoned, "To every cow belongs her calf, therefore to every book belongs its copy." Basically, copyright guarantees that a book's creator owns the copies. In the United Kingdom, modern copyright was enacted by the Statute of Anne (Copyright Act of 1709). Every nation extends copyright protection to authors. Today, copyright protection extends to the form and content of the text and images and does not apply to particular ideas that might be expressed in the copyrighted work. Copyright protection lasts much longer than patent protection. In the U.S., Copyright persists 70 years after the death of author, unless the author is a corporation, in which case, copyright extends 95 years from publication or 120 years from creation, whichever expires first. As in the case of patents, royalties are paid to the copyright holder, in lieu of the king.

Scientists have used and abused intellectual property protection. A legal and popular method of bypassing the patent system is through "trade secret." If nobody knew your secret, your exclusive use of the property could be leveraged to your financial advantage. Nobody understood the concept of trade secret better than the surgeon William Chamberlen. Circa 1570 Chamberlen invented or acquired the design of an improved delivery forceps (tongs with large curved grasping handles that can be pressed together with a scissors action). The forceps was highly profitable to William and to his heirs. His son Peter became the attending physician to Queen Anne, the wife of James I and to Queen Henrietta Maria, wife of Charles I. The forceps kept the Chamberlen family in riches for over a century. A descendant fell upon hard times and sold the secret of the forceps in 1720 to Dutch surgeons. The forceps monopoly was broken when several of the new owners published the secret. A largely apathetic world paid little notice until the highly influential William Smellie published his description of the improved model of the forceps, in 1750. Because an intellectual property was kept secret, the world was deprived of a life-saving medical advancement for approximately 180 years (1).

[1] Strathern P. A brief history of medicine from Hippocrates to gene therapy. Carroll and Graf Publishers, New York, pp 169-171, 2005.

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© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

ARCHIVE FOR JULES BERMAN'S BLOG

This blog, Specified Life, deals with the general topic of data specification (including data organization, data description, data retrieval and data sharing) in the life sciences and in medicine. Beyond data sharing issues, it covers a range of topics that might be of interest to biomedical researchers.

All of the blog entries have been collected and organized into a convenient web-linked archive.

- Jules J. Berman

REJECTION 11

This is the last blog in this series on REJECTION in the sciences. I'd like to thank Trish Parnell, Hua, and several anonymous visitors who, over the past several weeks, left encouraging comments on the Specified Life blog site. If you've read through this 11-part series on rejection, your comments would be greatly appreciated.

To summarize the first ten blogs, scientists live in a pervasive culture of rejection. Recent and past history provides ample proof that good science is not exempted from the withering effects of rejection. It would also appear that scientific advancement is stagnating, despite access to unprecedented funding largesse and a huge workforce of highly trained scientists.

There are many factors that contribute to the slowdown in scientific progress. I've heard claims that we've already made most of the scientific discoveries that will ever be made; that there's not much left to do. I've also heard that we've shifted into a new era of collective intelligence (e.g., twitter, facebook, social networking via texting) that transcends outmoded notions of scientific advancement.

Nonetheless, I can't get past the notion that unrelenting, spirit-crushing rejections take their toll on our societal effort to advance science. Rejections follow a scientist throughout his/her career: disappointing SAT scores, rejections to college of choice, disappointing grades, rejections to graduate schools, scornful treatment in graduate school, cold reception of research ideas, rejection of manuscripts, lack of any peer response to published manuscripts (i.e., research papers that nobody bothers to read), grant rejections, tenure rejections, and so on.

Many scientists cope by taking the path of least rejection throughout their careers: non-innovative grant applications (grant reviewers tend to approve applications that they can easily grasp, for work that can be easily accomplished ), never challenging existing paradigms (i.e., the paradigms championed by grant reviewers), big-budget research programs (favored by tenure committees), narrow, incremental advances (less likely to be rejected by reviewers), delegating lab work and paper authorship to post-docs (let somebody else get rejected), demise of the single author research paper (dozens of co-authors decrease rejection rate).

Maybe we should re-evaluate the way that scientists treat one another. Maybe there is a workable alternative to the rejection-based culture that permeates scientific life.

© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

REJECTION 10

This is the tenth in a multi-part blog on the topic of REJECTION in the sciences.

Among the many shortcomings of modern science, cancer research heads the list. Scientists tell us that they are making great advances in the treatment of cancer. Anyone can see that this is not so. The total U.S. age-adjusted cancer death rate today is about where it was 60 years ago (1). Though deaths from some types of cancer have dropped, these drops have been offset by the rise in other cancers. Of the cancers that have dropped the most: stomach cancer, cancer of the uterine cervix, and (most recently) lung cancer in men, improved mortality is due to a drop in cancer incidence, not due to any progress in treating advanced cancers. The reduced incidence of stomach cancer is generally credited to refrigeration and improved methods of food preservation. The drop in cervical cancer has been due to effective Pap smear screening for precancerous lesions (small lesions that precede the development of invasive cancer). When uterine precancers are excised, the cancer never develops. Further reduction in deaths from uterine cancer will probably result from population-wide inoculations with the new HPV vaccine; an effective measure that bypasses the need to treat advanced cancers. With the exception of curing a few types of rare tumors, cancer research has yielded none of the dramatic advances seen in the 1950s, with diseases such as polio and tuberculosis.

