Philosophical Society of Washington

Minutes of the 2360th Meeting

At the Cosmos Club, Washington, DC
March 18, 2016

President Larry Millstein called the 2360th meeting of the Society to order at 8:05 p.m.  He announced the order of business and welcomed new members.  The minutes of the previous meeting were read and approved.  President Millstein then introduced the speaker for the evening, William H. Velander, Distinguished Scholar and Fellow  of the Department of Chemical and Biomolecular Engineering at the College of Engineering of the University of Nebraska at Lincoln.  His lecture was titled "Genetically Engineered Livestock: Bringing 21st Century Medicines to the Developing World".


Dr. Velander began by noting that the majority of the world does not have access to the level of technology and medical care that we enjoy in the United States.  Some diseases, such as hemophilia, can be effectively treated using current biopharmaceutical production methods, but these methods are so expensive as to be effectively unavailable outside of the wealthiest healthcare systems.

Blood proteins Factor VIII and Factor IX are the basis for the blood clotting response, and the inability to produce these proteins (called Hemophilia A and Hemophila B, respectively), is primarily treated by replacement therapy with these proteins. 

Unfortunately, Dr. Velander explained, Factor IX is also one of the most complicated proteins known to science.  This complex structure is essential to its ability to identify a wound site, as well as its pharmacokinetics, that is, the duration of its availability in the blood stream.  Its complex structure makes it difficult to synthesize, even for human cells.

Today, these substances are produced in “bioreactors”, large stainless steel vats full of cells that produce small amounts of the desired protein.  Such factories can cost approximately $1 billion apiece and produce only 1-4 grams per liter over 72 hours.  This is far too slow to meet research needs, let alone therapeutic needs.

By contrast, production of the same proteins through the milk of transgenic animals could achieve a production of 1-50 grams per liter per hour, if we could achieve a suitable transgenic animal.

The first method attempted was pro-nuclear injection, in which modified DNA strands are simply injected into fertilized eggs.  This approach is imperfect because it creates “mosaic animals” in which some of the cells are modified and others are not.  An improved method is cloning via somatic cell nuclear transfer, in which the nucleus is removed from a fertilized egg and a transgenic nucleus is substituted.

Dr. Velander explained that pigs are his primary research animal for these experiments because they are easier to genetically engineer, they have a short gestation time, and they produce numerous of offspring.  Perhaps even more importantly, a pig’s liver and biochemistry is sophisticated enough to perform the post-translational modifications necessary to create complex molecules such as Factor VIII and Factor IX.

Dr. Velander explained Factor VIII is restricted at the transcription level, meaning that even the human liver does a poor job at making Factor VIII.  As a result, bioreactors have an extremely poor yield of Factor VIII.  Dr. Velander’s transgenic pigs produced greater volume of Factor VIII proteins, but tests showed that only a small portion of the output was correctly assembled into effective Factor VIII.

From this, Dr. Velander concluded that the protein needed to be re-engineered at the genetic level to be simpler for the cellular machinery to construct.  The resulting recombinant Factor VIII was as therapeutically effective as the best alternatives on the market, but could be created at one thousand times the volume.

To put these advances into context, Dr. Velander showed that in order to meet the current worldwide annual need for Factor IX to treat hemophilia B patients, we would need to process 8,000 liters of human plasma per year.  Using current transgenic techniques, this same volume of Factor IX could be produced from the milk of 2,500 pigs.

Dr. Velander concluded by noting that the project to bring Factor VIII, Factor IX, and other recombinant biopharmaceuticals into production will continue to require substantial investment, much of which is likely to be led by developing countries seeking to ensure that their citizens can benefit from these next-generation techniques.

After the conclusion of the talk, President Millstein invited questions from the audience.

One questioner asked if recombinant thrombin could be useful in treating traumatic wounds and massive bleeding.  Dr. Velander explained that there is generally insufficient endogenous fibrinogen at such wound sites for this to be effective, but that it remains a valuable treatment for smaller wounds such as during surgery.

Another questioner asked whether the genetically engineered animals or their milk are dangerous to humans.  Dr. Velander responded that these modifications are only expressed in the milk, and that in any case the GE proteins are substantially the same as those already existing in the animals.  In other words, the transgenic animals are safe enough to eat.

After the question and answer period, President Millstein thanked the speaker, made the usual housekeeping announcements, and invited guests to join the Society.  At 10:04 p.m., President Millstein adjourned the 2360th meeting of the Society to the social hour.


Attendance: 76
The weather: Clear
The temperature: 14°C

Respectfully submitted,

Preston Thomas
External Communications Director


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