Cancer death rates that have increased since 1950 include: esophageal cancer, liver cancer, pancreatic cancer, lung cancer, melanoma, kidney cancer, brain cancer, non-Hodgkins lymphoma, and multiple myeloma. The list includes some of the most common types of cancer. If cancer research were effective, we would expect to have ways of preventing the rise in incidence of these common cancers.

Over the decades, clever cancer researchers have discovered a successful strategy for attracting millions and millions of dollars of research funding for diseases that they cannot cure. Each year, they point to the number of people who will die from cancer, and they say, that cancer is a terrible disease, causing untold suffering, and killing hundreds of thousands of Americans each year. Certainly, they argue, research to cure this dreadful disease must be fully funded. They fail to mention that the reason that hundreds of thousands of people die each year from cancer is that prior funding efforts failed to deliver a cure. Every year, the bulk of cancer funding is awarded to the very same institutions and laboratories that failed to produce a reduction in the cancer death rate.

If you speak to any cancer researcher, he will tell you that we have made great advances in understanding cancer genetics: the mutations in DNA that contribute to the development of cancers. What they do not say is that all of the advances in our understanding of cancer genetics come in the form of bad news. We now know, after billions of dollars of funding, that cancer cells are remarkably complex, often containing thousands of genetic alterations. No two genetically complex cancers are characterized by the same set of mutations, and no two tissue samples from any one cancer will be genetically identical. The complexity of cancer far outstrips our ability to characterize the alterations in a cancer cell. Consequently, it is highly unlikely that any single drug will correct all of the genetic changes in the cells of advanced cancers. Breakthroughs in cancer genetics have taught us that it will be difficult to develop a cure for the advanced common cancers, any time soon. You won't hear this from funded cancer researchers; nobody wants to kill the goose that lays the golden egg.

[1] Fifty-six Year trends in U.S. cancer death rates. SEER Cancer Statistics Review 1975-2005 National Cancer Institute. http://seer.cancer.gov/csr/1975_2005/results_merged/topic_historical_mort_trends.pdf, viewed October 12, 2009.

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© 2010 Jules Berman

key words: history of science , specified life blog , Jules J Berman PhD, MD

REJECTION 9

This is the ninth in a multi-part blog on the topic of REJECTION in the sciences.

If the rate of scientific accomplishment is dependent upon the number of scientists on the job, you would expect that that rate of scientific accomplishment would be accelerating, not decelerating. According to the National Science Foundation, 18,052 science and engineering doctoral degrees were awarded in the U.S., in 1970. By 1997, that number had risen to 26,847, nearly a 50% increase in the annual production of the highest level scientists (1). The growing work force of scientists failed to advance science very much, but it was not for lack of funds. In 1953, according to the National Science Foundation, the total U.S. expenditures on research and development was $5.16 billion, expressed in current dollar values. In 1998, that number has risen to $227.173 billion, greater than a 40-fold increase in research and development spending (1).

Unproductive scientists always promise a breakthrough just around the corner. What else would you expect them to say? Humans live in hope, but funding agencies are expected to calculate the future based on measurements of past performance. The U.S. Department of Health and Human Services has published a sobering document, entitled, "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products. (2) " The authors note that fewer and fewer new medicines and medical devices are reaching the Food and Drug Administration. Significant advances in genomics, proteomics and nanotechnology have not led to significant advances in the treatment of diseases. Extrapolating from the level of scientific progress in the past half century, there's not much reason to expect great improvements in the next 50 years. The last quarter of the 20th century has been described as the "era of Brownian motion in health care" (3).

Meanwhile, science has become irrelevant for many people (4). A growing number of Americans (perhaps the majority), do not believe in global warming, do not believe in evolution, and do not believe that vaccines are safe and effective. A large number of people, without much evidence to support their fears, believe that vaccines cause autism, that water fluoridation is harmful, and that AIDS was invented by government scientists as a genocidal agent to be used against black populations. These days, scientists are met with suspicion, if not outright hostility, by a large percentage of the world.

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[1] National Science Board, Science & Engineering Indicators - 2000. Arlington, VA: National Science Foundation, 2000 (NSB-00-1).

[2] Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products. U.S. Department of Health and Human Services, Food and Drug Administration, 2004. http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html

[3] Crossing the Quality Chasm: A New Health System for the 21st Century. Quality of Health Care in America Committee, editors. Institute of Medicine, Washington, DC., 2001.

[4] Furedi F. Downsizing the Status of Science. The Scientist volume 18, Issue 21, Number 10, Nov. 8, 2004.

© 2010 Jules Berman

key words:informatics, Jules J Berman PhD, MD

REJECTION 8

This is the eigth in a series of blogs on the topic of REJECTION

When you watch a movie circa 1960, and you look at their streets and houses, and furniture, and clothing, do you see any differences between then and now? Not many. Basically, the scientific advances that shaped the world today were discovered prior to 1960. The only visible difference between people then and people now is personal appearance. The 1969 man in the street was trimmer, and better groomed.

What did we have in 1960? We had home television (1947), transistors (1948), commercial jets (1949), computers (Univac, 1951), nuclear bombs (fission , fusion in 1952), solar cells (1954), fission reactors (1954), satellites orbiting the earth (Sputnik I, 1957), integrated circuits (1958), photocopying (1958), probes on the moon (Lunik II, 1959), practical business computers (1959), lasers (1960).

These engineering and scientific advancements pale in comparison to the advances in medicine that occurred by 1960. We had the basic principles of metabolism, including the chemistry and functions of vitamins; the activity of the hormone system (including the use of insulin to treat diabetes and dietary methods to prevent goiter), the methodology to develop antibiotics and to use them effectively to treat syphilis, gonorrhea, and the most common bacterial diseases. We had effective vaccines that protected us from deadly viruses, such as smallpox, that had killed millions of people throughout human history. Sterile surgical technique was practiced, bringing a precipitous drop in maternal post-partum deaths. We could provide safe blood transfusions, using A,B,O compatibility testing (1900). X-ray imaging had improve medical diagnosis. Disease prevention was a practical field of medical science, bringing methods to prevent a wide range of common diseases using a clean water supply and improved waste management; and safe methods to preserve food, such as canning, refrigeration, and freezing. In 1941, Papanicolaou introduced the smear technique to screen for precancerous cervical lesions, resulting in a 70% drop in the death rate from uterine cervical cancer in populations that implemented screening. By 1947, we had overwhelming epidemiologic evidence that cigarettes caused lung cancer.

When we entered 1950, Linus Pauling had essentially invented the field of molecular genetics by demonstrating a single amino acid mutation accounting for the the defective gene responsible for sickle cell anemia. In 1950 Chargoff discovered base complementarity in DNA. Also, in 1950, Arthur Vineburg routed an internal mammary artery, in place, to vascularize the heart. In 1951, fluoridation was introduced, greatly reducing dental disease. Then came isoniazid, the drug that virtually erased tuberculosis (1952). Also, in 1952, Harold Hopkins designed the fibroscope, heralding fiberoptic endoscopy. In 1953, Watson and Crick showed that DNA was composed of a double helix chain of complementary nucleotides encoding human genes. John Gibbon performed the first open heart surgery using a cardiopulmonary bypass machine (1953), and D.W. Gordon Murray used arterial grafts to replace the left anterior descending coronary artery (the coronary artery bypass graft). Oral contraceptives (birth control pills) were invented in 1954. That same year, Salk developed an effective killed vaccine for polio, followed just three years later with Sabin's live polio vaccine. Thus, in the 1950s, the two most dreadful scourges of developed countries, tuberculosis and polio, were virtually eradicated.

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© 2010 Jules Berman

key words: history of science, history of medicine, Jules J Berman PhD, MD

REJECTION 7

This is the seventh in a series of blogs on the topic of REJECTION

"Intellectuals can tell themselves anything, sell themselves any bill of goods, which is why they were so often patsies for the ruling classes in nineteenth-century France and England, or twentieth-century Russia and America." - Lillian Hellman

It is often easier to believe a bad idea than a good idea. Bad ideas can be carefully designed to provide people with something they want to believe, unconstrained by reality.

Canals on Mars - Well into the twentieth century, scientists believed that there were canals on the planet Mars. Optical lines criss-crossing Mars were first observed by the Italian astronomer Giovanni Virginio Schiaparelli (1835–1910), in 1877. The observations stirred the public's imagination. Here was irrefutable evidence that a riparian civilization thrived on an alien-created canal system. We now know that the canals are an optical illusion, and do not represent any physical structure, water-filled or otherwise.

Status thymicolymphaticus - In the late nineteenth and early early twentieth centuries, doctors attributed childhood asthma and crib death (now known as sudden infant death syndrome) to enlarged thymus glands; they named the condition status thymicolymphaticus. In the 1920s, doctors radiated enlarged thymus gland of children as a preventive measure against crib death. It is estimated that about 20,000 - 30,000 people died from cancers produced by "therapeutic" radiation for this and other real or imagined disorders (1). We now know that status thymicolymphaticus is not a disease. Some children are born with larger thymus glands than other children, but no disease syndrome results from this anatomic disparity.

Stomach cancer produced by a worm - The 1926 Nobel prize for medicine went to Johannes A.G. Fibiger, who discovered a cause of cancer that that was eventually shown to be an artifact. According to Fibiger, a larval parasite caused stomach cancer in rats. Years later, scientists concluded that the tumors must have been caused by some other factors. Humiliated by their mistake, the Nobel Assembly waited four decades before they awarded the prize to another cancer researcher.

Frontal lobotomies - The frontal lobotomy was invented by Dr. Antonio de Egas Moniz in 1935 and popularized by Dr. Walter Freeman. For the procedure, Dr. Freeman applied a some local anesthetic, then inserted a gold-plated ice-pick just above the eyeball, and shoved it into the brain. The Doctor gingerly scraped the ice-pick through the frontal lobe, the presumed site of unrestrained emotions. Apathy and mental impairment often followed the procedure, and this was considered an improvement in most cases. Dr Freeman performed over 3,500 procedures; his disciples, performed about 40,000 more. The procedure has since been largely discredited, but not before Dr. Moniz received the 1945 Nobel prize in medicine for the dubious gift of frontal lobotomy.

Polywater - In the 1960s, soviet researcher Nikolai Fedyakin introduced polywater to the world; a polymerized form of water with a higher boiling point, lower freezing point, and higher viscosity than ordinary water. Other workers seemed able to repeat and extend Fedyakin's early observations. After many years of wasted effort, the scientific community finally conceded that polywater experiments were unrepeatable and that polywater does not exist.

Phrenology - Phrenology is the pseudoscience that predicts personality by inspecting the surface features of a person's skull. Phrenology was invented by the German physician, Franz Joseph Gall, in 1796, but was practiced well into the twentieth century. Nineteenth and twentieth century discoveries in brain science helped to establish a theoretical basis for phrenology by assigning specific cognitive functions to specific anatomic locations of the brain. Modern phrenologists reasoned that personality, the aggregate expression of many different brain functions, could be predicted by measuring protrusions of the skull overlying brain regions enlarged by high levels of activity or depressed by hypofunctioning regions. It was a nice idea, but completely wrong.

Cold fusion - Stars are fueled by fusion. For decades, physicists have been trying to develop a controlled fusion reactor that would provide unlimited energy, from hydrogen; without much success. In 1989 Martin Fleischmann and Stanley Pons held a press conference to announce that they had produced fusion in a tabletop experiment involving electrolysis of heavy water and a palladium electrode. Fleischmann and Pons did not fully specify the theoretical basis for their success, but physicists throughout the world were only too happy to oblige. Several laboratories reported that the observations of Fleischmann and Pons were repeatable! Meetings, seminars, and workshops were hastily assembled and attended by the top minds in physics. Lectures were delivered explaining how cold fusion worked. As time went by, despite early declarations of success, other laboratories could not achieve cold fusion. The theoretical works explaining cold fusion have been discredited. The long, frustrating quest for free, unlimited fusion energy continues.

The lesson is clear, scientists, like non-scientists, accept what they want to believe; and reject what they want don't want to believe.

[1] Jacobs MT, Frush DP, Donnelly LF. The right place at the wrong time: historical perspective of the relation of the thymus gland and pediatric radiology. Radiology 210:11-1, 1999.

© 2010 Jules Berman

key words: medical history, science history, Jules J Berman PhD, MD

REJECTION 6

This is the sixth in a series of blogs on the topic of REJECTION

Sudden Infant Death Syndrome (SIDS) is a disease feared by every infant's parent. Typically, the baby is left to sleep. When the parents check the baby, they find that it is dead. Moments of temporary sleep apnea are common in babies and adults. In SIDS, it is as though the process of breathing simply stops, and does not resume. Autopsies on SIDS patients have never shown any consistent conditions in organs that may have caused death. Many bright medical researchers have devoted their careers to SIDS. The obvious suspects (respiratory controls in the brain and lungs) were examined intensely, in hundreds of studies, extending over decades, with little to show for the effort. These expensive but fruitless research efforts were conducted in a time when an effective method to prevent SIDS was known (and ignored).

Simple observations of the circumstances made at the death scene were shown to have enormous import. As early as the 1940s, the observation was made that many victims of SIDS were found in the prone position on pliant bedding, often in soft layers of bedclothes (1). Similar observations were made again and again, and by the 1970s, people began to wonder whether babies could breathe adequately under these conditions (2). New Zealanders are credited with showing the drop in infant mortality when achieved with a supine sleep position on a firm mattress. Numerous population studies have confirmed these observations. Currently, the "back-to-sleep" campaign is a worldwide effort whose goal is to spread awareness of a new breakthrough in SIDS prevention, discovered more than six decades ago.

Scientists will reject observations that challenge their belief systems. No story better exemplifies this than the tale of seventeen centuries of night-blindness experienced by European astronomers. Hipparchus was an early Greek astronomer who correctly calculated the distance from the earth to the moon (250,000 miles) 150 B.C. Some years later, in 134 B.C. Hipparchus looked in the sky and saw a new star. He was certain that the star was new because he had just finished mapping the known heavens when the new star appeared. The next European to see a new star in the sky was Tycho Brahe, in 1572. The curious thing about this dark interim is that nova occur frequently. Several dozen nova, visible from earth with the naked eye, occur each year (3). Moreover, in the year 1054, the Crab Supernova was recorded by Chinese, Japanese, Persian/Arab and Indian astronomers. The Europeans, who were literally in the dark ages, missed the event.

The reason that no nova were observed in seventeen centuries is very simple. The Europeans believed in the fixed heavens. If you believe that the heavens are the same now as they were when the universe was created, and will stay the same until the universe ends, then you will not see new stars twinkling in the night sky.

For many, the purpose of science is to confirm a set of preconceptions. When something new comes along that contradicts a previously held belief, it is ignored or rejected.

[1] Abramson H. Accidental mechanical suffocation in infants. J Pediatr 25:404-413, 1944.

[2] Vennemann MM, Fischer D, Jorch G, Bajanowski T. Prevention of sudden infant death syndrome (SIDS) due to an active health monitoring system 20 years prior to the public "back-to-sleep-campaigns." Arch Dis Child. Jan 6, 2006.

[3] Baade W. Zwicky F. On Super-Novae. PNAS (U.S. Proceedings of the National Academy of Sciences) 20:254-259, 1934.

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© 2010 Jules Berman

key words: medical history, Jules J Berman PhD, MD

REJECTION 5

This is the fifth in a series of blogs on the topic of REJECTION

Reality is the thing that can kill you whether you believe in it or not. For centuries, navies refused to believe that citrus can cure scurvy (Vitamin C deficiency disease). Most animals can synthesize ascorbic acid (Vitamin C), and do not require a dietary source. Humans and guinea must acquire the vitamin in their diets, or they will die. Without Vitamin C, the body cannot properly synthesize collagen, the fibrous protein that braces connective tissues in animals. The first known large epidemic of Vitamin C deficiency occurred in 1497, when Vasco da Gama sailed from Lisbon to Calcutta. About three-fifths of his crew died. Prior to the age of European sea explorations, voyages were shorter, or they involved foraging for food along the way. The Europeans set larder on their ocean-going ships with provisions for the full journey. Unfortunately, their stored foods lacked sufficient Vitamin C, resulting in death by scurvy, a particularly nasty condition marked by a general collapse of the body's structural integrity, often ending with stroke due to vascular hemorrhage.

In 1593, Sir Richard Hawkins showed that scurvy could be prevented and cured by eating oranges and lemons. If citrus fruits were not to a sailor's liking, a type of salad cress was shown, in 1597, to work just as well. It would seem that by 1597, one century after the medical disaster aboard Vasco da Gama's ship, scurvy was eliminated as a threat to naval adventurers.

Not so. Soon after the cure for scurvy was found, it was abandoned. Scurvy deaths re-emerged on ships. It was up to James Lind to re-discover, in 1747, that citrus prevented and cured scurvy. Lind's re-discovery was lost on some explorers. A century later, in 1848, the ships Erebus and Terror, while navigating through the Northwest Passage, became trapped in ice. Citrus was absent from their provisions. The crew died of scurvy.

Asepsis is another idea whose time has come and gone and come and gone. The basic theory of asepsis is simple; keep wounds clean, and avoid contaminating anyone with infected materials from other persons, and everyone stands to live a lot longer. The limitation of asepsis, as a medical procedure, are three-fold: 1) humans are dirty; 2)humans are lazy, and 3) nobody in human history has ever been paid to wash his hands.

Asepsis has been used for millenia. Hippocrates (460-377 BC) irrigated wounds with wine or boiled water. Galen (130 - 200 A.D.) knew enough to boil his surgical instruments. In 1266 A.D., Todorico Borgognoni taught aseptic wound treatment.

In 1847, Ignaz Phillipp Semmelweis was working at the Vienna General Hospital's maternity clinic, on a three year contract. Through much of human history, mothers commonly died of infections arising in the days immediately following childbirth. As many as forty percent of mothers contracted and died from puerperal fever, also known as childbed fever. The cause of these deaths would have been obvious to Hippocrates, Galen or Borgognoni. Doctors scurried between sick patients and healthy patients without washing their hands. Semmelweis saw the problem, and contrived an experiment; Doctors and medical students would wash their hands between patient examinations. The staff doctors were skeptical, but they agreed to humor Semmelweis, if only to prove him wrong. The death rate from puerperal fever dropped precipitously. Unfortunately for the women at Vienna General, staff doctors abandoned the hand washing ritual when Semmelweis's contract expired. Hand washing was an annoying diversion. All told, they preferred the filth and the high death toll to the incessant hygienic obligations. The patients supported the staff. They didn't like to see doctors washing their hands after touching them; it made them feel dirty.


Source: Garrison FH. History of medicine.
WB Saunders, Philadelphia, 1921.

Aseptic techniques, including hand washing, have a firm scientific footing. Today, nobody doubts the effectiveness of a clean environment for patients, but hand washing is still a lot of work. Doctors, even in the best hospitals, neglect washing their hands (1).

Aseptic technique is an example of a great idea that is discovered over and over again. The medical community pushes each new re-discovery of aseptic technique back into obscurity. Why? For physicians, not hand washing is the perfect crime. It can kill as easily as a bullet, but no doctor has ever been punished for having dirty hands. As Dr. Robert M. Wachter, an expert in patient safety has said, "I can lose my hospital privileges if I fail to sign a dictated discharge summary or operative note. But if I don't clean my hands for the next 10 years, nothing will happen to me" (2). When hand washing becomes a billable procedure, its scientific value will be re-discovered, again.

[1] Lipsett PA, Swoboda SM. Handwashing compliance depends on professional status. Surg Infect (Larchmt) 2(3):241-245, 2001. Comment. In this study, physicians washed their hands much less frequently than nurses. Surprise!

[2] Chen PW. Holding doctors accountable for medical errors. The New York Times December 17, 2009.

© 2010 Jules Berman

key words:informatics, Jules J Berman PhD, MD

REJECTION 4

This is the fourth in a series of blogs on the topic of REJECTION

Back in 1668, just as Redi was trying to convince his colleagues that living organisms cannot generate from nothing, Richard Lower was putting the finishing touches on his Tractatus De Corde: Item De Motu Et Colore Sanguinis. Lower demonstrated experimentally that venous blood pumped from the heart, into the lungs, is transformed (from venous dark red, to arterial bright red) by aeration and returned to the heart, where arterial blood is pumped to the peripheral circulation. This seems obvious today; barely worthy of explanation. We need to be reminded that for about 1500 years, all medical thought in Europe was dominated by one honored physician whose legacy of medical dogma was held sacred.

Galen (129 - 199 C.E.) was a Greek physician who lived in Rome, and Pergamum (Turkey), and retired early to live a life of scholarship. He wrote many books, including "On Prognosis," (177 C.E.), and produced a total of about 3 million bon mots before he died (1). For the subsequent 1500 years, his words were accepted on blind faith by virtually all European physicians. To reject Galen was a type of heresy, that almost always resulted in professional ostracism.

Galen, great as he was, labored under the somewhat limited scope of second century science. Some of his most far-reaching thoughts fell into the realm of superstition, not science. For example, Galen believed that blood was embued with natural spirts by the liver, and vital spirits by the heart. Furthermore, Galen believed that blood moved through the septum of the heart through invisible pores. The concept of a closed circulation was unknown to Galen.

Probably every child who rides an escalator must wonder where the steps go when they reach the top. Mysteriously, they slink under the floor, and drop off into a hidden chamber. Meanwhile, another mysterious process creates new steps that emerge from the floor of the elevator, and rise upwards. The idea of a continuous belt of stairs seldom catches the imagination of very young children, who prefer magical beliefs over mundane observations. Basically, medieval physicians accepted Galen's magic stairs version of blood circulation. Blood was constantly replaced by the liver at a rate that equaled its issuance through invisible pores in the heart. It was just fantastic.

Anatomists who gave any thought to Galen's theory of blood circulation knew that Galen could not be correct. Still, to doubt Galen was clearly unacceptable. In frustration, Henri de Mondeville, the author of Cyrurgia (1312), an early textbook of surgery, wrote, "God did not exhaust all His creative power in making Galen (1)." Andreas Vesalius (1514 - 1564) published "De Fabrica Humani Corporis," in 1543. This book provided a detailed description of human anatomy that corrected some of the misconceptions and superstitions left by Galen. Vesalius' closest friends turned against him. Others in his profession condemned, mocked, or ignored his work. Die-hard Galen fans insisted that any discrepancies between Galen's second century human anatomy, and Vesalius' sixteenth century observations were due to naturally occurring modifications in the human condition. Sylvius, Vesalius' teacher in Paris, grumbled, "Man had changed but not for the better (1)." Vesalius departed Venice, and died alone, impoverished, ridiculed by his colleagues, shipwrecked on the Island of Zante (Zakynthos) (1).

Ten years later, Servetus (1509 - 1553) published Restitutio Christianismi, in which he noted that the pulmonary vessels deliver blood to the heart, after the blood has mixed with air in the lungs. That same year, Servetus was burned at the stake (along with most of the copies of his book) by Calvin for a poorly written sentence that seemed heretical at the time.

By 1628, the world was ready to take a second look at some of Galen's opinions. In this year, William Harvey (1578 - 1657) published De Motu Cordis, describing the circulation of blood from heart to lungs and back, and from the heart to the periphery and back. This brings us finally to 1669, when Richard Lowers' publication synthesized our current understanding of peripheral and pulmonary circulations with intrapulmonary transformation of blood, through aeration.

The Italians credit Andrea Cesalpino (1524 - 1603), a professor of medicine at Pisa, with discovering the closed heart-lung circulation prior to Harvey. The point is moot. In 1242 C.E., the Arabic polymath Ibn an-Nafis (1213 - 1288) described the heart-lung role in circulation and aeration; four centuries before either Harvey or Cesalpino. At the time, nobody in Europe cared to listen. Again we learn that new ideas will be rejected if they contradict cherished beliefs.

As Galen dictated medieval medicine, so did Ptolemy dictate medieval science. Claudius Ptolemaeus (90 - 168), known in English as Ptolemy, was contemporary with Claudius Galenus (129 - 199), known in English as Galen. Like Galen, much of what he said was wise and true. Some of what he said was false. According to Ptolemy, the earth sits in the center of the universe, and the size of the universe has a radius equal to 20,000 times the radius of the earth. Wrong or right, European scientists held his opinions correct and inviolate for nearly fifteen centuries.

[1] Garrison FH. History of medicine. WB Saunders, Philadelphia, 1921.
© 2010 Jules Berman

key words:informatics, Jules J Berman PhD, MD

REJECTION 3

This is the third in a series of blogs on the topic of REJECTION

In 1668, the world was modernized, in many ways. We had the fundamentals of cryptography (Viete, 1589), Pi calculated to 20 decimal places (Ludolf, 1596), logarithms (Napier, 1624), Fermat's last theorem (1637), the fundamentals of probability (Pascal, 1654), and the ability to diagnose cancers by pathologic examination (Malpighi, 1659). Differential equations were understood (1662), and the last details of integral calculus were being written, independently, by Newton and Leibnitz. Despite all of these scientific advancements, the world believed that the life of very small organisms arose spontaneously, from thin air, or possibly from inanimate particles of dirt. Otherwise rational intellects were comfortable with magical thinking, and believed that life could be explained by postulating forces acting in a realm beyond human perception.

Francesco Redi, in 1668, designed an experiment to test whether maggots arose through spontaneous generation. He incubated meat in flasks; some covered to stop the entry of flies, and others left uncovered, permitting flies to enter. After a some time, he examined the meat in both sets of flasks. Only the meat from the open flasks contained maggots. Redi correctly concluded that maggots do not generate spontaneously from dead meat. We now know that maggots generate from tiny eggs laid by flies.

Redi's experiment had very little influence on the prevailing belief systems. Seventy-two years later, John Turberville Needham conducted his own meat-related test for spontaneous generation. He heated mutton broth in a closed container, and examined the contents a few days later. The container swarmed with micro-organisms, proving, to the satisfaction of many, that micro-organisms arise by spontaneous generation. In retrospect, we can assume that the broth was not heated sufficiently to kill all of the organisms initially present in the container, or that the container was not sufficiently closed to exclude the entry of micro-organisms. For some time, though, Needham's experiment successfully vanquished many doubts regarding the validity of spontaneous generation.

In 1768, a full century after Redi's experiments, Lazzaro Spallanzani repeated Needham's experiment, this time boiling the broth for forty-five minutes. No organisms grew in the closed container.

Spallanzani's experiment should have put the kibosh on spontaneous generation, but it did not. Ninety-two years passed before Pasteur revisited the issue. In 1860, scientists knew enough about the biology of life to infer that spontaneous generation was a needless and absurd theory. At that time, Virchow, a highly influential pathologist, argued that cells arise from other cells, through cell division. Pasteur is often credited with settling any remaining beliefs in spontaneous generation. In 1860, Pasteur showed that dust particles in air carried micro-organisms. If boiled meat is exposed to purified air (without dust particles), bacterial growth does not occur.

Nearly two centuries were required to convince the world that Redi's experiment, disproving spontaneous generation, was valid. People reject ideas that undermine their chosen belief systems, even when the science is valid.

-- TO BE CONTINUED --

© 2010 Jules Berman

key words: history of science, Jules J Berman PhD, MD

REJECTION 2

This is the second in a series of blogs on the topic of REJECTION

Sometimes, the best works are found amongst the rejected efforts. In mid-nineteenth century France, rejected artists rose far above the level of orthodox painters. The story goes that the Salon de Paris, the official exhibition of art sponsored by the Academie des Beaux-Arts, rejected works by Monet, Manet, Pissarro, Cezanne, and many others whose concept of art conflicted with long-prevailing sensibilities. Complaints reached the ears of Napoleon III, who allowed rejected words to be displayed in a Salon de Refuses. These exhibitions of selected works are credited with the rise of impressionism. Today, the term "salon des refuses" refers to any exhibit of works that were rejected by a juried show.

Mathematicians have their equivalent of a Salon de Refuses. Today, mathematicians can publish their rejected papers in Rejecta Mathematica, available online at: http://math.rejecta.org/about-rejecta-mathematica. Sometimes, great ideas are not rejected; they're just ignored. Hundreds of years can pass while a deserving idea is discovered, lost, re-discovered, lost again, and so on.

-- TO BE CONTINUED --

© 2010 Jules Berman

key words:informatics, Jules J. Berman Ph.D., M.D., history of science

REJECTION 1

This is the first in a series of blogs on the topic of REJECTION

"That it will ever come into general use, notwithstanding its value, is extremely doubtful because its beneficial application requires much time and gives a good bit of trouble, both to the patient and to the practitioner because its hue and character are foreign and opposed to all our habits and associations."

- The London Times, 1834, reviewing a new medical device, the Stethoscope

The life of a scientist is full of rejection. Rejection is a judgment from your peer community that your work has no merit and should not be rewarded, or even acknowledged. It is an official indictment against your work, and your self-image. A few creative persons seem to thrive on rejection; most whither.

Perhaps nobody has been as deeply ignored, during his short, obscure lifetime, than Vincent Van Gogh (1853 - 1890) . In the last decade of his short life, he produced over 2,000 paintings. He just kept getting better and better at his craft, producing many of his most beloved works in the last two years of his life. Though he had connections to a successful art dealer (his brother Theo), his paintings had no buyers. Rejected and depressed, he took his own life.

John Milton (1608 - 1674) received only 5 pounds, from his publisher, for the manuscript and the copyright for Paradise Lost. The epic poem did not achieve critical acclaim until 30 years after Milton's death.

Herman Melville (1819 - 1891) finished Moby Dick in 1851. He considered it to be his greatest novel, but reviewers disagreed. His publisher printed a small number of first edition books; most went unsold. Melville's career delined after disappointing sales for Moby Dick. Finding publishers for his subsequent works was difficult. Melville was forced to take a job as a customs inspector to make ends meet. He died in almost total obscurity, leaving behind the unpublished manuscript of his last work, Billy Budd. Today, Moby Dick is considered one of America's greatest novels.

From the 1930s to 1960, publishers had little or no interest in Louis Zukofsky (1904 - 1978); he wrote with virtually no audience. His book Barely and Widely sold only 26 copies two months after release. Today, Zukofsky is considered to be one of the greatest poets of the 20th century (1).

David Oshinsky wrote an essay on book rejections discovered in the Alfred A. Knopf, Inc., archive (2). In 1950, Alfred A. Knopf Inc. rejected The Diary of a Young Girl, by Anne Frank. The publisher found the work dull and "a dreary record of typical family bickering, petty annoyances and adolescent emotions." After 15 other publishers passed on the title, Doubleday published the book (over 30 million copies sold). In the same essay, Oshinsky reported that Pearl Buck's The Good Earth was rejected by Knopf (Americans not interested in China), as was George Orwell's Animal Farm, (animal stories don't sell). Also rejected was Isaac Bashevis Singer (rich Jews again), and Sylvia Plath (not enough talent).

Art and literature are subject to personal taste. Science is tethered to objective reality. You would expect that scientific discoveries would be greeted with immediate acceptance because legitimate scientific assertions can be tested and verified. Such is not the case, and the history of discovery is filled with sad stories of great works rejected. A short chronology of scientific rejection follows (3):

480 B.C.E. Democritus (460 B.C.E. - 370 B.C.E.) invents atoms, a theory supplanted by the much more popular "Earth, air, fire, and water" school.

350 B.C. Aristotle (384 B.C.E. - 322 B.C.E.) recognizes that dolphins are mammals. The rest of the world disagrees, classifying dolphins as fish. After two thousand years of derisive laughter, the world eventually agrees with Aristotle.

325 B.C.E. Pytheas (350 B.C.E. - 285 B.C.E.)sails from Greece to Iceland. Pytheas describe Atlantic tides (absent in the smaller Mediterranean sea). When he returned from his remarkable voyage, Pytheas described his voyages and his observations. Nobody believed him.

280 B.C.E. Aristarchus of Samos (310 B.C.E. - 230 B.C.E.) reasons that the sun is the center of the heavens.

240 B.C.E. Eratosthenes of Cyrene (276 B.C.E. - 195 B.C.E.) working in Alexandria, computes size of earth correctly. At the time, the preponderance of scientific opinion favored a flat earth, supported by a giant (Atlas) or possibly a turtle.

134 B.C.E. Hipparchus (190 B.C.E. - 120 B.C.E.) observes a newly appearing star (nova). The western world remains incredulous until Tycho Brahe's observation 1500 years later.

1705 Edmond Halley (1656 - 1742), calculates that his comet would return to the solar system in 1758. Nobody took him seriously, until 1758, when Halley's comet returned.

1747 James Lind (1716 - 1794) determines that citrus prevents scurvy. Takes another 50 years and hundreds, perhaps thousands, of deaths, before British navy listens.

1796 Edward Jenner (1749-1823), writes paper on smallpox vaccination; rejected. Forced to self-publish research results RstrbR.

1847 Ignaz Philipp Semmelweis (1818 - 1865) reduces rate of puerperal fever by hand-washing. Hand washing was soon abandoned by the hospital staff. Semmelweis eventually lost his sanity. To this day, many physicians and healthcare professionals neglect to wash their hands.

1884 Svante August Arrhenius (1859 - 1927) defends his PhD thesis on ionic dissociation. His professors thought it was all wrong, reluctantly passing him with the lowest possible qualifying grade. In 1903, the very same thesis earned Arrhenius the Nobel prize.

1869 One-armed civil war veteran John Wesley Powell (1834 - 1902) is denied federal funding to explore the Grand Canyon; his privately funded exploration is credited with many of the significant discoveries of the Colorado basin.

1892 Georg Ferdinand Ludwig Phillip Cantor (1845 - 1918) publishes the theory of transfinite numbers, to the immediate and vociferous condemnation of the religious, philosophical, and scientific communities. Mathematics, unlike the natural sciences, yields to logic. In 1904, the Royal Society bestowed its highest honor on Cantor.

1987 Fred Cohen, who introduced the term, "computer virus" in a 1984 paper, and who was one of the first scientists to predict the threat of computer viruses, asks the National Science Foundation for a grant to study countermeasures. His grant was denied; not of current interest (4).

[1] Scroggins M. The Poem of a Life: A biography of Louis Zukofsky. Shoemaker & Hoard, Washington, D.C., 2008

[2] Oshinsky D. No thanks, Mr. Nabokov. The New York Times September 9, 2007.

[3] Asimov I. Asimov's Chronology of Science and Discovery. Harper Collins, New York, 1994.

[4] Lemos R. Decades after creation, viruses defy cure. CNET News.com November 25, 2003.

© 2010 Jules Berman

key words:informatics, rejection, history of science, Jules J. Berman Ph.D., M.D.